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CONTACT DETAILS FOR AUSTRALIAN, STATE AND TERRITORY GOVERNMENT HEALTH AUTHORITIES Australian Government health authorities Australian Government Health
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What’s new? – Changes introduced in this edition of the Handbook See Chapter 1.1
COMPARISON OF THE EFFECTS OF DISEASES AND THE SIDE EFFECTS OF VACCINES DISEASE
EFFECT OF DISEASE
SIDE EFFECT OF VACCINE
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ADVERSE EVENTS FOLLOWING IMMUNISATION Commonly observed adverse events following immunisation with vaccines used in the National Immunisation Program (NIP) schedule and what to do about them The following information can be photocopied and given as post-vaccination advice. All the common adverse events following immunisation are usually mild and transient and treatment is not usually required. If the adverse event following immunisation is severe or persistent, or if you are worried about yourself or your child’s condition, see your doctor or immunisation clinic nurse as soon as possible or go to a hospital. Adverse events may be reported via ADRAC, State and Territory Health Authorities or via immunisation service providers. Diphtheria-tetanus-pertussis (acellular) DTPa-containing vaccines and dTpa (adolescent/adult) vaccines
Haemophilus influenzae type b vaccine (Hib)
Hepatitis A vaccine (HepA) (Indigenous children NT, QLD, SA, WA)
Hepatitis B vaccine (HepB)
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t -PXHSBEFUFNQFSBUVSF GFWFS
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t -PXHSBEFUFNQFSBUVSF GFWFS
t -PXHSBEFUFNQFSBUVSF GFWFS
t -PXHSBEFUFNQFSBUVSF GFWFS
In children the following may also occur: t *SSJUBCMF DSZJOH VOTFUUMFEBOE generally unhappy t %SPXTJOFTTPSUJSFEOFTT Human papillomavirus vaccine (HPV)
Influenza vaccine
Measles-mumps-rubella vaccine (MMR)
Meningococcal C conjugate vaccine (MenCCV)
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t %SPXTJOFTTPSUJSFEOFTT
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t *SSJUBCMF DSZJOH VOTFUUMFEBOE generally unhappy
Seen 7–10 days after vaccination:
t -PTTPGBQQFUJUF
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t %SPXTJOFTTPSUJSFEOFTT
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t -PXHSBEFUFNQFSBUVSF GFWFS
t .JMEIFBEBDIF t .JMEOBVTFB
t .VTDMFBDIFT t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed) t -PXHSBEFUFNQFSBUVSF GFWFS
t 4XFMMJOHPGTBMJWBSZHMBOET
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t -PXHSBEFUFNQFSBUVSF GFWFS
Pneumococcal vaccines (conjugate 7vPCV and polysaccharide 23vPPV)
Inactivated poliomyelitis vaccine (IPV) and IPV-containing vaccines
Rotavirus vaccine
Varicella vaccine (VV)
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t .VTDMFBDIFT
t 7PNJUJOHBOEEJBSSIPFBDBOPDDVSVQ to 7 days following vaccination
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed) t -PXHSBEFUFNQFSBUVSF GFWFS
t -PDBMJTFEQBJO SFEOFTTBOE swelling at injection site
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t 0DDBTJPOBMMZJOKFDUJPOTJUFOPEVMF NBZ last many weeks (no treatment needed)
t 5FNQFSBUVSF GFWFS DBOCF 0C)
t -PXHSBEFUFNQFSBUVSF GFWFS
Seen 5–26 days after vaccination: t 1VTUVMBSSBTI oMFTJPOT VTVBMMZBUJOKFDUJPO site, occasionally other parts of the body
Key to table DTPa
diphtheria-tetanus-pertussis acellular (infant/child formulation)
IPV
inactivated poliomyelitis vaccine
dTpa
diphtheria-tetanus-pertussis acellular (adolescent/adult formulation)
MenCCV
meningococcal C conjugate vaccine
HepA
hepatitis A vaccine
MMR
measles-mumps-rubella vaccine
HepB
hepatitis B vaccine
7vPCV
7-valent pneumococcal conjugate vaccine
Hib
Haemophilus influenzaeUZQFCWBDDJOF 1310.1PS1315
23vPPV
WBMFOUQOFVNPDPDDBMQPMZTBDDIBSJEFWBDDJOF
HPV
human papillomavirus vaccine
Rotavirus
rotavirus vaccine
Influenza
influenza or flu vaccine
VV
varicella vaccine
What to do to manage injection site discomfort .BOZWBDDJOFJOKFDUJPOTNBZSFTVMUJOTPSFOFTT SFEOFTT JUDIJOH TXFMMJOHPSCVSOJOHBUUIFJOKFDUJPOTJUFGPSUPEBZT1BSBDFUBNPMNJHIUCFSFRVJSFEUPFBTFUIF EJTDPNGPSU4PNFUJNFTBTNBMM IBSEMVNQNBZQFSTJTUGPSTPNFXFFLTPSNPOUIT5IJTTIPVMEOPUCFPGDPODFSOBOESFRVJSFTOPUSFBUNFOU Managing fever after immunisation (JWFFYUSBøVJETUPESJOL%POPUPWFSESFTTBOJOGBOUJGIPU"MUIPVHIUIFSPVUJOFVTFPGQBSBDFUBNPMBUUIFUJNFPGWBDDJOBUJPOJTOPMPOHFSOFDFTTBSZ JUNBZCFSFRVJSFEJG GPSFYBNQMF BOJOGBOUPSDIJMEIBTBIJHIGFWFSGPMMPXJOHWBDDJOBUJPO5IFEPTFPGQBSBDFUBNPMJTNHLHPGQBSBDFUBNPMMJRVJE VQUPBNBYJNVNEBJMZEPTFPGNHLHQFSEBZ
Copyright © Australian Government 2008 Paper-based publication This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced by any process without written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney-General’s Department, Robert Garran Offices, National Circuit, Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca ISBN 1-74186-483-6 Electronic documents This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use, or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests for further authorisation should be directed to the Commonwealth Copyright Administration, Attorney-General’s Department, Robert Garran Offices, National Circuit, Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca Online ISBN: 1-74186-484-4 Publication Approval Number: 2923
Disclaimer While every effort has been made to check drug dosage recommendations in this Handbook, it is still possible that errors have been missed. Furthermore, dosage recommendations are continually being revised and new adverse events recognised. Trade names used in this publication are for identification purposes only. Their use does not imply endorsement of any particular brand of drug or vaccine. This Handbook is a general guide to appropriate practice subject to clinician’s judgement in each individual case. It is designed to provide information to assist decision making using the best information available at date of National Health and Medical Research Council approval (11 October 2007). The Australian Government Department of Health and Ageing does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information.
The NHMRC The National Health and Medical Research Council (NHMRC) is Australia’s leading funding body for health and medical research. The NHMRC also provides the government, health professionals and the community with expert and independent advice on a range of issues that directly affect the health and well being of all Australians. The NHMRC provided support to this project through its Guidelines Assessment Register (GAR) process. The GAR consultant on this project was Biotext Pty Ltd. These Guidelines, apart from Chapters 3.7 and 3.9, were approved by the Chief Executive Officer of the NHMRC under Section 14A of the National Health and Medical Research Council Act, 1992 on 17 July 2007. The remaining two chapters were approved on 11 October 2007.
The ATAGI The Australian Technical Advisory Group on Immunisation (ATAGI) was established by the then Minister for Health and Family Services in 1998 to provide expert technical and scientific advice on the Immunise Australia Program and to work cooperatively with the NHMRC on issues such as the The Australian Immunisation Handbook.
The Handbook This Handbook is published approximately every three years but changes to the recommendations or schedule may occur between publications. The Handbook and any changes between publications are available on the website: www.immunise.health.gov.au. This hardcopy version of the Handbook does not contain any references — these are available on the electronic version. Ninth Edition January 2008
ii The Australian Immunisation Handbook 9th Edition
PREFACE The 9th edition of The Australian Immunisation Handbook was prepared by the Australian Technical Advisory Group on Immunisation of the Australian Government Department of Health and Ageing.
Members of the Australian Technical Advisory Group on Immunisation Chair Professor Terry Nolan, Paediatrician and Epidemiologist and Head, School of Population Health, The University of Melbourne, VIC.
Members Ms Jenny Bourne, Assistant Secretary, Targeted Prevention Programs Branch, Population Health Division, Australian Government Department of Health and Ageing, ACT. Ms Sue Campbell-Lloyd, Manager, Immunisation Unit, AIDS/Infectious Diseases Branch, NSW Health, NSW. Dr Grahame Dickson, Medical Officer, Drug Safety and Evaluation Branch, Therapeutic Goods Administration, Australian Government Department of Health and Ageing, ACT. Dr Nicole Gilroy, Staff Specialist, Infectious Diseases, Westmead Hospital, Centre for Infectious Diseases and Microbiology, Western Sydney Area Health Service, and Infectious Diseases Physician, BMT Network, NSW. Dr Jeffrey Hanna, Medical Director, Communicable Disease Control, Tropical Population Health Unit, Queensland Health, QLD. Ms Jenni Howlett, State President, Child Health Association, TAS. Clinical Professor David Isaacs, Paediatrician, Department of Immunology and Infectious Diseases, The Children’s Hospital at Westmead, NSW. Ms Ann Kempe, Surveillance Manager, CCRE in Child and Adolescent Immunisation, Murdoch Children’s Research Institute, Royal Children’s Hospital, VIC. Dr Rosemary Lester, Assistant Director, Public Health Branch, Communicable Disease Control Unit, Department of Human Services, VIC. Professor Peter McIntyre, Professor of Paediatrics and Preventive Medicine, The University of Sydney, and Director, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The Children’s Hospital at Westmead, NSW. Dr Joanne Molloy, General Practitioner, Medical Officer of Health, City of Greater Geelong, and Immunisation Program Manager, GP Association of Geelong, VIC. Associate Professor Michael Nissen, Director of Infectious Diseases and Clinical Microbiologist, Unit Head of Queensland Paediatric Infectious Disease Laboratory, and Associate Professor in Biomolecular, Biomedical Science and Health, Royal Children’s Hospital, QLD.
Preface iii
Dr Rod Pearce, General Practitioner, Medical Officer of Health, Eastern Health Authority, Adelaide and GP Immunisation Advisor, Adelaide Central and Eastern Division of General Practice, SA. Dr Peter Richmond, Senior Lecturer, University of Western Australia, School of Paediatrics and Child Health, and General Paediatrician and Paediatric Immunologist, Princess Margaret Hospital for Children, WA. Dr Sue Skull, Paediatrician, Clinical Epidemiologist and Public Health Physician, and Senior Lecturer, Department of Paediatrics, The University of Melbourne, VIC.
Secretary Ms Letitia Toms, Director, Immunisation Policy Section, Targeted Prevention Programs Branch, Population Health Division, Australian Government Department of Health and Ageing, ACT.
Secretariat support, Australian Technical Advisory Group on Immunisation Ms Brigid Dohnt, Mrs Claire Kellie, Ms Jacinta Holdway, Mr John Mohoric, Ms Sally Warild.
Technical Editors Dr Jane Jelfs, Immunisation Handbook and Policy Support Coordinator, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The Children’s Hospital at Westmead, NSW. Dr Kristine Macartney, Senior Research Fellow, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The Children’s Hospital at Westmead, NSW.
Handbook Technical Support Ms Catherine King, Information Manager, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The Children’s Hospital at Westmead, NSW. Ms Donna Armstrong, Communications Officer, National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The University of Sydney and The Children’s Hospital at Westmead, NSW.
Technical Writers Dr Julia Brotherton, Dr Tony Gherardin, Ms Heather Gidding, Dr Kate Hale, Dr Jeffrey Hanna, Ms Anita Heywood, Professor David Isaacs, Dr Jane Jelfs, Ms Ann Kempe, Dr Kristine Macartney, Professor Peter McIntyre, Mr Robert Menzies, Dr Joanne Molloy, Dr Helen Quinn, Dr Yashwant Sinha, Dr Nicholas Wood.
iv The Australian Immunisation Handbook 9th Edition
Acknowledgments Associate Professor Ross Andrews
Dr Amanda Leach
Professor Graeme Barnes
Dr Julie Leask
Professor Richard Benn
Professor Raina MacIntyre
Associate Professor Beverley Biggs
Professor Barrie Marmion
Professor Julie Bines
Dr Helen Marshall
Dr Ian Boyd
Dr Brad McCall
Professor Anthony Brown
Dr Treasure McGuire
Professor Margaret Burgess
Ms Cathlyn McInnes
Dr Jim Buttery
Dr Moira McKinnon
Professor Jonathan Carapetis
Dr Jodie McVernon
Dr Louise Causer
Dr Ann Mijch
Ms Patricia Coward
Professor Kim Mulholland
Dr Angela Dean
Dr Neil Parker
Dr Ki Douglas
Ms Karen Peterson
Ms Barbara Eldred
Ms Susie Prest
Mr Lloyd Ellis
Professor William Rawlinson
Professor Kevin Forsyth
Dr Jenny Royle
Professor Lyn Gilbert
Dr Tilman Ruff
Dr Mike Gold
Ms Andrea Schaffer
Dr Robert Hall
Dr Rosalie Schultz
Dr Alan Hampson
Dr Christine Selvey
Professor Mark Harris
Dr Linda Selvey
Ms Trish Harris
Ms Barbara Steadman
Dr Bronwen Harvey
Dr John Sullivan
Dr Bob Kass
Mr Sean Tarrant
Dr Heath Kelly
Dr Diana Thomas
Dr Vicki Krause
Dr Bruce Thorley
Dr Andrew Langley
Dr Melanie Wong
Dr Glenda Lawrence
Dr Margaret Young
Preface v
Contents PART 1: VACCINATION PROCEDURES
1
Introduction to The Australian Immunisation Handbook
1
1.1 What’s new?
3
1.2 An overview of vaccination – preface to Chapters 1.3–1.5
7
1.3 Pre-vaccination procedures 1.3.1 Preparing an anaphylaxis response kit 1.3.2 Effective cold chain: transport, storage and handling of vaccines 1.3.3 Valid consent 1.3.4 Pre-vaccination screening 1.3.5 Catch-up
8 8 8 12 14 21
1.4 Administration of vaccines 1.4.1 Occupational health and safety issues 1.4.2 Equipment for vaccination 1.4.3 Route of administration 1.4.4 Preparation for vaccine administration 1.4.5 Vaccine injection techniques 1.4.6 Recommended injection sites 1.4.7 Positioning for vaccination 1.4.8 Identifying the injection site 1.4.9 Administering multiple vaccine injections at the same visit
39 39 39 41 43 44 45 47 51 56
1.5 Post-vaccination procedures 1.5.1 Immediate after-care 1.5.2 Adverse events following immunisation 1.5.3 Documentation of vaccination 1.5.4 The Australian Childhood Immunisation Register
58 58 58 66 67
PART 2: Vaccination for special risk groups
70
2.1 Vaccination for Aboriginal and Torres Strait Islander people
70
2.2 Vaccination for international travel
75
2.3 Groups with special vaccination requirements 2.3.1 Vaccination of children who have had a serious adverse event following immunisation (AEFI) 2.3.2 Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants 2.3.3 Vaccination of individuals with impaired immunity due to disease or treatment 2.3.4 Vaccination of recent recipients of normal human immunoglobulin 2.3.5 Vaccination of patients following receipt of other blood products including blood transfusions 2.3.6 Vaccination of patients with bleeding disorders 2.3.7 Vaccination before or after anaesthesia/surgery 2.3.8 Vaccination of those at occupational risk
84
vi The Australian Immunisation Handbook 9th Edition
84 84 90 102 102 104 104 104
2.3.9 2.3.10 2.3.11 2.3.12
Vaccination of immigrants to Australia Vaccination of inmates of correctional facilities Vaccination of men who have sex with men Vaccination of injecting drug users
PART 3: Vaccines listed by disease
108 108 108 109
110
3.1 Australian bat lyssavirus infection and rabies
110
3.2 Cholera
120
3.3 Diphtheria
124
3.4 Haemophilus influenzae type b (Hib)
131
3.5 Hepatitis A
139
3.6 Hepatitis B
149
3.7 Human papillomavirus
164
3.8 Immunoglobulin preparations
175
3.9 Influenza
184
3.10 Japanese encephalitis
195
3.11 Measles
201
3.12 Meningococcal disease
213
3.13 Mumps
223
3.14 Pertussis
227
3.15 Pneumococcal disease
240
3.16 Poliomyelitis
251
3.17 Q fever
257
3.18 Rotavirus
265
3.19 Rubella
274
3.20 Smallpox
283
3.21 Tetanus
288
3.22 Tuberculosis
297
3.23 Typhoid
303
3.24 Varicella
309
3.25 Yellow fever
322
3.26 Zoster (herpes zoster)
329
Contents vii
Appendix 1: Contact details for Australian, State and Territory Government health authorities and communicable disease control
332
Appendix 2: Handbook development
334
Appendix 3: Products registered in Australia but not currently available
339
Appendix 4: Components of vaccines used in the National Immunisation Program
340
Appendix 5: Commonly asked questions about vaccination
344
Appendix 6: Definitions of adverse events following immunisation
360
Appendix 7: Glossary of technical terms
364
Appendix 8: List of commonly used abbreviations
369
Appendix 9: Dates when vaccines became available in Australia
372
Appendix 10: Summary table – procedures for a vaccination encounter
375
Index
378
viii The Australian Immunisation Handbook 9th Edition
Index of Tables Table 1.3.1: Pre-vaccination screening checklist
16
Table 1.3.2: Responses to relevant conditions or circumstances identified by the pre-vaccination screening checklist
17
Table 1.3.3: Live attenuated parenteral and oral vaccines
20
Table 1.3.4: False contraindications to vaccination
21
Table 1.3.5: Number of vaccine doses that should have been administered by the current age of the child (table to be used in conjunction with Catch-up Worksheet)
28
Table 1.3.6: Minimum dose intervals for NIP vaccines for children <8 years of age (table to be used in conjunction with Catch-up Worksheet)
29
Table 1.3.7: Minimum age for the first dose of vaccine in exceptional circumstances
30
Table 1.3.8: Recommendations for Hib catch-up vaccination for children <5 years of age when doses have been delayed or missed
33
Table 1.3.9: Recommendations for pneumococcal catch-up vaccination for low-risk children (including Indigenous children living in ACT, NSW, VIC and TAS) <2 years of age, when doses have been delayed or missed
34
Table 1.3.10: Recommendations for pneumococcal catch-up vaccination for Indigenous children <2 years of age in NT, QLD, SA and WA, when doses have been delayed or missed
35
Table 1.3.11: Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age with underlying medical conditions
36
Table 1.3.12: Catch-up schedules for individuals ≥8 years of age
38
Table 1.4.1: Route of administration for vaccines commonly used in Australia
42
Table 1.4.2: Recommended needle size, length and angle for administering vaccines
45
Table 1.5.1: Clinical features which may assist differentiation between a vasovagal episode and anaphylaxis
62
Table 1.5.2: Doses of intramuscular 1:1000 (one in one thousand) adrenaline for anaphylaxis
64
Table 1.5.3: Contact details for notification of AEFI
66
Table 2.2.1: Dose and routes of administration of commonly used vaccines in adult travellers (≥15 years of age)
80
Table 2.2.2: Recommended lower age limits of travel vaccines for children
82
Table 2.3.1: Vaccinations in pregnancy
86
Table 2.3.2: Recommendations for vaccinations for solid organ transplant (SOT) recipients
95
Contents ix
Table 2.3.3: Post-transplantation vaccination schedules for allogeneic and autologous haematopoietic stem cell transplant recipients
98
Table 2.3.4: Immunological categories based on age-specific CD4 counts and percentage of total lymphocytes
99
Table 2.3.5: Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination
103
Table 2.3.6: Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases
105
Table 3.1.1: Summary of Australian bat lyssavirus and rabies postexposure treatment for non-immune individuals
117
Table 3.5.1: Recommended dosages and schedules for use of the inactivated hepatitis A vaccines
143
Table 3.5.2: Recommended doses of normal human immunoglobulin (NHIG) to be given as a single intramuscular injection to close contacts of hepatitis A cases
146
Table 3.6.1: Hepatitis B and hepatitis A/hepatitis B combination vaccination schedules
155
Table 3.6.2: Accelerated hepatitis B vaccination schedules
156
Table 3.6.3: Post-exposure prophylaxis for non-immune individuals exposed to an HBsAg positive person
162
Table 3.9.1: Recommended doses of influenza vaccine
189
Table 3.11.1: Management of significant measles exposure using vaccination or normal human immunoglobulin (NHIG)
212
Table 3.12.1: Early clinical management of suspected meningococcal disease
220
Table 3.14.1: Recommended antimicrobial therapy and chemoprophylaxis regimens for pertussis in infants, children and adults
236
Table 3.15.1: Summary table – pneumococcal vaccination schedule for children ≤9 years of age (see also Section 1.3.5, Catch-up)
245
Table 3.15.2: Underlying medical conditions predisposing children ≤9 years of age to IPD
246
Table 3.15.3: Revaccination with 23vPPV for people ≥10 years of age
248
Table 3.17.1: Interpretation and action for serological and skin test results
261
Table 3.18.1: Age limits for dosing of oral rotavirus vaccines
269
Table 3.21.1: Guide to tetanus prophylaxis in wound management
294
Table 3.24.1: Recommendations for varicella vaccination with monovalent VV (currently available), and once MMRV vaccines are available
313
Table 3.24.2: Zoster immunoglobulin-VF (ZIG) dose based on weight
320
Table 3.25.1: Yellow fever endemic countries
324
x The Australian Immunisation Handbook 9th Edition
Index of Figures Figure 1.3.1: Catch-up Worksheet for children <8 years of age
27
Figure 1.4.1: The cuddle position for vaccination of a child <12 months of age
47
Figure 1.4.2: Positioning an infant on an examination table for vaccination
48
Figure 1.4.3: Positioning an older child in the cuddle position
49
Figure 1.4.4: Positioning a child in the straddle position
50
Figure 1.4.5: Diagram of the muscles of the thigh showing the anatomical markers to identify the recommended (vastus lateralis) injection site
52
Figure 1.4.6: Photograph of the thigh showing the recommended (vastus lateralis) injection site
52
Figure 1.4.7: Diagram showing the anatomical markers to identify the ventrogluteal injection site
53
Figure 1.4.8: Photograph with infant prone across carer’s lap, showing markers to identify the ventrogluteal injection site
54
Figure 1.4.9: Diagram showing the anatomical markers to identify the deltoid injection site
55
Figure 1.4.10: A subcutaneous injection into the deltoid area of the upper arm using a 25 gauge, 16 mm needle, inserted at a 45° angle
55
Figure 1.4.11: Recommended technique for giving multiple vaccine injections to an infant <12 months of age into the anterolateral thigh
56
Figure 3.4.1:
aemophilus influenzae type b (Hib) notifications, presumed H Hib hospitalisations and deaths of children aged 0 to 4 years from Hib, Australia 1993 to 2005
133
Figure 3.5.1: Notifications of hepatitis A in Australia, 1991 to 2006
140
Figure 3.6.1: The influence of age of infection with the hepatitis B virus on the likelihood of becoming a hepatitis B carrier
150
Figure 3.7.1: The dynamic relationship between HPV infection and cervical health
167
Figure 3.9.1: Influenza notification rates 2003–2005 and hospitalisation rates 2002/2003 to 2004/2005, Australia, by age group
186
Figure 3.10.1: Map of the Torres Strait
196
Figure 3.14.1: Pertussis notifications by year of onset, Australia 1993–2005
228
Figure 3.17.1: Q fever notifications and hospitalisations, Australia, 1993 to 2005, by month of diagnosis or admission
258
Contents xi
xii The Australian Immunisation Handbook 9th Edition
PART 1: VACCINATION PROCEDURES Introduction to The Australian Immunisation Handbook For more than 200 years, since Edward Jenner first demonstrated that vaccination offered protection against smallpox, the use of vaccines has continued to reduce the burden of many bacterial and viral diseases. As a result of successful vaccination programs, deaths from tetanus, diphtheria, Haemophilus influenzae type b and measles are now extremely rare in Australia.1 Vaccination not only protects individuals, but also others in the community, by increasing the general level of immunity and minimising the spread of infection. It is vital that healthcare professionals take every available opportunity to vaccinate children and adults. It is also important that the public be made aware of the proven effectiveness of immunisation to save lives and prevent serious illness. The purpose of The Australian Immunisation Handbook is to provide clinical guidelines for health professionals on the safest and most effective use of vaccines in their practice. These recommendations are developed by the Australian Technical Advisory Group on Immunisation (ATAGI) and endorsed by the National Health and Medical Research Council (NHMRC). The Handbook provides clinical recommendations based on the best scientific evidence available at the time of publication from published and unpublished literature. Further details regarding the Handbook revision procedures are described in Appendix 2. Where specific empiric evidence was unavailable, recommendations were formulated using the best available expert opinion relevant to Australia. The reference lists for all chapters are included in the electronic version of the Handbook which is available via the Immunise Australia website (www.immunise.health.gov.au). The electronic version of the Handbook has additional information regarding recommendations in the new vaccine chapters, including systematic reviews of the literature. In some instances, the NHMRC recommendations differ from vaccine product information sheets (PI); these differences are detailed in the relevant vaccine chapters under the heading ‘Variations from product information’. Where a variation exists, the NHMRC recommendation should be considered best practice. The information contained within the Handbook was correct at the time of printing. However, the content of the Handbook is reviewed regularly. The 9th edition of The Australian Immunisation Handbook will remain current unless amended electronically via the Immunise Australia website or until the 10th edition of the Handbook is published.
Introduction 1
ELECTRONIC UPDATES to the 9th edition of The Australian Immunisation Handbook will be available at: www.immunise.health.gov.au
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
2 The Australian Immunisation Handbook 9th Edition
1.1 What’s new? All chapters have been updated and revised where necessary. The 9th edition introduces new vaccines, changes to the schedules, changes to recommendations and procedures regarding the administration of vaccines, and changes to the presentation of the Handbook. Some changes made since the publication of the hard copy of the 8th edition of the Handbook in September 2003, and before the 9th edition, were available online on the Immunise Australia website and are not described below. The term Australian Standard Vaccination Schedule (ASVS) is no longer used in the Handbook. The National Immunisation Program (NIP) is used throughout the Handbook and refers to funded vaccines as they appear on the National Immunisation Program (NIP) schedule. The NIP schedule may change over time and is available via the Immunise Australia website (www.immunise.health.gov.au).
New chapters and chapters which no longer appear in the Handbook • Three new chapters have been included in the Handbook – 3.7 Human papillomavirus, 3.18 Rotavirus and 3.26 Zoster. • There are 4 new appendices in the Handbook. These are ‘Handbook development’ (Appendix 2); a list of vaccines which are registered in Australia but either not currently available or no longer available in Australia (Appendix 3); a list of major components in the vaccines in the National Immunisation Program (Appendix 4); and a table that is a summary of procedures for a vaccination encounter (Appendix 10). • Two chapters have been deleted: anthrax and plague. For information about anthrax, please go to the Australian Government website www.health.gov.au and use the index option to select the anthrax fact sheet. • Three chapters previously in the 8th edition, botulism, cytomegalovirus and respiratory syncytial virus, have been incorporated into the immunoglobulin chapter (3.8 Immunoglobulin preparations).
Overview of major changes to existing recommendations and procedures Part 1 • The layout of Part 1 has been altered from previous editions of the Handbook into 3 chapters which are described in Chapter 1.2 An overview of vaccination. The new layout applies to Chapter 1.3 Pre-vaccination procedures (including cold chain, consent, pre-vaccination screening and catch-up); Chapter 1.4
What's new? 3
1.1 What’s new?
Changes introduced in this edition of the Handbook
Administration of vaccines (including route, needle size and injection site); and Chapter 1.5 Post-vaccination procedures (including adverse events following immunisation, and the recording of vaccinations). • Advice on preparing an anaphylaxis response kit has been added to prevaccination procedures, Chapter 1.3. • The pre-vaccination screening checklist and assessment table have been revised and recommended steps for screening added to the section, Chapter 1.3. • The cold chain guidelines have been updated in Chapter 1.3 and the recommendations summarised to reflect and reference the National Vaccine Storage Guidelines: Strive for 5. • The valid consent section has been redrafted and updated. • The recommended anatomical site for intramuscular (IM) administration of vaccines in infants <12 months of age is the anterolateral thigh. • The recommended anatomical site for IM administration of vaccines in those ≥12 months of age is the deltoid. • The ventrogluteal area is included as an alternative anatomical site for the administration of vaccines at any age. This is based on published data. It is important that vaccine providers using this site are trained in the recognition of the relevant anatomical landmarks. • The recommended needle size and length for IM injection is 23 or 25 gauge, 25 mm in length. • The recommended angle of insertion of the needle for IM administration of vaccines is 90º to the skin surface. • Injection techniques have been described in more detail with additional photographs and/or diagrams demonstrating positions and the recommended anatomical sites. • Catch-up schedules have been updated for vaccines in the National Immunisation Program and practical tools to assist with catch-up added. • A table of catch-up schedules for individuals aged ≥8 years has been included. • Information on reporting of adverse events following immunisation has been updated to reflect recent changes to the national reporting arrangements. • Information on the Australian Childhood Immunisation Register has been updated. • The table previously in the 8th edition Handbook entitled ‘Information on vaccines exposed to different temperatures’ has been deleted as some of the information is no longer considered valid. • Management of anaphylaxis with 1:10 000 adrenaline is no longer recommended; use of 1:1000 adrenaline is recommended.
4 The Australian Immunisation Handbook 9th Edition
• Tools to photocopy include the pre-vaccination checklist, catch-up work sheet, and Appendix 10 Summary table – procedures for a vaccination encounter. • Recommendations for groups with special vaccination requirements (Chapter 2.3) have undergone substantial revision and incorporate new tables and separate sections for pregnant and breastfeeding women and women planning pregnancy, preterm infants, people with impaired immunity, oncology patients and transplant recipients. • Recommendations for immunisation of certain occupational groups have been expanded (Chapter 2.3). • A comprehensive table outlining the suggested intervals between receipt of either a blood product or an immunoglobulin-containing product and administration of either measles, mumps, rubella or varicella vaccines is included (Chapter 2.3).
Part 3 Chapters 3.3 Diphtheria and 3.21 Tetanus • For adults requiring a primary course of dT, dTpa is recommended for the first dose followed by 2 doses of dT (or dTpa only if dT is unavailable).
Chapter 3.6 Hepatitis B • For preterm babies, recommendations for hepatitis B vaccination have been revised.
Chapter 3.8 Immunoglobulin preparations • Botulism, cytomegalovirus and respiratory syncytial virus are now incorporated into this chapter.
Chapter 3.9 Influenza • For children aged 6 months to <3 years the dose of influenza vaccine is 0.25 mL. • It is recommended that all Aboriginal and Torres Strait Islander people aged ≥15 years receive annual influenza vaccination. • It is recommended that children ≥6 months of age and adults with a chronic neurological condition receive annual influenza vaccination.
Chapters 3.11 Measles, 3.13 Mumps and 3.19 Rubella • The second dose of MMR vaccine is recommended at 18 months of age, not at 4 years of age. • The use of MMRV vaccines, when available, is discussed.
What's new? 5
1.1 What’s new?
Part 2
Chapter 3.12 Meningococcal disease • Close household contacts of a case of invasive meningococcal disease should be vaccinated as well as receiving antibiotic prophylaxis.
Chapter 3.14 Pertussis • For adults requiring a primary course of dT, dTpa is recommended for the first dose followed by 2 doses of dT (or dTpa only if dT is unavailable). • A new table detailing antibiotic prophylaxis for pertussis cases and their contacts has been included.
Chapter 3.15 Pneumococcal disease • Children ≤9 years of age with specified underlying medical conditions should receive 2 doses of 7-valent pneumococcal conjugate vaccine followed by a dose of 23-valent pneumococcal polysaccharide vaccine. • Recommendations for revaccination of adults with 23-valent pneumococcal polysaccharide vaccine have been revised and tabulated.
Chapter 3.24 Varicella • When combination measles, mumps, rubella and varicella vaccine/s (MMRV) become available, it is recommended that varicella vaccination be given at 12 months of age, using MMRV. • Administration of a second dose of varicella-containing vaccine in children aged <14 years is recommended to minimise the risk of breakthrough disease.
Chapter 3.25 Yellow fever • Yellow fever vaccine is now recommended for travellers (provided there are no contraindications) going to urban and/or rural areas of endemic countries.
6 The Australian Immunisation Handbook 9th Edition
1.2 An overview of vaccination – preface to Chapters 1.3–1.5 The following sections of Part 1 (Chapters 1.3–1.5) describe chronologically the steps involved around a vaccination encounter, starting with pre-vaccination requirements (Chapter 1.3), then administration of vaccines (Chapter 1.4) and post-vaccination considerations (Chapter 1.5).
Chapter 1.4 provides detailed sections on the administration of vaccines. This chapter discusses occupational health and safety issues and the equipment required for vaccination. Techniques for vaccine administration, including the route and site of vaccine administration, positioning, identifying the vaccination site, and methods for administering multiple vaccine injections at the same visit are described in detail. Chapter 1.5 provides readers with information on post-vaccination care, including immediate after-care and the recognition and management of adverse events following immunisation (AEFI), including anaphylaxis. There are also sections on how to report AEFI, documentation of vaccination, and details about the Australian Childhood Immunisation Register. A summary of the key points discussed in these chapters is provided in the table in Appendix 10, Summary table – procedures for a vaccination encounter. This is suitable for photocopying for training and auditing purposes.
An overview of vaccination – preface to Chapters 1.3–1.5 7
1.2 An overview of vaccination – preface to Chapters 1.3–1.5
Chapter 1.3 describes the steps required in preparing for a vaccination encounter. This includes preparation of an anaphylaxis response kit and effective cold chain management (transport, storage and handling of vaccines) as described in National Vaccine Storage Guidelines: Strive for 5. The next section discusses obtaining valid consent and is followed by information on comprehensive pre-vaccination health screening, including a standard screening checklist and summary tables of precautions and contraindications to vaccination. The chapter ends with a section on how to manage catch-up vaccination. The section is divided into two categories; the first for children <8 years of age and the second for people ≥8 years of age.
1.3 Pre-vaccination procedures The following sections discuss steps and procedures that should occur before a vaccination encounter. In addition, Appendix 10, Summary table – procedures for a vaccination encounter provides a table summarising the procedures described in this chapter.
1.3.1 Preparing an anaphylaxis response kit The availability of protocols, equipment and drugs necessary for the management of anaphylaxis should be checked before each vaccination session. An anaphylaxis response kit should be on hand at all times and should contain: • adrenaline 1:1000 (minimum of 3 ampoules – check expiry dates), • minimum of three 1 mL syringes and 25 mm length needles (for IM injection), • cotton wool swabs, • pen and paper to record time of administration of adrenaline, and • laminated copy of Recognition and treatment of anaphylaxis (back cover of this Handbook). Section 1.5.2 provides details on recognition and treatment of adverse events following immunisation.
1.3.2 Effective cold chain: transport, storage and handling of vaccines1,2 The cold chain is the system of transporting and storing vaccines within the temperature range of +2°C to +8°C from the place of manufacture to the point of administration. All immunisation service providers should be familiar with and adhere to the National Vaccine Storage Guidelines: Strive for 5. This publication can be accessed free of charge from http://www.immunise.health.gov.au/internet/immunise/ publishing.nsf/Content/provider-store The National Vaccine Storage Guidelines: Strive for 5 contain specific details on setting up the infrastructure for a vaccination service, and immunisation service providers should refer to this to ensure that satisfactory equipment and procedures are in place before commencing vaccination services. The Guidelines also provide instructions on how to best transport vaccines from the main storage facility to outreach or external clinics using a cooler. With correct temperature monitoring and adherence to the cold chain Guidelines, any problems in vaccine storage should be detected early and handled appropriately before compromised vaccine is administered.
8 The Australian Immunisation Handbook 9th Edition
Purpose-built vaccine refrigerators (PBVR) are the preferred means of storage for vaccines. Domestic refrigerators are designed and built for food and drink storage, not for the special temperature needs of vaccines. Cyclic defrost and bar refrigerators are not recommended because they produce wide fluctuations in internal temperatures and regular internal heating. Bar refrigerators, in particular, should not be used because of the risk of freezing, temperature instability and susceptibility to ambient temperatures. If the only alternative is to use a domestic refrigerator for vaccine storage, modification of the refrigerator is essential to reduce the risk of adverse vaccine storage events. Please refer to the cold chain Guidelines for further information. The following checklist summarises the ongoing activities required by immunisation service providers to ensure optimal storage of vaccines: (a) Ensure one staff member is designated as administrator of vaccines and vaccine storage; only one staff member should be responsible for refrigerator thermostat controls at any one time. (b) Name a back-up vaccine administrator, to take responsibility for vaccines in the absence of the primary vaccine administrator. (c) Ensure your healthcare service has a written Vaccine Management policy and protocol which, as a minimum, should include: • how and when to monitor and record the minimum and maximum temperatures of the vaccine refrigerator,
• how to order and receive vaccines and rotate stock, • how to store the vaccine, diluents and ice/gel packs correctly in the refrigerator, • how to maintain the refrigerator including a regimen of regular servicing, • what steps to take if the refrigerator temperature goes outside +2°C to +8°C, including identification of a cold chain breach, response procedures, documentation, recording and prevention of recurrences, • how to manage the vaccines during a power failure, • how to pack a portable cooler properly, including correct conditioning of ice packs/gel packs, • training required for staff handling vaccines. (d) Storage of all vaccines: • Maintain refrigerator temperature between +2°C to +8°C, check and record the current plus minimum/maximum temperatures at least daily or immediately before vaccines are used.
Pre-vaccination procedures 9
1.3 Pre-vaccination procedures
• how to check the accuracy of the thermometer and/or the data logger, and how and when to change the thermometer battery,
• Twice-daily temperature checks will give a better indication of any problems in the refrigerator’s function and temperature fluctuations over the course of the day. • Keep the door closed as much as possible. • Ensure one person is responsible for adjusting refrigerator controls and that all staff are appropriately trained to ensure continuous monitoring. • Establish and document protocols for response to cold chain breaches. • A vaccine storage self-audit should be undertaken by the clinic/practice at least every 12 months. • Most vaccines must be protected from freezing. Diluents must also be protected from freezing, as freezing could cause tiny cracks within the wall of the diluent container. Protect all vaccines from UV and fluorescent light. • If vaccines have been exposed to temperatures below +2°C or above +8°C, follow the practice protocol for response to a breach of the cold chain. Isolate vaccines and contact the State/Territory health authority for advice on the National Immunisation Program vaccines and the manufacturer/supplier for privately purchased vaccines. Recommendations for the discarding of vaccines may differ between health authorities and manufacturers. Do not discard any vaccines until you discuss the necessary actions. • Perform monthly vaccine stocktake, ensure vaccines with the shortest expiry date are stored at the front of the refrigerator, record and dispose of vaccines that have passed the ‘expiry date’. • Order appropriate levels of stock to ensure the refrigerator is not overcrowded and that sufficient doses of vaccine are available until the arrival of the next order. Monthly usage from previous years can assist with more accurate ordering. • Ensure all reception staff are familiar with and adhere strictly to the practice vaccine delivery protocols, including timely unpacking of vaccines. • Ensure people purchasing vaccines from a pharmacy understand the need to handle/transport the vaccines correctly. • Minimum/maximum thermometers and/or loggers should be checked for accuracy (calibrated) annually. Refer to manufacturer for assistance. Change the battery in digital minimum/maximum thermometers every 12 months. • Ensure the refrigerator is placed out of direct sunlight and the manufacturer’s instructions for air circulation around the back and sides are followed. • Ensure the refrigerator is in a secure area accessible to staff only.
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• Ensure the power source is marked clearly in a way to prevent the refrigerator from being accidentally unplugged or turned off. • During a power failure, monitor the temperature of your refrigerator. If vaccines are at risk, use alternative storage arrangements with appropriate monitoring. (e) Using a purpose-built vaccine refrigerator (PBVR): • PBVRs maintain a stable, uniform and controlled cabinet temperature unaffected by ambient air temperature, and have a defrost cycle that allows defrosting without rises in cabinet temperature. • PBVRs have a standard alarm and safety feature alert and good temperature recovery. • Ensure that the PBVR does not constantly display minimum/maximum and ambient temperatures. Separate minimum/maximum temperatures must be used to monitor the refrigerator. There are some PBVRs that require a daily data-logger download to view temperature data. • PBVRs should alarm if temperatures outside +2°C to +8°C are reached. • Some PBVRs have a back-plate that may vary in temperature during the defrost cycle. Ensure vaccines are kept 4 cm from the back-plate. Check with PBVR manufacturer to ensure that vaccines can be stored in the bottom of the refrigerator.
• Do not overstock or crowd the vaccines by overfilling the shelves. Allow space between stock for air circulation. • If very small amounts of vaccine are stored in a PBVR it is necessary to add thermal mass (such as bottles of water) to the vacant space to ensure even temperature is maintained throughout the refrigerator. • If a chart recorder is used, the chart recorder paper must be changed every 7 days and stored in a safe place for auditing purposes. (f) Using a domestic refrigerator: • Fill the lower drawers and the door with plastic bottles/containers filled with water. • Get to know the temperatures throughout the refrigerator by monitoring and recording to identify any ‘cold spots’. • Store the vaccines in an enclosed plastic container, in their original packaging, and label the containers clearly. • Vaccines must never be stored in the door of the refrigerator.
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1.3 Pre-vaccination procedures
• In the event of a power failure, PBVRs with glass doors will lose their cool temperature quickly. Ensure the protocol for responding to power failures is up-to-date and that staff are aware of the procedures.
• Ensure each domestic refrigerator has a Celsius digital minimum/ maximum thermometer, with the thermometer probe placed inside vaccine packaging, inside and near the back of an enclosed plastic container. A temperature recording chart is also required.
Cold chain breaches Do not use vaccines exposed to temperatures below +2°C or above +8°C without obtaining further advice. Do not discard these vaccines. Isolate vaccines and contact the State/Territory health authorities for advice on the National Immunisation Program vaccines and the manufacturer/supplier for privately purchased vaccines. Recommendations for the discarding of vaccines may differ between health authorities and manufacturers. Do not discard any vaccines until you discuss the necessary actions.
1.3.3 Valid consent Valid consent can be defined as the voluntary agreement by an individual to a proposed procedure, given after appropriate and reliable information about the procedure, including the potential risks and benefits, has been conveyed to the individual.3-7
For consent to be legally valid, the following elements must be present:8 • It must be given by a person with legal capacity, and of sufficient intellectual capacity to understand the implications of being vaccinated. • It must be given voluntarily. • It can only be given after the relevant vaccine(s) and their potential risks and benefits have been explained to the individual. • The individual must have sufficient opportunity to seek further details or explanations about the vaccine(s) and/or their administration. Consent should be obtained before each vaccination, once it has been established that there are no medical conditions that contraindicate vaccination.
Consent on behalf of a child or adolescent In general, a parent or legal guardian of a child has the authority to consent to vaccination of a child.3,7 A child in this context is defined as being under the age of 18 years in all States and Territories except New South Wales, where the age is 14 years, and in South Australia and the Northern Territory, where the age is 16 years. If they are of sufficient age and maturity to understand the proposed procedure and the risks and benefits associated with same, children at younger ages may be able to provide consent for procedures such as vaccination. Please refer to your own State or Territory immunisation service provider guidelines for more information.
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Should a child or adolescent refuse vaccinations for which a parent/guardian has given consent, the child’s wishes should be respected and the parent/guardian informed.3
Consent on behalf of people with impaired decision-making ability A responsible adult family member, preferably with authority to make medical decisions, may give consent for vaccination of an adult with a significant disability. For example, this may occur for influenza vaccination of an elderly person with dementia.
Resources to help communicate the risks and benefits of vaccines Plain language should be used in communicating information about vaccines and their use to an individual. The individual must be allowed to ask for further information and have time to make a decision about whether to consent or not.9,10 It is preferable that printed information is available to supplement any verbal explanations.11 The summary table Comparison of the effects of diseases and the side effects of vaccines inside the front cover of this Handbook provides some basic information necessary to communicate the risks and benefits of vaccination. The table can be photocopied and used freely as required. More detailed information concerning vaccines and their use is available from the following sources:
• www.ncirs.usyd.edu.au The National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases website includes fact sheets related to specific vaccines, vaccine-preventable diseases and vaccine safety. See also Appendix 5, Commonly asked questions about vaccination.
Evidence of consent General practice or public immunisation clinics Consent may be given either in writing or verbally, according to the protocols of the health facility, but it must meet the criteria for valid consent. Evidence of verbal consent should be documented in the clinical records. If a standard procedure is routinely followed in a practice or clinic, then a stamp, a sticker or a provider’s signature indicating that the routine procedure has been followed, may be used. For paperless medical records, a typed record of verbal consent may be made in the patient’s file, or a copy of written consent scanned into the file.
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• www.immunise.health.gov.au The Immunise Australia website includes ‘Common questions and answers (fact sheets)’, ‘Understanding childhood immunisation’ and links to State and Territory Health Department websites. Several of these sites offer multilingual fact sheets.
Consent is often given and recorded at the first vaccination visit. Explicit verbal consent is required before subsequent vaccinations even when written consent has been given at previous vaccination encounters. School-based vaccination programs Consent is often given for the entire vaccination program and is valid for the number of doses to be given during a school-based vaccination program. In school-based (and other large-scale) vaccination programs, the parent or guardian usually does not attend with the child on the day the vaccination is given, and written consent from the parent or guardian is desirable in these circumstances. However, if further clarification is required, verbal consent may be sought by telephone from the parent or guardian by the immunisation service provider. This should be clearly documented on the child’s consent form. Older adolescents may be able to provide their own consent for vaccinations.12 However, the vaccination program may vary between jurisdictions. Please refer to your own State or Territory immunisation service provider guidelines for more information.
1.3.4 Pre-vaccination screening Immunisation service providers should perform a pre-vaccination health screen of all recipients to determine: • if there are any contraindications or precautions to the vaccines that are to be administered, and • whether alternative or additional vaccines should be considered. For some individuals, alterations to the routinely recommended vaccines may be necessary to either eliminate or minimise the risk of adverse events, to optimise an individual’s immune response, or to enhance the protection of a household contact against vaccine-preventable diseases. Such changes to the recommended vaccines may require discussion with an immunisation expert such as the local immunisation coordinator or a medical practitioner with expertise in vaccination.
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Steps for pre-vaccination screening A comprehensive pre-vaccination health screening is necessary to assess a person’s medical fitness for vaccination and to determine whether a different vaccine schedule may be recommended. Follow these steps to complete the screening process: 1. Provide the person to be vaccinated or the parent/carer with the Prevaccination screening checklist (Table 1.3.1). NB. Some of the questions in this checklist are deliberately non-specific so as to elicit as much important information as possible. • The pre-vaccination screening checklist may be photocopied and handed to the parent/carer or person to be vaccinated just before vaccination. • It may also be photocopied and displayed in the clinic/surgery for easy reference for the immunisation service provider. 2. When any of the conditions or circumstances are identified by using the pre-vaccination screening checklist, refer then to Table 1.3.2 which lists the specific issues pertaining to these conditions or circumstances and provides the appropriate action with a rationale. 3. Where necessary, further expert advice should be sought from a medical practitioner with expertise in vaccination, the immunisation section within your State or Territory health authority, or your local Public Health Unit (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
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4. No one should be denied the benefits of vaccination by withholding vaccines for inappropriate reasons (see Table 1.3.4 False contraindications to vaccination).
Table 1.3.1: Pre-vaccination screening checklist Pre-vaccination screening checklist This checklist helps your doctor/nurse decide about vaccinating you or your child. Please tell your doctor/nurse if the person about to be vaccinated: is unwell today has a disease which lowers immunity (eg. leukaemia, cancer, HIV/AIDS) or is having treatment which lowers immunity (eg. oral steroid medicines such as cortisone and prednisone, radiotherapy, chemotherapy) has had a severe reaction following any vaccine has any severe allergies (to anything) has had any vaccine in the past month has had an injection of immunoglobulin, or received any blood products or a whole blood transfusion within the past year is pregnant has a past history of Guillain-Barré syndrome was a preterm infant has a chronic illness has a bleeding disorder A different vaccine schedule may be recommended if the person to be vaccinated: identifies as an Aboriginal or Torres Strait Islander does not have a functioning spleen is planning a pregnancy or anticipating parenthood is a parent, grandparent or carer of a newborn lives with someone who has a disease which lowers immunity (eg. leukaemia, cancer, HIV/AIDS), or lives with someone who is having treatment which lowers immunity (eg. oral steroid medicines such as cortisone and prednisone, radiotherapy, chemotherapy) Note: Please ask your doctor/nurse questions about this information or any other matter relating to vaccination before the vaccines are given. Before any vaccination takes place, the immunisation service provider will ask you: Did you understand the information provided to you about immunisation? Do you need more information to decide whether to proceed? Did you bring your/your child’s vaccination record card with you? It is important for you to receive a personal record of your or your child’s injections. If you do not have a record, ask your immunisation service provider to give you one. Bring this record with you every time you or your child visit for vaccination. Make sure your doctor/nurse records all vaccinations on it. Your child may need this record to enter childcare, preschool or school.
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Conditions or circumstances identified using the pre-vaccination screening checklist The recommended responses for immunisation service providers to any conditions or circumstances identified by the pre-screening checklist is summarised in Table 1.3.2. NB. Only vaccines recommended on the National Immunisation Program schedule are included in Table 1.3.2. For information on other vaccines, refer to the relevant chapter within this Handbook (Part 3) or to vaccine product information. For reference, Table 1.3.3 provides a classification of live attenuated vaccines. Table 1.3.2: Responses to relevant conditions or circumstances identified by the pre-vaccination screening checklist Condition or circumstance
Action
Rationale13-15
Unwell today:
Defer all vaccines until afebrile.
To avoid an adverse event in an already unwell child, or to avoid attributing symptoms to vaccination.
• Acute febrile illness (current T ≥38.5°C). • Acute systemic illness.
Has a disease which lowers immunity or receiving treatment which lowers immunity.
Seek expert advice before vaccination (see Appendix 1). NB. People living with someone with lowered immunity should be vaccinated, including with live viral vaccines.
Anaphylaxis following a previous dose of the relevant vaccine.
Do not vaccinate.
A severe (anaphylactic) allergy to a vaccine component.
Do not vaccinate (seek specialist advice as per Appendix 1).
Refer to Appendix 4 for vaccine component checklist.
See also ‘Contraindications to vaccination’ below.
Received live parenteral vaccine or BCG vaccine in past 4 weeks.
Delay live vaccines by 4 weeks.
See also ‘Contraindications to vaccination’ below.
The safety and effectiveness of the vaccine may be suboptimal in people with impaired immunity.
Anaphylaxis to a previous dose of vaccine is a contraindication to receiving the vaccine. Anaphylaxis to a vaccine component is a contraindication to receiving the vaccine.
The immune response to a live viral vaccine may interfere with the response to a second live viral vaccine if given within 4 weeks of the first.
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1.3 Pre-vaccination procedures
See Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment.
NB. Children with minor illnesses (without acute systemic symptoms/signs) should be vaccinated.
Condition or circumstance
Action
Rationale13-15
Has had any blood product in the past 7 months, or has had IM or IV immunoglobulin in the past 11 months.
Make a return appointment for this vaccination, and send a reminder later if necessary.
Antibodies within these products may interfere with the immune response to these vaccines.
Live vaccines* should be deferred until after delivery.
There is insufficient evidence to ensure the safety of administering live vaccines during pregnancy or within 28 days before conception.
Refer to Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination. Is pregnant. Refer to Table 2.3.1 Vaccinations in pregnancy.
History of Guillain-Barré syndrome (GBS). See Chapter 3.9, Influenza.
Was born preterm. See Section 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants.
Conception should be deferred until at least 28 days after administration of live viral vaccines. Inactivated vaccines are generally not contraindicated in pregnancy.
NB. Influenza vaccine is recommended for pregnant women. Vaccination of household contacts of pregnant women should be completed according to the NIP schedule.
Risks and benefits of influenza vaccine should be weighed against the potential risk of GBS recurrence (seek specialist advice as per Appendix 1).
People with a history of GBS may be at risk of recurrence of the condition following influenza vaccine.
Preterm infants born at <28 weeks’ gestation or <1500 g birth weight require an extra dose of PRP-OMP Hib vaccine at 6 months of age.
Preterm infants may be at increased risk of vaccinepreventable diseases (eg. invasive pneumococcal disease (IPD)), and may not mount an optimal immune response to certain vaccines (eg. hepatitis B, PRP-OMP).
Preterm infants born at <28 weeks’ gestation and/or with chronic lung disease require extra pneumococcal vaccinations. Preterm infants born at <32 weeks’ gestation or <2000 g birth weight may require an extra dose of hepatitis B vaccine.
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Condition or circumstance
Action
Rationale13-15
Has a severe or chronic illness.
These people should receive pneumococcal vaccine and annual influenza vaccination.
People with a severe or chronic illness may be at increased risk of vaccinepreventable diseases (eg. IPD) but may not mount an optimal immune response to certain vaccines.
See Chapter 2.3, Groups with special vaccination requirements.
Has a bleeding disorder. See Section 2.3.6, Vaccination of patients with bleeding disorders.
Identifies as an Aboriginal or Torres Strait Islander. See Chapter 2.1, Vaccination for Aboriginal and Torres Strait Islander people. Does not have a functioning spleen.
Is planning a pregnancy or anticipating parenthood.
Is a parent, grandparent or carer of a newborn.
The subcutaneous route could be considered as an alternative to the intramuscular route (seek specialist advice as per Appendix 1).
Intramuscular injection may lead to haematomas in patients with disorders of haemostasis.
See the National Immunisation Program Indigenous schedules.
Some groups of Indigenous people are at increased risk of some of the vaccinepreventable diseases.
Check vaccination status for pneumococcal, meningococcal and Hib vaccinations.
Individuals with an absent or dysfunctional spleen are at an increased risk of severe bacterial infections, most notably IPD.
Ensure prospective parents have been offered vaccines recommended for their agegroup including 2nd dose of MMR if born after 1966, and dTpa† (unless they have had a previous dose of dTpa).
Vaccinating before pregnancy may prevent maternal illness which could affect the infant, and may confer passive immunity to the newborn.
Ensure parents, grandparents and carers of a newborn have been offered all vaccines recommended for their age-group including dTpa (unless they have had a previous dose of dTpa).
People in close contact are the most likely sources of vaccine-preventable diseases, in particular pertussis, in the newborn.
NB. Advise women not to become pregnant within 28 days of receiving live viral vaccines.
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See Section 2.3.3, Subsection 2.3.3.5, Individuals with functional or anatomical asplenia.
If there is significantly impaired immunity, they should not receive live vaccines, but inactivated vaccines should be considered (seek expert advice).
Condition or circumstance
Action
Rationale13-15
Lives with someone who has impaired immunity.
Ensure all vaccines (in particular MMR, varicella and influenza vaccines) recommended for their age-group have been offered to household members of people with impaired immunity.
Household members are the most likely sources of vaccine-preventable diseases among people with impaired immunity (who often are unable to be vaccinated, especially with live viral vaccines).
* Live attenuated vaccines are classified in Table 1.3.3 below. † See Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus for further information.
Table 1.3.3: Live attenuated parenteral and oral vaccines Live attenuated parenteral vaccines
Live attenuated oral vaccines
Viral
Bacterial
Viral
Bacterial
MMR
BCG
Oral rotavirus vaccine
Oral typhoid vaccine
MMRV Varicella vaccine (VV) Monovalent rubella vaccine Yellow fever
Contraindications to vaccination There are only 2 absolute contraindications applicable to all vaccines: (i) anaphylaxis following a previous dose of the relevant vaccine, and (ii) anaphylaxis following any component of the relevant vaccine. There are 2 further contraindications applicable to live (both parenteral and oral) vaccines: (iii) Live vaccines should not be administered to individuals with impaired immunity, regardless of whether the impairment is caused by disease or treatment. The exception is that, with specialist advice, MMR can be administered to HIV-infected individuals in whom impaired immunity is mild. (See Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment, and individual vaccine chapters.) (iv) In general, live vaccines should not be administered during pregnancy, and women should be advised not to become pregnant within 4 weeks of receiving a live vaccine (see Table 2.3.1 Vaccinations in pregnancy).
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False contraindications to vaccination Conditions listed in Table 1.3.4 below are not contraindications to vaccination. People with these conditions should be vaccinated with all recommended vaccines. Table 1.3.4: False contraindications to vaccination The following conditions are not contraindications to any of the vaccines in the National Immunisation Program schedule: • mild illness without fever (T <38.5°C), • family history of any adverse events following immunisation, • past history of convulsions, • treatment with antibiotics, • treatment with locally acting (inhaled or low-dose topical) steroids, • replacement corticosteroids, • asthma, eczema, atopy, hay fever or ‘snuffles’, • previous pertussis-like illness, measles, rubella, mumps or meningococcal disease, • prematurity (vaccination should not be postponed), • history of neonatal jaundice, • low weight in an otherwise healthy child, • any neurological conditions including cerebral palsy and Down syndrome, • contact with an infectious disease, • child’s mother is pregnant, • woman to be vaccinated is breastfeeding, • recent or imminent surgery, • poorly documented vaccination history.
1.3.5 Catch-up Every opportunity should be taken to review an individual’s vaccination history and, based on documentation, administer the appropriate vaccine(s). If the individual has not received vaccines scheduled in the National Immunisation Program appropriate for his/her age, plan and document a catch-up schedule and discuss this with the individual. The assessment of vaccination status should be based on the schedule for the State/Territory in which the individual is residing. The objective of catch-up vaccination is to complete a course of vaccination and provide optimal protection as quickly as possible. The information and tables below will assist in planning a catch-up schedule. If the immunisation service provider is still uncertain about how to plan the catch-up schedule, expert advice should be sought (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
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• child to be vaccinated is being breastfed,
An on-line ‘catch-up calculator’ is available at www.health.sa.gov.au/immunisationcalculator This calculator is regularly updated for all catch-up scenarios relevant to the NIP. For non-NIP vaccines or complicated catch-up scenarios, expert advice should be sought (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control). To calculate a catch-up schedule, the on-line calculator requires the child’s date of birth, State of residence, past vaccination history and Indigenous status. The calculator can be used for children ≤7 years of age (the age up to which vaccinations will be recorded on the ACIR) and can calculate catch-up schedules for children from all States and Territories. For recently arrived immigrants, the World Health Organization web site www.who.int/countries/en lists an immunisation schedule (where provided by that particular country) and may supplement information regarding which vaccines a child/adult may have received (see also Section 2.3.9, Vaccination of immigrants to Australia). Alternatively, the instructions and guidelines below will assist in the manual calculation of a catch-up schedule.
Determining a vaccination history Individuals with incomplete vaccination records The most important requirement for assessment of vaccination status is to have written documentation of vaccination. The approach of providers to the problem of inadequate records should be based on the age of the individual, whether previous vaccines have been given in Australia or overseas, and the vaccines being considered for catch-up.
Vaccines given from 1 January 1996 The Australian Childhood Immunisation Register (ACIR) commenced on 1 January 1996 and all vaccinations given to children since then should be available from the ACIR. If the parent states that vaccines not recorded on the ACIR have been given, every effort should be made to contact the relevant immunisation service provider. If confirmation from the nominated provider or the ACIR cannot be obtained, and no written records are available, the vaccines should be considered as not received, and the child should be offered a catch-up course of vaccination appropriate for age (see Section 1.3.5). Parents can obtain an ACIR Immunisation History Statement from Medicare (see Section 1.5.4).
Older children and adolescents <18 years of age No vaccination information is recorded on the ACIR after a child turns 7 years of age, but any information already held is retained. The information will relate only to vaccines received between birth and the 7th birthday. The ACIR Enquiry Line can be contacted on 1800 653 809 and any record held for an individual who
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is ≥7 years of age can be made available to an immunisation service provider or parent/carer. In older children and adolescents, alternative sources of documentation (such as personal health records) will be needed, but are less likely to be available with increasing age. Individuals who do not have personal vaccination records may seek evidence of past vaccination from their parents, their past and present healthcare providers or immunisation service providers, including Local Government immunisation service providers. Those born after 1990 may have some vaccinations recorded on the ACIR (see Section 1.5.4). For most vaccines, there are no adverse events associated with additional doses in immune individuals. In the case of diphtheria and tetanus vaccines, additional doses may occasionally be associated with an increase in local adverse events in immune individuals (see Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus). However, the benefits of protection against pertussis are likely to outweigh the risk of an adverse reaction.
Adults (≥18 years of age)
Guidelines for planning catch-up vaccination There are a number of tables in this section which are designed to help plan a catch-up schedule if not using the on-line calculator. • Figure 1.3.1 is a worksheet for calculating and recording which vaccines are required, the number of doses outstanding and the timing of these doses. • Table 1.3.5 can be used to assess the number of doses a child would have received if they were on schedule. Check under the current age of the child to see how many doses they should have already received and use that number of doses as the starting point for calculating a catch-up schedule. For example, a child who is 18 months old now should have received 3 doses of DTPa, 3 doses of IPV etc. • Table 1.3.6 lists the minimum interval between doses. • Tables 1.3.8–1.3.11 are for calculating catch-up for Hib and pneumococcal vaccination. If documentation cannot be produced, assume that the vaccine has not been given previously, unless contact can be made with the immunisation service provider.
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1.3 Pre-vaccination procedures
In adults, written documentation of previous vaccination history may not be available. It is important, however, to seek information of any previous doses of diphtheria and tetanus vaccines, and of pneumococcal polysaccharide vaccination in the previous 5 years, as increased local reactions may occasionally occur in immune individuals (see Chapter 3.3, Diphtheria, Chapter 3.15, Pneumococcal disease or Chapter 3.21, Tetanus). Additional doses of MMR, varicella, IPV or hepatitis B vaccine are rarely associated with significant adverse events in adults.
• Vaccine doses should not be administered at less than the recommended minimum interval16 (see Table 1.3.6). • In exceptional circumstances, where early vaccination is required, Table 1.3.7 indicates the minimum age that the first dose of a vaccine may be given. • Doses administered earlier than the minimum interval should not be considered as valid doses and should be repeated as appropriate using Table 1.3.5. • When commencing the catch-up schedule, the standard scheduled interval between doses may be reduced or extended, and the numbers of doses required may reduce with age. For example, from 15 months of age, only 1 dose of (any) Hib vaccine is required. • As a child gets older, the recommended number of vaccine doses may change (or even be omitted from the schedule), as the child becomes less vulnerable to specific diseases. • For incomplete or overdue vaccinations, build on the previous documented doses. Never start the schedule again, regardless of the interval since the last dose. • If more than 1 vaccine is overdue, 1 dose of each due or overdue vaccine should be given now. Further required doses should be scheduled after the appropriate minimum interval (see Table 1.3.6). • A catch-up schedule may require multiple vaccinations at a visit. Give all the due vaccines at the same visit – do not defer. See Section 1.4.9 for procedures for administering multiple injections at the same visit. • The standard intervals and ages recommended in the NIP schedule should be used once the child or adult is up-to-date with the schedule. • Some individuals will require further doses of antigens that are available only in combination vaccines. In general, the use of the combination vaccine(s) is acceptable, even if this means the number of doses of another antigen administered exceeds the required number. • If different Hib vaccines are inadvertently used in the primary series, then 3 doses (of any Hib vaccine) are required at 2, 4 and 6 months of age, with a booster at 12 months of age (see Chapter 3.4, Haemophilus influenzae type b). NB. Routine rotavirus vaccine ‘catch-up’ of older children is not recommended. Infants should commence the course of rotavirus vaccination within the recommended age limits for the first dose. It is also necessary to ensure that doses are not given beyond the upper age limits for the final dose of the vaccine course (see Chapter 3.18, Rotavirus).
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Interruption to a vaccination • If the process of administration of a vaccine given parenterally (IM or SC) is interrupted (eg. by syringe-needle disconnection) the whole dose should be repeated as soon as practicable. • If an infant regurgitates or vomits part of a dose of oral rotavirus vaccine, it is not necessary to repeat the dose. Therefore, the regurgitated (and incomplete volume) dose is still considered as the valid dose (see Chapter 3.18, Rotavirus).
Determining a catch-up schedule for children <8 years of age A catch-up schedule for a child <8 years of age should be planned by taking into account the guidelines above and using Table 1.3.5. The Catch-up Worksheet (Figure 1.3.1) provides a method of recording these steps. All catch-up vaccines administered to children aged <7 years should be reported as soon as is practicable to the ACIR.
Using the Catch-up Worksheet 1. Record the child’s details including date of birth and current age in the top left corner of the worksheet. 2. For each vaccine, determine how many doses have been received and the date that the last dose was given. Record this on the worksheet.
4. Assess other factors that may affect the type or number of vaccines required, including: • anaphylaxis to any vaccine or one of its components (that vaccine is contraindicated), • impaired immunity due to disease or treatment (see Chapter 2.3, Groups with special vaccination requirements), • identifying as an Aboriginal or Torres Strait Islander (see Chapter 2.1, Vaccination for Aboriginal and Torres Strait Islander people), • children with an underlying medical risk condition which predisposes them to invasive pneumococcal disease (see Chapter 3.15, Pneumococcal disease), • a reliable history of previous varicella infection (varicella vaccine not required), and • babies born at <32 weeks’ gestation (see Hib vaccine and hepatitis B vaccine catch-up below).
Record any relevant factor in the ‘comments’ column beside the relevant vaccine.
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1.3 Pre-vaccination procedures
3. Refer to Table 1.3.5 to check how many doses of each vaccine are required for the child’s current age. Enter this number in the appropriate column of the worksheet.
5. If any variations to the schedule are necessary due to recorded factors (eg. a child with impaired immunity may require different vaccines), adjust the ‘number of doses required’ accordingly. 6. For each vaccine, compare the ‘last dose given’ with the number required for the child’s current age. 7. If the child has already received the number of doses required, the relevant ‘dose number due now’ and ‘further doses’ cells should be crossed through. 8. If the number of the ‘last dose given’ is less than the number required, a dose of the relevant vaccine should be administered now, and recorded in the ‘dose number due now’ cell. If this dose still does not complete the required doses, enter the further dose numbers in the ‘further doses’ cell. 9. Refer to Table 1.3.6 to determine the recommended minimum intervals required between doses and record in the relevant ‘further doses’ cells. 10. Convert this information into a list of proposed appointment dates, detailing vaccines and dose number needed at each visit on the Catch-up Worksheet. 11. Record this catch-up schedule in your provider records and provide a copy to the parent/carer.
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Figure 1.3.1: Catch-up Worksheet for children <8 years of age CATCH-UP WORKSHEET Name: DOB:
Last dose given Dose number and date
Number of doses required at current age*
Dose number due now
Further doses
Comments
Interval or date
Age: DTPa Poliomyelitis (IPV) Hepatitis A Hepatitis B Hib 7vPCV & 23vPPV MenCCV MMR Rotavirus
DO NOT give after upper age limits for each dose.
Varicella CATCH-UP APPOINTMENTS Date
Vaccines & Dose number
Interval to next dose
Comments
* See step 5 ‘Using the Catch-up Worksheet’ above.
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1.3 Pre-vaccination procedures
See Table 3.18.1.
Table 1.3.5: Number of vaccine doses that should have been administered by the current age of the child (table to be used in conjunction with Catch-up Worksheet) VACCINE
CURRENT AGE 0–<2mo
2–<4mo
4–<6mo
6–<12mo
12–18mo
>18mo–<4yr
4yr–<8yr
DTPa*
1
2
3
3
3
4
Poliomyelitis (IPV)
1
2
3
3
3
4†
1‡
2‡
2‡
Hepatitis A‡ Hepatitis B
birth dose given§
2
3
4
4
4
4
birth dose not given
1
2
3^
3
3
3
1
1
1
1
2
2
Hib
Complex – see Table 1.3.8 for Hib vaccine catch-up
7vPCV & 23vPPV
Complex – see Tables 1.3.9, 1.3.10 and 1.3.11 for pneumococcal vaccine catch-up
MenCCV MMR Rotavirus#
There are specific age limits as per Chapter 3.18, Rotavirus, Table 3.18.1.
NO CATCH-UP
Varicella
1
1
* Some children may have received 4 doses of DTP by 18 months of age, especially if moved from overseas. These children will require a 5th dose of DTPa at 4 years of age. † If the 3rd dose of IPV is given after 4 years of age, a 4th dose is not required. However, if using a combination vaccine it is acceptable to receive a 4th dose. ‡ Indigenous children resident in NT, QLD, SA and WA only. Dependent on jurisdiction, the 1st dose is given at 12–18 months of age followed by the 2nd dose 6 months later at 18–24 months of age. Consult relevant State/Territory authorities for advice regarding catch-up in children older than 2 years of age. § Birth dose should be given within 7 days of birth. Although a birth dose of hepatitis B vaccine is recommended for all infants, a catch-up dose is not necessary if it was not given. Even if the birth dose was given, a further 3 doses of hepatitis B vaccine are required. ^ Some States/Territories schedule a 3rd dose (or the 4th dose) of hepatitis B vaccine at 6 months of age rather than 12 months. # There is no catch-up for rotavirus vaccine (see Chapter 3.18, Rotavirus).
28 The Australian Immunisation Handbook 9th Edition
Table 1.3.6: Minimum dose intervals for NIP vaccines for children <8 years of age (table to be used in conjunction with Catch-up Worksheet) Vaccine
Minimum interval between dose 1&2
Minimum interval between dose 2&3
Minimum interval between dose 3&4
DTPa*
4 weeks
4 weeks
6 months
Poliomyelitis (IPV)
4 weeks
4 weeks
4 weeks†
Hepatitis A
6 months
8 weeks
(Indigenous children in NT, QLD, SA & WA only) Hepatitis B If first dose given at birth or at ≤7 days after birth‡
4 weeks
8 weeks
If first dose is not given at birth or at >7 days after birth§
4 weeks
8 weeks
Hib (PRP-OMP)
See Table 1.3.8 Hib vaccine catch-up
Hib (PRP-T) Pneumococcal (7vPCV)
See Tables 1.3.9, 1.3.10, 1.3.11 Pneumococcal vaccine catch-up
MenCCV^
Rotavirus**
Varicella
4 weeks Rotarix
4 weeks
RotaTeq
4 weeks
4 weeks
4 weeks
* If DTPa is only available in combination with other antigens (eg. DTPa-IPV, DTPa-hepBIPV-Hib or DTPa-HepB-IPV), these formulations can be used where necessary for primary course or catch-up doses in children <8 years of age. † If the 3rd dose of IPV is given after 4 years of age, a 4th dose is not required. However, if using a combination vaccine, it is acceptable to receive a 4th dose. ‡ If dose given at birth or within 7 days of birth (considered dose 1 for this table), then 3 subsequent doses should be given. § If dose 1 is not given at birth or within 7 days of birth, then it should be given at 2 months of age, followed by a further 2 doses. ^ The schedule is a single dose given at 12 months of age. Alternative schedules are available for children <12 months of age (see Chapter 3.12, Meningococcal disease). # MMR vaccine may be given from 9 months of age if in contact with case, but dose must be repeated at 12 months of age. ** Consult Chapter 3.18, Rotavirus, Table 3.18.1 for upper age limits for administration of rotavirus vaccines. Catch-up is not recommended.
Pre-vaccination procedures 29
1.3 Pre-vaccination procedures
MMR#
Table 1.3.7: Minimum age for the first dose of vaccine in exceptional circumstances* Vaccine
Minimum age for first dose in exceptional circumstances
Minimum age accepted as valid by ACIR
DTPa
6 weeks
6 weeks
Poliomyelitis (IPV)
6 weeks
6 weeks
Hepatitis A
12 months
12 months
(Indigenous children in NT, QLD, SA & WA only) Hepatitis B
6 weeks
6 weeks
Hib (PRP-OMP)
6 weeks
6 weeks 6 weeks
Hib (PRP-T)
6 weeks
MenCCV
6 weeks†
MMR
9 months
12 months ‡
11 months
Pneumococcal (7vPCV)
6 weeks
6 weeks
Rotavirus
6 weeks
not stated
Varicella
9 months§ (Varilrix)
not stated
12 months^ (Varivax) * Exceptional circumstances may include infants/children being vaccinated before overseas travel, or opportunistic vaccination following early attendance to a provider. These ages may differ from routinely recommended ages of administration under the NIP. † If 2 doses of MenCCV are given before 12 months of age, then a booster dose should be given at 12 months of age (see Chapter 3.12, Meningococcal disease). ‡ MMR vaccine may be given from 9 months of age if in contact with case, but dose must be repeated at 12 months of age. § If a child receives varicella vaccine at <12 months of age, a further dose should be given at 18 months of age. ^ Receipt of at least 1 dose of varicella vaccine is recommended from 12 months of age.
30 The Australian Immunisation Handbook 9th Edition
Catch-up guidelines for individual vaccines • DTPa Monovalent pertussis vaccine is not available in Australia. If a child has received previous doses of DT and requires pertussis catch-up, then DTPa or DTPa-combination vaccines can be used provided that no more than 6 doses of diphtheria and tetanus toxoids are given before the 8th birthday. NB. If no birth dose of hepatitis B vaccine was given, and a DTPa-hepatitis B-containing combination vaccine is used, there should be a minimum interval of 8 weeks between doses 2 and 3. • Hepatitis B vaccine If the infant received the birth dose of hepatitis B vaccine, catch-up doses can be given 4–8 weeks apart. If the infant did not receive the birth dose, a catch-up of this dose is not necessary. In this circumstance, hepatitis B vaccination should commence at 2 months of age. There should be a minimum interval of 8 weeks between doses 2 and 3. In preterm babies under 32 weeks’ gestation at birth or <2000 g birth weight, it is recommended to give hepatitis B vaccine at 0, 2, 4 and 6 months of age, and either: (a) measure anti-HBs at 7 months of age and give a booster at 12 months of age if antibody titre is <10 mIU/mL, or (See also Section 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants and Chapter 3.6, Hepatitis B). • Hib vaccine The recommended number of doses and recommended intervals of Hib vaccines vary with the vaccine type and with the age of the child (see Table 1.3.8). PRPOMP is the Hib formulation contained in Liquid PedvaxHIB and COMVAX. PRP-T is the Hib formulation contained in Hiberix and Infanrix hexa. Where possible, the same brand of Hib vaccine should be used for all doses. If different Hib vaccines are used in the primary series, then 3 doses (of any Hib vaccine) are required at 2, 4 and 6 months of age, with a booster at 12 months of age. Only 1 dose (of any Hib vaccine) is required after 15 months of age. When PRP-OMP is used in an extremely preterm baby (<28 weeks’ gestation or <1500 g birth weight), an additional dose should be given at 6 months of age, ie. doses should be given at 2, 4, 6 and 12 months of age (see Section 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants).
Pre-vaccination procedures 31
1.3 Pre-vaccination procedures
(b) give a booster at 12 months of age without measuring the antibody titre.
• MMR vaccine If no previous documented doses have been given, catch-up for MMR consists of 2 doses given at least 4 weeks apart. • MenCCV MenCCV is recommended on the NIP for children at 12 months of age. If no dose was received at ≥12 months of age or if all doses have been received at <12 months of age, a single dose of any meningococcal conjugate vaccine is recommended (see Chapter 3.12, Meningococcal disease). • 7vPCV The number of doses and recommended intervals of 7vPCV for catch-up vary with the age of the child, health and Indigenous status of the child, as well as the State/Territory of residence (see Tables 1.3.9, 1.3.10 and 1.3.11 below). Low-risk children (including all Indigenous children) aged ≥2 years of age do not require catch-up. If <2 years of age at presentation, use Table 1.3.9 for low-risk children (including Indigenous children living in the Australian Capital Territory, New South Wales, Victoria and Tasmania) and Table 1.3.10 for Indigenous children residing in the Northern Territory, Queensland, South Australia and Western Australia. Table 1.3.11 provides catch-up details for children aged ≤5 years with an underlying medical condition. Please also refer to Chapter 3.15, Pneumococcal disease for further details. • Poliomyelitis vaccine If no previous documented doses of poliomyelitis vaccine have been given, give 3 doses of IPV or IPV-containing vaccines at least 4 weeks apart. (Previous doses of OPV are interchangeable with IPV.) If the third dose of IPV is administered before 4 years of age, give the fourth (booster) dose at either the 4th birthday or 4 weeks after the third dose, whichever is later. If the third dose is given after the 4th birthday, a fourth dose is not required. However, if the use of combination vaccines is necessary, a further IPVcontaining dose may be given. • Rotavirus vaccine Infants should commence the course of rotavirus vaccination within the recommended age limits for the first dose, that is by either 12 or 14 weeks of age depending on the vaccine to be used. It is recommended that vaccine doses are not given beyond the upper age limits specified in Table 3.18.1, Chapter 3.18, Rotavirus. • Varicella vaccine If a child receives varicella vaccine at <12 months of age, a further dose should be given at 18 months of age.
32 The Australian Immunisation Handbook 9th Edition
Table 1.3.8: Recommendations for Hib catch-up vaccination for children <5 years of age when doses have been delayed or missed Previous vaccination history
Age at presentation
Type of Hib vaccine to be used
1st dose
2nd dose
3rd dose
Booster dose
0 doses
3–6 months
PRP-OMP
Give now
1 month later
Not needed
12 months of age
PRP-T
Give now
1 month later
1–2 months later
12 months of age
PRP-OMP
Give now
2 months later
Not needed
12 months of age or 2 months after 2nd dose (whichever is later)
PRP-T
Give now
2 months later
Not needed
12 months of age or 2 months after 2nd dose (whichever is later)
7–11 months
12–14 months
Give now
Not needed
Not needed
2 months later
Give now
Not needed
Not needed
18 months of age
15–59 months
PRP-OMP or PRP-T
Give now
Not needed
Not needed
Not needed
3–6 months
PRP-OMP
PRP-OMP previously given
Give now
Not needed
12 months of age
PRP-T
Either PRP-OMP or PRP-T previously given
Give now
1–2 months later
12 months of age
7–14 months
PRP-OMP or PRP-T
Previously given
Give now
Not needed
12 months of age or 2 months after 2nd dose (whichever is later)
15–59 months
PRP-OMP or PRP-T
Previously given
Not needed
Not needed
Give now*
2 previous doses of PRPOMP
12–59 months
PRP-OMP or PRP-T
Previously given
Previously given
Not needed
At least 2 months after last dose*
2 previous doses of PRP-T (or 1 of each of PRP-OMP and PRP-T)
7–14 months
PRP-OMP or PRP-T
Previously given
Previously given
At least 1 month after last dose
12–18 months of age, at least 2 months after last dose
15–59 months
PRP-OMP or PRP-T
Previously given
Previously given
Not needed
At least 2 months after last dose*
1 previous dose (given at least 4 weeks previously)
*A booster dose is not needed if the last previous dose was given at >15 months of age.
Pre-vaccination procedures 33
1.3 Pre-vaccination procedures
PRP-OMP PRP-T
Table 1.3.9: Recommendations for pneumococcal catch-up vaccination for lowrisk children (including Indigenous children living in ACT, NSW, VIC and TAS) <2 years of age, when doses have been delayed or missed CATEGORY
Previous doses of 7vPCV
Age at presentation
1st dose 7vPCV
2nd dose 7vPCV
3rd dose 7vPCV
All nonIndigenous children
None
3–6 months
Give now
1 month later
1–2 months later*
7–17 months
Give now
1–2 months later*
Not needed
and Indigenous children living in ACT, NSW, VIC and TAS
18–23 months
Give now
Not needed
Not needed
1 previous dose (given at least 4 weeks previously)
5–11 months
Previously given
Give now
1–2 months later*
12–23 months
Previously given
Give now
Not needed
2 doses
7–11 months
Previously given
Previously given
Give now
12–23 months
Previously given
Previously given
Not needed
* Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged <12 months. For children aged ≥12 months, there should be a 2 month interval between doses of 7vPCV.
34 The Australian Immunisation Handbook 9th Edition
Table 1.3.10: Recommendations for pneumococcal catch-up vaccination for Indigenous children <2 years of age in NT, QLD, SA and WA, when doses have been delayed or missed CATEGORY
Previous doses of 7vPCV
1st dose 7vPCV
2nd dose 7vPCV
3rd dose 7vPCV
23vPPV*
3–6 months
Give now
1 month later
1–2 months later†
18–24 months of age
7–17 months
Give now
1–2 months later†
Not needed
18–24 months of age or 2 months after 2nd dose of 7vPCV (whichever is later)
18–23 months Give now
Not needed
Not needed
18–24 months of age or 2 months after 1st dose of 7vPCV (whichever is later)
1 dose 5–11 months Previously (given given at least 4 weeks previously) 12–23 months Previously given
Give now
1–2 months later†
18–24 months of age
Give now
Not needed
18–24 months of age or 2 months after 2nd dose of 7vPCV (whichever is later)
2 doses
Previously given
Previously given
Give now
18–24 months of age
12–23 months Previously given
Previously given
Not needed
18–24 months of age or 2 months after 2nd dose of 7vPCV (whichever is later)
Indigenous None children living in NT, QLD, SA and WA
7–11 months
* The timing of 23vPPV varies between States and Territories. Contact your State or Territory health authority for the appropriate timing. † Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged <12 months. For children aged ≥12 months, there should be a 2 month interval between doses of 7vPCV.
Pre-vaccination procedures 35
1.3 Pre-vaccination procedures
Age at presentation
36 The Australian Immunisation Handbook 9th Edition
3 doses
2 doses
12–59 months
Previously given
Previously given
12–59 months
Previously given
12–59 months Previously given
Previously given
7–11 months
7–11 months
Previously given
Give now
12–59 months
5–6 months
Give now
7–11 months
1 dose
Give now
3–6 months
None
1st dose 7vPCV
Age at presentation
Previous doses of 7vPCV
Previously given
Previously given
Previously given
Give now
Give now
Give now
2 months later
1–2 months later†
1 month later
2nd dose 7vPCV
Previously given
Give now
Give now
Not needed
Not needed
1 month later
Not needed
Not needed
1–2 months later†
3rd dose 7vPCV
Give now
Not needed
12 months of age or 2 months after 3rd dose of 7vPCV (whichever is later)
Not needed
12 months of age or 2 months after 2nd dose of 7vPCV (whichever is later)
12 months of age
Not needed
4–5 years of age or 2 months after booster dose of 7vPCV (whichever is later)
4–5 years of age or 2 months after 3rd dose of 7vPCV (whichever is later)
4–5 years of age
4–5 years of age or 2 months after 2nd dose of 7vPCV (whichever is later)
4–5 years of age
4–5 years of age
4–5 years of age or 2 months after 2nd dose of 7vPCV (whichever is later)
4–5 years of age
4–5 years of age
12 months of age
12 months of age or 2 months after 2nd dose of 7vPCV (whichever is later)
23vPPV
Booster dose 7vPCV
† Catch-up doses of 7vPCV can be given a minimum of 1 month apart to infants aged <12 months. For children aged ≥12 months, there should be a 2 month interval between doses of 7vPCV.
* Children up to the age of 10 years who, after the 6th birthday, develop asplenia, HIV infection, or a haematological malignancy, or who receive a transplant, should receive 2 doses of 7vPCV 2 months apart, and a dose of 23vPPV 2 months later. If these children need catch-up doses of 7vPCV, the recommendations are the same as for the 12–59 month age-group in Table 1.3.11, with a dose of 23vPPV 2 months after the last dose of 7vPCV. See Chapter 3.15, Pneumococcal disease recommendations and Table 3.15.1
Children ≤5 years of age with underlying medical conditions
CATEGORY
Table 1.3.11: Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age* with underlying medical conditions
Catch-up schedules for children ≥8 years of age, adolescents and adults Catch-up is much less commonly required for these age groups than for young children. Nevertheless, issues surrounding booster doses or revaccinations are common, particularly in adults. People who escaped natural infection as children and were not vaccinated remain at unnecessary risk of vaccine-preventable diseases. If a vaccine course is incomplete, never start the course again, regardless of the interval since the last dose. Recommendations on vaccination for adults at occupational risk or in a special risk group can be found in Chapter 2.3, Groups with special vaccination requirements. Use Table 1.3.12 to determine: • how many doses of a particular vaccine a person should have received to be considered completely vaccinated (column 2: Doses required), • deduct any previous doses of the vaccine from that number, and • go to the appropriate minimum interval column. For example, a 32-year-old woman who has received only 1 dose of hepatitis B vaccine, 4 doses of the oral poliomyelitis vaccine, 1 dose of MMR vaccine and 2 doses of DTPw as a child, would require: • 2 adult doses of hepatitis B, 1 dose given now and a further dose in 8 weeks, • no further doses of poliomyelitis vaccine (is fully vaccinated against poliomyelitis), • varicella vaccine if non-immune, • 1 dose of MMR vaccine. Where several vaccines are required, eg. dTpa, hepatitis B and poliomyelitis vaccines, never use the available childhood combination vaccines as the antigen content differs and may result in a severe adverse event. The childhood combination vaccines are not registered for use in children aged ≥8 years, adolescents or adults.
Pre-vaccination procedures 37
1.3 Pre-vaccination procedures
• 1 dose of dT (preferably given as dTpa),
Table 1.3.12: Catch-up schedules for individuals ≥8 years of age Vaccine
dT (dTpa*)
Doses required
Minimum interval Minimum interval between Dose 1 between Dose 2 &2 &3
3 doses
4 weeks
4 weeks
Hepatitis B
Aged 8–19 years
3 paediatric doses
4 weeks
8 weeks
Hepatitis B
Aged 11–15 years only
2 adult doses
4–6 months
Not required
Hepatitis B
Aged ≥20 years
3 adult doses
4 weeks
8 weeks
IPV
3 doses
4 weeks
4 weeks
Human papillomavirus (females aged 10–26 years only)
3 doses
4 weeks
3 months
MMR
2 doses
4 weeks
Not required
Varicella vaccine†
At least 1 dose if aged <14 years
If 2nd dose given, a 4 week interval is required
Not required
2 doses if aged ≥14 years
4 weeks
Not required
* One of the doses should be given as dTpa (or dTpa-IPV if poliomyelitis vaccination is also needed) and complete the course with dT. In the unlikely event that dT is not available, dTpa or dTpa-IPV may be used for all 3 primary doses but this is not routinely recommended as there are no data on the safety, immunogenicity or efficacy of dTpa for primary vaccination (see also Chapter 3.14, Pertussis). † Varicella vaccine should be given to either non-immune people or people with no history of previous varicella infection. At least 1 dose should be given to those aged <14 years, and all must receive 2 doses if aged ≥14 years.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
38 The Australian Immunisation Handbook 9th Edition
1.4 Administration of vaccines 1.4.1 Occupational health and safety issues Standard occupational health and safety guidelines should always be followed during a vaccination encounter to minimise the risk of needle-stick injury.1 Gloves are not routinely recommended for immunisation service providers. Work practices should include the use of standard precautions to minimise exposure to blood and body fluids. If exposure does occur, guidelines for post-exposure prophylaxis should be followed (refer to Chapters 23 and 24 of the Australian Government Department of Health and Ageing Infection control guidelines for the prevention of transmission of infectious diseases in the health care setting).1 A new, sterile, disposable syringe and needle must be used for each injection. Disposable needles and syringes must be discarded into a clearly labelled, puncture-proof, spill-proof container that meets Australian standards in order to prevent needle-stick injury or re-use.1 Always keep sharps containers out of the reach of children. All immunisation service providers should be familiar with the handling and disposal of sharps according to the Australian Government Department of Health and Ageing Infection control guidelines for the prevention of transmission of infectious diseases in the health care setting, Chapters 14 and 23.1
1.4.2 Equipment for vaccination Preparing for vaccination • Depending on the vaccine(s) that are to be administered, and the age and size of the person to be vaccinated, decide on the appropriate injection site and route, and the injection equipment required (ie. syringe size, needle length and gauge). • The equipment chosen will vary depending on whether the vaccine is a reconstituted vaccine, a vaccine from an ampoule or vial, or a vaccine in a pre-filled syringe.
Equipment may include: • medical waste (sharps) container, • vaccine, plus diluent if reconstitution is required, • appropriate drawing-up needle (19 or 21 gauge needle if required, to draw up through rubber bung and for reconstitution of vaccine), • appropriate injecting needle (see Table 1.4.2 Recommended needle size, length and angle for administering vaccines), • clean cotton wool and hypoallergenic tape to apply to injection site after vaccination, and • a rattle or noisy toy for distraction after the injection.
Administration of vaccines 39
1.4 Administration of vaccines
• 2 or 3 mL syringe (unless vaccine is in pre-filled syringe),
Preparing the vaccine • Wash hands carefully and prepare the appropriate injection equipment for the vaccine to be administered. • Ensure that the minimum/maximum thermometer displays temperatures within the +2°C to +8°C range before removing vaccine from the refrigerator. • Ensure that the correct vaccine is taken from the refrigerator and that it is within the expiry date. • Check that there is no particulate matter or colour change in the vaccine. • Ensure that the diluent container is not damaged and potentially contaminated. PRECAUTIONS: If a pre-filled syringe is provided, check carefully whether reconstitution with vaccine (provided in a separate vial) is required. The diluent of one brand of oral rotavirus vaccine (Rotarix) is provided in a syringe-like oral plunger. Do not administer this vaccine by injection (parenteral) after reconstitution. Both rotavirus vaccines are administered orally.
Preparing vaccine provided in a pre-filled syringe, ampoule or liquid vial • If the vaccine is in a vial, remove the cap carefully to maintain sterility of the rubber bung. Do not wipe the rubber bung. Use a 19 or 21 gauge needle to draw up the recommended dose through the bung. • If the vaccine is in an ampoule, use a 23 gauge, 25 mm needle to draw up the recommended dose. • Needles should be changed after drawing up from a vial with a rubber bung, but it is not necessary to change needles between drawing up a vaccine from an ampoule and giving the injection. • Small air bubbles do not need to be extruded through the needle. • A needle or syringe that has already been used to inject an individual must never come into contact with the vial because of the risk of cross-contamination.
40 The Australian Immunisation Handbook 9th Edition
Preparing vaccines requiring reconstitution • Reconstitute the vaccine as needed immediately before administration. • Never mix other vaccines together in the one syringe (unless that is the manufacturer’s registered recommendation, eg. Infanrix hexa). • Never mix a local anaesthetic with a vaccine. • A sterile 21 gauge needle should be used for reconstitution and a separate 23 or 25 gauge needle, 25 mm in length, should be used for administration of the vaccine in most circumstances. • Use only the diluent supplied with the vaccine; do not use sterile water for injection instead of a supplied diluent. Ensure that the diluent and vaccine are completely mixed. • Reconstituted vaccines should be checked for signs of deterioration, such as a change in colour or clarity. • Reconstituted vaccines may deteriorate rapidly and, in general, should be administered as soon as practicable after they have been reconstituted. • Never freeze a vaccine after it has been reconstituted.
1.4.3 Route of administration Almost all vaccines are given by either IM or SC injection, and a few vaccines are given orally. Rotavirus vaccines are only available for oral administration and must never be injected. Special training is required for intradermal administration, which is important for several vaccines (see Chapter 3.17, Q fever and Chapter 3.22, Tuberculosis). Table 1.4.1 below summarises the route of administration for vaccines commonly used in Australia.
1.4 Administration of vaccines
Administration of vaccines 41
Table 1.4.1: Route of administration for vaccines commonly used in Australia Intramuscular (IM) injection
Subcutaneous (SC) injection
IM or SC injection
Oral
Diphtheria, tetanus vaccine (dT)
Inactivated polio vaccine (IPV)*
Influenza vaccine†
Rotavirus vaccine Cholera vaccine
Diphtheria, tetanus, acellular pertussis vaccine (DTPa and dTpa)
Meningcoccal polysaccharide vaccine (4vMenPV)
Measles, mumps, rubella vaccine (MMR)
DTPa- and dTpacombination vaccines Hepatitis A vaccine Hepatitis B vaccine Hepatitis B combination vaccines
Varicella vaccine (VV) Q fever vaccine‡ Japanese encephalitis vaccine Measles, mumps, rubella, varicella vaccine (MMRV) (when available)
Typhoid vaccine
Rubella vaccine 23-valent pneumococcal polysaccharide vaccine (23vPPV) Rabies vaccine (HDCV) Yellow fever vaccine
Haemophilus influenzae type b (Hib) vaccine Human papillomavirus vaccine (HPV) IPV-containing combination vaccines* 7-valent pneumococcal conjugate vaccine (7vPCV) Typhoid Vi polysaccharide vaccine Meningococcal C conjugate vaccine (MenCCV) Rabies vaccine (PCECV) * IPV-containing combination vaccines are administered by IM injection; IPV (IPOL) is administered by SC injection. † The IM route is preferred because it causes fewer local adverse events.2 ‡ Q fever vaccine should be administered only by specially trained immunisation service providers.
42 The Australian Immunisation Handbook 9th Edition
1.4.4 Preparation for vaccine administration Skin cleaning Provided the skin is visibly clean, there is no need to wipe it with an antiseptic (eg. alcohol wipe).3,4 If the immunisation service provider decides to clean the skin, or if the skin is visibly not clean, alcohol and other disinfecting agents must be allowed to dry before vaccine injection (otherwise there may be some increased injection pain).
Distraction techniques The routine use of distraction, relaxation and other measures have been shown to reduce distress and pain following vaccination in young children.5-8 Reducing infant distress may enhance parents’ timely attendance for subsequent vaccinations. Distraction measures that may decrease discomfort following vaccination in young children include:5-8 • swaddling and holding the infant securely (but not excessively), • shaking a noisy toy (for infants and very young children), • playing music, • encouraging an older child to pretend to blow away the pain using a windmill toy or bubbles, or • administering sweet-tasting fluid orally immediately before the injection (with parental consent). In infants, 15–20% sucrose drops have been used. Topical anaesthetic agents, including vapocoolant sprays, are available but to be effective must be applied at the correct time before vaccine administration. Topical anaesthetics, such as EMLA, are not recommended for routine use, but could be considered in a child with excessive fear or dislike of needles, and require application 30 to 60 minutes before an injection.9 Vapocoolant sprays are applied 15 seconds before vaccination. Topical lignocaine/prilocaine is not recommended for children younger than 6 months due to the risk of methaemoglobinaemia.5
1.4 Administration of vaccines
Administration of vaccines 43
1.4.5 Vaccine injection techniques IM injection technique10,11 • For IM injection, a 25 mm needle should be used in most cases (see Table 1.4.2 below). • Depending on the injection site, the limb should be positioned so as to relax the muscle into which the vaccine is to be injected. • The 25 mm needle should pierce the skin at an angle of 90° to the skin, and can be safely inserted to the hub.12 Provided an injection angle of >70° is used, the needle should reach the muscle layer.13 • Studies have demonstrated that, for most vaccines, local adverse events are minimised and immunogenicity enhanced by ensuring vaccine is deposited into the muscle and not into the subcutaneous layer.5,14-17 However, some vaccines, eg. inactivated poliomyelitis, varicella and meningococcal polysaccharide vaccines, are only licensed for SC administration. • A recent clinical trial demonstrated that long (25 mm) needles (with the skin stretched flat and the needle inserted at 90°) for infant vaccination were associated with significantly fewer local adverse events while achieving comparable immunogenicity. Little difference was found between needles the same length but with different gauges in local adverse events or immune response.12 • If using a 25 gauge needle for an IM vaccination, ensure the vaccine is injected slowly over a count of 5 seconds to avoid injection pain and muscle trauma. • It is not considered necessary to draw back on the syringe plunger before injecting a vaccine.5 However, if this is done, and a flash of blood appears in the needle hub, the needle should be withdrawn and a new site selected for injection.18 • After completing the injection, perform post-vaccination care (see Chapter 1.5, Post-vaccination procedures).
SC injection technique • SC injections are usually administered at a 45° angle to the skin. • The standard needle for administering vaccines by SC injection is a 25 or 26 gauge needle, 16 mm in length.
Intradermal injection technique For intradermal injection of BCG vaccine or Q fever skin test vaccine, a 26 or 27 gauge, 10 mm needle is recommended. The intradermal injection technique requires special training, and should be performed only by a trained provider (see Chapter 3.22, Tuberculosis and Chapter 3.17, Q fever).
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Table 1.4.2: Recommended needle size, length and angle for administering vaccines5,10,12,14,19 Age or size of child/adult
Needle type
Angle of needle insertion
Infant, child or adult for IM vaccines
23 or 25 gauge,* 25 mm in length†
90° to skin plane
Preterm babies (<37 weeks’ gestation) up to age 2 months; very small infants
23 or 25 gauge,* 16 mm in length
90° to skin plane
Very large or obese patient
23 gauge, 38 mm in length
90° to skin plane
Subcutaneous injection in all individuals
25 or 26 gauge, 16 mm in length
45° to skin plane
* If using a narrow 25 gauge needle for an IM vaccination, ensure vaccine is injected slowly over a count of 5 seconds to avoid injection pain and muscle trauma. † The use of short needles for administering IM vaccines may lead to inadvertent subcutaneous (SC) injection and increase the risk of significant local adverse events, particularly with aluminium-adjuvanted vaccines (eg. hepatitis B vaccine, DTPa, DTPacombinations or tetanus vaccine).
1.4.6 Recommended injection sites The choice of injection sites depends primarily upon the age of the individual being vaccinated. The 2 anatomical sites recommended as routine injection sites are the anterolateral thigh (Figure 1.4.6) and the deltoid muscle (Figure 1.4.9). All practitioners should ensure that they are familiar with the landmarks used to identify any anatomical sites used for vaccination. Photographs and diagrams are provided in this section but are not a substitute for training. Further detail on identifying the recommended injection sites is provided in Section 1.4.8.
Infants <12 months of age The vastus lateralis muscle in the anterolateral thigh is the recommended site for IM vaccination in infants <12 months of age (see Figures 1.4.5 and 1.4.6, Section 1.4.8).
The deltoid muscle is not recommended for IM vaccination of infants <12 months of age.
Children ≥12 months of age The deltoid muscle is the recommended site for IM vaccination in children ≥12 months of age (see Figure 1.4.9, Section 1.4.8).
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1.4 Administration of vaccines
The ventrogluteal area (see Figures 1.4.7 and 1.4.8, Section 1.4.8) is an alternative site for IM vaccination of infants. It is important that vaccine providers who choose to use this site are familiar with the landmarks used to identify it. The reactogenicity and immunogenicity of vaccines given in this site are comparable to those of vaccines given in the anterolateral thigh.20-22
The ventrogluteal area is an alternative site for IM vaccination of children ≥12 months of age. However, vaccine providers should be familiar with the landmarks used to identify this site. The vastus lateralis in the anterolateral thigh may also be used in children ≥12 months of age, but if this site is used, the less locally reactogenic vaccines, eg. MMR, should be given in the thigh.
Adolescents and adults The deltoid muscle is the recommended site for IM vaccination in adolescents and adults (see Figure 1.4.9, Section 1.4.8). The anterolateral thigh can also be used in older children and adults. The ventrogluteal area is an alternative injection site. However, vaccine providers should be familiar with the landmarks used to identify this site. PRECAUTION: Vaccine injections should not be given in the dorsogluteal site or upper outer quadrant of the buttock because of the possibility of a suboptimal immune response.23,24 Immunoglobulin can be administered intramuscularly into the upper outer quadrant of the buttock, but care must be taken to ensure that the other quadrants are not used.
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1.4.7 Positioning for vaccination It is important that infants and children do not move during injection of vaccines. However, excessive restraint can increase their fear and result in increased muscle tension. The following section describes a variety of positions which may be used for vaccinating different age groups.
Positioning of infants <12 months of age • Cuddle position for infants Position the infant in a semi-recumbent cuddle position on the lap of the parent/carer. The infant’s arm adjacent to the parent/carer should be restrained underneath the parent/carer’s arm or against the parent/ carer’s chest. The knee should be flexed to encourage relaxation of the vastus lateralis for IM vaccinations. The infant’s other arm must also be held securely (see Figure 1.4.1). This position can also be used for young children. Figure 1.4.1: The cuddle position for vaccination of a child <12 months of age
1.4 Administration of vaccines
Photo courtesy Dr Joanne Molloy, VIC
Administration of vaccines 47
• Positioning infant on an examination table An alternative is to lay infants on their backs on an examination table, with the infant’s feet towards the immunisation service provider, and the parent/carer beside the provider to immobilise and distract the baby (see Figure 1.4.2). Keep the infant’s hip and knee flexed by cupping the patella in the non-injecting hand. The thumb and index finger of the non-injecting hand may be used to stabilise the hub of the needle once the needle has been inserted. Figure 1.4.2: Positioning an infant on an examination table for vaccination
Photo courtesy Dr Joanne Molloy, VIC
• Prone position across the lap for ventrogluteal vaccination For ventrogluteal injection, position the child face-down across the parent/ carer’s lap. This allows the hips to be flexed and provides access to the ventrogluteal area (see Figure 1.4.8).
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Positioning of children ≥12 months of age • Cuddle position for older child Sit the child sideways on the lap of the parent/carer, with the arm to be injected held close to the child’s body while the other arm is tucked under the armpit and behind the back of the parent/carer. The child’s exposed arm should be secured at the elbow by the parent/carer, and the child’s legs also secured by the parent/carer (see Figure 1.4.3). Figure 1.4.3: Positioning an older child in the cuddle position
Photo courtesy Ann Kempe, MCRI, VIC
1.4 Administration of vaccines
Administration of vaccines 49
• Straddle position An older child may be positioned facing the parent/carer with the legs straddled over the parent/carer’s lap. The child’s arms should be folded in front, with the parent/carer hugging the child’s body to the parent/carer’s chest. Alternatively, the child may be positioned to ‘hug’ the parent with the parent’s arms holding the child’s arms in a reciprocal hug (see Figure 1.4.4). This position allows access to both deltoids and both anterolateral thighs. Figure 1.4.4: Positioning a child in the straddle position
Photo courtesy Dr Joanne Molloy, VIC
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• Prone position across the lap for ventrogluteal vaccination For ventrogluteal injection, position the child face-down across the parent/ carer’s lap (see Figure 1.4.8).
Positioning of older children, adolescents and adults • Solo sitting position for deltoid injections Most vaccines can be administered into the deltoid area. Adults should sit in a straight-backed chair, feet resting flat on the floor with forearms and hands in a relaxed position on the upper thighs. Keep the arms flexed at the elbow to encourage the deltoid muscle to relax. Encourage shoulders to drop by asking the person to raise the shoulders up while taking a deep breath in and to drop them while breathing out fairly forcefully. Use distraction to keep muscles relaxed during the procedure, eg. have an interesting poster or similar for the person to concentrate on during the procedure and ask him/her to give you a detailed description of what can be seen. The ventrogluteal and vastus lateralis are alternative sites if needed (see above, and below).
1.4.8 Identifying the injection site The choice of injection site depends upon the age of the person, and is discussed in Section 1.4.6.
The anterolateral thigh (vastus lateralis) • The infant’s nappy must be undone to ensure the injection site is completely exposed and the anatomical markers easily identified. • Position the leg so that the hip and knee are flexed and the vastus lateralis is relaxed (see Figure 1.4.6). • The upper anatomical marker is the midpoint between the anterior superior iliac spine and the pubic tubercle, and the lower marker is the upper part of the patella. • Draw an imaginary line between the 2 markers down the front of the thigh. The correct site for IM vaccination is lateral to the midpoint of this line, in the outer (anterolateral) aspect (see Figures 1.4.5 and 1.4.6).
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1.4 Administration of vaccines
• Do not inject into the anterior aspect of the thigh where neurovascular structures can be damaged.
Figure 1.4.5: Diagram of the muscles of the thigh showing the anatomical markers to identify the recommended (vastus lateralis) injection site (X)
Figure 1.4.6: Photograph of the thigh showing the recommended (vastus lateralis) injection site (X)
Photo courtesy Lloyd Ellis, RCH, VIC
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The ventrogluteal area NB. This area should not be confused with the dorsogluteal area (buttock). The ventrogluteal site provides an alternative site for administering vaccines to a child of any age, especially when multiple injections at the same visit are required. The ventrogluteal area is relatively free of major nerves and blood vessels, and the area provides the greatest thickness of gluteal muscle.25,26 There is a relatively consistent thinness of subcutaneous tissue over the injection site.26,27 • The child’s nappy must be undone to ensure the injection site is completely exposed and the anatomical markers easily identified by sight and palpation. Anatomical markers are the anterior superior iliac spine (ASIS), the greater trochanter of the femur and the iliac crest (see Figure 1.4.7). • Place the child in a prone position (face-down) on parent/carer’s lap or on the clinic table/bed with arms tucked against the child’s chest. Allow the child’s legs to dangle towards the floor (see Figure 1.4.8). • The knee and hip should be turned inwards to encourage muscle relaxation at the injection site. • The injection site should be that which is closest to the immunisation service provider. • Place the palm over the greater trochanter (the uppermost bony prominence of the thigh bone) with the thumb pointing towards the umbilicus. The index finger points to the anterior superior iliac spine, and the middle finger is spread so that it aims at the iliac crest, thus creating a ‘V’ outlining the ventrogluteal triangular area. The injection site is at the centre of this area (see Figures 1.4.7 and 1.4.8). Figure 1.4.7: Diagram showing the anatomical markers to identify the ventrogluteal injection site (X) (ASIS = anterior superior iliac spine)
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Administration of vaccines 53
Figure 1.4.8: Photograph with infant prone across carer’s lap, showing markers to identify the ventrogluteal injection site (X)
Photo courtesy Dr Joanne Molloy, VIC
The deltoid area It is essential to expose the arm completely from the top of the shoulder to the elbow when locating the deltoid site (see Figure 1.4.9). Roll up the sleeve or remove the shirt if needed. • The injection site is halfway between the shoulder tip (acromion) and the muscle insertion at the middle of the humerus (deltoid tuberosity). • Draw an imaginary, inverted triangle below the shoulder tip, using the identified anatomical markers. • The deltoid site for injection is the middle of the muscle (triangle) (see Figure 1.4.9).
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Figure 1.4.9: Diagram showing the anatomical markers to identify the deltoid injection site
Subcutaneous injection sites Subcutaneous injections should be administered either over the deltoid muscle or over the anterolateral thigh. There are no data to demonstrate any difference in technique between administration of a SC injection and a deep SC injection. Figure 1.4.10 demonstrates the recommended technique for any SC injection. Figure 1.4.10: A subcutaneous injection into the deltoid area of the upper arm using a 25 gauge, 16 mm needle, inserted at a 45° angle
1.4 Administration of vaccines
Photo courtesy Ann Kempe, MCRI, VIC
Administration of vaccines 55
1.4.9 Administering multiple vaccine injections at the same visit The location of each separate injection given should be recorded, so that if a local adverse event occurs, the implicated vaccine(s) can be identified.
Infants <12 months of age The suitable sites for this age group are the anterolateral thighs and the ventrogluteal areas. Two vaccines can be given into the same anterolateral thigh, separated by at least 2.5 cm. However, only 1 vaccine should be given into each ventrogluteal area. When 3 or 4 IM vaccines are to be given at the same visit, the options are: • 2 injections can be administered in the same anterolateral thigh, separated by at least 2.5 cm (see Figure 1.4.11); further IM vaccines can be given in this way in the other thigh, or • 1 injection can be given into each anterolateral thigh and 1 injection can be administered into each ventrogluteal area. Figure 1.4.11: Recommended technique for giving multiple vaccine injections to an infant <12 months of age into the anterolateral thigh
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Children ≥12 months of age, adolescents and adults A single injection can be given into each deltoid muscle. When 3 or 4 IM vaccines are to be given to a child at the same visit, the options will depend on the muscle mass of the child’s deltoid. If the deltoid mass is adequate: • a further injection can be given into each deltoid muscle (separated by 2.5 cm from the initial vaccine). If the deltoid muscle mass is small: • further injections can be given into either the anterolateral thighs (2.5 cm apart if 2 vaccines are given in the same thigh), or • give 1 injection into each ventrogluteal area. For younger children, the cuddle or straddle position (Figures 1.4.3 and 1.4.4) are suitable for accessing multiple limbs during the one vaccination encounter.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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1.5 Post-vaccination procedures 1.5.1 Immediate after-care • Dispose of clinical waste, including sharps and vaccine vials, immediately after administration of the vaccine and at its point of use. Refer to the State/ Territory health authority for management guidelines for the safe disposal of clinical waste or refer to the Australian Government Department of Health and Ageing Infection control guidelines for the prevention of transmission of infectious diseases in the health care setting.1 • Cover the site quickly with a dry cotton ball and tape as needed. • Gently apply pressure for 1 or 2 minutes. Do not rub the site as this will encourage the vaccine to leak back up the needle track, which can cause pain and may lead to local irritation. • Remove the cotton wool after a few minutes and leave the injection site exposed to the air. • Paracetamol is not routinely used before or at the time of vaccination, but may be recommended as required for fever or pain. • To distract the individual and reduce distress, immediately change the position of the child/person after completing the vaccination, eg. ask the parent/carer to put the infant over the shoulder and move around with the infant.2 • The vaccinated person and/or parent/carer should be advised to remain in a nearby area for a minimum of 15 minutes after the vaccination. The area should be close enough to the immunisation service provider, so that the individual can be observed and medical treatment rapidly provided if needed. • Take the opportunity to check the vaccination status of other family members (as appropriate) and provide (or refer) for catch-up vaccination. • Record the relevant details of the vaccines given in a record to be retained by the person or parent/carer, in the surgery/clinic record and, for children aged <7 years, forward records to the ACIR (see Section 1.5.3, Documentation of vaccination). • Before departure, inform the individual or parent/carer, preferably in writing, of the date of the next scheduled vaccinations.
1.5.2 Adverse events following immunisation What are AEFI? An adverse event following immunisation (AEFI) is an unwanted or unexpected event occurring after the administration of vaccine(s). Such an event may be caused by the vaccine(s) or may occur by chance after vaccination (ie. it would have occurred regardless of vaccination). Most vaccines cause minor adverse events such as low-grade fever, pain or redness at the injection site and these
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The frequency of adverse events can be classified as follows: very common (>10%), common (1–10%), uncommon (0.1–1%), rare (0.01–0.1%) and very rare (<0.01%).4
Common adverse events The following common adverse events should be anticipated following vaccination.5 They can be distressing for parents/carers, but they do not contraindicate further vaccination. In general, unless these adverse events are significant, they do not need to be reported by immunisation service providers to the Adverse Drug Reactions Advisory Committee (ADRAC) (see Table 1.5.3, Contact details for notification of AEFI). Parents/carers should be given advice (preferably written) as part of the consent procedure on what common adverse events are likely and what they should do about them (the table inside the back cover of this Handbook, Commonly observed adverse events following immunisation with vaccines used in the National Immunisation Program (NIP) schedule and what to do about them, can be used for this purpose). • DTPa, dTpa, hepatitis B, Hib, IPV and their various combinations may cause transient minor adverse events including swelling, redness or soreness at the injection site, and low-grade fever, crying and irritability (in infants). • There is an increased risk of more extensive local adverse events after booster doses of DTPa and DTPa-combination vaccines.6 A local adverse event that involves extensive limb swelling should be reported. For the definition of extensive limb swelling, see Appendix 6, Definitions of adverse events following immunisation. • MMR vaccine may be followed 5 to 12 days later by a fever lasting 2 or 3 days, malaise and/or rash. This is not infectious. Fever >39.4°C is very common, occurring in 5 to 15% of vaccinees, 5 to 12 days after vaccination. • Human papillomavirus vaccine may cause mild injection site adverse events (pain, swelling and erythema) and, occasionally, headache, fever and nausea. • Influenza vaccine may cause soreness at the injection site. Fever, malaise, and myalgia occur less commonly. • The 7vPCV causes low-grade fever and/or mild pain at the injection site in about 10% of infant recipients. The 23-valent pneumococcal polysaccharide vaccine (23vPPV) causes mild local adverse events in up to half the adult recipients. • MenCCV is generally well tolerated. Very common (>10%) adverse events are pain, redness and swelling at the injection site, fever, irritability, anorexia and headache.
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should be anticipated3 (see the table Comparison of the effects of diseases and the side effects of vaccines inside the front cover of this Handbook).
• Varicella vaccine may cause mild local soreness and swelling. A mild maculopapular or papulovesicular rash occurs in up to 5% of vaccinated children (see also Chapter 3.24, Varicella). • Injection site nodules are not uncommon. They are fibrous remnants of the body’s interaction with the vaccine components (usually an adjuvant) in the muscle, and they may remain for many weeks after the vaccination. Injection site nodules do not require any specific treatment. • Oral rotavirus vaccine may cause mild fever and/or diarrhoea (see Chapter 3.18, Rotavirus).
Managing common adverse events Advice to parents on common adverse events Vaccine injections may result in soreness, redness, itching, swelling or burning at the injection site for 1 to 2 days. Paracetamol might be required to ease the discomfort.
Managing fever after vaccination Routine use of paracetamol at the time of vaccination is no longer recommended. If an infant or child has a fever of >38.5°C following vaccination, paracetamol can be given. The dose of paracetamol is 15 mg/kg/dose of paracetamol liquid, up to a maximum daily dose of 90 mg/kg per day in 4 to 6 divided doses for up to 48 hours.
Preventing AEFI The key to preventing uncommon or rare adverse events is to screen each person to be vaccinated using pre-vaccination screening (Tables 1.3.1 and 1.3.2) to ensure that the person does not have a condition which either increases the risk of an adverse event or is a contraindication to vaccination. The correct injection technique is also important. Immunisation service providers should also check the relevant chapters of this Handbook or the product information supplied with the vaccine for more details on precautions and contraindications for each vaccine they are to administer.
Uncommon and rare AEFI Some vaccines have been shown to cause uncommon or rare adverse events, although the rate is always hundreds to thousands times less frequent than the disease complications. Examples are given below.
Rare, late events shown to be causally related to some vaccines The use of oral poliomyelitis vaccine (OPV) in Australia was discontinued in 2005. OPV can rarely cause vaccine-associated paralytic poliomyelitis (VAPP). The incidence is 1 in 2.4 million doses of OPV, which means that Australia would have expected 1 case of VAPP every 3 years when OPV was in use. However,
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Vaccines containing diphtheria and tetanus have been described as causing brachial neuritis, with an incidence of approximately 1 in 100 000 (adults).
Events where evidence demonstrates no causal link with immunisation There is epidemiological evidence which indicates that there is no causal association between immunisation and the following events: • sudden infant death syndrome (SIDS) and any vaccine,8-10 • autism and MMR vaccine,11-14 • multiple sclerosis and hepatitis B vaccine,15-18 • inflammatory bowel disease and MMR vaccine,19 • diabetes and Hib vaccine,20-22 • asthma and any vaccine.23
Management of an immediate AEFI Observation after vaccination Recipients of vaccines should remain under observation for a short interval to ensure that they do not experience an immediate adverse event. It is recommended that recipients remain in the vicinity of the place of vaccination for at least 15 minutes. Severe anaphylactic reactions usually have a rapid onset; most life-threatening adverse events begin within 10 minutes of vaccination. The most serious immediate AEFI is anaphylaxis. However, in adults and older children, the most common immediate adverse event is a vasovagal episode (fainting), either immediately or soon after vaccination. Because fainting after vaccination can lead to serious consequences, anyone who complains of giddiness or light-headedness before or after vaccination should be advised to lie down until free of symptoms. Most faints following vaccination occur within 5 minutes, and 98% occur within 30 minutes. Adults should, therefore, be warned of the risk of driving or operating machinery for at least 30 minutes after vaccination.24 Children who have had a serious adverse event (other than a contraindication, such as anaphylaxis) to a previous vaccine may subsequently be vaccinated under close medical supervision. Check with State/Territory health authorities for more information (see Section 2.3.1, Vaccination of children who have had a serious adverse event following immunisation and Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
Anaphylaxis and vasovagal episodes Anaphylaxis following routine vaccination is very rare, but can be fatal. All immunisation service providers must be able to distinguish between anaphylaxis, convulsions and fainting.
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the reported incidence of VAPP was only 1 case every 8 to 9 years in Australia.7 VAPP does not occur from vaccination with IPV or IPV-containing vaccines.
Fainting (vasovagal episode) is relatively common after vaccination of adults and adolescents, but infants and children rarely faint. Sudden loss of consciousness in young children should be presumed to be an anaphylactic reaction, particularly if a strong central pulse is absent. A strong central pulse (eg. carotid) persists during a faint or convulsion. The features listed in Table 1.5.1 may be useful in differentiating these 2 conditions. If the diagnosis is unclear and anaphylaxis is considered, management for this should be instituted with the prompt administration of adrenaline. Table 1.5.1: Clinical features which may assist differentiation between a vasovagal episode and anaphylaxis Vasovagal episode
Anaphylaxis
Immediate, usually within minutes of or during vaccine administration.
Usually within 15 minutes, but can occur within hours, of vaccine administration.
Skin
Generalised pallor, cool, clammy skin.
Skin itchiness, generalised skin erythema (redness), urticaria (weals) or angioedema (localised oedema of the deeper layers of the skin or subcutaneous tissues).
Respiratory
Normal respiration; may be shallow, but not laboured.
Cough, wheeze, stridor, or signs of respiratory distress (tachypnoea, cyanosis, rib recession).
Cardiovascular
Bradycardia, weak/ absent peripheral pulse, strong carotid pulse.
Tachycardia, weak/absent peripheral and carotid pulse.
ONSET
Symptoms/ Signs
Hypotension – usually transient and corrects in supine position. Neurological
Feels faint, light-headed. Loss of consciousness – improves once supine or head down position.
Hypotension – sustained and no improvement without specific treatment. Sense of severe anxiety and distress. Loss of consciousness – no improvement once supine or head down position.
Signs of anaphylaxis Anaphylaxis is a severe adverse event of rapid onset, characterised by sudden respiratory compromise and/or circulatory collapse. Early signs include involvement of the skin, eg. generalised erythema, urticaria and/or angioedema (swelling), and/or gastrointestinal tract, eg. diarrhoea, vomiting. In severe cases, there is circulatory collapse with alteration in the level of consciousness,
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Immunisation service providers should be able to recognise all the following symptoms and signs of anaphylaxis: • cutaneous, such as the rapid development of widespread urticarial lesions (circumscribed, intensely itchy weals with erythematous, raised edges and pale, blanched centres) and/or erythema and/or angioedema (soft tissue swelling usually affecting the face and/or limbs), • upper airway obstruction, such as hoarseness and stridor, resulting from angioedema of the hypopharynx, epiglottis and larynx, • lower airway obstruction, such as subjective feelings of retrosternal tightness, and dyspnoea with audible expiratory wheeze from bronchospasm, • limpness and pallor, which are signs of hypotension in infants and young children, • profound hypotension in association with other signs of cardiovascular disturbance, such as sinus tachycardia or severe bradycardia, absent central pulses and reduced peripheral circulation, and/or • abdominal cramps, diarrhoea and/or vomiting.
Management of anaphylaxis Rapid IM administration of adrenaline is the cornerstone of treatment of anaphylaxis. Anaphylaxis occurs without warning, usually within 15 minutes of giving a vaccine. A protocol for the management of anaphylaxis, adrenaline, and 1 mL syringes must always be immediately at hand whenever vaccines are given. • If the patient is unconscious, lie him/her on the left side and position to keep the airway clear. If the patient is conscious, lie supine in ‘head down and feet up’ position (unless this results in breathing difficulties). • Give adrenaline by IM injection (see below for dosage) for any signs of anaphylaxis with respiratory and/or cardiovascular symptoms or signs. Adrenaline is not required for generalised non-anaphylactic reactions (such as skin rash or angioedema). If in doubt, IM adrenaline should be given. • If there is no improvement in the patient’s condition by 5 minutes, repeat doses of adrenaline every 5 minutes until improvement occurs. • If oxygen is available, administer by facemask at a high flow rate. • Call for assistance. Never leave the patient alone. • Begin expired air resuscitation for apnoea, check for a central pulse. If pulse is not palpable, commence external cardiac massage (ECM). • All cases should be admitted to hospital for further observation and treatment.
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hypotension and weak or absent pulses, and/or marked respiratory compromise from upper airway oedema or bronchospasm.
• Document the time and dose of adrenaline given. Experienced practitioners may choose to use an oral airway if the appropriate size is available, but its use is not routinely recommended unless the patient is unconscious. Antihistamines and/or hydrocortisone are not recommended for the emergency management of anaphylaxis.
Adrenaline dose Adrenaline 1:1000 (one in one thousand) Adrenaline 1:1000 contains 1 mg of adrenaline per mL of solution in a 1 mL glass vial. Adrenaline 1 in 10 000 is no longer recommended for the treatment of anaphylaxis. The use of 1:1000 adrenaline is recommended because it is universally available. Use a 1 mL syringe to improve the accuracy of measurement when drawing up small doses. The recommended dose of 1:1000 adrenaline is 0.01 mL/kg body weight (equivalent to 0.01 mg/kg or 10 µg/kg) up to a maximum of 0.5 mL, given by deep IM injection (not the deltoid). Adrenaline 1:1000 must not be administered intravenously. Table 1.5.2 lists the dose of 1:1000 adrenaline to be used if the exact weight of the individual is not known. Table 1.5.2: Doses of intramuscular 1:1000 (one in one thousand) adrenaline for anaphylaxis Less than 1 year
0.05–0.1 mL
1–2 years (approx. 10 kg)
0.1 mL
2–3 years (approx. 15 kg)
0.15 mL
4–6 years (approx. 20 kg)
0.2 mL
7–10 years (approx. 30 kg)
0.3 mL
11–12 years (approx. 40 kg)
0.4 mL
13 years and over (over 40 kg)
0.5 mL
The dose of 1:1000 (one in one thousand) adrenaline may be repeated every 5 minutes as necessary until there is clinical improvement.
Reporting AEFI Surveillance for adverse events following immunisation is an integral part of a national vaccination program. Through surveillance, it is hoped to detect changes in the rates of known adverse events and any adverse events that either were previously undocumented, or result from program errors, such as incorrect vaccine schedule, delivery or storage.
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Any of the adverse events listed in Appendix 6, Definitions of adverse events following immunisation should be reported. No time limit has been set to report AEFI. Notification of an adverse event does not necessarily imply a causal association with vaccination, as some events may occur coincidentally following vaccination. Immunisation service providers are also advised to report any adverse events of concern that do not fit into any of the categories listed in Appendix 6. They should be reported as ‘other reactions’ with a full description of the adverse event. This will enable new and unexpected AEFI to be identified.
How should AEFI be reported? AEFI are notifiable directly to the relevant health authority in Australian Capital Territory, New South Wales, Northern Territory, Queensland, South Australia, Victoria and Western Australia. In Tasmania, AEFI should be reported using the Adverse Drug Reactions Advisory Committee (ADRAC) blue card. AEFI are notifiable conditions in Australian Capital Territory, New South Wales, Northern Territory, Queensland, South Australia, Victoria and Western Australia and must be reported directly to the relevant health authority (see Table 1.5.3 below). These State and Territory health authorities then forward AEFI notifications to ADRAC. The Adverse Drug Reactions Advisory Committee (ADRAC) receives reports of unexpected and serious adverse events for all medicines, including vaccines. Any person (medical or non-medical) can report an AEFI to ADRAC by telephoning the numbers listed in Table 1.5.3 below, or by filling in a blue card or completing a web-based report (https://www.tgasime.health.gov.au/ SIME/ADRS/ADRSLodg.nsf/wNotification?OpenForm). Additional blue cards are available from: The Secretary Adverse Drug Reactions Advisory Committee PO Box 100 Woden ACT 2606 Telephone: 1800 044 114 or on-line at www.tga.gov.au/adr/bluecard.htm ADRAC will forward copies of individual reports of AEFI with vaccines on the National Immunisation Program schedule to those States/Territories that have follow-up surveillance. In addition, reports from ADRAC and State/Territory Health Departments are aggregated and published in Communicable Diseases Intelligence.25
Post-vaccination procedures 65
1.5 Post-vaccination procedures
Any serious or unexpected adverse event following immunisation should be reported. Providers should use clinical judgement and common sense in deciding which adverse events to report, and parents/carers should be encouraged to notify the immunisation service provider or health authorities of an AEFI.
Table 1.5.3: Contact details for notification of AEFI State/Territory
Report adverse events directly to:
Telephone number
*Australian Capital Territory
ACT Health Department
02 6205 2300
*New South Wales
NSW Public Health Units
Contact your local Public Health Unit, found under ‘Health’ in the White Pages
*Northern Territory NT Department of Health and Community Services
08 8922 8044
*Queensland
Queensland Health
07 3234 1500
*South Australia
Department of Health
08 8226 7177
In SA, parents can also report adverse events by calling
1300 364 100 (24 hours)
Tasmania
ADRAC
Use blue card
*Victoria
Department of Human Services, SAEFVIC
1300 822 924
*Western Australia
State Health Department
08 9321 1312
* AEFI are notifiable in these States/Territories and health professionals should report directly to their respective Health Department as listed above.
1.5.3 Documentation of vaccination A personal health record should be established for each vaccinee and newborn infant, and kept by that person or the parent/carer. The parent/carer should be urged to present the record every time a child is seen by a health professional. The following details should be recorded in the personal health record, and in the clinical file: • the vaccinee’s full name and date of birth, • the details of the vaccine given, including the dose, brand name, batch number, and site of administration, • the name of the person providing the vaccination, • the date of vaccination, and • the date the next vaccination is due. If the vaccinee is a child <7 years of age, the Australian Childhood Immunisation Register (ACIR) must also be notified of the vaccination details (see ‘The Australian Childhood Immunisation Register’ below).
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1.5.4 The Australian Childhood Immunisation Register
Children enrolled in Medicare are automatically included on the ACIR. Children not enrolled in Medicare will be included when an immunisation service provider sends details of a vaccination to the ACIR. No vaccination information is recorded on the ACIR after a child turns 7 years of age, but any information already held is retained. The information will relate only to vaccines received between the ages of birth and the 7th birthday. The ACIR Enquiry Line can be contacted on 1800 653 809 (free call) and any record held for an individual who is ≥7 years of age can also be made available to an immunisation service provider or parent/carer. The ACIR provides an important means of accountability and evaluation of the childhood vaccination program. It is the primary means of determining vaccination coverage at national, State/Territory and local levels. It also provides a central vaccination history for each child that is accessible to any Australian immunisation service provider wishing to assess vaccination status. Since 1998, data held on the ACIR have been used to determine a family’s entitlement to the Child Care Benefit and Maternity Immunisation Allowance family assistance payments. It is, therefore, important that vaccination data are submitted to the ACIR promptly.
Reporting to ACIR Immunisation service providers should send to the ACIR details of all NIP and private vaccinations given to children <7 years of age. Vaccination details may be submitted by sending data electronically via Medicare Australia’s on-line claiming facility, Electronic Data Interchange (EDI) on the Internet, or by using a paper form. Providers in Queensland and the Northern Territory currently sending data to the ACIR via their State/Territory Health Department should continue to do so. Providers in all other States/Territories should send data directly to the ACIR. A child’s vaccination record can also be updated with vaccination details where the vaccination was performed by another immunisation service provider, including those given while the child was overseas, by completing and sending an Immunisation History form to Medicare Australia. Forms are available on the ACIR website at www.medicareaustralia.gov.au/providers/forms/acir.htm.
Post-vaccination procedures 67
1.5 Post-vaccination procedures
The Australian Childhood Immunisation Register (ACIR) is a national database for recording details of vaccinations given to children <7 years of age who live in Australia. It commenced on 1 January 1996 and is administered by Medicare Australia under the legislative mandate of the Commonwealth Health Insurance Act 1973 Part IVA. Section 46B of the Health Insurance Act specifies how the ACIR is to be implemented and managed. Section 46E sets out the provisions for giving both de-identified and identified information to recognised immunisation service providers and other specified agencies.
When relevant, immunisation service providers should complete the Conscientious Objection and Medical Contraindication forms and forward to the ACIR. For further information about the ACIR and reporting vaccination information, see ‘The ACIR Internet site’ below. In addition, assistance on any reporting issues can be obtained from the ACIR Enquiry Line, 1800 653 809 (free call).
Immunisation History Statement Immunisation History Statements, which contain details of all vaccines administered to the child and recorded on the ACIR, and those that may be missing, are automatically generated when a child turns 12 months, 2 and 5 years of age and on completion of the childhood vaccination schedule. Statements will be mailed to the address most recently recorded on the ACIR for that child. Parent/carers can also get a Statement at any other time: • on-line at www.medicareaustralia.gov.au, • from their local Medicare office, • by calling 1800 653 809 (free call). Immunisation History Statements can be used when proof of vaccination is needed. For example, Statements can be used to meet vaccination requirements for: • primary school enrolment – a sentence will be displayed at the bottom of the statement that says the child has received all the vaccinations required by 5 years of age, and/or • eligibility for the Child Care Benefit and Maternity Immunisation Allowance; an up-to-date status for the Family Assistance Office will be displayed.
Recording details of a deceased child The ACIR should be notified of a deceased child to prevent an Immunisation History Statement being sent to bereaved parents/carers. Advice of a child’s death can be provided by calling 1800 653 809 (free call), or by sending details on practice stationery. Details should include the child’s name, address, date of birth, Medicare number and date of death.
Children who have moved to live overseas A child who has moved overseas can be removed from the ACIR by sending details to the ACIR by fax, phone or secure site email. This prevents the child’s name continuing to appear on ACIR reports of overdue children.
Ascertaining individual vaccination status Parents/carers can telephone the ACIR on 1800 653 809 (free call) for information about their child’s vaccination status, regardless of where the child’s vaccination was given. Immunisation service providers can also request a child’s vaccination status by telephone.
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Vaccination coverage and other reports
Practices that are registered for the General Practice Immunisation Incentive (GPII) scheme can receive quarterly reports on vaccination coverage for children within that practice. Other reports, including those that identify a child’s vaccinations and due/overdue details, are available through the secure area of the ACIR Internet site to approved immunisation service providers.
The ACIR Internet site The ACIR Internet site has 2 main parts, a general information area and a secure area. The Internet address for the ACIR is www.medicareaustralia.gov.au. Any person with Internet access may view the ACIR site for general vaccination information and statistics. Approved immunisation service providers are able to access the secure area of the ACIR Internet site and obtain a range of statistical and identified reports. These reports are available, depending on the access level granted to the provider, and enable approved providers to view a child’s vaccination details, record vaccination information and access a range of other reports. To register for access to the secure area of the ACIR Internet site, providers should complete the online request form at http://www.medicareaustralia.gov.au/providers/programs_ services/acir/index.htm. Further information or assistance may be obtained by calling the ACIR Internet Helpline on 1300 650 039 (free call).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
Post-vaccination procedures 69
1.5 Post-vaccination procedures
ACIR reports assess progress towards national targets, and help to identify areas with low vaccination levels and assist in planning vaccination programs.
PART 2: Vaccination for special risk groups 2.1 Vaccination for Aboriginal and Torres Strait Islander people Aboriginal and Torres Strait Islander people historically had a very high burden of infectious diseases, including those for which vaccines were subsequently developed. These high rates of disease in the early period of European colonisation were mainly due to a lack of previous exposure and acquired immunity,1 and in more recent years have been associated with lower standards of living and poorer access to water, housing and health care.2 For some vaccine-preventable diseases (VPDs), such as diphtheria, polio, tetanus, hepatitis B, measles, mumps and rubella, vaccination has been very successful in eliminating or substantially reducing disease in all Australians, and has made a substantial contribution to improvements in Aboriginal and Torres Strait Islander child mortality in recent decades.3 For some other VPDs, in particular invasive pneumococcal disease and influenza in adults, greater burdens of illness still occur in Indigenous compared to non-Indigenous people and remain a major cause of illness and death.3 Detailed information on the current status of VPDs and vaccination status in Aboriginal and Torres Strait Islander people is available elsewhere.3 This chapter discusses the vaccines for which there are different recommendations for Aboriginal and Torres Strait Islander people in at least some parts of Australia. These are, for children, BCG, hepatitis A, Haemophilus influenzae type b, and pneumococcal vaccines, and, for adults, influenza and pneumococcal polysaccharide vaccines.
CHILDREN BCG vaccine and tuberculosis In the past, Aboriginal and Torres Strait Islander people have suffered from much higher rates of tuberculosis, more than 20 times the rate of non-Indigenous Australian-born people in some areas.4 While there have been substantial improvements in disease rates in recent decades, tuberculosis remains more common in Indigenous than non-Indigenous Australian-born people in many parts of Australia, particularly northern and central Australia.5,6 Although there is uncertainty about the efficacy of BCG in preventing pulmonary tuberculosis, it provides substantial protection against disseminated forms of the disease in young children.7 BCG is therefore recommended for Aboriginal and Torres Strait Islander neonates in regions of high incidence (Northern Territory, far northern Queensland, some regions of both Western Australia and South
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Haemophilus influenzae type b Before the introduction of an effective Haemophilus influenzae type b (Hib) vaccine, not only was the incidence of invasive Hib disease very high in Aboriginal and Torres Strait Islander children, particularly in more remote areas, it also occurred at a younger age than in non-Indigenous children. Thus, a vaccine to prevent Hib disease in Aboriginal and Torres Strait Islander children needed to be immunogenic as early as possible in infancy. The vaccine known by the abbreviation PRP-OMP (PedvaxHIB or COMVAX) is more immunogenic at 2 months of age than the other conjugate Hib vaccines, and so was the preferred Hib vaccine for Aboriginal and Torres Strait Islander children from the inception of the Hib vaccination programs in 1993. Since then, there has been a dramatic decline of Hib disease in Aboriginal and Torres Strait Islander children.10,11 The experience in other high incidence populations indicates that it is important to continue to use PRP-OMP vaccine in Aboriginal and Torres Strait Islander populations demonstrated to be at highest risk, as in central and northern Australia. However, the available data indicate that Indigenous children in areas of low incidence, and non-Indigenous children, have a pattern of Hib disease which is adequately covered by a vaccine not prompting significant immune response until after the second dose.12 New combination vaccines which include a Hib (PRP-T) component have the advantage of reducing the number of injections required. Therefore, in the Northern Territory, Queensland, South Australia and Western Australia, all Aboriginal and Torres Strait Islander children should receive a Hib vaccine with a PRP-OMP component, while Indigenous children in other jurisdictions, and non-Indigenous children, may receive either PRP-T or PRP-OMP Hib vaccines (see Chapter 3.4, Haemophilus influenzae type b). State/Territory health authorities should be contacted about the vaccination schedule for each jurisdiction.
Vaccination for Aboriginal and Torres Strait Islander people 71
2.1 Vaccination for Aboriginal and Torres Strait Islander people
Australia), where infants are at higher risk of acquiring this serious, and often fatal, condition. State and Territory guidelines should be consulted where BCG is being considered for neonates <2.5 kg in weight. Nevertheless, as the incidence of pulmonary tuberculosis in adults and the risk of disseminated tuberculosis in infants decreases, the risk of severe complications of BCG, documented in native peoples elsewhere, may become a significant consideration.8 State/Territory health authorities should be consulted to determine the recommendations for particular areas. It is usually administered to eligible infants by hospital staff (ie. midwives or nurses who have been specially trained) soon after delivery. Injection technique is particularly important for BCG vaccination which must be administered intradermally. Adverse events, such as regional lymphadenitis, are less common when administration is performed by trained staff.9 See Chapter 3.22, Tuberculosis for more information.
Hepatitis A Hepatitis A infection has been shown to be very common in Aboriginal and Torres Strait Islander children across northern Australia.13-15 Although the symptoms of infection in early childhood are usually mild or absent, cases complicated by liver failure and death have been reported among Indigenous children in far north Queensland15 and the Kimberley13 and recorded hospitalisation rates have been found to be at least 50 times higher in Indigenous compared to non-Indigenous children.3 A vaccination program for Indigenous children was introduced in north Queensland in 1999, which resulted in substantial decreases in disease rates not only in Indigenous but also in nonIndigenous children, suggesting a substantial herd immunity effect.16 Vaccination is now recommended for Aboriginal and Torres Strait Islander children in those jurisdictions with high incidence: the Northern Territory, Queensland, South Australia and Western Australia (see Chapter 3.5, Hepatitis A). Two doses should be given, commencing in the second year of life. As the exact recommended ages of administration vary between States and Territories, jurisdictional health authorities should be contacted about their vaccination schedules.
Pneumococcal vaccines Some of the highest rates of invasive pneumococcal disease (IPD) ever reported in the world were in young central Australian Aboriginal children before the availability of the conjugate vaccine,17 and very high rates were also reported in Indigenous children in other parts of northern Australia.18,19 High rates of pneumococcal pneumonia have also been documented in central Australian children,20 and Streptococcus pneumoniae has been implicated in the high rates of otitis media.21 In response to this, the 7-valent pneumococcal conjugate vaccine (7vPCV) was made available for Aboriginal and Torres Strait Islander children from 2001. As well as higher rates of IPD, a wider range of serotypes is responsible for disease in Aboriginal and Torres Strait Islander children, resulting in a lower percentage of cases (below 60%) caused by serotypes included in the 7vPCV.18,19 Therefore, a booster dose of 23-valent pneumococcal polysaccharide vaccine at 18–24 months of age, following the primary course of 7vPCV, is recommended in areas of high incidence, ie. the Northern Territory, Queensland, South Australia and Western Australia. See Chapter 3.15, Pneumococcal disease for more information. There has been a rapid decline in invasive pneumococcal disease in Indigenous children since the introduction of the pneumococcal vaccines in 2001.22
ADULTS Influenza Influenza and/or pneumonia is the primary cause of around 2.5% of deaths in Aboriginal and Torres Strait Islander people, the vast majority being adults.2 The disease burden is greatest in the elderly, with hospitalisation and death more than twice as frequent in Indigenous adults aged ≥50 years, compared
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to non-Indigenous adults.3 Younger Indigenous adults suffer an even greater relative burden than non-Indigenous younger adults, at least 7 times higher for hospitalisations, and 28 times higher for death,3 probably related to a high prevalence of risk factors such as diabetes, renal disease and excessive alcohol use.2 The most common complication of influenza is secondary bacterial pneumonia, and influenza vaccine has been shown to be effective in preventing pneumonia and death in the elderly.23 Therefore, yearly influenza vaccination is recommended for all Aboriginal and Torres Strait Islander adults aged ≥15 years.
Pneumococcal polysaccharide vaccine
23vPPV is recommended for all Aboriginal and Torres Strait Islander people aged ≥50 years, and for those aged 15–49 years who have high-risk underlying conditions, and has been funded nationally for people in these categories since 1999. Eligibility for Indigenous adults may be broader than this in some regions; jurisdictional health authorities should be contacted for further information. A single revaccination is recommended after 5 years, and a second revaccination is recommended in some circumstances. See Chapter 3.15, Pneumococcal disease for more details.
Other vaccines The first ever outbreak of Japanese encephalitis (JE) in Australia occurred in the remote outer islands of the Torres Strait in 1995. JE vaccine was first offered to the residents of these islands in late 1995 and, since then, the vaccine has been integrated into the childhood vaccination schedule commencing at 12 months of age (see Chapter 3.10, Japanese encephalitis).27
Service delivery General Practitioners, Aboriginal Community Controlled Health Services, Community Health Services, the Royal Flying Doctor Service and State/Territory Corrective Services all provide substantial levels of vaccination services to Aboriginal and Torres Strait Islander people, and are important to the success of programs to vaccinate Indigenous people. While vaccination coverage estimates
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2.1 Vaccination for Aboriginal and Torres Strait Islander people
Studies in far north Queensland and the Kimberley have demonstrated a favourable impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) on rates of invasive pneumococcal disease in Indigenous adults,18,24,25 but, at a national level, disparities in disease rates between Indigenous and nonIndigenous adults remain. As is the case for influenza and pneumonia, rates of invasive pneumococcal disease are highest in older Indigenous adults, with rates around 4 times higher in Indigenous compared to non-Indigenous adults aged ≥50 years.3 Rates in younger adults are slightly lower, but the relative difference between Indigenous and non-Indigenous is much greater, around 12 times higher in Indigenous compared to non-Indigenous adults aged 25–49 years.3 This has been attributed to a high prevalence of at-risk conditions such as diabetes, renal disease and excessive alcohol use.26
vary over time and between communities, a relatively consistent finding has been higher coverage in Aboriginal and Torres Strait Islander people in remote compared to urban areas.28,29 Recent estimates suggest that, for vaccines recommended for both Indigenous and non-Indigenous people, coverage is as high or higher in Indigenous people as non-Indigenous people,3 but vaccination is more frequently delayed.30 Coverage for vaccines recommended only for Aboriginal and Torres Strait Islander people is generally lower than for vaccines which are funded for all people in a particular age group.31 This points to the importance of identification of Indigenous status, particularly in mainstream health services, and particularly in urban areas. The use of patient information systems to record Indigenous status and schedule preventive health services has the potential to increase opportunistic vaccination and enable the provision of patient reminders, with improved coverage and timeliness.32
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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2.2 Vaccination for international travel Introduction The number of Australians who travel overseas has increased steadily over recent years and now between 3.5 and 4.5 million exits are made annually. Although many of these trips are to countries where health risks exist, the majority of Australians travelling overseas do not seek pre-travel health advice.1 Every year, Australian travellers are injured, become ill, or even die, while travelling abroad. Some of the infectious diseases that cause some of this morbidity and mortality are preventable through vaccination.2,3 There is a range of travel vaccines that target infectious diseases that are more common in different or less-developed environments, and therefore travel itineraries should be assessed for the level of risk for these diseases.3 Factors such as the interval between the initial presentation and the departure date, destination, length of stay, activities during travel, type of accommodation, personal medical history, age of the traveller, previous vaccination status and financial constraints, all have a potential impact on vaccine recommendations. It is important to identify travellers who may be at increased risk for travel related illness, such as pregnant women, children, people with chronic systemic illness or people with impaired immunity. Recent immigrants and their Australian-born children are at particular risk of acquiring some of these infections when they return to their country-of-origin to visit relatives and friends.4
Common infections acquired by travellers include those which follow ingestion of contaminated food or water.2,5 Most of these are diarrhoeal diseases due to enteric pathogens, but infections with extra-intestinal manifestations, such as hepatitis A and typhoid, are also acquired this way. Vaccines are available for cholera, hepatitis A and typhoid. Insect-borne (particularly mosquito) infections, such as malaria and dengue, are important causes of fever in Australian travellers returning from endemic areas, southeast Asia and Oceania in particular.5 Japanese encephalitis occurs throughout much of Asia and probably throughout Papua New Guinea. Yellow fever occurs only in parts of Africa and Central and South America, while tickborne encephalitis occurs in parts of Europe and Asia. Vaccines are available for Japanese encephalitis, yellow fever and tick-borne encephalitis. Vaccine-preventable infections transmitted via respiratory droplets include influenza, invasive meningococcal disease and measles; influenza may be the most frequent vaccine-preventable infection among travellers.6 Tuberculosis, although rare, is mostly acquired by expatriates who live in high-risk areas for long periods.
Vaccination for international travel 75
2.2 Vaccination for international travel
Infections acquired by travellers
Blood-borne infections, such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV), may pose a threat to some Australian travellers. In remote areas of some countries, there is the possibility that these viruses are transmitted by healthcare workers using non-sterile medical equipment. Hepatitis B vaccine is relevant to many travellers. Travellers may be exposed to a variety of other exotic infections such as rabies from dog (and other mammal) bites in many countries, schistosomiasis after swimming in African lakes, and leptospirosis after rafting or wading in contaminated streams. Of these, only rabies can be prevented by vaccination.
Practical aspects of travel vaccine administration Consider each traveller individually, in the context of the specific itinerary. There is no ‘correct’ list of vaccines for any single country. Ideally the vaccinations should be started early, to minimise any adverse events around the time of departure and allow sufficient time for adequate immunity to develop. First, consider routine vaccines; all travellers should be up-to-date with current standard vaccine recommendations. Then consider any other vaccines that may be relevant to the individual’s usual health status, occupation or lifestyle (eg. pneumococcal polysaccharide vaccine for an elderly person, hepatitis B vaccine for a first aid officer). These should be offered before consideration of the travel vaccines. Travel vaccines should be considered according to risk. Priority should be given to vaccines for diseases that are common and of significant impact (such as influenza and hepatitis A), and to those diseases which, although less common, have severe potential adverse outcomes (such as Japanese encephalitis and rabies). Booster doses should be considered where appropriate (see Table 2.2.1); a ‘rapid schedule’ for a combined hepatitis A/B vaccine is available for those ≥16 years of age with limited time before travel (see the appropriate vaccine chapters). For children, consider the lower age limits for recommendation of selected vaccines (see Table 2.2.2). It is important to document travel vaccines appropriately, not only in the clinic’s record but also in a suitable record that can be carried by the traveller.
Vaccines All intending travellers should have been vaccinated according to the recommended vaccination schedule for the traveller’s age. All children should be vaccinated according to the National Immunisation Program (NIP) schedule. In exceptional circumstances, the NIP vaccines may be administered at the minimum age rather than the recommended age (see Section 1.3.5, Catch-up, Table 1.3.7 Minimum age for the first dose of vaccine in exceptional circumstances). Children vaccinated using the minimum age rather than the recommended age may require extra vaccine doses to ensure adequate protection. The minimum
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interval between doses must be adhered to (see Section 1.3.5, Catch-up, Table 1.3.6 Minimum dose intervals for NIP vaccines for children <8 years of age).
Measles Most measles outbreaks now follow infection imported by inadequately vaccinated young travellers. Therefore, Australians born during or since 1966 who have not received 2 doses of a measles-containing vaccine should be vaccinated with MMR before travelling. Varicella vaccine should be offered to travellers who have not had clinical disease or where serology demonstrates lack of immunity (remembering that 2 doses, separated by at least a month, are required by those ≥14 years of age).
Tetanus Adult travellers should be adequately protected against tetanus before departure, particularly if there could be delays in accessing health services. They should receive a booster dose of dT if more than 10 years have elapsed since the last dose. Protection against pertussis may also be offered at this opportunity (as dTpa) if no previous dose of dTpa has been given.
Poliomyelitis
Influenza and pneumococcal disease Travellers aged ≥65 years, and those with any medical risk factor, should receive the seasonal influenza vaccine and should have received the 23-valent pneumococcal polysaccharide vaccine. All travellers should consider influenza vaccine, especially when heading to the northern hemisphere winter.
Hepatitis B All children and adolescents should have been vaccinated against hepatitis B according to the NIP schedule. As they could be exposed to hepatitis B virus during unplanned medical procedures, all travellers intending to spend a month or more in Central and South America, Africa, Asia or Oceania should be vaccinated against hepatitis B.
Vaccination for international travel 77
2.2 Vaccination for international travel
All travellers should be age-appropriately immunised against polio. If travelling to countries where wild polio virus still exists (Afghanistan, India, Nigeria, and Pakistan), inactivated poliomyelitis vaccine (IPV) should be offered to those who have not completed a 3-dose primary course of any polio vaccine, and a single booster dose should be given to those who have previously completed the primary course. For an up-to-date list of affected countries see http://www.polioeradication.org.
Hepatitis A Hepatitis A vaccine should be given to all travellers ≥1 year of age travelling to moderately to highly endemic countries (including all developing countries). There is no place for the routine use of normal human immunoglobulin to prevent hepatitis A in travellers (see Chapter 3.5, Hepatitis A).
Typhoid Typhoid vaccine should be given to travellers ≥2 years of age travelling to endemic regions, which include the Indian subcontinent, most southeast Asian countries, many south Pacific nations and Papua New Guinea (see Chapter 3.23, Typhoid).
Cholera Cholera vaccination is rarely indicated for travellers,3 as the risk of acquiring cholera is extremely low, and the protection is of relatively short duration. It is only indicated for those travellers at considerable risk, such as those working in humanitarian disaster situations. However, it can also be considered for those travellers with achlorhydria and for those at increased risk of severe or complicated diarrhoeal disease (see Chapter 3.2, Cholera). Certification of cholera vaccination has been abandoned globally, and no countries have official entry requirements for cholera vaccination (see Chapter 3.2, Cholera).
Rabies Travellers to rabies-endemic regions should be advised of the risk, and to avoid close contact with either wild or domestic animals, and they should be advised on what to do should they be either bitten or scratched by an animal while abroad (see Chapter 3.1, Australian bat lyssavirus infection and rabies and also refer to the World Health Organization website www.who.int). Pre-travel (ie. pre-exposure) rabies vaccination (or, if appropriate, booster doses) is recommended for expatriates and travellers who will be spending prolonged periods (ie. more than a month) in rabies-endemic areas. (NB. This time interval, of more than a month, is arbitrary, and rabies has occurred in travellers following shorter periods of travel). Vaccination before travel simplifies the management of a subsequent exposure because fewer doses of vaccine are needed, and because rabies immunoglobulin (which is often difficult or even impossible to obtain in many developing countries) is not required.
Japanese encephalitis Vaccination is recommended for travellers spending a month or more in either the rural areas of Asia or in Papua New Guinea, particularly if travel is during the wet season and/or there is considerable outdoor activity and/or the standard of accommodation is suboptimal. Vaccination is also recommended for expatriates spending a year or more in Asia, even if much of the stay is in urban areas (see Chapter 3.10, Japanese encephalitis).
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Meningococcal infections All children ≥12 months of age and all teenagers should have received the meningococcal C conjugate vaccine. In addition, the tetravalent meningococcal polysaccharide vaccine (4vMenPV) is recommended for those who intend travelling to parts of the world where epidemics of meningococcal disease occur, in particular the ‘meningitis belt’ of sub-Saharan Africa.7 Of note, large epidemics of meningococcal meningitis occurred in Delhi, India, in 1966, 1985 and 2005.8 The Saudi Arabian authorities require that all pilgrims attending the annual Hajj have evidence of recent vaccination with 4vMenPV9 (see Chapter 3.12, Meningococcal disease).
Yellow fever The World Health Organization no longer routinely reports on yellow fever ‘infected areas’. Rather, the yellow fever vaccine is now recommended for travellers to yellow fever-endemic countries, in particular those that have reported yellow fever since 1950 (see Chapter 3.25, Yellow fever, Table 3.25.1 Yellow fever endemic countries).10 Briefly, provided there is no specific contraindication, the vaccine is recommended for all those ≥9 months of age travelling anywhere in any country in West Africa, and for all those ≥9 months of age travelling outside urban areas of all other yellow fever-endemic countries (see Table 3.25.1).
Tuberculosis
Tick-borne encephalitis This disease is prevalent in central and northern Europe and across northern Asia during the summer months. The vaccine is available only through Special Access Scheme arrangements in Australia.
Vaccination for international travel 79
2.2 Vaccination for international travel
Vaccination is generally recommended for tuberculin-negative children <5 years of age who will be living in developing countries for more than 3 months. There is less evidence of the benefit of vaccination in older children and adults, although consideration should be given to vaccination of tuberculin-negative children <16 years of age who may be living for long periods in high-risk countries (defined as having an incidence ≥100 per 100 000 population) (see Chapter 3.22, Tuberculosis).
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JE-VAX
Priorix
Japanese encephalitis
Measlesmumps-rubella
Live attenuated measlesmumps-rubella viruses
Inactivated Japanese encephalitis virus
15 µg haemagglutinin of 2 current influenza A and 1 influenza B strains
10 µg hepatitis B surface antigen protein
H-B-VAX II
Various
20 µg hepatitis B surface antigen protein
25 µg S. typhi polysaccharide and 160 EIA U inactivated HAV antigen
Engerix-B
Influenza
Hepatitis B
NB. Only for use in people ≥16 years of age
Vivaxim*
Hepatitis A/ typhoid combined
720 EIA U inactivated HAV antigen and 20 µg recombinant hepatitis B virus surface antigen
50 U inactivated HAV antigen
VAQTA Adult
Twinrix (720/20)
1440 EIA U inactivated HAV antigen
Havrix 1440
Hepatitis A/B combined
160 EIA U inactivated HAV antigen
Avaxim
Hepatitis A
Main constituents
Brand name
Vaccine (adults)
0.5 mL
1 mL
0.5 mL
1 mL
1 mL
1 mL combined vaccine
1 mL
1 mL
1 mL
0.5 mL
Dose (adults)
IM/SC
SC
IM
IM
IM
IM
IM
IM
IM
IM
Route
Australians born during or since 1966 who do not have documented evidence of having received 2 doses of a measlescontaining vaccine should receive at least 1 dose of MMR before travel.
0, 7, 28 days
Single dose
0, 1, 6 months
0, 1, 6 months, or 0, 1, 2, 12 months, or † 0, 7, 21 days, and 12 months
Single dose
0, 1, 6 months , or † 0, 7, 21 days, and 12 months
0, 6 to 18 months
0, 6 to 12 months
0, 6 to 12 months
Primary schedule
Boosters at 3-yearly intervals.
As different strains circulate from year to year, annual vaccination with the current formulation is necessary.
A completed series probably gives life-long immunity.
A dose of monovalent hepatitis A vaccine given 6–36 months later probably gives life-long immunity. The duration of protection against typhoid is probably 3 years.
A completed series probably gives life-long immunity to both hepatitis A and B.
All probably give life-long immunity.
Duration of immunity/booster recommendations
Table 2.2.1: Dose and routes of administration of commonly used vaccines in adult travellers (≥15 years of age)
Stamaril
Typhim Vi
or
Typherix
Vivotif Oral
Adacel
or
Boostrix
Live attenuated yellow fever virus
25 µg purified Vi capsular polysaccharide
Live attenuated typhoid bacteria
≥20 IU tetanus toxoid, ≥2 IU diphtheria toxoid, purified antigens of B. pertussis
≥20 IU tetanus toxoid, ≥2 IU diphtheria toxoid
2.5 IU inactivated rabies virus antigens
Rabipur Inactivated Rabies Vaccine
ADT Booster
2.5 IU inactivated rabies virus antigens
Single dose
IM/SC
‡ A fourth capsule of oral typhoid vaccine can be given on day 7 (see Chapter 3.23, Typhoid).
10-yearly boosters if at ongoing risk.
Booster doses at 3-yearly intervals
Single dose
IM
Providing pertussis (as well as tetanus and diphtheria) immunity is preferred.
Provides protection for 10 years.
If at continued high risk of exposure, either measure rabies antibody titres (and boost if titres reported as inadequate) or give single booster dose 2-yearly.
Repeat 3-dose course after 3 years if 3 doses given initially; 4-dose course after 5 years if 4 doses given initially.
0, 7, 28 days
0, 7, 28 days
Revaccinate 3–5-yearly if at continuing risk.
Duration of immunity/booster recommendations
Days 1, 3 and 5 (+/– day 7)‡
Oral
IM
IM
IM
IM/SC
Single dose
Primary schedule
† This ‘rapid’ schedule should be used only if there is very limited time before departure to endemic regions.
0.5 mL
0.5 mL
A single capsule
0.5 mL
0.5 mL
1 mL
1 mL
SC
0.5 mL
50 µg capsular polysaccharides from N. meningitidis serogroups A, C, W135 & Y
Mérieux Inactivated Rabies Vaccine
Menomune
Route
Dose (adults)
Main constituents
* Vivaxim is registered for use in people aged ≥16 years.
Yellow fever
Typhoid
+ pertussis (dTpa)
Tetanus, diphtheria (dT)
Rabies (pre-exposure prophylaxis)
Mencevax ACWY
Meningococcal (tetravalent polysaccharide)
or
Brand name
Vaccine (adults)
2.2 Vaccination for international travel
Vaccination for international travel 81
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Rabipur
Mérieux
Rabies
Mencevax ACWY or Menomune
Meningococcal ACW135Y
JE-VAX
No lower age limit
2 years
1 year
1 year
Twinrix (720/20)
Japanese encephalitis
1 year
Twinrix Junior (360/10)
1.0 mL IM
1.0 mL IM/SC
0, 7, 28 days
0, 7, 28 days
Pre-exposure:
Single dose
0, 7, 28 days
>3 years of age: 1.0 mL SC
0.5 mL SC
0, 7, 28 days
*0, 6 to 12 months
1–3 years of age: 0.5 mL SC
1.0 mL IM
0, 1, 6 months
0, 6 to 18 months
0.5 mL IM
1 year
VAQTA Paediatric/ Adolescent
0.5 mL IM
0, 6 to 12 months
0.5 mL IM
Hepatitis A/B combined
0, 6 to 12 months
0.5 mL IM
2 years
Primary schedule
2 years
Dose/route
Havrix Junior
Lower age limit
Avaxim
Hepatitis A
Vaccine
Table 2.2.2: Recommended lower age limits of travel vaccines for children
The doses of rabies vaccines for pre-exposure are the same for both children and adults (1.0 mL).
Should be preceded by MenCCV by at least 2 weeks.
Revaccinate 3–5-yearly if at continuing risk.
Recommended for travellers spending more than 4 weeks in rural areas of Asia and Papua New Guinea, or those staying in urban areas of Asia for more than 1 year.
Recommended for travel to developing countries.
Recommended for travel to developing countries.
Comments
See Chapter 2.3, Groups with special vaccination requirements and the specific vaccine chapters for recommendations for travellers who are either pregnant or have impaired immunity. Children should receive the relevant travel vaccines, according to age (see Table 2.2.2). Particular effort should be made to encourage the families of recent migrants to Australia to seek health advice before travelling to their country of origin to visit relatives and friends.11
Vaccinating the traveller with special risk factors
0.5 mL IM/SC
0.5 mL IM
Oral capsule
Dose/route
Single dose
Single dose
One capsule on days 1, 3, and 5 (+/– day 7)†
Primary schedule
Yellow fever vaccine is contraindicated in infants <9 months of age.
Do not give live oral vaccine with antibiotics or antimalarials. Do not give within 8 hours of inactivated oral cholera vaccine.
Recommended for travel to developing countries.
Comments
Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
References
It should be noted that information on travellers’ risks is changing constantly. Up-to-date knowledge requires an understanding of the changing epidemiology of a variety of infectious and emerging diseases. The World Health Organization’s comprehensive publication International Travel and Health is available at www.who.int/ith and the CDC’s publication Health Information for International Travel, 2005–2006 (the ‘Yellow Book’) is available at www.cdc.gov/travel/index.htm. As recommendations for specific countries change frequently, such sources should be checked regularly.
Further information
† A fourth capsule of oral typhoid vaccine can be given on day 7 (see Chapter 3.23, Typhoid).
* This schedule is not recommended if prompt protection against hepatitis B is required.
Stamaril
9 months
2 years
Typherix or Typhim Vi (parenteral vaccine)
Yellow fever
6 years
Lower age limit
Vivotif Oral (oral live vaccine)
Typhoid
Vaccine
2.2 Vaccination for international travel
Vaccination for international travel 83
2.3 Groups with special vaccination requirements This chapter considers the use of vaccines in people who have special vaccination requirements, those who may experience more frequent adverse events, and those who may have a suboptimal response to vaccination. Recommendations for vaccination of those at occupational risk are also included.
2.3.1 Vaccination of children who have had a serious adverse event following immunisation (AEFI) Children who have had a serious AEFI (other than a contraindication, such as anaphylaxis) may be subsequently vaccinated under close medical supervision (see Appendix 6, Definitions of adverse events following immunisation). Not all States and Territories offer an adverse event immunisation clinic. However, in States or Territories where there are no clinics, there is often a paediatrician or infectious diseases specialist who will review families who have concerns regarding future vaccinations following a previous adverse event. To make an enquiry, or for more information about making a referral to a vaccination serious adverse events service, please go to the website below: http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/ provider-reactions.
2.3.2 Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants (i) Women planning pregnancy The need for measles, mumps, rubella, varicella, diphtheria, tetanus and pertussis vaccination should be assessed as part of any pre-conception health check. Where previous vaccination history or infection is uncertain, relevant serological testing should be undertaken to ascertain immunity. Influenza vaccine is recommended routinely and pneumococcal vaccination is recommended for women with risk factors, including smokers. Women receiving live viral vaccines must be advised against falling pregnant within 28 days of vaccination. Please refer to individual disease chapters for more information about primary vaccination for these diseases.
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(ii) Pregnancy Although the use of most vaccines during pregnancy is not usually recommended on precautionary grounds, there is no convincing evidence that pregnancy should be an absolute contraindication to the use of any vaccine, particularly inactivated vaccines. The only exception is vaccinia virus (smallpox vaccination), which has been shown to cause fetal malformation. There is some evidence, however, that fever per se is teratogenic.1,2 With the exception of the use of influenza vaccine, the NHMRC takes the conservative position that the use of vaccines during pregnancy might cause fever and should be avoided other than in situations of increased risk, where the benefits of protection from vaccination outweigh the risks. Eliminating the risk of exposure to vaccine-preventable diseases during pregnancy (eg. by changing travel plans, avoiding high-risk behaviours or occupational exposures) is an alternative to vaccination. Live attenuated vaccines are contraindicated for pregnant women because of the hypothetical risk of harm to the fetus should transmission occur. If a live attenuated vaccine is inadvertently given to a pregnant woman, or if a woman becomes pregnant within 4 weeks of vaccination, she should be counselled about the potential transmission, albeit extremely unlikely, to the fetus. There is, however, no indication to consider termination of a pregnancy in this situation. The following table may be used as a guide to the recommended use of vaccinations in pregnancy. Information regarding pregnancy status in women of reproductive age should be part of the routine pre-vaccination screening checklist (see Section 1.3.4, Pre-vaccination screening).
2.3 Groups with special vaccination requirements
Groups with special vaccination requirements 85
86 The Australian Immunisation Handbook 9th Edition Hypothetical risk only. Despite concerns that attenuated rubella vaccine virus might cause congenital abnormalities, rubella vaccine (either monovalent or as MMR) has been given to pregnant women (usually inadvertently) without harm to the fetus. Even though the rubella vaccine virus can infect the fetus if given in early pregnancy, there is no evidence that it causes congenital rubella syndrome in infants born to susceptible mothers vaccinated during pregnancy and, in particular, rubella vaccination during pregnancy is not an indication for termination.3
Should not be given to women who are pregnant or considering becoming pregnant. Pregnancy should be avoided for 3 months after vaccination. Hypothetical risk only. Congenital varicella syndrome has (to date) not been identified in women who have been inadvertently vaccinated in early pregnancy.4 This provides some reassurance of the safety of the vaccine.
Contraindicated.
Contraindicated.
Contraindicated.
Contraindicated, unless travelling to yellow fever endemic area.
Measles-mumpsrubella (MMR) vaccine
Smallpox vaccine
Varicella vaccine
Yellow fever vaccine
The administration of yellow fever vaccine in early pregnancy is not an indication for termination.
Hypothetical risk only. Yellow fever vaccine has been given to a large number of pregnant women with no adverse outcomes.5 Pregnant women who travel to a yellow fever-endemic area against medical advice should receive yellow fever vaccine.
Women of child-bearing age should avoid becoming pregnant for 28 days after vaccination.
It is standard practice to test all pregnant women for immunity to rubella, and to vaccinate susceptible women as soon as possible after delivery (preferably using MMR).
Women of child-bearing age should avoid pregnancy for 28 days after vaccination.
Comments
Recommendation
Viral
Live attenuated vaccines
Contraindicated.
Studies in animals are inadequate but available data show no evidence of an increased occurrence of fetal damage with oral live attenuated vaccine. Inactivated typhoid Vi polysaccharide vaccine is preferred.
Rotavirus vaccine can be safely administered to household contacts of pregnant women.
Contraindicated.
Rotavirus vaccine
Oral typhoid vaccine
Hypothetical risk only. BCG has not been shown to cause fetal damage.
Contraindicated.
BCG vaccine (Live attenuated strain M. bovis)
Not registered for use in adults.
Comments
Recommendation
Bacterial
Live attenuated vaccines
Table 2.3.1: Vaccinations in pregnancy
Comments
Inadequate information on safety of oral cholera vaccine in pregnancy. Data on use of adolescent/adult formulation dTpa during pregnancy are not available, so it should be given in pregnancy only when the possible advantages outweigh the possible risks to the fetus. All women who are planning pregnancy should be encouraged to receive a single dose of dTpa before pregnancy; if not given before pregnancy, it should be given as soon as possible after delivery. Available clinical data suggest that it is unlikely that use of Hib vaccine in pregnant women would have any deleterious effects on the pregnancy. Although no clinical study data are available on the use of MenCCV in pregnant women, it is unlikely that it would have any deleterious effects on the pregnancy.
No adverse effects when administered in pregnancy. Data are limited to clinical trials and deferral of vaccine is recommended unless there is an increased risk of IPD. Women of reproductive age with known risk factors for IPD (including smokers) should be vaccinated before planned pregnancy.
Safety of use in pregnancy has not been established. There is no evidence of risk to the fetus from vaccination with Vi polysaccharide vaccine.
Not recommended.
Recommended for pregnant women who work in close contact with infants eg. childcare, neonatal units.
Recommended for pregnant women at increased risk of Hib disease (eg. hyposplenia, asplenia).
Recommended for pregnant women at increased risk of meningococcal disease (eg. hyposplenia, asplenia), or possible exposure to serogroup C.
Recommended for pregnant women at increased No documented adverse events in either pregnant women or their newborns when vaccinated risk of meningococcal disease who have not been with 4vMenPV administered in the second and third trimesters of pregnancy. The number of vaccinated with 4vMenPV in the past 3 years (eg. pregnant vaccinees reported in the literature is small. hyposplenia, asplenia), or possible exposure to serogroup A, W135 or Y. Vaccination during pregnancy has not been evaluated for potential harmful effects to mother or fetus. Although unlikely to result in adverse effects, the vaccine is currently only registered for use in children ≤9 years of age.
Recommendation
Not recommended.
Recommended for pregnant women at increased risk of invasive pneumococcal disease (IPD) (eg. asplenia, impaired immunity, chronic illness, CSF leak) who have not received 23vPPV in the past 5 years (and provided they have not received 2 previous doses).
Not recommended.
In pregnant women travelling to endemic countries where water quality and sanitation is poor.
Bacterial
Cholera (oral) vaccine
Adolescent/adult formulation dTpa vaccine
Haemophilus influenzae type b (Hib) vaccine
Meningococcal C conjugate vaccine (MenCCV)
Meningococcal polysaccharide vaccine (4vMenPV)
7-valent pneumococcal conjugate vaccine (7vPCV)
23-valent pneumococcal polysaccharide vaccine (23vPPV)
Q fever vaccine
Typhoid Vi polysaccharide vaccine
Inactivated vaccines
2.3 Groups with special vaccination requirements
Groups with special vaccination requirements 87
88 The Australian Immunisation Handbook 9th Edition Hepatitis A vaccine should only be given to pregnant women who are non-immune and where there is a clear indication. As for any inactivated viral vaccines, although data are limited, no adverse effects on the developing fetus are expected.
Hepatitis B vaccine should only be given to pregnant women who are non-immune and where there is a clear indication. As for any inactivated viral vaccines, although data are limited, no adverse effects on the developing fetus are expected. There are no concerns that HPV vaccines are teratogenic and animal studies have found no evidence of teratogenicity or adverse fetal outcomes. However, where vaccine has inadvertently been administered during pregnancy, further doses should be deferred until after delivery. There is no evidence of congenital defects or adverse effects on the fetus of women who are vaccinated against influenza in pregnancy.
No adverse effects on pregnancy have been attributed to JE vaccine, whereas JE infection is associated with miscarriage. IPV should only be given to pregnant women when clearly indicated. There is no convincing evidence of risk to the fetus from IPV administered in pregnancy. Pregnancy is never a contraindication to rabies vaccination in situations where there is a significant risk of exposure (related to occupation or travel), or where there has been a possible exposure to rabies virus or Australian bat lyssavirus.
Recommended for susceptible pregnant women travelling to areas of moderate to high endemicity or who are at increased risk of exposure through lifestyle factors, or where severe outcomes may be expected (eg. preexisting liver disease).
Recommended for susceptible pregnant women for whom this vaccine would otherwise be recommended.
Not recommended.
Recommended for all pregnant women who will be in the second or third trimester during the influenza season, including those in the first trimester at the time of vaccination.
Recommended for pregnant women at risk of acquiring JE.
Recommended for pregnant women at risk of poliovirus exposure (eg. travel to endemic countries).
Recommended for pregnant women for whom this vaccine would otherwise be recommended (eg. travellers to rabies endemic countries).
Hepatitis A vaccine
Hepatitis B vaccine
Human papillomavirus (HPV) vaccine
Influenza vaccine
Japanese encephalitis (JE) vaccine
Inactivated polio vaccine (IPV)
Rabies vaccine
Toxoids are safe in pregnancy. There is no known risk to the fetus from passive immunisation of pregnant women with immunoglobulins.
Recommended for pregnant women.
Recommended for susceptible pregnant women exposed to: measles, hepatitis A, hepatitis B, rabies or Australian bat lyssavirus, varicella viruses and tetanus.
Tetanus/diphtheria toxoid
Pooled or hyperimmune immunoglobulins
Toxoids and immunoglobulins
Comments
Recommendation
Viral
Inactivated vaccines
Contact between pregnant women and individuals who have recently received live vaccines Although there is no risk of transmission of the MMR vaccine viruses (MMR vaccine viruses are not transmissible), and an almost negligible risk of transmission of varicella vaccine virus, there is a very small risk of transmission of the rotavirus vaccine viruses to a susceptible pregnant woman. However, there is no evidence that there is any risk to the fetus if pregnant women are in contact with recently vaccinated individuals. Therefore, it is safe to administer varicella vaccine and rotavirus vaccine to household contacts of pregnant women.
(iii) Breastfeeding and vaccination The rubella vaccine virus may be secreted in human breast milk and transmitted to breastfed infants but, where infection has occurred in an infant, it has been mild. Otherwise, there is no evidence of risk to the breastfeeding baby if the mother is vaccinated with any of the live or inactivated vaccines described in this Handbook. Breastfeeding does not adversely affect immunisation and is not a contraindication for the administration of any vaccine to the baby.
(iv) Preterm babies Preterm (premature) infants have a special need for protection and, despite their immunological immaturity, they generally respond well to vaccines. Provided they are well and there are no contraindications to vaccination they should be vaccinated according to the recommended schedule at the usual chronological age.6-14 Routine childhood vaccines can cause an increase in apnoea in preterm babies vaccinated in hospital, particularly babies still requiring special care, but these are generally self-limiting and do not affect the clinical course.8 Preterm babies in hospital should be monitored for apnoea or bradycardia for up to 48 hours post vaccination.6-8 Vaccinations have not caused an increase in apnoeas in babies at home, and are not associated with an increased risk of SIDS.6-8 • Vaccines as recommended on the National Immunisation Program (NIP) schedule
• Pneumococcal vaccines All preterm babies born at less than 28 weeks’ gestation or with chronic lung disease should be offered the 7-valent pneumococcal conjugate vaccine at 2, 4 and 6 months of age, with a fourth dose at 12 months of age, and a 23-valent pneumococcal polysaccharide vaccine booster at 4–5 years of age (see Chapter 3.15, Pneumococcal disease).
Groups with special vaccination requirements 89
2.3 Groups with special vaccination requirements
Preterm babies produce good antibody responses to most vaccines in the NIP. They should be vaccinated at the standard recommended ages without correction for prematurity.14
• Haemophilus influenzae type b vaccine Some smaller preterm babies do not respond as well as term babies to PRP-OMP (Liquid PedvaxHIB or COMVAX) Hib vaccine.9-14 When PRP-OMP is used in an extremely preterm baby (<28 weeks’ gestation or <1500 g birth weight), an extra dose of vaccine should be given at 6 months of age (ie. doses should be given at 2, 4, 6 and 12 months of age) (see Chapter 3.4, Haemophilus influenzae type b). • Hepatitis B vaccine Preterm babies do not respond as well to hepatitis B-containing vaccines as term babies.7,12,13,15 Thus, for babies born at <32 weeks’ gestation or <2000 g birth weight, it is recommended to give vaccine at 0, 2, 4 and 6 months of age and either: (a) measure anti-HBs at 7 months of age and give a booster at 12 months of age if antibody titre is <10 mIU/mL, or (b) give a booster at 12 months of age without measuring the antibody titre. (See Chapter 3.6, Hepatitis B.) • Influenza vaccine Preterm infants with ongoing problems at 6 months of age, particularly respiratory, cardiac or neurological disease, should receive influenza vaccine.
2.3.3 Vaccination of individuals with impaired immunity due to disease or treatment16-18 The vaccination of individuals with impaired immune systems presents several problems. First, the immune response to vaccines may be inadequate and, second, there is a risk that some live vaccines may themselves cause progressive infection. Degrees of impaired immunity vary from insignificant to profound, and this should be taken into account when considering a vaccination schedule, as should the risk of acquiring the vaccine-preventable diseases. Although it may seem logical to give higher or more frequent doses of vaccines to these patients, in many cases there are insufficient data to advocate such measures. Because of the uncertainty of the immune response in some patients with impaired immunity, it may be useful to measure post-vaccination antibody titres in groups such as children who have received haematopoietic stem cell transplants (see ‘2.3.3.3 Re-vaccination following haematopoietic stem cell transplantation (HSCT)’ below). Administration of certain vaccines is a priority for some patients with medical conditions that increase the risk from infectious diseases, even in the absence of specific immune defects. These include: the use of influenza vaccine in individuals with severe asthma, chronic lung disease, congenital heart disease, diabetes and Down syndrome; pneumococcal conjugate vaccine in children
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with renal failure, persistent nephrotic syndrome and certain anatomical abnormalities; and pneumococcal polysaccharide vaccine in adults with certain chronic medical conditions. See the appropriate chapters for current recommendations.
Live viral and bacterial vaccines Although most live vaccines are contraindicated in patients with significantly impaired immunity, the risk of progressive infection varies. The following is a list of current recommendations: • Vaccines for smallpox (vaccinia virus) and tuberculosis (BCG) are always contraindicated. • Live vaccines such as MMR and varicella vaccines must not be given to people with severely impaired immunity, but are safe to be given to the siblings or other household contacts of such people. • MMR and varicella vaccines may be given to children with HIV infection with mildly impaired immunity (see ‘2.3.3.4 HIV-infected individuals’ below). • Travellers with impaired immunity should not receive oral typhoid vaccines. Use parenteral typhoid Vi polysaccharide vaccine instead. • Yellow fever vaccine is contraindicated in travellers with impaired immunity going to endemic countries. If they must proceed with the travel, they should obtain a letter from a doctor, clearly stating the reason for withholding the vaccine. The letter should be formal, signed and dated, and on the practice’s letterhead.
Household contacts vaccinated with live vaccines who live with a person who has impaired immunity
Groups with special vaccination requirements 91
2.3 Groups with special vaccination requirements
Healthy siblings and household contacts of children with impaired immunity should be vaccinated with MMR, varicella and rotavirus vaccines (where indicated) to prevent them from infecting the children with impaired immunity. Although there is no risk of transmission of the MMR vaccine viruses, and an almost negligible risk of transmission of varicella vaccine virus, there is a small risk of transmission of the rotavirus vaccine viruses (see Chapter 3.18, Rotavirus and Chapter 3.24, Varicella). Annual influenza vaccination is recommended for contacts (including children ≥6 months of age) of people with impaired immunity.
Influenza and pneumococcal vaccines Morbidity and mortality from influenza and invasive pneumococcal disease are increased in all people with severely impaired immunity. Annual influenza vaccination should be given to all people ≥6 months of age with severely impaired immunity. Such individuals should also receive either the 7-valent pneumococcal conjugate vaccine (7vPCV), or 23-valent pneumococcal polysaccharide vaccine (23vPPV), depending on their age (see Chapter 3.15, Pneumococcal disease). Although the immune response to 23vPPV may be suboptimal in those who most need protection, the vaccine is nevertheless strongly recommended for these individuals. While it may seem logical to give 7vPCV followed by 23vPPV to adults with impaired immunity, studies evaluating the effectiveness of such a regimen are not yet available.
Impaired immunity associated with corticosteroid administration In adults, daily doses of oral corticosteroids in excess of 60 mg of prednisolone (or equivalent) and, in children, doses in excess of either 2 mg/kg per day for more than a week or 1 mg/kg per day for more than 4 weeks, are associated with significantly impaired immunity. However, even lower doses may be associated with some impairment of the immune response.19 Children on daily doses of ≤2 mg/kg per day of systemic corticosteroids for less than 1 week, and those on lower doses of 1 mg/kg per day or alternate-day regimens for periods of up to 4 weeks, may be given live viral vaccines. Children receiving >2 mg/kg per day or ≥20 mg per day in total of prednisolone (or equivalent) for >14 days can receive live viral vaccines after corticosteroid therapy has been discontinued for at least 1 month. For adults treated with systemic corticosteroids in excess of 60 mg per day, live vaccines (such as MMR and varicella vaccines) should be postponed until at least 3 months after treatment has stopped.
2.3.3.1 Oncology patients16,20-24 • Paediatric and adult patients undergoing cancer chemotherapy who have not completed a primary vaccination schedule before diagnosis Live viral vaccines, including varicella and MMR vaccines, are contraindicated in cancer patients receiving immunosuppressive therapy and/or with poorly controlled malignant disease. These vaccines may be administered to seronegative children at least 3 months after completion of chemotherapy and/or high-dose steroid therapy, provided the underlying malignancy is in remission. Administration of live viral vaccines (MMR, varicella or MMRV [when available]) should be deferred if blood products or immunoglobulins have been recently administered (see Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination).
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Influenza vaccination is recommended annually in all cancer patients ≥6 months of age and should be started as close to the time of cancer diagnosis as possible. During chemotherapy, and for 6 months afterwards, patients may receive inactivated vaccines (eg. DTPa if <8 years old, Hib if <5 years old, hepatitis B, IPV) according to the routine vaccination schedule, but it should be remembered that patients are unlikely to mount a full immune response while they are on therapy. Antibody responses to hepatitis B should be checked 4 weeks after completing the third dose and, where antibody titres are <10 IU/mL, HBsAg carriage should be investigated. If HBsAg negative, then patients should be given a fourth double dose of vaccine or a further 3 doses of vaccine at monthly intervals (see Chapter 3.6, Hepatitis B). Vaccines should not be administered during times of severe neutropenia (absolute neutrophil count <0.5 x 109/L), to avoid precipitating an acute febrile episode. Pneumococcal vaccination is recommended in oncology patients with an increased risk of invasive pneumococcal disease (IPD), especially patients with underlying haematological malignancies (multiple myeloma, Hodgkin’s lymphoma, nonHodgkin’s lymphoma, chronic lymphocytic leukaemia). In patients ≥10 years of age, 23vPPV should ideally be given as early as possible after diagnosis and before chemotherapy and/or radiotherapy is initiated.25,26 When this is not practicable, vaccination should be given after completion of chemotherapy.27 For children <10 years of age with haematological malignancies, primary and catchup pneumococcal vaccination should be administered as detailed in Table 1.3.11 Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age with underlying medical conditions (see footnote accompanying this Table). Any deviations from these guidelines should be discussed with an oncologist. • Paediatric and adult patients with cancer who have completed cancer therapy and have received a primary course of vaccination before diagnosis
• DTPa if <8 years of age (use dT or adolescent/adult formulation dTpa if ≥8 years of age), • MMR, IPV, hepatitis B, 7vPCV and Hib (if <5 years of age or with previous splenectomy/hyposplenism). These vaccines may be given without checking antibody titres beforehand, and may be given together on 1 day. Measles and rubella antibody status should be checked 6 to 8 weeks after vaccination. Patients who have not seroconverted should receive a further dose.
Groups with special vaccination requirements 93
2.3 Groups with special vaccination requirements
The following schedule of booster vaccination is recommended if the patient is well and infection-free 6 months after chemotherapy, and if the underlying disease is in remission:
Children who are seronegative to varicella-zoster virus, especially those with acute lymphoblastic leukaemia, should receive a 2-dose schedule of varicella vaccine, at least 3 months after chemotherapy has been ceased.28 Administration of live vaccines (MMR, varicella or MMRV [when available]) should be deferred if blood products or immunoglobulins have been recently administered (see Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination).
2.3.3.2 Solid organ transplant recipients23 For solid organ transplant (SOT) recipients, depending on the transplanted organ, and to prevent rejection, differing doses of immunosuppressive agents are needed, which may influence the effectiveness of vaccines. Where possible, children undergoing solid organ transplantation should be vaccinated well before transplantation, and inactivated vaccines can be used 6 to 12 months after transplantation. Live vaccines are contraindicated in most post-transplantation protocols due to concerns of disseminated infection, although data in this population are limited. Recommended vaccinations for child and adult SOT recipients are given in Table 2.3.2.
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Yes
Yes
Hepatitis A vaccine
Hepatitis B vaccine
[If <10 years of age see Table 1.3.11.]
Yes
7-valent pneumococcal Yes, if <10 years of age conjugate vaccine (7vPCV)
23-valent pneumococcal polysaccharide vaccine (23vPPV)
Yes, depending on serological status
Yes, if seronegative
Adult
Yes
Yes
Yes
Child
Yes, depending on serological status
Yes, if seronegative
Adult
Vaccines recommended after transplantation if not given beforehand
Yes
[If <10 years of age see Table 1.3.11.]
Yes
Yes, if <10 years of age
Yes
Annual vaccination starting before transplantation for people ≥6 months of age.
Yes
Hib vaccine
Influenza vaccine
Child
Vaccine
Vaccines recommended before transplantation
See Table 3.15.3 Revaccination with 23vPPV for people ≥10 years of age.
For children <10 years of age, 7vPCV should be administered as detailed in Table 1.3.11 Recommendations for pneumococcal catch-up vaccination for children ≤5 years of age with underlying medical conditions (see footnote accompanying this Table).
The primary schedule should be completed before transplantation.
Accelerated schedules can be used (see Table 3.6.2 Accelerated hepatitis B vaccination schedules).
Recommended for all seronegative SOT recipients.
Recommended for all seronegative SOT recipients.
If possible complete vaccination at least 6 weeks before transplantation.23
Comments
Table 2.3.2: Recommendations for vaccinations for solid organ transplant (SOT) recipients
2.3 Groups with special vaccination requirements
Groups with special vaccination requirements 95
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Yes
Diphtheria-tetanuspertussis vaccine
Yes, unless 2 previous documented doses
Yes
Yes
MMR vaccine
Varicella vaccine Yes
Yes
Yes
Yes, provided dTpa has not been given previously
Yes, if no booster in past 10 years
Adult
Meningococcal Yes, if >2 years polysaccharide vaccine of age (4vMenPV)
Meningococcal C conjugate vaccine (MenCCV)
Yes, if ≥1 year of age
Yes
Inactivated poliovirus vaccine (IPV)
(DTPa for children <8 years of age; dTpa for people ≥8 years of age)
Child
Vaccine
Vaccines recommended before transplantation
Contraindicated
Contraindicated
Yes, if >2 years of age
Yes, if ≥1 year of age
Yes
Yes
Child
Yes
Yes
Yes, provided dTpa has not been given previously
Yes, if no booster in past 10 years
Adult
Vaccines recommended after transplantation if not given beforehand
Vaccination should be completed before transplantation provided the recipient is no longer on immunosuppressive therapy.
The primary schedule should be completed before transplantation provided the recipient is no longer on immunosuppressive therapy.
Give 4vMenPV at an interval of at least 2 weeks after MenCCV.
The primary schedule should be completed before transplantation.
The primary schedule should be completed before transplantation.
Comments
2.3.3.3 Re-vaccination following haematopoietic stem cell transplantation (HSCT)29-33 Haematopoietic stem cells are sourced from peripheral blood, bone marrow or umbilical cord. Protective immunity to vaccine-preventable diseases is partially or completely lost following either allogeneic or autologous stem cell transplantation. Impaired immunity following allogeneic transplantation is caused by a combination of the preparative chemotherapy given before transplantation, graft-versus-host disease (GVHD), and immunosuppressive therapy following transplantation. Persisting impaired immunity is common, particularly in patients with chronic GVHD. Immunity is also impaired in autologous stem cell transplant recipients due to high-dose chemotherapy and radiotherapy, but GVHD is not a concern as donor and recipient are the same. In most cases, autologous transplant recipients will recover their immunity more quickly than allogeneic transplant recipients. Separate transplant schedules for autologous and allogeneic transplant recipients have not been supported in published guidelines because of limited data. For practical purposes, a similar schedule is therefore recommended, regardless of donor source (peripheral blood, bone marrow or umbilical cord), preparative chemotherapy (ablative or reduced intensity), or transplant type (allogeneic or autologous).32,34 HSCT recipients with ongoing GVHD or remaining on immunosuppressive therapy should not be given live vaccines. Chronic GVHD (cGVHD) is associated with functional hyposplenism and patients are therefore susceptible to infections with encapsulated organisms, especially Streptococcus pneumoniae. For patients with cGVHD who remain on active immunosuppression, antibiotic prophylaxis is recommended.35 The immune response to vaccinations is usually poor during the first 6 months after HSCT. Donor immunisation with hepatitis B, tetanus, Hib and pneumococcal conjugate vaccines before stem cell harvesting has been shown to elicit improved early antibody responses in HSCT recipients vaccinated in the post-transplantation period.36-39 However, practical and ethical considerations currently limit the use of donor immunisation.
A recommended schedule of vaccination is outlined in Table 2.3.3.31,32,34
Groups with special vaccination requirements 97
2.3 Groups with special vaccination requirements
Routine serological testing for several infectious agents increases costs, and antibody levels conferring protective immunity are poorly defined. For those vaccines that are recommended for all HSCT recipients (tetanus, diphtheria, polio, influenza, pneumococcal, Hib), pre-vaccination testing is not recommended as the response to a primary course of these vaccines is generally adequate. The serological response to pneumococcal polysaccharide vaccine is less predictable. Pneumococcal serology is only available in a few specialised laboratories and is not routinely recommended. Immunity testing before and after vaccination for hepatitis B, measles, rubella and varicella is recommended, as antibody levels will determine the need for revaccination.34
Table 2.3.3: Post-transplantation vaccination schedules for allogeneic and autologous haematopoietic stem cell transplant recipients32,34 Vaccine
Months after HSCT
Comments
12
14
24
Yes
Yes
Yes
Hib
Yes
Yes
Yes
Hepatitis A
Not routinely recommended, see Chapter 3.5, Hepatitis A.
Hepatitis B
Yes
Influenza
Annual vaccination for life, starting 6 months post HSCT, for people ≥6 months of age.
MMR
No
MenCCV
Yes, ≥1 year of age
People ≥1 year of age should receive 1 dose of MenCCV.
4vMenPV
Yes, ≥2 years of age (see comment)
People ≥1 year of age should receive 1 dose of MenCCV (as above). This should be followed by a dose of 4vMenPV when ≥2 years of age or, if already aged >2 years, give after an interval of at least 2 weeks following the MenCCV.
7vPCV
Although there are limited data on the effectiveness of 7vPCV in HSCT recipients, vaccination is recommended for children ≤9 years of age starting 6 months post HSCT (see Table 3.15.1 Summary table – pneumococcal vaccination schedule for children ≤9 years of age).
23vPPV
Yes
Diphtheria-tetanuspertussis
(DTPa for children <8 years of age; dTpa for people ≥8 years of age)
Yes
No
Yes
Yes
For recipients ≥8 years of age, give first dose as dTpa followed by 2 doses dT. If dT unavailable, dTpa may be used for all 3 doses.
High dose (H-B-VAX II dialysis formulation) vaccine is recommended.
Vaccination of measles or rubella seronegative HSCT recipients at 24 months post HSCT is recommended, provided that immunosuppressive therapy has been discontinued, there is no chronic GVHD, and cell-mediated immunity has been reconstituted.
See Table 3.15.3 Revaccination with 23vPPV for people ≥10 years of age. Adjunctive antibiotic prophylaxis is recommended for patients with chronic GVHD.
IPV
Yes
Yes
Yes
Varicella vaccine
No
No
Yes
98 The Australian Immunisation Handbook 9th Edition
Vaccination of seronegative HSCT recipients at 24 months post HSCT is recommended, provided that immunosuppressive therapy has been discontinued, there is no chronic GVHD, and cell-mediated immunity has been reconstituted.
2.3.3.4 HIV-infected individuals Vaccination schedules for HIV-infected patients should be determined by the patient’s age, degree of impaired immunity (CD4 count) and the risk of infection. Children with perinatally acquired HIV differ substantially from adults as immunisation and first exposure to vaccine antigens occurs after HIV infection, whereas for adults, most vaccines are inducing a secondary immune response.40 HIV-infected individuals of any age who are well controlled on combination antiretroviral therapy (undetected or low viral load with good preservation of CD4 lymphocyte count) are likely to respond well to vaccines. HIV-infected patients should be vaccinated as follows: • Diphtheria-tetanus-pertussis (DTPa/dTpa), Hib and IPV vaccines – use the standard schedule.41 • MMR vaccine should be routinely administered to HIV-infected children at 12 months of age unless they have severely impaired immunity. Table 2.3.4 shows age-specific definitions of moderately and severely impaired immunity. Measles may cause severe disease in HIV-infected children and children with severely impaired immunity who are exposed to measles should, therefore, be given normal immunoglobulin (in a dose of 0.5 mL/kg), regardless of their vaccination status.40 • While varicella vaccine is contraindicated in adults with HIV, its use may be considered for asymptomatic or mildly affected children ≥12 months and <13 years of age.42 The Advisory Committee on Immunization Practices (ACIP) recommends use of the vaccine, given in 2 doses, 3 months apart, in children with age-specific CD4 T-lymphocyte percentages greater than 25%.43 Table 2.3.4: Immunological categories based on age-specific CD4 counts and percentage of total lymphocytes44 Category
<12 months
1–5 years
≥6 years
%
CD4 per µL
%
CD4 per µL
%
No evidence of impaired immunity
≥1500
≥25
≥1000
≥25
≥500
≥25
Moderately impaired immunity
750–1499
15–24
500–999
15–24
200–499
15–24
Severely impaired immunity
<750
<15
<500
<15
<200
<15
Groups with special vaccination requirements 99
2.3 Groups with special vaccination requirements
CD4 per µL
• Pneumococcal disease, both respiratory and invasive, is a frequent cause of morbidity in HIV-infected children and adults. Infants and children <10 years of age should be vaccinated with the 7vPCV (see Table 3.15.1 Summary table – pneumococcal vaccination schedule for children ≤9 years of age) and older children and adults should be vaccinated with the 23vPPV (see also Chapter 3.15, Pneumococcal disease).45,46 • Influenza vaccine is recommended even in symptomatic HIV-infected adults and children.47-49 Viral loads may increase after vaccination, but CD4 counts are unaffected and the benefits exceed the risk.50-53 • Hepatitis B vaccine is safe to use, but the immunological response may be poor. HIV-positive adults should receive 3 doses of the H-B-VAX II dialysis formulation and HIV-positive children should receive 3 doses of Engerix-B adult formulation. Antibody level should be measured at the completion of the vaccination schedule. Because many HIV-positive men who have sex with men may already have been exposed to the hepatitis B and hepatitis A viruses, their susceptibility should be determined in order to avoid unnecessary vaccination. • Susceptible HIV-infected individuals should be vaccinated against hepatitis A.54 • BCG must not be given to HIV-infected children or adults because of the risk of disseminated BCG infection. • Yellow fever and oral live attenuated typhoid vaccines should not be given to HIV-infected individuals. Vi polysaccharide typhoid, Japanese encephalitis and rabies vaccines are safe and can be used for the usual indications (see Chapter 2.2, Vaccination for international travel).
2.3.3.5 Individuals with functional or anatomical asplenia55,56 Individuals with an absent or dysfunctional spleen are at an increased risk of fulminant bacteraemia, most notably pneumococcal, for the rest of their lives.57 • Pneumococcal vaccination All individuals with functional or anatomical asplenia should be vaccinated against invasive pneumococcal disease. In elective splenectomy, the vaccination should be completed, if possible, 2 weeks before the operation; in unplanned splenectomy, the vaccination should commence when the patient has recovered from the surgery.58 Children ≤5 years of age with functional or anatomical asplenia should be given the age-appropriate course of pneumococcal vaccines for medical-risk children (see Table 3.15.1 Summary table – pneumococcal vaccination schedule for children ≤9 years of age and Section 1.3.5, Catch-up). Children who develop functional or anatomical asplenia between 6 and ≤9 years of age should be given 2 doses of 7vPCV 2 months apart, followed by a dose of 23vPPV 2 months later.
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Individuals ≥10 years of age with functional or anatomical asplenia should be given: • an initial dose of 23vPPV, • revaccination with 23vPPV 5 years after the initial dose (of 23vPPV), and • 1 further revaccination (third dose) should be given at either 5 years after the first revaccination or at 50 years (Indigenous adults) or 65 years (nonIndigenous adults) of age, whichever is later. It should be noted that the above regimens cannot provide prolonged protection against all invasive pneumococcal disease. It is particularly important that individuals with functional or anatomical asplenia are informed of the altered immune status associated with asplenia and the increased life-long risk of severe bacterial infection, that they should seek urgent medical assessment for any febrile illness, and that they should always wear a medical alert bracelet or necklace. NB. Children ≤5 years of age with splenic dysfunction, most frequently due to sickle cell disease, should also be treated with daily doses of penicillin V, commencing before the age of 4 months and continuing until 5 years of age (penicillin V 125 mg twice daily, increasing to 250 mg twice daily when they reach 4 years of age). • Meningococcal vaccination All individuals ≥1 year of age with functional or anatomical asplenia should be vaccinated with a single dose of MenCCV, although the vaccine can be given from 6 weeks of age (see also Chapter 3.12, Meningococcal disease). This should be followed by a dose of the 4vMenPV at ≥2 years of age (see also Chapter 3.12, Meningococcal disease). If MenCCV is given, a period of at least 2 weeks should elapse before 4vMenPV is administered. A single revaccination with 4vMenPV is recommended 3 to 5 years later. • Hib vaccination Children should be up-to-date with Hib vaccination. A single dose of Hib vaccine is recommended for splenectomised adults. Adults with conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS) should be given influenza and pneumococcal polysaccharide vaccines, due to potential morbidity and mortality from infection, despite the potential for reduced immunogenicity in some patients (described below).59-61 For conditions such as SLE and RA, theoretical concerns that vaccines may exacerbate or cause these diseases have not been substantiated, despite a number of sporadic case reports. There is potential for reduced immunogenicity of vaccines, due to both immunosuppressive therapies and the underlying disease.62
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2.3 Groups with special vaccination requirements
2.3.3.6 Individuals with autoimmune diseases
Small controlled studies suggest that approximately one-third of patients with SLE or RA receiving immunosuppressive therapies may mount a lower antibody response to influenza and pneumococcal vaccines compared with healthy controls.60,62 A small proportion of patients may mount very little or no response to the pneumococcal vaccine.60 Importantly, clinical and laboratory measures of disease activity, and the choice, duration and dose of immunosuppressive therapies, do not predict who these poor responders will be.60,62,63 In a study involving 149 patients with RA taking immunosuppressive agents, including tumour necrosis factor (TNF) blockers, and 47 healthy controls, patients on TNF blockers showed similar responses to pneumococcal vaccination to controls.63 Patients treated with methotrexate (as monotherapy or with TNF blockers) had a reduced antibody response to vaccination.63 There is clear evidence that multiple sclerosis is not exacerbated by influenza vaccination, and either insufficient or no evidence that other vaccines increase this risk.64
2.3.4 Vaccination of recent recipients of normal human immunoglobulin The immune response to live viral vaccines (with the exception of yellow fever vaccine) may be inhibited by normal human immunoglobulin. The interval recommended is dependent on the type of immunoglobulin given (see Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination). When hyperimmune globulin is used against a specific infection, such as varicella, vaccination against other live viruses need not be deferred. Specialist advice should be sought if high-dose or intravenous immunoglobulins have been used.
2.3.5 Vaccination of patients following receipt of other blood products including blood transfusions People who have received a blood transfusion, including mass blood transfusions, do not require revaccination. However, following the receipt of any blood product, including plasma or platelets, an interval of 3 to 7 months should elapse, dependent on the blood product transfused, before vaccination with an MMR, MMRV or varicella vaccine (see Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination). An interval is suggested because there may be low levels of antibodies present in the blood product that may impair the immune response to the live vaccine.
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Table 2.3.5: Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination65 Route
Blood transfusion: Washed RBCs
Dose IU or mL
Estimated mg IgG/kg
Interval (months)
IV
10 mL/kg
Negligible
0
RBCs, adenine-saline added
IV
10 mL/kg
10
3
Packed RBCs
IV
10 mL/kg
20–60
5
Whole blood
IV
10 mL/kg
80–100
6
Cytomegalovirus immunoglobulin
IV
3 mL/kg
150
6
Hepatitis A prophylaxis (as NHIG)
IM
0.5 mL (<25 kg)
3
1.0 mL (25–50 kg) 2.0 mL (>50 kg)
Hepatitis B prophylaxis (as HBIG)
IM
ITP (as NHIG [Intravenous]) ITP (as NHIG [Intravenous]) ITP or Kawasaki disease (as NHIG [Intravenous])
100 IU
10
3
IV
400
8
IV
1000
10
IV
1600–2000
11
400 IU
(max. dose 15 mL)
Measles prophylaxis (as NHIG):
Standard
IM
0.2 mL/kg
Immunocompromised
IM
0.5 mL/kg
Plasma or platelet products
IV
10 mL/kg
160
7
Rabies prophylaxis (as RIG)
IM
20 IU/kg
22
4
Replacement (or therapy) of immune deficiencies (as NHIG [Intravenous], various doses)
IV
300–400
9
Rh (D) IG (anti-D)
IM
Tetanus (as TIG for IM use)
IM
IM
6
0 250 IU (given within 24 hrs of injury)
10
500 IU (>24 hrs after injury)
20
200 IU (0–10 kg)
3
5
400 IU (11–30 kg) 600 IU (>30 kg)
Groups with special vaccination requirements 103
2.3 Groups with special vaccination requirements
Varicella prophylaxis (as ZIG)
5
2.3.6 Vaccination of patients with bleeding disorders Intramuscular injection may lead to haematoma formation in patients with disorders of haemostasis, and to pressure necrosis, muscle contractures or nerve compression in patients with severe coagulopathies. Children with inherited coagulopathies should receive factor replacement before intramuscular injection. Unless warfarin doses are known to be stable, patients receiving this anticoagulant should have prothrombin times measured before intramuscular injections, which should be deferred if the INR (international normalised ratio) is greater than 3.0. Patients with platelet counts of less than 50 x 109/L should not receive intramuscular injections. The subcutaneous route could be considered as an alternative to the intramuscular route in patients with bleeding disorders; seek expert advice.19
2.3.7 Vaccination before or after anaesthesia/surgery Recent or imminent surgery is not a contraindication to vaccinations and recent vaccination is not a contraindication to surgery (see Section 1.3.4, Pre-vaccination screening). There are no randomised controlled trials providing evidence of adverse outcomes with anaesthesia and surgery in recently vaccinated children. It is possible that the systemic effects from recent vaccination, such as fever and malaise, may cause confusion in the post-operative period. Elective surgery and anaesthesia may be postponed for 1 week after inactive vaccination and for 3 weeks after live attenuated viral vaccination in children, and routine vaccination may be deferred for 1 week after surgery.66 A patient who receives any blood products during surgery will need to be informed of the need to delay any vaccinations (see Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination).
2.3.8 Vaccination of those at occupational risk Certain occupations, particularly those associated with healthcare, are associated with an increased risk of some vaccine-preventable diseases.67,68 Furthermore, some infected workers, particularly healthcare workers and childcare workers, may transmit infections such as influenza, rubella, measles, mumps, varicella and pertussis to susceptible contacts with the potential for serious health outcomes. Many infectious diseases, measles in particular, are highly infectious several days before symptoms become apparent. Where workers are at significant occupational risk of acquiring a vaccinepreventable disease, the employer should implement a comprehensive occupational vaccination program which includes a vaccination policy, current staff vaccination records, provision of information about the relevant vaccine-preventable diseases, and the management of vaccine refusal (which should, for example, include reducing the risk of a healthcare worker (HCW) transmitting disease to a vulnerable
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patient). Employers should take all reasonable steps to encourage non-immune workers to be vaccinated. Current recommended vaccinations for people at risk of occupationally acquired vaccine-preventable diseases are listed in Table 2.3.6. Standard precautions should be adopted where there is risk of occupational exposure to blood and body fluids. Preventive measures include the appropriate handling and disposal of sharps, and the donning of gloves, when handling body fluids, and goggles/face shields, when splashes are likely. If a non-immune person is exposed to a vaccine-preventable disease, postexposure prophylaxis should be administered where indicated. Table 2.3.6: Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases* OCCUPATION
DISEASE/VACCINE
HEALTHCARE WORKERS (HCW) All HCW:
Hepatitis B
including all workers and students directly involved in patient care or the handling of human tissues
Influenza Pertussis (dTpa, provided dTpa has not been given previously) MMR (if non-immune)† Varicella (if seronegative)
HCW who work with remote Indigenous communities in NT, QLD, SA and WA; medical, dental and nursing undergraduate students (in some jurisdictions)
Vaccines listed for ‘All HCW’, plus hepatitis A
HCW who may be at high risk of exposure to drug-resistant cases of tuberculosis
Vaccines listed for ‘All HCW’, plus BCG
THOSE WHO WORK WITH CHILDREN All those working with children including: Childcare and preschool staff (including childcare students)
School teachers (including student teachers)
MMR (if non-immune)† Varicella (if seronegative)
Outside school hours carers Child counselling services workers Youth services workers Childcare and preschool staff
Vaccines listed for ‘All those working with children’ plus hepatitis A vaccine
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2.3 Groups with special vaccination requirements
Correctional staff working where infants/ children cohabitate with mothers
Pertussis (dTpa, provided dTpa has not been given previously)
OCCUPATION
DISEASE/VACCINE
CARERS Carers of people with intellectual disabilities
Hepatitis A Hepatitis B
Staff of nursing homes and long-term care facilities
Influenza
Providers of home care to people at risk of high influenza morbidity Influenza EMERGENCY AND ESSENTIAL SERVICE WORKERS Police and Emergency Workers
Hepatitis B, influenza
Armed Forces personnel
Hepatitis B, influenza (and other vaccines relevant to deployment)
Staff of correctional facilities
Hepatitis B, influenza
LABORATORY PERSONNEL Laboratory personnel handling veterinary specimens or working with Q fever organism (Coxiella burnetii)
Q fever
Laboratory personnel handling either bat tissues or ABL or rabies virus
Australian bat lyssavirus (ABL) and rabies
Laboratory personnel routinely working with other infectious agents
Anthrax‡ Vaccinia poxviruses Poliomyelitis Typhoid Yellow fever Meningococcal disease Japanese encephalitis
WORKING WITH SPECIFIC COMMUNITIES Workers who live with or make frequent visits to remote Indigenous communities in NT, QLD, SA and WA
Hepatitis A
Workers assigned to the outer Torres Strait Islands for a month or more during the wet season
Japanese encephalitis
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OCCUPATION
DISEASE/VACCINE
WORKING WITH ANIMALS Veterinarians, veterinary students, veterinary nurses
Q fever Australian bat lyssavirus (ABL) and rabies
Agricultural college staff and students exposed to high-risk animals Q fever Abattoir workers and contract workers in abattoirs (excluding pig abattoirs)
Q fever
Livestock transporters Sheep shearers and cattle, sheep and dairy farmers Those culling/processing kangaroos or camels Tanning and hide workers Goat farmers Livestock saleyard workers Those handling animal products of conception Those who come into regular contact with bats (both flying foxes and microbats), bat-handlers, bat scientists, wildlife officers, zoo curators
Australian bat lyssavirus (ABL) and rabies
Poultry workers, and others handling poultry, including those who may be involved in culling during an outbreak of avian influenza
Influenza
OTHERS EXPOSED TO HUMAN TISSUE, BLOOD, BODY FLUIDS OR SEWAGE Embalmers
Hepatitis B, BCG
Sex industry workers
Hepatitis A Hepatitis B
Workers who perform skin penetration procedures, eg. tattooists, body-piercers
Hepatitis B
Funeral workers and other workers who have regular contact with human tissue, blood or body fluids and/or used needles or syringes
Hepatitis B
Plumbers or other workers in regular contact with untreated sewage Hepatitis A
† All adults born during or since 1966 should have evidence of either receiving 2 doses of MMR vaccine or immunity. Adults born before 1966 are considered to be immune due to extensive measles circulating widely in the community during this period of time (see Chapter 3.11, Measles). ‡ People with a repeated risk of exposure or working with large quantities or concentrations of Bacillus anthracis cultures. For information regarding anthrax vaccination, please contact the Office of Health Protection in the Australian Government Department of Health and Ageing, Canberra.
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2.3 Groups with special vaccination requirements
* Work activities, rather than job title, should be considered on an individual basis to ensure an appropriate level of protection is afforded to each worker.
2.3.9 Vaccination of immigrants to Australia69 Vaccination status is not routinely assessed in children and adults entering Australia as refugees or immigrants. They may be incompletely vaccinated according to the Australian schedule or have incomplete records of vaccination. The World Health Organization website www.who.int/countries/en lists immunisation schedules for most countries and may provide some information regarding vaccine schedules. • If an immigrant has no valid documentation of vaccination, the standard ‘catch-up’ schedule should be commenced. Serological testing to determine the need for specific vaccinations is not recommended in the absence of documented vaccination. If a child is ≥12 months of age, the first doses of DTPa, hepatitis B, IPV, MMR, MenCCV, 7vPCV and Hib vaccines can be given at the same visit. For details, see Section 1.3.5, Catch-up. • If there is a valid record of vaccination, the history of previous doses should be taken into account when planning a catch-up vaccination schedule. • Immigrant adults need to be targeted for vaccination, especially against rubella using MMR. This is particularly important for women of childbearing age. • All vaccines administered to children <7 years of age should be documented on the ACIR, including those for children not enrolled with Medicare and vaccinations documented pre-arrival. • ACIR History Statements can be issued after documentation of overseas vaccination(s) have been recorded on ACIR. • The Australian Government Department of Immigration and Citizenship (DIAC) may in some circumstances be able to provide information regarding vaccine(s) administered to refugees before entering Australia.
2.3.10 Vaccination of inmates of correctional facilities Inmates of correctional facilities are at risk of acquiring influenza, hepatitis A and hepatitis B, and should be vaccinated against these infections (see Chapter 3.5, Hepatitis A, Chapter 3.6, Hepatitis B and Chapter 3.9, Influenza).70,71
2.3.11 Vaccination of men who have sex with men Men who have sex with men are at risk of acquiring hepatitis A and hepatitis B, and should be vaccinated against these infections (see Chapter 3.5, Hepatitis A and Chapter 3.6, Hepatitis B).
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2.3.12 Vaccination of injecting drug users Injecting drug users are at risk of acquiring hepatitis A and hepatitis B, and should be vaccinated against these infections (see Chapter 3.5, Hepatitis A and Chapter 3.6, Hepatitis B).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
2.3 Groups with special vaccination requirements
Groups with special vaccination requirements 109
PART 3: Vaccines listed by disease 3.1 Australian bat lyssavirus infection and rabies Virology Australian bat lyssavirus (ABL) and rabies virus are members of the family Rhabdoviridae, genus Lyssavirus. There are 7 known genotypes within the genus Lyssavirus; ABL (genotype 7) is more closely related to rabies virus (genotype 1) than any of the other 6 genotypes.
Clinical features Based on the 2 recognised human cases of ABL infection, it has to be assumed that ABL has the same clinical features as rabies. The incubation period of rabies is usually 3 to 8 weeks, but can range from as short as a week to, on rare occasions, several years. The risk of rabies is higher, and the incubation period shorter, after severe and multiple wounds proximate to the central nervous system (such as on the head and neck) and in richly innervated sites (such as the fingers). Typically, in the prodromal phase of rabies, which lasts up to 10 days, the patient may experience non-specific symptoms such as anorexia, cough, fever, headache, myalgia, nausea, sore throat, tiredness and vomiting.1 Paraesthesiae and/ or fasciculations at or near the site of the wound may be present at this stage. Anxiety, agitation and apprehension may also occur. Most rabies patients present with the furious or encephalitic form.1 In the encephalitic phase, objective signs of nervous system involvement include aerophobia, hydrophobia, bizarre behaviour, disorientation and hyperactivity. Signs of autonomic instability such as hypersalivation, hyperthermia and hyperventilation may occur.1 The neurological status of the patient deteriorates over a period of up to 12 days, and the patient either dies abruptly from cardiac or respiratory arrest, or lapses into a coma. Rabies is almost invariably fatal.
Epidemiology Rabies is endemic throughout much of Africa, Asia, the Americas and Europe, where the virus is maintained in certain species of mammals.1 Australia, New Zealand, Japan, Papua New Guinea and Pacific Island nations are free of endemic rabies. Human rabies characteristically follows a bite from a rabid animal, most frequently a dog, but in some parts of the world, other animals, such as jackals and bats, are important sources of exposure. In countries where rabies vaccination of domestic animals is widespread (North America and Europe), wild animals such as raccoons and foxes are important reservoirs.1
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Although rabies in travellers is rare, such cases – always fatal – continue to be reported in the medical literature.4,5 Travellers to rabies-endemic regions should be advised of the risk and to avoid close contact with either wild or domestic animals; this is particularly important for children. They should be advised about pre-travel (ie. pre-exposure) rabies vaccination (or, if appropriate, booster doses), and they should be advised on what to do should they be either bitten or scratched by an animal while abroad. In Australia, 2 cases of a fatal rabies-like illness caused by ABL have been reported, one in 1996 and the other in 1998.6 Both patients had been bitten by bats. Evidence of ABL infection has since been identified in all 4 species of Australian fruit bats (flying foxes) and in several species of Australian insectivorous bats. It should therefore be assumed that all Australian bats have the potential to be infected with ABL.
Rabies vaccine • Mérieux Inactivated Rabies Vaccine – Sanofi Pasteur Pty Ltd. Each 1.0 mL monodose vial of lyophilised vaccine contains at least 2.5 IU inactivated rabies virus; 100–150 µg neomycin; ≤70 mg human serum albumin; trace of phenol red (indicator). 1.0 mL distilled water as diluent. • Rabipur Inactivated Rabies Virus Vaccine – CSL Biotherapies/Novartis Vaccines. Each 1.0 mL monodose vial of lyophilised vaccine contains at least 2.5 IU inactivated rabies virus; trace amounts of neomycin, chlortetracycline and amphotericin B; may contain trace amounts of bovine gelatin. May contain traces of egg protein. 1.0 mL distilled water as diluent. The Mérieux vaccine is a lyophilised, stabilised suspension of inactivated Wistar rabies virus that has been cultured on human diploid cells and then inactivated by beta-propiolactone. This human diploid cell vaccine (HDCV) is coloured offwhite, but after reconstitution with the diluent it turns a pinkish colour due to the presence of phenol red. The vaccine does not contain a preservative. Rabipur is a lyophilised, stabilised suspension of inactivated Flurey LEP rabies virus that has been cultured on purified chick embryo cells and then inactivated by beta-propiolactone. This purified chick embryo cell vaccine (PCECV) does not contain a preservative. The above two vaccines, and other tissue culture vaccines, are interchangeable.
Australian bat lyssavirus infection and rabies 111
3.1 Australian bat lyssavirus infection and rabies
Cases of rabies after animal scratches, the licking of open wounds or saliva contact with intact mucous membranes are very rare.2,3 Cases have been recorded after exposure to aerosols in a laboratory and in caves infested with rabid bats, and cases have been reported following tissue transplantation from donors who died with undiagnosed rabies.1
Rabies immunoglobulin • Imogam Rabies – Sanofi Pasteur Pty Ltd (human rabies immunoglobulin). Each 1.0 mL contains IgG class human rabies antibodies with a minimum titre of 150 IU; 22.5 mg glycine; 1 mg sodium chloride. It is supplied in 2 mL and 10 mL vials. Human rabies immunoglobulin (HRIG) is prepared by cold ethanol fractionation from the plasma of hyperimmunised human donors.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.7 Rabies vaccine, diluent and HRIG should be transported and stored at +2°C to +8°C. Do not freeze. Reconstituted vaccine should be used immediately after reconstituting. The HRIG should be used immediately once the vial is opened.
Dosage and administration NB. The doses of rabies vaccines are the same for both children and adults.
(i) Pre-exposure prophylaxis The dose of rabies vaccine for pre-exposure prophylaxis is 1.0 mL by IM injection, on days 0, 7 and 28. (HDCV can also be given by the subcutaneous (SC) route.)
(ii) Post-exposure treatment The dose of rabies vaccine for post-exposure treatment is 1.0 mL by IM injection, on days 0, 3, 7, 14 and 28–30. (HDCV can also be given by the SC route.) The dose of HRIG is 20 IU/kg body mass by infiltration around the wounds; the remainder of the dose should be administered by IM injection.
Recommendations (i) Pre-exposure prophylaxis for Australian bat lyssavirus infection and rabies Rabies vaccine is effective and safe when used for pre-exposure prophylaxis for rabies.8 Although data on the effectiveness of rabies vaccine as prophylaxis against ABL infection are limited, the available animal data9 and clinical experience support its use. Pre-exposure prophylaxis simplifies the management of a subsequent exposure because fewer doses of vaccine are needed and because HRIG is not required. (Rabies immunoglobulin is often difficult, or even impossible, to obtain in many developing countries.)
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Pre-exposure prophylaxis with rabies vaccine is recommended for:
• expatriates and travellers who will be spending prolonged periods (ie. more than a month) in rabies-endemic areas. (NB. This time interval, of more than a month, is arbitrary, and rabies has occurred in travellers following shorter periods of travel),5 • people working with mammals in rabies-endemic areas, and • research laboratory personnel working with live lyssaviruses. Pre-exposure prophylaxis for both ABL infection and rabies, for all ages, consists of a total of 3 IM (IM or SC if HDCV is used) injections of 1 mL of rabies vaccine, the second given 7 days after the first, and the third given 28 days after the first. Although the third dose can be given at 21 days,1 there are no data to support the use of an even more accelerated schedule for those with limited time before travel to a rabies endemic area. Doses should be given in the deltoid area, as rabies neutralising antibody titres may be reduced after administration in other sites. In particular, vaccine should never be given in the buttock, as failure of pre-exposure prophylaxis has been reported when given by this route. Because the antibody response is reported as satisfactory after the pre-exposure prophylaxis regimen, routine serological testing to confirm seroconversion is not necessary. However, people with impaired immunity who are at risk of exposure to ABL or rabies should have their antibody titres determined 2 to 3 weeks after the third dose of vaccine. Booster doses of rabies vaccine are recommended for immunised people who have ongoing exposure to either ABL or rabies. People who work with live lyssaviruses in research laboratories should have rabies antibody titres measured every 6 months. If the titre is reported as inadequate (<0.5 IU/mL), they should have a booster dose. Others with occupational exposures to bats in Australia, and those who are likely to be exposed to potentially rabid animals in endemic countries, should have rabies antibody titres measured every 2 years. If the titre is reported as inadequate, they should have a booster dose. Alternatively, a booster dose may be offered every 2 years without determining the antibody titre.
Intradermal pre-exposure prophylaxis There are no data on the protection provided by intradermal (ID) rabies vaccination for the prevention of ABL infection. Therefore, ID pre-exposure administration of rabies vaccine should not be used for pre-exposure prophylaxis of ABL. Antibody titres are lower and wane more rapidly after ID compared to either IM or SC administration of rabies vaccine, and there may be a slow initial immune
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• people in Australia liable to receive bites or scratches from bats (this includes bat handlers, veterinarians, wildlife officers and others who come into direct contact with bats),
response following exposure to rabies virus in those given ID rabies vaccine.10 For these 2 reasons, it is strongly recommended that the IM (IM or SC if HDCV is used) route be used for pre-exposure prophylaxis. However, the cost of IM (IM or SC if HDCV is used) rabies vaccination may be prohibitive for some travellers. In this circumstance, ID rabies vaccination, using a dose of 0.1 mL on days 0, 7 and 28, may be considered, provided that: • it is given by those with not only expertise in, but also regular practice of, the ID technique, • it must not be administered to anyone known to have impaired immunity, • it must not be administered to those taking either chloroquine or other antimalarials structurally related to chloroquine (eg. mefloquine) at either the time of, or within a month following, vaccination, • any remaining vaccine is discarded at the end of the session during which the vial is opened, and • the rabies antibody level should be checked 2 to 3 weeks following completion of the pre-exposure course of ID vaccine. The use of the ID route for rabies vaccination is the practitioner’s own responsibility, as rabies vaccines are not licensed for use via this route in Australia. The ID route should never be used to administer rabies vaccine by practitioners who only occasionally provide travel medicine services.
(ii) Post-exposure treatment for Australian bat lyssavirus and rabies exposures Rabies vaccine and HRIG are effective and safe when used for post-exposure treatment following rabies exposures. Although data on the effectiveness of rabies vaccine and HRIG as post-exposure treatment against ABL infection are limited, the available animal data9 and clinical experience support its use. The essential components of post-exposure treatment for either ABL or rabies exposures are prompt local wound management and, for people who have not previously been vaccinated, administration of HRIG and rabies vaccine as soon as is practicable.8 Both HRIG and rabies vaccine are available for post-exposure treatment from the relevant State/Territory health authorities (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control). Post-exposure treatment should be considered whenever a bite, scratch or mucous membrane exposure to saliva from any Australian bat has occurred, regardless of the extent of the bite or scratch, the time lapsed since the exposure, the species of bat involved, and even if the bat was apparently normal in appearance and behaviour. (Although ABL is more likely to be found in bats that either appear unwell or are behaving abnormally,11 it has to be assumed that any bat is potentially infected with ABL.)
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However, exposure to bat blood, urine or faeces, or to a bat that has been dead for more than 4 hours, does not warrant post-exposure treatment.
The relevant State/Territory health authority should be contacted about any animal bite or scratch sustained in a rabies-endemic area. Dogs and monkeys comprise the usual exposures in Asia, Africa and Central and South America, but exposures to other mammals must also be assessed for potential rabies transmission. If a traveller presents >10 days after being bitten or scratched by either a dog or cat in an endemic country, and it can be reliably ascertained that the animal has remained healthy (>10 days after the exposure), post-exposure treatment is not required;8,12 otherwise, a complete course of treatment should be administered, even if there has been a considerable delay in reporting the incident. Immediate and thorough washing of all bite wounds and scratches with soap and water, and the application of a virucidal preparation such as povidoneiodine solution after the washing, is an important measure in the prevention of ABL infection and rabies.1 Consideration should be given at this stage of wound management to the possibility of tetanus and other wound infections, and appropriate measures taken. Primary suture of a bite from a potentially rabid animal should be avoided. Bites should be cleaned, debrided and well infiltrated with HRIG (see below).
a) Use of rabies vaccine in post-exposure treatment Following the local wound management, the subsequent post-exposure treatment for either ABL or rabies exposures consists of: (i) a total of 5 doses of 1.0 mL of rabies vaccine given by IM (IM or SC if HDCV is used) injection; and (ii) HRIG (see below). The volume of rabies vaccine administered to infants and children is the same as that given to adults (ie. 1.0 mL). The first dose of vaccine is given as soon as is practicable (day 0), and subsequent doses are given on days 3, 7, 14 and 28–30; deviations of a few days from this schedule are probably unimportant.8 In adults and children, the vaccine should be administered into the deltoid area, as administration in other sites may result in reduced neutralising antibody titres.
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Where post-exposure treatment for a potential exposure to ABL is indicated, the bat should, if possible, without placing others at risk of exposure, be kept and arrangements promptly made for testing by the relevant State/ Territory veterinary or health authority. Following the wound management, the administration of HRIG and rabies vaccine can be withheld if the result (concerning the bat’s ABL status) will be available within 48 hours of the exposure; if the result will not be available within 48 hours, full post-exposure treatment should begin as soon as is practicable. Where a bat is tested at a reference laboratory and later found to be negative for ABL, then post-exposure treatment for individuals exposed to that bat can be discontinued.
In infants <12 months of age, administration into the anterolateral aspect of the thigh is recommended. Serological testing to measure response is unnecessary except in unusual circumstances, such as when the patient is known to have impaired immunity. In such cases, the antibody titre should be measured 2 to 3 weeks after the dose given at 28–30 days and a further dose given if the titre is reported as inadequate.
b) Use of rabies immunoglobulin in post-exposure treatment Rabies has occurred in people who have received post-exposure rabies vaccine without rabies immunoglobulin being infiltrated in and around the wound.13 Therefore, post-exposure treatment should always include the infiltration of HRIG in and around wounds at the same time as the first dose of rabies vaccine, the only exceptions being people with documented evidence of either completion of the pre-exposure prophylaxis regimen or adequate rabies antibody titres. These people should receive vaccine only (see below). A single dose of HRIG is given to provide localised anti-rabies antibody protection while the patient responds to the rabies vaccine. It should be given at the same time as the first post-exposure dose of vaccine (day 0). If not given with the first vaccine dose, it may be given up to day 7, but should not be given any later in the vaccination course. From day 8 onwards, an antibody response to rabies vaccine is presumed to have occurred. The dose of HRIG for all age groups is 20 IU per kg body mass. HRIG should be infiltrated in and around all wounds using as much of the calculated dose as possible, and the remainder administered intramuscularly at a site away from the injection site of rabies vaccine. If the wounds are severe and the calculated volume of HRIG is inadequate for complete infiltration of all wounds (eg. extensive dog bites in a young child), the HRIG should be diluted in saline to make up an adequate volume for the careful infiltration of all wounds. However, many bat bites occur as small puncture wounds on the fingers;8 such exposures are probably high-risk exposures because of the extensive nerve supply to the fingers and hand. Therefore, although infiltration of HRIG into finger wounds is likely not only to be technically difficult but also to be painful for the recipient, it must be undertaken. As much of the calculated dose of HRIG as possible should be infiltrated into finger and hand wounds using either a 25 or 26 gauge needle. To avoid the development of a compartment syndrome, the HRIG should be infiltrated very gently, and should not cause the adjacent finger tissue to go frankly pale or white. If necessary, a ring-block using a local anaesthetic may be required.
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Table 3.1.1: Summary of Australian bat lyssavirus and rabies post-exposure treatment for non-immune individuals Immediate (Day 0)
Local treatment
Thorough wound cleansing
Follow-up
Rabies vaccine
1.0 mL
1.0 mL on days 3, 7, 14, 28–30
Human rabies immunoglobulin (150 IU/mL)
20 IU/kg – no later than 7 days after the first rabies vaccine dose
Do not give later than 7 days after the first rabies vaccine dose
c) Post-exposure treatment of previously vaccinated people People who have either completed a recommended course of pre-exposure prophylaxis, or previous post-exposure treatment, or who have documented adequate rabies neutralising antibodies, require a modified post-exposure treatment regimen if potentially exposed to either rabies virus or ABL. Local wound management as described above must be carried out, and a total of 2 doses of rabies vaccine (1.0 mL each) should be given by IM (IM or SC if HDCV is used) injection on day 0 and day 3. HRIG is not necessary in these cases. In cases where the vaccination status is uncertain because the documentation of a full course of rabies vaccine is not available, the standard post-exposure treatment regimen (HRIG plus 5 doses of rabies vaccine) should be administered.
d) Post-exposure treatment commenced overseas Australians travelling abroad who are exposed to a potentially rabid animal may be given post-exposure treatment with vaccines not available in Australia. However, it is very likely that they will receive a cell culture derived vaccine, all of which (including both vaccines available in Australia) are considered interchangeable.14 Therefore, if a person has received a cell culture-derived vaccine abroad, the standard post-exposure treatment regimen should be continued in Australia with either HDCV or PCECV. If the post-exposure treatment was started overseas but HRIG was not given, and the person presents in Australia within 7 days of commencing post-exposure treatment, HRIG should be given as soon as is practicable (and within 7 days of the first rabies vaccine). If the person presents in Australia 8 days or more after commencing post-exposure treatment, then HRIG should be withheld.
Contraindications There are no contraindications to post-exposure treatment in a person with a possible exposure to either ABL or rabies. A person with an anaphylactic sensitivity to eggs, or to egg proteins, should not receive PCECV; HDCV should be used instead.
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Treatment
Adverse events Cell culture-derived vaccines are generally well tolerated. In a large study, the following adverse events were reported after administration of HDCV to adults: sore arm (15 to 25% very common), headache (5 to 8% common), malaise, nausea or both (2 to 5% common); and allergic oedema (0.1% uncommon).14 Similar adverse event profiles have been reported for the PCECV; these reactions occur at the same rates in children.14 Although anaphylactic reactions are rare (approximately 1 per 10 000 vaccinations) following administration of HDCV, approximately 6% (common) of people receiving booster doses may experience allergic reactions.14 The reactions typically occur 2 to 21 days after a booster dose, and are characterised by generalised urticaria, sometimes with arthralgia, arthritis, oedema, nausea, vomiting, fever and malaise. These reactions are not life-threatening; they have been attributed to the presence of beta-propiolactone-altered human albumin in the implicated vaccines.14 NB. HDCV contains human albumin, whereas PCECV does not.
Management of adverse events Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local reactions or mild systemic reactions. Such reactions can usually be managed with simple analgesics. Because ABL infection and rabies are lethal diseases, the recommended vaccination regimens, in particular the post-exposure treatment regimen, should be continued even if a significant allergic reaction occurs following a dose of rabies vaccine. Antihistamines can be administered in an attempt to ameliorate any subsequent reactions. A patient’s risk of developing either ABL infection or rabies must be carefully considered before deciding to discontinue vaccination.
Use of steroids and immunosuppressive agents Corticosteroids and immunosuppressive agents can interfere with the development of active immunity and, therefore, if possible, should not be administered during post-exposure treatment. A person who either has an immunosuppressing illness or is taking immunosuppressant medications should have his/her rabies antibody titres checked 2 to 4 weeks after completion of the vaccination regimen (see above).
Use in pregnancy Pregnancy is never a contraindication to rabies vaccination. Follow-up of 202 Thai women vaccinated during pregnancy did not indicate either increased medical complications or birth defects.15
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Variations from product information
The HDCV product information recommends a routine sixth dose at 90 days in the post-exposure treatment regimen. This dose is not considered necessary on a routine basis but a further dose should be offered to a person with impaired immunity who has an inadequate antibody level following the standard regimen. It also recommends a pre-exposure booster after a year; boosters are usually recommended in Australia after 2 years (see above).
Rabies in Indonesia No cases of Bali-acquired rabies have ever been reported in the medical literature despite many people being bitten and scratched by animals in Bali every year. Therefore, post-exposure treatment following animal bites sustained in Bali is currently not warranted, but obviously this situation could change. However, rabies still exists in other parts of Indonesia including the islands of Flores, Sulawesi, Sumatra, Ambon and Kalimantan. Post-exposure treatment is necessary for any animal bite or scratch sustained in any of these locations. Any doubts or concerns about the need for post-exposure treatment following animal bites should be discussed with the State/Territory public health authority.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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Neither of the product information sheets (of the 2 vaccines available in Australia) mentions that they can be used for both pre-exposure prophylaxis and post-exposure treatment for ABL exposures.
3.2 Cholera Bacteriology Vibrio cholerae is a motile, curved Gram-negative bacillus and differences in the O antigens have led to the description of more than 150 serogroups, only two of which have been found to cause cholera. Cholera is caused by enterotoxin producing V. cholerae of serogroups O1 and O139 (sometimes referred to as the ‘Bengal’ strain). Serogroup O1 includes 2 biotypes (classical and El Tor), each of which includes organisms of Inaba, Ogawa and Hikojima serotypes. The ability of V. cholerae to persist in water is determined by the temperature, pH, salinity and availability of nutrients; it can survive under unfavourable conditions in a viable dormant state.1 Transmission predominantly occurs when people ingest faecally contaminated food or water.
Clinical features Cholera is an acute bacterial infection that is generally characterised by the sudden onset of painless, profuse, watery diarrhoea. If untreated, more than half the severe cases will die. Mild cases also occur, as does subclinical infection.1 The cholera toxin does not produce intestinal inflammation. The cholera toxin induces secretion of increased amounts of electrolytes into the intestinal lumen, resulting in mild to severe dehydration and, in some cases, metabolic acidosis.
Epidemiology Cases of cholera in Australia (about 2 to 6 cases a year) almost always occur in individuals who have been infected in endemic areas of Asia, Africa, the Middle East, South America or parts of Oceania.2-4 The disease is usually transmitted via food and water contaminated with human excreta. Shellfish obtained from contaminated waters have also been responsible for outbreaks.1 In 1977, a locally acquired case led to the discovery of V. cholerae in some rivers of the Queensland coast.5 Because of this, health workers should be aware that sporadic cases of cholera may, on rare occasions, follow contact with estuarine waters. As the incubation period of the disease may extend up to 5 days, surveillance of household contacts or those exposed to a possible common source should be maintained for 5 days from the date of last exposure. Stool cultures (cultured using specific media) may be taken from close contacts if required. Food handlers should not be allowed to return to work until 2 consecutive stool samples, taken at least 24 hours apart, are negative. Contacts should also be advised to maintain high standards of personal hygiene to avoid becoming infected. Cases should be reported immediately to the public health authorities (for contact details, refer
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to Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
Vaccines • Dukoral – Sanofi Pasteur Pty Ltd (inactivated whole-cell V. cholerae O1 in combination with a recombinant cholera toxin B subunit (rCTB)). Each 3.0 mL liquid vaccine dose vial contains heat and formalin inactivated Inaba, Ogawa, classic and El Tor strains of V. cholerae O1, 2.5 x 1010 vibrios of each, combined with 1.0 mg rCTB. The buffer consists of a sachet of effervescent granules of anhydrous sodium carbonate, sodium bicarbonate, anhydrous citric acid, sodium citrate, saccharin sodium and raspberry flavour.
Trials of the inactivated vibrio combined with rCTB vaccine have been done mainly in Bangladesh and Peru.9,13-16 In Bangladesh, a 2-dose regimen showed protective efficacy of 44% in children 2 to 6 years of age and 76% in adults at the end of 1 year, and 33% and 60%, respectively, after 2 years. The studies in Peru showed an overall efficacy of 61% in 2–65-year-olds. A recent study undertaken during a mass oral cholera vaccination program in Mozambique concluded that 1 or more doses of the inactivated oral cholera vaccine was 78% protective.17 To date, there is no vaccine marketed to protect against infection with V. cholerae O139. A killed oral whole cell cholera bivalent vaccine (against both serogroups O1 and O139) is currently being evaluated in Vietnam.18,19 A study in short-term Finnish tourists20 showed that the inactivated oral cholera vaccine also provided a 60% reduction in diarrhoea caused by heat-labile toxin producing enterotoxigenic E. coli (LT-ETEC). A study in Bangladesh, an endemic area, showed 67% protection against LT-ETEC for 3 months only.21 It can be expected that the inactivated vaccine will reduce the proportion of travellers’ diarrhoea that is caused by LT-ETEC. Approximately 30 to 40% of travellers to developing countries contract travellers’ diarrhoea, with an average of 20% of cases caused by LT-ETEC; hence, the 60% efficacy of the oral inactivated vaccine against LT-ETEC could be expected to prevent around 10 to 12% of travellers’ diarrhoea.22 However, in Australia this vaccine is only registered for the prevention of cholera.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.23 Store in a refrigerator at +2°C to +8°C. Do not freeze. Protect from light.
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Trials of the safety, immunogenicity and efficacy of oral vaccines, both killed and live attenuated, have been carried out in the United States, Bangladesh, Thailand, Indonesia, Chile, Peru and Switzerland.6-12
Dosage and administration For adults and children over the age of 6 years, Dukoral is administered orally after dissolving the buffer granules in 150 mL of water and adding the vaccine to the solution. Two doses are required, given a minimum of 1 week and up to 6 weeks apart. If the second dose is not administered within 6 weeks, re-start the vaccination. For children aged 2–6 years, Dukoral is administered orally after dissolving the buffer granules in 150 mL of water. Half the solution is then poured away and the entire content of the vaccine vial is mixed with the remaining 75 mL. Children aged 2–6 years should receive 3 doses of the vaccine. Doses are to be administered with a minimum interval of 1 week between doses up to a maximum interval of 6 weeks. If an interval of more than 6 weeks occurs between any of the doses, re-start the vaccination. Food and drink should be avoided for 1 hour before and 1 hour after administration of the inactivated cholera vaccine, as it is acid labile. The inactivated oral cholera vaccine can be given at the same time as other travel vaccines. However, there should be an interval of at least 8 hours between the administration of the inactivated oral cholera and oral typhoid vaccines, as the buffer in the cholera vaccine may affect the transit of the capsules of oral typhoid vaccine through the gastrointestinal tract. Adults and children >6 years of age should receive a single booster dose after 2 years and children 2–6 years of age should receive a booster dose 6 months after completion of the primary course.
Recommendations Despite the endemicity of cholera in some countries often visited by Australians, routine cholera vaccination is not recommended as the risk to travellers is very low. Careful and sensible selection of food and water is of far greater importance to the traveller than vaccination. Immunisation should be considered for people at increased risk of diarrhoeal disease, such as those with achlorhydria, and for people at increased risk of severe or complicated diarrhoeal disease, such as those with poorly controlled or otherwise complicated diabetes, inflammatory bowel disease, HIV/AIDS or other conditions resulting in impaired immunity, or significant cardiovascular disease. It could also be considered for humanitarian disaster workers. Vaccination against cholera is not an official requirement for entry into any foreign country.
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Contraindications The only contraindications to the use of cholera vaccine are: • anaphylaxis following a previous dose of the vaccine, • anaphylaxis following any component of the vaccine, • inactivated oral cholera vaccine is not recommended for children <2 years of age.
Precautions • Postpone administration during either an acute febrile illness or acute gastrointestinal illness with persistent diarrhoea or vomiting, until recovered.
• There should be an interval of at least 8 hours between the administration of the inactivated oral cholera and oral typhoid vaccines, as the buffer in the cholera vaccine may affect the transit of the capsules of oral typhoid vaccine through the gastrointestinal tract.
Adverse events The inactivated oral vaccine is uncommonly (<1%) associated with mild gastrointestinal disturbances.
Use in pregnancy There is inadequate information on the use of inactivated oral cholera vaccines during pregnancy and breastfeeding.24
Variations from product information None.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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• Although the vaccine is not contraindicated in immune impaired individuals, including HIV-infected individuals, data on effectiveness in this population is limited.
3.3 Diphtheria Bacteriology Diphtheria is an acute illness caused by toxigenic strains of Corynebacterium diphtheriae, a Gram- positive, non-sporing, non-capsulate bacillus. The exotoxin produced by C. diphtheriae acts locally on the mucous membranes of the respiratory tract or, less commonly, on damaged skin, to produce an adherent pseudomembrane. Systemically, the toxin acts on cells of the myocardium, nervous system and adrenals.
Clinical features The incubation period is 2 to 5 days. The disease is communicable for up to 4 weeks, but carriers may shed organisms for longer. Spread is by respiratory droplets or by direct contact with skin lesions or articles soiled by infected individuals. Pharyngeal diphtheria is characterised by an inflammatory exudate which forms a greyish or green membrane in the upper respiratory tract which can cause acute severe respiratory obstruction. Diphtheria toxin can cause neuropathy and cardiomyopathy, which may be fatal. The introduction of diphtheria antitoxin in the 1890s reduced the death rate to about 10%, but the mortality has not been further reduced by the use of antibiotics and other modern treatments.1 Effective protection against diphtheria is achieved by active immunisation with diphtheria vaccine.
Epidemiology In the early 1900s, diphtheria caused more deaths in Australia than any other infectious disease, but increasing use of diphtheria vaccines since World War II has led to its virtual disappearance.2 The current epidemiology of diphtheria in Australia is similar to that in other developed countries. Almost all recent cases in the United Kingdom and the United States have been associated with imported infections.3 Hence, there is still the possibility of an imported case occurring in Australia, particularly from developing countries, as occurred in 2001 when a case, acquired in East Timor, was notified in Australia.4 There is now little possibility of acquiring natural immunity or boosting declining immunity with subclinical infection. It is therefore important for Australians to retain high levels of immunity through high vaccination coverage. Disruption of vaccination programs following the collapse of the Soviet Union resulted in the re-emergence of diphtheria throughout the Newly Independent States. From 1991 to 1996, there were more than 140 000 cases and more than 4000 deaths.5 Cases also occurred in neighbouring European countries and in visitors to the area. Mass vaccination eventually brought the epidemic under control.6,7 This experience illustrates the importance of maintaining high levels of vaccination coverage against diphtheria.
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Vaccines Diphtheria toxoid is available in Australia only in combination with tetanus and other antigens. The acronym DTPa, using capital letters, signifies child formulations of diphtheria, tetanus and acellular pertussis-containing vaccines. The acronym dTpa is used for adolescent/adult formulations which contain substantially lesser amounts of diphtheria toxoid and pertussis antigens (see formulations). Formulations for children aged <8 years • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheriatetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccineHaemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/ phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins.
• Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. May also contain yeast proteins.
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• Infanrix-IPV – GlaxoSmithKline (DTPa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin.
Formulations for people aged ≥8 years Adsorbed diphtheria-tetanus vaccine • ADT Booster – Statens Serum Institut/CSL Biotherapies (dT; diphtheriatetanus, adult formulation). Each 0.5 mL pre-filled syringe or monodose vial contains ≥2 IU diphtheria toxoid and ≥20 IU tetanus toxoid adsorbed onto 0.5 mg aluminium hydroxide. Combination vaccines • Adacel – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg pertussis fimbriae (FIM) 2+3; 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde. • Adacel Polio – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg FIM 2+3, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett); 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin, neomycin and streptomycin. • Boostrix – GlaxoSmithKline (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial or pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, adsorbed onto 0.5 mg aluminium hydroxide/phosphate; 2.5 mg phenoxyethanol as preservative. May contain traces of formaldehyde. • Boostrix-IPV – GlaxoSmithKline (dTpa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde, polymyxin and neomycin. Diphtheria vaccination stimulates the production of antitoxin, which protects against the toxin produced by the organism. The immunogen is prepared by treating a cell-free preparation of toxin with formaldehyde, thereby converting it into the innocuous diphtheria toxoid. Diphtheria toxoid is usually adsorbed onto an adjuvant, either aluminium phosphate or aluminium hydroxide, to increase
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its immunogenicity. Antigens from Bordetella pertussis, in combination vaccines, also act as an effective adjuvant. Circulating levels of antitoxin are closely related to protection from diphtheria. Antitoxin levels of <0.01 IU are poorly protective, 0.01 to 0.1 IU are usually protective, and titres of >0.1 IU are associated with more certain and prolonged protection.8 Complete immunisation induces protective levels of antitoxin lasting throughout childhood but, by middle age, at least 50% of vaccinees have levels <0.1 IU.9-11 This has been confirmed in Australia by a recent national serosurvey.12 Single low doses of toxoid in previously immunised adults induce protective levels within 6 weeks.13 Production of DT (CDT vaccine), registered for use in children <8 years of age, ceased in June 2005. ADT Booster can be used for the booster dose of dT in people aged ≥8 years or, if necessary, for the primary dT course (see ‘Variations from product information’).
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.14 Store at +2°C to +8°C. Protect from light. Do not freeze.
Dosage and administration The dose of diphtheria-containing vaccine is 0.5 mL by IM injection. Do not mix DTPa-containing vaccines or dT vaccine with any other vaccine in the same syringe, unless specifically registered for use in this way.
(i) Vaccination in childhood The recommended primary course of vaccination is at 2, 4 and 6 months of age. A booster dose of DTPa is given at 4 years of age. Immunity to diphtheria will not be compromised before the booster dose, as the serological response to the primary course of vaccination is usually sufficient for those years. A second booster, using the adolescent/adult formulation, dTpa, at 12–17 years of age, is essential for maintaining immunity to diphtheria in adults. Vaccination against diphtheria is part of the National Immunisation Program (NIP) schedule, diphtheria toxoid being given in combination with tetanus toxoid and acellular pertussis as DTPa vaccine. Before the 8th birthday, DTPa-containing vaccines should be given, as they contain a larger dose of diphtheria toxoid. After the 8th birthday, smaller doses of toxoid (dT or adolescent/adult formulation dTpa) should be given. Dose reduction is necessary because of the increased incidence of local and systemic reactions to diphtheria toxoid in older children and adults. For details on the management of children who have missed doses in the NIP schedule, see Section 1.3.5, Catch-up.
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3.3 Diphtheria
Recommendations
(ii) Vaccination of adults Individuals who have not received any diphtheria vaccines are also likely to have missed tetanus vaccination. Three doses of dT should be received at minimum intervals of 4 weeks, followed by booster doses at 10 and 20 years after the primary course. It is prudent to give the first of these doses as dTpa, to also provide boosting to natural immunity from exposure to pertussis, which is almost universal in unvaccinated adults. In the event that dT vaccine is not available, dTpa can be used for all primary doses. This is not recommended routinely because there are no data on the safety, immunogenicity or efficacy of dTpa in multiple doses for primary vaccination. All adults who reach the age of 50 years without having received a booster dose of dT in the previous 10 years should receive a further booster dose of dT, or preferably dTpa, if this has not been given previously, to also provide protection against pertussis.
(iii) Other people at special risk Diphtheria can be a significant risk for travellers to some countries (particularly southeast Asia, the Newly Independent States of the former Soviet Union, Baltic countries or eastern European countries). Travellers to high-risk countries should receive a booster dose of dT (or dTpa) if they have not received one in the previous 10 years.
Contraindications The only absolute contraindications to diphtheria vaccine are: • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis following any component of the vaccine.
Adverse events Mild discomfort or pain at the injection site persisting for up to a few days is common. Uncommon general adverse events following dT vaccine include headache, lethargy, malaise, myalgia and fever. Acute anaphylactic reactions, urticaria and peripheral neuropathy very rarely occur (brachial neuritis occurs in 0.001% of cases). (For specific adverse events following combination vaccines containing both diphtheria and pertussis antigens, see Chapter 3.14, Pertussis).
The public health management of diphtheria cases A suspected case of diphtheria is of considerable public health importance, and should be notified immediately to the State/Territory public health authorities, who will advise on further management. In general, contacts of a proven or presumptive diphtheria case will require vaccination (either primary or booster, depending on vaccination status), and appropriate prophylactic antibiotics.15
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Diphtheria antitoxin and penicillin should be given immediately to suspected cases. Do not wait for bacteriological confirmation of the disease. Diphtheria antitoxin derived from horse serum is used because sera of sufficient titre are not available from humans. Due to the presence of foreign protein, diphtheria antitoxin may provoke acute, severe, allergic reactions or serum sickness. Consequently, a test dose should be administered, and if there is evidence of hypersensitivity, it may be necessary to administer diphtheria antitoxin under corticosteroid, adrenaline, and antihistamine cover. The therapeutic dose of antitoxin will depend on the clinical condition of the patient, and may be given either intramuscularly or diluted for administration in an intravenous infusion. Expert advice should be sought with respect to antitoxin dose and special arrangements made if hypersensitivity is suspected. This can be coordinated through the relevant State/Territory health authority (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control). • Diphtheria antitoxin – This is currently available only through the Special Access Scheme.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information
The product information for Infanrix-IPV states that this vaccine may be used as a booster dose for children ≤6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis. NHMRC recommends that booster doses of DTPa and IPV be given at 4 years of age; however, this product may be used for catch-up of the primary schedule or as a booster in children <8 years of age. The product information for ADT Booster states that this vaccine is indicated for a booster dose only in children aged ≥5 years and adults who have previously received at least 3 doses of diphtheria and tetanus vaccines. NHMRC recommends that, where a dT vaccine is required for any person ≥8 years of age, ADT Booster can be used, including for primary immunisation against diphtheria and tetanus.
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3.3 Diphtheria
The product information for both Infanrix hexa and Infanrix Penta states that these vaccines may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 months of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age.
The product information for adolescent/adult formulations of dTpa-containing vaccines states that these vaccines are indicated for booster doses only. NHMRC recommends that, where dT is unavailable for the primary course, dTpa can be used. The product information for Adacel and Boostrix (adolescent/adult formulations of dTpa) states that these vaccines are recommended for use in those aged >10 years. However, NHMRC recommends that they may be used in people aged ≥8 years. The product information also states that dTpa should not be given within 5 years of a tetanus toxoid-containing vaccine. However, NHMRC recommends that dTpa vaccines can be administered at any time following receipt of a diphtheria and tetanus toxoid-containing vaccine.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.4 Haemophilus influenzae type b (hib) Bacteriology Haemophilus influenzae is a Gram-negative coccobacillus that is a normal part of upper respiratory tract flora. Strains isolated from respiratory tract specimens such as sputum and middle ear or sinus fluid usually do not have a capsule, and are known as non-typable (NT). Six capsular types (a to f) have been described and, before the introduction of vaccination against Haemophilus influenzae type b (Hib), almost all H. influenzae isolates from sterile sites (blood, cerebrospinal fluid, joint or pleural fluid) were of the b capsular type. Before Hib immunisation, invasive disease caused by Hib rarely occurred after the age of 5 years. This was because the prevalence of antibody to Hib progressively increased from the age of 2 years, thought to be related to exposure to Hib (or cross-reacting organisms) colonising the nasopharynx or other sites. Children <2 years of age are usually unable to mount an antibody response to the type b capsular polysaccharide, even after invasive disease.1
Clinical features Clinical categories of invasive disease caused by Hib include meningitis, epiglottitis and a range of other infections such as septic arthritis, cellulitis and pneumonia. Hib is rarely isolated from the blood without a focal infection such as the above being evident or developing subsequently. The classical clinical signs of meningitis – neck stiffness and photophobia – are often not detected in infants, who present with drowsiness, poor feeding and high fever. Epiglottitis (inflammation of the epiglottis) presents with respiratory obstruction, associated with soft stridor and often drooling in a pale, febrile, anxious child who remains upright to maximise his or her airway. Meningitis and epiglottitis are almost invariably fatal without appropriate treatment. There are no specific clinical features of any of the focal infections due to Hib which enable them to be differentiated from those due to other organisms. However, before the introduction of Hib vaccines, epiglottitis was due to Hib in over 95% of cases.2
(i) Before Hib vaccination Before the introduction of routine Hib vaccination in 1993, there were at least 500 cases of Hib disease in Australian children <6 years of age every year, and a total of 10 to 15 deaths.3 Hib meningitis accounted for approximately 60% of all invasive Hib disease, most cases occurring in children <18 months of age. The case fatality rate for Hib meningitis was approximately 5%, and up to 40% of the survivors had neurological sequelae such as deafness and intellectual impairment.4 Hib epiglottitis was a more common disease presentation than
Haemophilus influenzae type b (Hib) 131
3.4 Haemophilus influenzae type b (hib)
Epidemiology
in many other countries,5 and usually occurred in children >18 months of age. Other manifestations such as cellulitis, septic arthritis and pneumonia occurred at a similar age to meningitis.6 The incidence of Hib disease in Aboriginal and Torres Strait Islander children, especially those in remote and rural areas, was considerably higher than in non-Indigenous children.7 Most importantly, the onset of Hib disease in this population was at a much younger age, manifesting mostly as meningitis, with epiglottitis being rare. Rates of death and long-term morbidity following Hib meningitis were similar to those observed in non-Indigenous children.7
(ii) After the introduction of Hib vaccination Since Hib vaccines were included in the routine vaccination schedule in 1993, there has been a reduction of >90% in notified cases of Hib disease from 502 in 1992 to an average of 30 cases per year between 1999 and 2002, with approximately 15 cases per year currently reported in Australia (see Figure 3.4.1).8 This reduction has been particularly marked in Indigenous children.9 Similar impressive reductions in Hib disease have been seen in other countries with routine childhood vaccination.5,10 Since Hib disease has become relatively rare, cases of epiglottitis can no longer be assumed to be due to H. influenzae type b and, moreover, even when H. influenzae is isolated from a normally sterile site, it may not be type b. Thus, laboratory confirmation of H. influenzae infection and serotype should always be sought before vaccination failure is assumed.11,12
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Figure 3.4.1: Haemophilus influenzae type b (Hib) notifications, presumed Hib hospitalisations and deaths* of children aged 0 to 4 years from Hib, Australia 1993 to 2005†8 25
25 Deaths Hospitalisation rate Notification rate
20
15
15
10
10
5
5
0
Number of deaths
Rate per 100,000 population
20
0 1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Year
* Hospitalisations and deaths include those for Haemophilus meningitis for the period up to 30 June 2005 (hospitalisations) and 31 December 2004 (deaths). † Notifications where the month of diagnosis was between July 1993 and December 2005; hospitalisations where the month of admission was between 1 July 1993 and 30 June 2005; deaths where the date of death was recorded between January 1993 and December 2004.
Vaccines The first generation Hib vaccines, consisting of purified polysaccharide (PRP) from the Hib capsule, were not effective in children <18 months of age. A review of the efficacy data for the second generation Hib vaccines, which consist of PRP chemically linked (‘conjugated’) to a variety of carrier proteins, found 3 of the 4 Hib vaccines to be immunogenic against invasive Hib disease, PRP-OMP, PRP-T and HbOC.13 The fourth vaccine, PRP-D, was not found to be highly protective in high-risk populations, such as Indigenous children.13
Haemophilus influenzae type b (Hib) 133
3.4 Haemophilus influenzae type b (hib)
There are 2 main groups of carrier proteins associated with a different temporal pattern of PRP antibody response. The vaccine using the outer membrane protein of Neisseria meningitidis as a carrier protein (PRP-OMP) (COMVAX, Liquid PedvaxHIB) gives protective PRP antibody responses after the first dose, and requires only 2 doses to complete the primary course. For this reason, its main application worldwide has been in populations with a high incidence of early onset disease.5 Vaccines using other protein carriers such as tetanus (PRP-T) (Hiberix, Infanrix hexa) and diphtheria (HbOC) toxoids do not achieve protective PRP antibody levels until at least a second dose has been given, and
require 3 doses to complete primary immunisation. No or minimal immunologic interference has been observed when children are vaccinated with 7vPCV and Infanrix hexa at the same immunisation visit.14,15 Many Hib combination vaccines containing acellular pertussis are known to produce lower Hib antibody responses than similar formulations containing whole-cell pertussis.16 When administered according to the United Kingdom’s schedule as 3 primary doses at 2, 3 and 4 months of age without a booster, their use has been associated with an increased risk of vaccine failure.17 In other European countries that routinely give a fourth dose around the time of the 1st birthday, as is included in the Australian schedule, no loss of effectiveness has been observed.18,19 • Liquid PedvaxHIB – CSL Biotherapies/Merck & Co Inc (PRP-OMP). Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg meningococcal protein; liquid formulation with 35 µg borax and 225 µg aluminium hydroxide. • Hiberix – GlaxoSmithKline (PRP-T). Each 0.5 mL monodose lyophilised vaccine contains 10 µg PRP conjugated to 30 µg tetanus toxoid (with a lactose stabiliser) for reconstitution with 0.9% saline. Combination vaccines that include Hib • COMVAX – CSL Biotherapies/Merck & Co Inc (Hib (PRP-OMP)-hepatitis B). Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg meningococcal protein, 5 µg hepatitis B surface antigen; 225 µg aluminium hydroxide; 35 µg borax. May contain yeast proteins. • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheriatetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccineHaemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/ phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins.
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Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.20 Store conjugate Hib vaccines at +2°C to +8°C. Do not freeze.
Dosage and administration The dose of Hib vaccine is 0.5 mL to be given by IM injection. Conjugate Hib vaccines may be administered in separate sites on the same day as any of the other childhood vaccines such as the 7-valent pneumococcal conjugate (7vPCV), meningococcal serogroup C conjugate (MenCCV), hepatitis B, DTPa-containing and monovalent IPV (or IPV-containing) vaccines.
Recommendations (i) Hib vaccine is recommended for all infants from 2 months of age Immunisation using PRP-OMP (COMVAX or Liquid PedvaxHIB) requires 2 primary doses at 2 and 4 months, followed by a booster at 12 months of age. If PRP-T (Infanrix hexa or Hiberix) is used, 3 primary doses at 2, 4 and 6 months are needed, with a booster at 12 months of age.
(ii) Indigenous children living in the Northern Territory, Queensland, South Australia and Western Australia Many Indigenous populations experienced high Hib attack rates associated with early peak disease onset before the introduction of Hib immunisation. While vaccination has reduced the overall incidence of invasive Hib infection in these vulnerable groups, increased disease risk during the first year of life remains. It is therefore important that Aboriginal and Torres Strait Islander children in jurisdictions (the Northern Territory, Queensland, South Australia and Western Australia) where such different patterns of Hib disease remain evident continue to receive PRP-OMP, because of the early antibody response seen with this vaccine.7 In Alaskan natives, who experienced similar pre-vaccination attack rate profiles, re-emergence of Hib disease was observed when the Hib vaccine in use was changed from PRP-OMP to HbOC.21
(iii) Non-Indigenous children and Indigenous children living in Australian Capital Territory, New South Wales, Tasmania and Victoria
Haemophilus influenzae type b (Hib) 135
3.4 Haemophilus influenzae type b (hib)
Any licensed Hib vaccine may be used in these children as the period of significant risk does not begin until after 6 months of age. Although there are limited data on the epidemiology of Hib disease before vaccination in Indigenous children in south-eastern Australia, available data since vaccination commenced in 1993 suggest that the epidemiology in these children does not differ substantially from that in non-Indigenous children living in these areas (NCIRS data, unpublished).
(iv) Interchangeability of Hib vaccines It is recommended that the same conjugate vaccine be used for all doses. However, if necessary, after the first dose, any Hib vaccine may be used to complete the primary course.22 For primary vaccination, only 2 doses of PRPOMP are required, but if any other Hib vaccine is given, a total of 3 doses is required to complete the primary course.23 This means that if the previous Hib vaccine type is unknown for any doses, or the same vaccine type is unavailable, the primary course can be completed with a total of 3 doses of any combination of registered Hib vaccines. For booster doses and in children >15 months of age, regardless of previous Hib vaccinations, a single dose of any registered Hib vaccine is sufficient for protection. Details of catch-up vaccination schedules are given in Section 1.3.5, Catch-up.
(v) Vaccine failures Children who have developed confirmed Hib disease after 2 or more doses of PRP-OMP or 3 or more doses of PRP-T may warrant immunological investigation. Consultation with an immunologist with paediatric expertise is recommended.
(vi) Preterm babies Preterm babies can be immunised at the normal age, without correction for prematurity24 (see Section 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants). Extremely preterm babies (<28 weeks’ gestation or <1500 g birth weight) who are vaccinated with PRP-OMP should be given an extra dose at 6 months of age, resulting in a 4-dose schedule at 2, 4, 6 and 12 months of age.25 When other Hib vaccines, including Infanrix hexa, are used, no change in the usual schedule is required. Preterm babies have been shown to produce good antibody responses to all the antigens in Infanrix hexa following administration at 2, 4 and 6 months of age, although the responses to hepatitis B and Hib are not quite as high as in term babies.
(vii) Splenectomy Hib is an uncommon cause of post-splenectomy sepsis in adults and children. Children >2 years of age who have received all scheduled doses of Hib vaccine do not require a booster dose after splenectomy. A single dose of Hib vaccine is recommended for other splenectomised individuals who were not vaccinated in infancy or are incompletely vaccinated. The vaccine should be given 2 weeks before a planned splenectomy. Subsequent booster doses of Hib vaccine are not required.26 For other recommendations for asplenic or splenectomised individuals, see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment.
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(viii) Allogeneic and autologous haematopoietic stem cell transplant (HSCT) recipients These patients should also be considered for Hib vaccination post transplant. The Hib conjugate vaccine should be administered to recipients at 12, 14, and 24 months after HSCT. See Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment.
Contraindications The only contraindications to any of the Hib vaccines are: • anaphylaxis following a previous dose of any of the vaccines, or • anaphylaxis following any component of the vaccine.
Adverse events Swelling and redness at the injection site after the first dose are common and have been reported in up to 5% of vaccinated children. Fever in up to 2% (common) has also been reported. These adverse events usually appear within 3 to 4 hours and resolve completely within 24 hours. The incidence of these adverse events declines with subsequent doses, so it is recommended that the course of vaccination be completed regardless.
The public health management of contacts of a child with invasive Hib disease Healthcare workers should be guided by public health authorities in the public health management of cases of invasive Hib disease.
Household As the incidence of invasive Hib disease is now very low, rifampicin chemo prophylaxis is no longer routinely indicated unless the household contains either: • an infant <7 months of age (regardless of vaccination status), or • a child aged 7 months to 5 years who is inadequately vaccinated according to the Hib schedule.
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3.4 Haemophilus influenzae type b (hib)
In this case, everybody in the household should receive rifampicin prophylaxis after a case of invasive Hib disease in any household member, with the exception of pregnant women for whom ceftriaxone may be used. The recommended dose of rifampicin is 20 mg/kg as a single daily dose (maximum daily dose 600 mg) for 4 days. Neonates (<1 month of age) should receive 10 mg/kg daily for 4 days.
Childcare facilities Similarly, if the index case attends a child day-care facility for more than 18 hours a week, rifampicin should be given to all children and staff who were in the same room group (as the case) in the 7 days preceding the case’s onset, provided that at least one of these close contacts is a child <24 months of age who is inadequately vaccinated. Although there may have been some intermingling of all the children at the facility at the beginning and end of the day, this is usually of a short duration only and not enough to justify extending the use of rifampicin. Rifampicin prophylaxis is of no value more than 30 days after initial contact with a case.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information The product information for Hib vaccines recommends the vaccine for use in children aged 2 months to 5 years. NHMRC recommends administration of Hib vaccine to older people with asplenia or following either allogeneic or autologous haematopoietic stem cell transplantation. With the exception of PRP-OMP, the product information for Hib vaccines recommends use as a booster at 18 months, but the NHMRC regards a booster at 12 months of age as likely to result in an equivalent immune response. The product information for Infanrix hexa states that this vaccine may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 month of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.5 Hepatitis A
Hepatitis A is an acute infection of the liver caused by a hepatovirus, the hepatitis A virus (HAV).1 The virus survives well in the environment – it persists on hands for several hours and in food kept at room temperature for considerably longer – and is relatively resistant to heat and freezing.
Clinical features Hepatitis A is an infection of humans; there is no animal reservoir. HAV is predominantly transmitted by the faecal-oral route. The infecting dose is unknown but it is presumed to be low. The incubation period of hepatitis A is 15 to 50 days, with a mean of about 30 days.1 HAV is excreted in faeces for up to 2 weeks before the onset of illness and for at least 1 week afterwards.1 In young children, HAV usually causes either an asymptomatic infection or a very mild illness without jaundice. Patients with symptomatic illness typically have a 4 to 10 day prodrome of systemic (fever, malaise, weakness and anorexia) and gastrointestinal (nausea and vomiting) symptoms. Dark urine is usually the first specific manifestation of acute hepatitis A, followed a day or 2 later by jaundice and pale faeces. The prodromal symptoms tend to wane with the onset of jaundice, although the anorexia and malaise may persist; pruritus and localised hepatic discomfort or pain may follow.1 The duration of illness varies but most patients feel better and have normal, or near normal, liver function tests within a month of the onset of illness. Complications of hepatitis A are uncommon but include, on rare occasion, fulminant hepatitis.2 Hepatitis A does not cause chronic liver disease. The diagnosis is made by detecting anti-HAV IgM in serum during the acute illness. Anti-HAV IgM is invariably present by the time the patient presents and persists for 3 to 6 months after the acute illness.1 Serum anti-HAV IgG indicates past infection (or possibly immunisation) and therefore immunity; it probably persists for life.
Epidemiology Hepatitis A was a considerable public health problem in Australia in the 1990s. During this time numerous outbreaks occurred in child day-care centres and preschools,3 communities of men who have sex with men,4 schools and residential facilities for the intellectually disabled,5 and communities of injecting drug users.4 A very large outbreak of hepatitis A associated with the consumption of raw oysters occurred in New South Wales in 1997 (see Figure 3.5.1).6 However, there has been a marked decline in notifications of hepatitis A in Australia in recent years (see Figure 3.5.1). This is probably a consequence of
Hepatitis A 139
3.5 Hepatitis A
Virology
the liberal use of hepatitis A vaccine among travellers, and those at increased risk because of lifestyle or occupation. A hepatitis A vaccination program for Indigenous children in north Queensland that began in 1999 has also contributed substantially to the decline in notifications.7 Nevertheless, Indigenous Australian children remain at considerably greater risk, not only of acquiring hepatitis A but also for being hospitalised with the infection, compared to non-Indigenous children.8 This is particularly true for Indigenous children residing in other regions of Queensland, the Northern Territory, South Australia and Western Australia. Figure 3.5.1: Notifications of hepatitis A in Australia, 1991 to 2006
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+BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM +BO +VM
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Vaccines • Avaxim – Sanofi Pasteur Pty Ltd (formaldehyde inactivated hepatitis A virus (GBM strain)). Each 0.5 mL pre-filled syringe contains 160 ELISA units of hepatitis A virus (HAV) antigens inactivated by formaldehyde; 0.3 mg aluminium hydroxide; 2.5 µL phenoxyethanol; 12.5 µg formaldehyde; trace of neomycin. • Havrix Junior – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain)). Each 0.5 mL monodose vial or pre-filled syringe contains 720 ELISA units of HAV antigens; 0.25 mg as aluminium hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin. • Havrix 1440 – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain)). Each 1.0 mL monodose vial or pre-filled syringe contains 1440 ELISA units of HAV antigens; 0.5 mg aluminium hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin.
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• Twinrix (720/20) – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 1.0 mL monodose vial or syringe contains 720 ELISA units of HAV antigens, 20 µg recombinant DNA hepatitis B surface antigen protein; 0.45 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin. May contain yeast proteins. • VAQTA Paediatric/Adolescent formulation – CSL Biotherapies/Merck & Co Inc (formaldehyde inactivated hepatitis A virus (CR326F strain)). Each 0.5 mL monodose vial contains approximately 25 units (U) of hepatitis A virus protein; 0.225 mg aluminium hydroxide; 35 µg borax; trace of formaldehyde. • VAQTA Adult formulation – CSL Biotherapies/Merck & Co Inc (formaldehyde inactivated hepatitis A virus (CR326F strain)). Each 1.0 mL monodose vial contains approximately 50 units (U) of hepatitis A virus protein; aluminium 0.45 mg as aluminium hydroxide; 70 µg borax; trace of formaldehyde. • Vivaxim – Sanofi Pasteur Pty Ltd (inactivated hepatitis A virus and typhoid Vi capsular polysaccharide). Supplied in a unique dual-chamber syringe which enables the 2 vaccines to be mixed just before administration. Each 1.0 mL dose of mixed vaccine contains 160 ELISA units of inactivated hepatitis A virus antigens, 25 µg purified typhoid capsular polysaccharide; 0.3 mg aluminium hydroxide; 2.5 µL phenoxyethanol; formaldehyde; traces of neomycin and bovine serum albumin. The inactivated hepatitis A vaccines are prepared from HAV harvested from human diploid cell cultures, which are then purified by ultrafiltration and chromatography, inactivated by formaldehyde, and then adsorbed onto aluminium hydroxide adjuvant. Although the vaccines are prepared from differing strains of HAV, there is only one known serotype; immunity induced by a particular strain probably provides protection against all strains.1 The Avaxim, Havrix, Twinrix and Vivaxim vaccines contain a preservative, 2-phenoxyethanol. All the vaccines contain minute amounts of residual formaldehyde. Although the manufacturers use slightly different production methods and quantify the HAV antigen content in their respective vaccines
Hepatitis A 141
3.5 Hepatitis A
• Twinrix Junior (360/10) – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 0.5 mL monodose vial or pre-filled syringe contains 360 ELISA units of HAV antigens, 10 µg recombinant DNA hepatitis B surface antigen protein; 0.225 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin. May contain yeast proteins.
differently, the ‘equivalent’ vaccines of the different manufacturers are interchangeable. The inactivated hepatitis A vaccines induce HAV antibodies (anti-HAV) at titres many-fold greater than that provided by the recommended dose of normal human immunoglobulin. Although the vaccines are highly immunogenic (see below), the titres are usually below the detection limits of the routinely available commercial tests for anti-HAV.1 Therefore, serological testing to assess immunity after vaccination against hepatitis A is neither necessary nor appropriate. Likewise, it is also inappropriate to undertake testing if an individual cannot recall if he/she has been vaccinated against hepatitis A in the past; if no vaccination records are available, vaccination should be advised. Hepatitis A vaccines are highly immunogenic in both children and adults, with virtually universal seroconversion 4 weeks after vaccination.1 Two randomised clinical trials conducted in the early 1990s showed that the vaccines have a very high protective efficacy, approaching 100%.9,10 This finding is supported by the apparent eradication of hepatitis A from Indigenous communities in north Queensland since the introduction of the vaccination program in the region.7 The duration of immunity and, therefore, protection following vaccination is not certain. However, vaccine-induced anti-HAV probably persists for many years. There is no current evidence that booster doses are required; in healthy individuals, it is quite possible that they will never be required.11
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.12 Hepatitis A vaccines should be transported and stored at +2°C to +8°C. Do not freeze.
Dosage and administration The inactivated hepatitis A vaccines are administered by IM injection. The recommended dosages and schedules for use in Australia are given in Table 3.5.1.
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Table 3.5.1: Recommended dosages and schedules for use of the inactivated hepatitis A vaccines Vaccinee’s age (years)
Dose Volume (HAV antigen) per dose (mL)
Vaccination schedule (mo=months)
Monovalent hepatitis A vaccines Avaxim
≥2
160 EIA U
0.5
0, 6 to 12 mo
Havrix Junior
2– <16
720 EIA U
0.5
0, 6 to 12 mo
Havrix 1440
≥16
1440 EIA U
1.0
0, 6 to 12 mo
VAQTA Paediatric/ 1– <18 Adolescent
25 U
0.5
0, 6 to 18 mo
VAQTA Adult
50 U
1.0
0, 6 to 18 mo
≥18
Combination hepatitis A/hepatitis B vaccines Twinrix Junior (360/10)
1– <16
360 EIA U
0.5
0, 1, 6 mo
Twinrix (720/20)
≥16
720 EIA U
1.0
0, 1, 6 mo
Twinrix (720/20)*
1– <16
720 EIA U
1.0
0, 6 to 12 mo
Twinrix (720/20)
≥16
720 EIA U
1.0
0, 7, 21 days, 12 mo
1.0 (mixed vaccine)
0; a single dose of monovalent adult formulation hepatitis A vaccine should be given at 6 to 36 mo.
†
Combination hepatitis A/typhoid vaccine Vivaxim
≥16
160 EIA U
* This schedule should not be used for those who require prompt protection against hepatitis B; for example, if there is close contact with a known hepatitis B carrier. † This ‘rapid’ schedule should be used only if there is very limited time before departure to either moderately or highly endemic regions.
Recommendations To avoid unnecessary vaccination, it is recommended that the following groups be screened for pre-existing natural immunity to hepatitis A: • those born before 1950, • those who spent their early childhood in endemic areas, and • those with an unexplained previous episode of hepatitis or jaundice. (NB. Such a previous episode cannot be assumed to be hepatitis A.) If, upon screening, a person has either total hepatitis A antibodies or anti-HAV IgG, he/she has presumably had previous, perhaps unrecognised, HAV infection (or less likely, has been previously immunised) and can be assumed to be immune and, therefore, does not need hepatitis A vaccination.
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3.5 Hepatitis A
Vaccine
(i) Hepatitis A vaccination is recommended for: • all travellers to, and all expatriates living in, moderately to highly endemic areas (including all developing countries) A single dose of a monovalent hepatitis A vaccine provides protective levels of anti-HAV for at least a year;1 the second dose is recommended to increase the duration of protection. As they do not contain live viruses, hepatitis A vaccines can be administered either simultaneously with, or within a month of, all other vaccines relevant to international travel.13 There is no place for the routine use of normal human immunoglobulin to prevent hepatitis A in travellers. It should only be given (at the same time as hepatitis A vaccine) to those, such as aid-workers about to be deployed in emergency refugee camps, who will be living in very inadequate circumstances. Otherwise, it is only recommended for contacts of hepatitis A cases (see ‘The public health management of contacts of hepatitis A cases’ below). • Aboriginal and Torres Strait Islander children residing in the Northern Territory, Queensland, South Australia and Western Australia Hepatitis A vaccination for these children should commence in the second year of life. State/Territory health authorities should be contacted about the local hepatitis A vaccination schedules, including catch-up. • those whose occupation may put them at risk of acquiring hepatitis A This includes those who live or work in rural and remote Indigenous communities, child day-care and preschool personnel, carers of people with intellectual disabilities, healthcare workers who regularly provide care for Aboriginal and Torres Strait Islander children, plumbers or sewage workers, and sex workers. • those whose lifestyle may put them at risk of acquiring hepatitis A This includes men who have sex with men, and injecting drug users. • people with intellectual disabilities • people chronically infected with either hepatitis B or hepatitis C viruses • patients with chronic liver disease Hepatitis A vaccination is recommended for patients with chronic liver disease of any aetiology. Those with chronic liver disease of mild to moderate severity mount a satisfactory immune response following vaccination, but those with end-stage liver disease do not respond as well, and liver transplant recipients may not respond at all.14,15 Nevertheless, all those with chronic liver disease should be vaccinated, preferably as early in the course of the disease as possible.
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(ii) Combined hepatitis A/hepatitis B vaccines Combined hepatitis A/hepatitis B vaccines should be considered for: NB. Twinrix (720/20) can be administered according to a ‘rapid’ schedule if there is limited time before departure.16 This consists of a single dose on each of days 0, 7 and 21. It is important that a fourth dose be given as a booster 12 months after the first dose to ensure longer-term protection. • medical, dental and nursing undergraduate students, • men who have sex with men, • sex industry workers, • injecting drug users, • patients with chronic liver disease, • solid organ transplant recipients (see Table 2.3.2 Recommendations for vaccinations for solid organ transplant (SOT) recipients), • people with intellectual disabilities and their carers. NB. Twinrix (720/20) can be administered in a 2-dose regimen in people 1 to 15 years of age (see Table 3.5.1). However, this regimen should not be used in those who require prompt protection against hepatitis B; for example, if there is close contact with a known hepatitis B carrier. Combined hepatitis A/hepatitis B vaccines can be administered simultaneously with, or within a month of, all other vaccines relevant to international travel.
(iii) Combined hepatitis A/typhoid vaccine The combined hepatitis A/typhoid vaccine can be recommended for all those ≥16 years of age who intend travelling to developing countries, and is particularly useful for those already immunised against hepatitis B. The vaccine can be administered simultaneously with, or within a month of, all other vaccines relevant to international travel. A single dose of a monovalent adult formulation hepatitis A vaccine 6 to 36 months later is required to provide longer-term protection against hepatitis A. A booster dose of typhoid capsular polysaccharide vaccine is required after 3 years if there is a continued risk. The combined hepatitis A/typhoid vaccine may be used as a ‘booster’ vaccine if a person received a previous dose of a monovalent adult formulation hepatitis A vaccine. This may be given 6 to 36 months after primary vaccination.
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3.5 Hepatitis A
• expatriates and long-term visitors to developing countries,
Contraindications The only contraindications to any of the hepatitis A vaccines are: • anaphylaxis following a previous dose of any of the hepatitis A vaccines, or • anaphylaxis following any component of the vaccine. Combination vaccines containing the hepatitis B component are contraindicated where there is a history of anaphylaxis to yeast.
Adverse events The most common adverse events following administration of hepatitis A vaccines are mild local events of a short duration, probably caused by the aluminium hydroxide adjuvant. About 15% (very common) of adults report headache and approximately 5% (common) report malaise or fatigue following vaccination.17 Up to 20% (very common) of children who received either Havrix or VAQTA experienced soreness at the injection site. In both adults and children, systemic adverse events such as headache and fever are much less common than local adverse events.17 Hepatitis A vaccines do not affect liver enzyme levels. They can be safely given to HIV-infected people, and do not adversely affect either the HIV load or CD4 cell count.18
The public health management of contacts of hepatitis A cases Normal human immunoglobulin (NHIG) can be used to prevent secondary cases in close contacts of hepatitis A cases. (NB. A hepatitis A IgM positive test in an adult without either clinical or epidemiological features of hepatitis A should be considered as a false-positive result.19 In this circumstance, no interventions are necessary for the close contacts.) NHIG should be administered to close contacts within 2 weeks (of the last exposure to the cases) in the doses given in Table 3.5.2; NHIG may not be effective if given >2 weeks after the exposure.17 ‘Close contacts’ are those who have had contact with a case during the 2 weeks before, up until 1 week after, the onset of jaundice, and usually include only household and/or sexual contacts (but in some circumstances may include close occupational exposure). Table 3.5.2: Recommended doses of normal human immunoglobulin (NHIG) to be given as a single intramuscular injection to close contacts of hepatitis A cases Weight
Dose NHIG
Under 25 kg
0.5 mL
25–50 kg
1.0 mL
Over 50 kg
2.0 mL
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Although 1 study suggests that hepatitis A vaccine may be effective in preventing secondary cases of hepatitis A in close contacts,20 there is currently insufficient evidence to be able to recommend it for this purpose. If a person with hepatitis A was a food-handler by occupation while infectious, a review of the food-handling procedures in the food establishment should be undertaken and the staff at the establishment reminded of standard food and personal hygiene practices.17 If the review identifies issues which raise the possibility of transmission of HAV, NHIG should be administered to the other food-handlers in the establishment. State/Territory public health authorities should determine the need for recall of customers of the establishment for NHIG. A food-handler with hepatitis A should be excluded from work until at least 1 week after the onset of jaundice. A single case of hepatitis A associated with a day-care or preschool facility (ie. a case in an attendee child, a staff member or a household contact of an attendee or staff member) does not require any mass intervention.3 However, the supervisor of the facility should be contacted to: • explore the possibility of within-centre transmission by the case (eg. faecal accidents, other hygiene control concerns), and • determine if there could be other cases associated with the facility. In particular, it should be ascertained whether an attendee child arrived from an endemic region overseas about a month before the case’s onset, and whether any other children at the facility have recently been vaguely unwell with a change in bowel motions. Should there be any concerns about the potential for further transmission of hepatitis A virus within the facility, mass interventions (as per 2 or more cases below) may be considered. The supervisor should be reminded of the relevant infection control practices that should be in place at all times at the facility, and that hepatitis A vaccine is routinely recommended for day-care and preschool staff (unless they have either had hepatitis A in the past or been vaccinated previously). A useful reference is ‘Staying Healthy in Child Care’ available at http://www.nhmrc.gov.au/publications/synopses/ch43syn.htm. Two or more cases of hepatitis A (associated with the same day-care or preschool facility) that occur in different households are strongly suggestive that transmission of HAV is occurring within that facility.3 These cases may be in attendee children or staff or household contacts of an attendee or staff member. As soon as transmission of HAV is recognised within a day-care or preschool facility, NHIG should be offered to children and susceptible staff in the relevant age groups (or classes) at that facility. Parents and staff need to be reminded that live virus vaccines, MMR and varicella vaccines in particular, should not be administered within 3 months of receiving IM NHIG.3
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3.5 Hepatitis A
Further public health considerations
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information None.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.6 Hepatitis B Virology Hepatitis B virus (HBV) contains partially double-stranded DNA. The outer surface of the virus is glycolipid which contains the hepatitis B surface antigen (HBsAg). Other important antigenic components are hepatitis B core antigen (HBcAg), and hepatitis B e antigen (HBeAg). HBcAg is not detectable in serum, but can be detected in liver tissue in people with acute or chronic hepatitis B infection. Antibodies developed to HBsAg (anti-HBs) indicate immunity, whereas persistence of HBsAg denotes infectivity, which is greater if HBeAg and HBV DNA are positive.1
In approximately 30 to 50% of adults, infection causes symptomatic acute hepatitis, but in young children, particularly those <1 year of age, infection is usually asymptomatic. The incubation period is 45 to 180 days and the period of communicability extends from several weeks before the onset of acute illness usually to the end of the period of acute illness. Acute illness is indistinguishable from other forms of hepatitis, and symptoms include fever, jaundice, malaise, anorexia, nausea and vomiting, abdominal pain (especially in the right upper quadrant), myalgia, and the passage of dark-coloured urine and light-coloured stools. Jaundice may be preceded by an acute febrile illness with arthralgia or arthritis and rash, most typical of hepatitis B. During recovery, malaise and fatigue may persist for many weeks. Fulminant hepatitis occurs in approximately 1% of acute cases.1,2 Following acute infection, 1 to 10% of those infected as adults2,3 and up to 90% of those infected as neonates1,2 remain persistently infected for many years (see Figure 3.6.1). Chronically infected carriers of HBV are identified by the long-term presence (longer than 6 months) of circulating HBsAg.4
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3.6 Hepatitis B
Clinical features
Figure 3.6.1: The influence of age of infection with the hepatitis B virus on the likelihood of becoming a hepatitis B carrier
(Modified and used with permission from: Edmunds WJ, Medley GF, Nokes DJ, Hall AJ, Whittle HC. The influence of age on the development of the hepatitis B carrier state. Proceedings. The Royal Society Biological Sciences.1993;253:197-201.)
Carriers of HBV are capable of transmitting the disease, though often remain asymptomatic and may not be aware that they are infected. Most of the serious complications associated with hepatitis B infection occur in HBV carriers. Chronic active hepatitis develops in more than 25% of carriers, and up to 25% die prematurely of cirrhosis or hepatocellular carcinoma.1,2
Epidemiology The prevalence of HBV carriage differs in different parts of the world, and may be quite variable within countries. Carrier rates vary from 0.1 to 0.2% among Caucasians in the United States, northern Europe and Australia, 1 to 5% in the Mediterranean countries, parts of eastern Europe, China, Africa, Central and South America, and some Australian Aboriginal populations, and greater than 10% in many sub-Saharan African, southeast Asian and Pacific island populations.5-7 First-generation immigrants usually retain the carrier rate of their country of origin, but subsequent generations show a declining carrier rate irrespective of vaccination.5 Transmission of hepatitis B may result from percutaneous inoculation or mucosal contact with blood or sexual secretions from an HBsAg-positive individual. Screening of blood and organ donors has virtually eliminated the risk of transmission of hepatitis B through blood transfusion and organ transplants.8,9 Saliva may also contain levels of virus which are likely to be infective only if inoculated directly into tissue (ocular or mucous membranes). Transmission by inadvertent parenteral inoculation, such as by toothbrush, razor etc., through close personal contact in households in which 1 or more carriers or other infected individuals reside, is a low but significant risk. Routes of transmission include: • sharing injecting equipment (such as occurs in injecting drug use), • needle-stick injury, and other types of parenteral inoculation,
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• sexual contact (including heterosexual or homosexual intercourse, although the latter has a higher risk), • transmission from infected mother to neonate (vertical transmission), usually occurring at or around the time of birth, • child-to-child (horizontal) transmission, usually through contact between open sores or wounds, • breastfeeding,10 • nosocomial transmission in overseas healthcare facilities if infection control procedures are unsatisfactory.
Australian vaccination policy
Vaccines • Engerix-B – GlaxoSmithKline (recombinant DNA hepatitis B vaccine). Adult formulation – Each 1.0 mL monodose vial contains 20 µg recombinant hepatitis B surface antigen (HBsAg) protein, adsorbed onto 0.5 mg aluminium hydroxide. Paediatric formulation – Each 0.5 mL monodose vial contains 10 µg HBsAg protein, adsorbed onto 0.25 mg aluminium hydroxide. Both formulations contain traces of yeast proteins and thiomersal (<2 µg/mL). Both are available in packs of 10. • H-B-VAX II – CSL Biotherapies/Merck & Co Inc (recombinant DNA hepatitis B vaccine). Adult formulation preservative free – Each 1.0 mL pre-filled syringe or vial contains 10 µg recombinant HBsAg protein, adsorbed onto 0.5 mg aluminium hydroxide. May contain yeast proteins. Paediatric formulation preservative free – Each 0.5 mL pre-filled syringe or vial contains 5 µg recombinant HBsAg protein, adsorbed onto 0.25 mg aluminium hydroxide. May contain yeast proteins. Both are available in packs of 10. Dialysis formulation preservative free – Each 1.0 mL vial contains 40 µg recombinant HBsAg protein, adsorbed onto 0.5 mg aluminium hydroxide. May contain yeast proteins. Available as single pack only.
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3.6 Hepatitis B
The initial strategy for the control of hepatitis B in Australia commenced in 1988, targeting groups at particular risk of infection for vaccination at birth. In addition to vaccine, hepatitis B immunoglobulin (HBIG) was given if the mother was a hepatitis B carrier. In 1990, universal infant vaccination commenced in the Northern Territory. In 1996, the NHMRC recommended a universal hepatitis B vaccination program for infants and adolescents. The adolescent program commenced in some States and Territories in 1997 and the universal infant program, with the first dose given at birth, began nationally in 2000. The adolescent program will continue until those immunised for hepatitis B in the childhood program reach adolescence.
Combination vaccines that include both DTPa and hepatitis B • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheriatetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccineHaemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/ phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins. • Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. May also contain yeast proteins. Other combination vaccines that include hepatitis B • COMVAX – CSL Biotherapies/Merck & Co Inc (Hib (PRP-OMP)-hepatitis B). Each 0.5 mL monodose vial contains 7.5 µg PRP conjugated to 125 µg meningococcal protein, 5 µg hepatitis B surface antigen; 225 µg aluminium hydroxide; 35 µg borax. May contain yeast proteins. • Twinrix Junior (360/10) – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 0.5 mL monodose vial or pre-filled syringe contains 360 ELISA units of HAV antigens, 10 µg recombinant DNA hepatitis B surface antigen protein; 0.225 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin. May contain yeast proteins. • Twinrix (720/20) – GlaxoSmithKline (formaldehyde inactivated hepatitis A virus (HM175 strain) and recombinant hepatitis B vaccine). Each 1.0 mL monodose vial or syringe contains 720 ELISA units of HAV antigens, 20 µg recombinant DNA hepatitis B surface antigen protein; 0.45 mg aluminium phosphate/hydroxide; 0.5% w/v phenoxyethanol; traces of formaldehyde and neomycin. May contain yeast proteins.
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Hepatitis B vaccines are prepared using recombinant technology. After purification, the HBsAg protein is adsorbed onto elemental aluminium (as hydroxide and/or phosphate). Preservatives, including thiomersal, may be added. Hepatitis B vaccines may contain up to 1% yeast proteins (but no yeast DNA). Thiomersal-free vaccines, such as H-B-VAX II preservative free paediatric formulation, are now available and are recommended for administration to newborns and infants.11 Engerix-B paediatric formulation contains a trace amount of thiomersal (<2 µg/mL). All other infant and childhood hepatitis B-containing combination vaccines, such as Infanrix Penta, Infanrix hexa, COMVAX and Twinrix Junior (360/10), are thiomersal-free.
Transport, storage and handling
Dosage and administration Monovalent hepatitis B vaccines are white, slightly opalescent liquids. Any visible change in the product, such as an amorphous flocculent or a granular precipitate may indicate incorrect storage conditions. (i) Administer by deep IM injection. (ii) 3-dose regimen For children and young adults <20 years of age, a total of 3 doses of 0.5 mL of paediatric formulation is recommended. The optimal interval is 1 month between the first and second doses and a third dose 5 months after the second dose. The use of longer time intervals between doses does not impair the immunogenicity of hepatitis B vaccine, especially in adolescents and young children.13,14 The minimum interval between the second and third doses is 2 months. (iii) For adults ≥20 years of age, a full course of hepatitis B vaccine consists of 3 doses of 1 mL of adult formulation. There should be an interval of 1 to 2 months between the first and second doses with a third dose 2 to 5 months after the second dose (this schedule applies to both Engerix-B and H-B-VAX II). The minimum interval between the second and third doses is 2 months. This induces protective levels of neutralising antibody against hepatitis B virus in more than 90% of adults. The frequency of seroconversion increases progressively from approximately 35% after the first injection to more than 90% after the third injection. There is evidence of immunity (anti-HBs) in most vaccinated subjects after administration of 2 doses of the 3-dose vaccine regimen. However, the third dose is necessary to increase the percentage of responders and to provide long-term protection.
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3.6 Hepatitis B
Transport according to National Vaccine Storage Guidelines: Strive for 5.12 Store at +2°C to +8°C. Do not freeze.
(iv) Alternative 2-dose regimens A randomised controlled trial, involving 1026 adolescents, demonstrated that adolescents 11–15 years of age who received 2 doses of the adult formulation at 0 and 4–6 months, developed similar protective antibody levels to those vaccinated using the paediatric formulations in the standard 3-dose regimen administered at 0, 1 and 6–12 months.15 An open label comparative study in adults found increased compliance among those receiving a 2-dose schedule (86%) over those who completed the 3-dose schedule (18%). Antibody responses were found to be similar among the 2 groups.16 A 2-dose schedule used in the 11–15 years age group will improve compliance and provide comparable immunogenicity to that of a 3-dose paediatric schedule. Adolescents (11–15 years of age) can be vaccinated with H-B-VAX II 10 µg (adult formulation) or Engerix-B 20 µg (adult formulation) in a 2-dose regimen of 0 and 4–6 months (H-B-VAX II) or 0 and 6 months (Engerix-B). In older adolescents up to the age of 19 years, in whom compliance with a 3-dose paediatric dosing schedule is in doubt, a 2-dose schedule using an adult formulation may also be used in order to improve protection. When protection is required against both hepatitis A and hepatitis B in children 1–15 years of age, administration of Twinrix (720/20) in a 2-dose regimen at 0 and 6–12 months results in protective antibody levels for both hepatitis A and hepatitis B (see Table 3.6.1).
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Table 3.6.1: Hepatitis B and hepatitis A/hepatitis B combination vaccination schedules Vaccine
Age
Dose (HBsAg protein)
Volume
Schedule (mo=months)
Monovalent hepatitis B vaccines <20 years
10 µg
0.5 mL
0, 1, 6 mo (3-dose schedule)
Engerix-B (adult)
11–15 years
20 µg
1.0 mL
0, 6 mo (2-dose schedule)
Engerix-B (adult)
≥20 years
20 µg
1.0 mL
0, 1, 6 mo (3-dose schedule)
H-B-VAX II (paediatric)
<20 years
5 µg
0.5 mL
0, 1, 6 mo (3-dose schedule)
H-B-VAX II (adult) 11–15 years
10 µg
1.0 mL
0, 4–6 mo (2-dose schedule)
H-B-VAX II (adult) ≥20 years
10 µg
1.0 mL
0, 1, 6 mo (3-dose schedule)
H-B-VAX II (dialysis formulation)
40 µg
1.0 mL
0, 1, 6 mo (3-dose schedule)
≥20 years
Combination hepatitis A/B vaccines Twinrix (720/20)*
1– <16 years
20 µg
1.0 mL
0, 6–12 mo (2-dose schedule)
Twinrix Junior (360/10)
1– <16 years
10 µg
0.5 mL
0, 1, 6 mo (3-dose schedule)
Twinrix (720/20)
≥16 years
20 µg
1.0 mL
0, 1, 6 mo (3-dose schedule)
* This schedule should not be used for those who require prompt protection against hepatitis B; for example, if there is close contact with a known hepatitis B carrier.
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3.6 Hepatitis B
Engerix-B (paediatric)
(v) Accelerated schedule Engerix-B formulations (paediatric and adult) and Twinrix (720/20) are registered for use in accelerated schedules. Accelerated schedules should only be used if there is very limited time before departure to endemic regions (see Table 3.6.2). Table 3.6.2: Accelerated hepatitis B vaccination schedules* Vaccine
Age
Dose (HBsAg protein)
Volume
Schedule (mo=months)
Engerix-B (paediatric)
<20 years
10 µg
0.5 mL
0, 1, 2, 12 mo
Engerix-B (adult)
≥20 years
20 µg
1.0 mL
0, 1, 2, 12 mo or 0, 7, 21 days, 12 mo
Twinrix (720/20)
≥16 years
20 µg
1.0 mL
0, 7, 21 days, 12 mo
* As higher seroprotective rates are seen after the 0, 1, 2 month schedule, it is recommended that the 0, 7, 21 days schedule be used only in adults and only in exceptional circumstances. In both schedules, a booster dose at 12 months is recommended for long-term protection.
Recommendations (i) Infants and young children A birth dose of thiomersal-free monovalent hepatitis B vaccine, followed by doses given in combination vaccines (such as DTPa-hepB, DTPa-hepB-IPV, DTPa-hepB-IPV-Hib or Hib (PRP-OMP)-hepB) at 2, 4 and either 6 or 12 months, is recommended for all children. The rationale for the universal birth dose is not only to prevent vertical transmission from a carrier mother (recognising that there may be errors or delays in maternal testing, reporting, communication or appropriate response), but also to prevent horizontal transmission in the first months of life from a carrier among household or other close contacts.17 The birth dose should be given as soon as the baby is physiologically stable, and preferably within 24 hours of birth. Every effort should be made to administer the vaccine before discharge from the obstetric hospital. Extensive experience indicates that the birth dose of hepatitis B vaccine is very well tolerated by newborn infants. It does not interfere with either the establishment or maintenance of breastfeeding, and it is not associated with an increased risk of either fever or medical investigation for sepsis in the newborn.18-20 If an infant has missed the birth dose and is aged 8 days or older, a catchup schedule is not required. A primary course of a hepatitis B-containing
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combination vaccine should be given at 2, 4 and either 6 or 12 months of age (provided the mother is HBsAg negative). NB. All babies (preterm or term) of carrier mothers must be given a birth dose of hepatitis B vaccine and HBIG.
Management of infants born to hepatitis B carrier mothers
The first dose of monovalent hepatitis B vaccine should be given at the same time as HBIG, but in the opposite anterolateral thigh, as soon as possible – preferably within 24 hours of birth, and definitely within 7 days. This regimen results in seroconversion rates of more than 90% in neonates, despite concurrent administration of HBIG. If concurrent administration is not possible, vaccination should not be delayed beyond 7 days after birth as (providing it is given early) vaccine alone has been shown to be effective in preventing carriage.21 Three subsequent doses of a multivalent/combination vaccine should be given at 2, 4 and either 6 or 12 months of age (depending on the vaccine used), so that the infant is given a total of 4 doses of hepatitis B-containing vaccines.
Preterm babies Preterm babies do not respond as well to hepatitis B-containing vaccines as term babies.22-25 Thus, for babies at <32 weeks’ gestation or <2000 g birth weight, it is recommended to give vaccine at 0, 2, 4 and 6 months of age and either: (a) measure anti-HBs at 7 months of age and give a booster at 12 months of age if antibody titre is <10 mIU/mL, or (b) give a booster at 12 months of age without measuring the antibody titre.
(ii) Adolescents Vaccination of adolescents 10 to 13 years of age is recommended for all those in this age group who have not already received a primary course of hepatitis B vaccine. Please refer to your State/Territory health authority for further information (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
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3.6 Hepatitis B
Routine antenatal screening for HBsAg is essential for correct implementation of the strategy to prevent newborn infants from becoming infected with, and therefore carriers of, HBV. It also has benefits of enabling appropriate followup and management of a carrier, identification of the immune status of other household members, and protection of those who are susceptible to HBV infection. Infants born to HBsAg positive mothers should be given HBIG and a dose of thiomersal-free monovalent hepatitis B vaccine on the day of birth. The dose of HBIG is 100 IU to be given by IM injection. Administration of HBIG is preferable within 12 hours of birth, as its efficacy decreases markedly if administration is delayed beyond 48 hours after birth.
(iii) Adults for whom hepatitis B vaccination is recommended Note: the combined hepatitis A/hepatitis B vaccine should be considered for susceptible individuals in the groups marked with an asterisk (*). • Household contacts of acute and chronic hepatitis B carriers There is a low, but definite, risk of transmission from a person with acute or chronic hepatitis B. This can be reduced by avoiding contact with blood or other body fluids and not sharing household items which can penetrate skin (such as combs, nail brushes, toothbrushes and razors). The risk of contacts acquiring hepatitis B infection varies according to the HBeAg status of the carrier, and with cultural and socioeconomic factors. However, it should be recognised that in many situations, family members may have been exposed by the time the risk is recognised. Testing before planned vaccination is recommended for such families, as well as for members of families who have migrated from high prevalence countries. • Sexual contacts Susceptible (anti-HBc and anti-HBs negative) sexual partners of patients with acute hepatitis B should be offered post-exposure HBIG and hepatitis B vaccination; both should be initiated within 14 days of the last sexual contact. Susceptible partners of asymptomatic carriers should also be offered vaccination. Hepatitis B is relatively common in clients of sexual health services and vaccination should be offered to susceptible individuals at the time of first attendance. *Sexually active men who have sex with men should be vaccinated, unless they are already HBsAg positive or have serological evidence of immunity. The combined hepatitis A/hepatitis B vaccine may be appropriate for men who have sex with men, if they are not immune to either disease, as they are at increased risk of both. • Haemodialysis patients, HIV-positive individuals and other adults with impaired immunity Dialysis patients, HIV-positive individuals and other adults with impaired immunity should be given a larger than usual dose of hepatitis B vaccine. Adults should be given either (i) 1 mL of normal adult formulation in each arm on each occasion (double dose), or (ii) a single dose of dialysis formulation vaccine on each occasion, at 0, 1 and 6 months. HIV-positive children should receive 3 doses using an adult formulation. • *Injecting drug users Injecting drug users who have not been infected with hepatitis B should be vaccinated.
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• Recipients of certain blood products Screening of all blood donors for HBsAg has greatly decreased the incidence of transfusion-related hepatitis B virus infection. However, patients with clotting disorders who receive blood product concentrates have an elevated risk of hepatitis B virus infection, and should therefore be vaccinated. • *Individuals with chronic liver disease and/or hepatitis C Hepatitis B vaccination is recommended for those in this category who are seronegative for hepatitis B.26 • *Residents and staff of facilities for people with intellectual disabilities Vaccination of carers, staff and susceptible residents is recommended in both residential and non-residential care of people with intellectual disabilities. • Individuals adopting children from overseas
• *Liver transplant recipients If seronegative for hepatitis B, such individuals should be vaccinated before transplantation as they may be at increased risk of infection from the transplanted organ. • *Inmates and staff of long-term correctional facilities Inmates are at risk of hepatitis B because of the prevalence of homosexual intercourse, injecting drug use and amateur tattooing in some correctional facilities. Therefore, they should be screened upon incarceration, and vaccinated if susceptible. • Healthcare workers, ambulance personnel, dentists, embalmers, tattooists and body-piercers The risk to such workers differs considerably from setting to setting in different parts of Australia, but it is recommended that all staff directly involved in patient care,27 embalming, or in the handling of human blood or tissue, be vaccinated. In addition, standard precautions against exposure to blood or body fluids should be used as a matter of routine. • Others at risk • Police, members of the armed forces and emergency services staff should be vaccinated if they are assigned to duties which may involve exposure. • Funeral workers and other workers who have regular contact with human tissue, blood or body fluids and/or used needles or syringes. • People travelling to regions of intermediate or high endemicity, either long-term or for frequent short terms, should be vaccinated.
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These children should be tested for hepatitis B, and if they are HBsAg positive, members of the adoptive family should be vaccinated.
• Staff of child day-care centres will normally be at minimal risk of hepatitis B. If advice on risk is sought, the enquiry should be directed to the local public health authority. • Contact sports generally carry a low risk of hepatitis B infection. Vaccination is nevertheless encouraged. • As the risk in Australian schools is very low,28 vaccination of classroom contacts is seldom indicated. Nevertheless, vaccination of all children and adolescents should be encouraged. • Sex industry workers.
(iv) Serological confirmation of post-vaccination immunity Post-vaccination serological testing 4 to 8 weeks after completion of the primary course is recommended only for those in the following categories: • those at significant occupational risk (eg. healthcare workers whose work involves frequent exposure to blood and body fluids), • those at risk of severe or complicated disease (eg. people with impaired immunity, and individuals with pre-existing liver disease not related to hepatitis B), • those in whom a poor response to hepatitis B vaccination is expected (eg. haemodialysis patients), • sexual partners and household contacts of recently notified hepatitis B carriers.29 Anti-HBs and HBsAg levels should be measured in infants born to known HBsAg/HBeAg positive carrier mothers 3 to 12 months after completing the primary vaccine course. If anti-HBs levels are adequate and HBsAg is negative, then children are considered to be protected.29
(v) Non-responders to primary vaccination If adequate anti-HBs levels (≥10 mIU/mL) are not reached after the third dose, the possibility of HBsAg carriage should be investigated. Those who are HBsAg negative and do not respond should be offered further doses. These can be given as either a fourth double dose or a further 3 doses at monthly intervals, with further testing at least 4 weeks after the last dose. There is limited evidence from several trials that HBsAg negative healthcare workers, who are non-responders to a primary course of vaccination and subsequent intramuscular booster schedule, as above, may respond to 5µg of Engerix-B (0.25 mL of the adult formulation) administered intradermally at fortnightly intervals (up to 4 doses) with anti-HBs levels measured before each dose to assess for seroconversion.30-32 Persistent non-responders should be informed that they are not protected and should minimise exposures, and about the need for HBIG within 72 hours of parenteral exposure to HBV (see Table 3.6.3 Post-exposure prophylaxis for non-immune individuals exposed to an HBsAg positive person).
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Individuals who are at significant occupational risk who have a documented history of a primary course of hepatitis B vaccine, but it is not known whether they ever seroconverted, and they now have an antiHBs level <10 mIU/mL, should be given a single booster dose of vaccine and have their anti-HBs level checked 4 weeks later. If the anti-HBs level is <10 mIU/mL, regard the individual as a non-responder, give 2 further doses of hepatitis B vaccine at monthly intervals, and re-test for anti-HBs levels at least 4 weeks after the last dose.
(vi) Booster doses
(vii) Interchangeability of vaccines Although switching of brands is not recommended, in cases where the brand of vaccine used for previous doses is not known, any age-appropriate formulation may be used as there is no reason to believe that use of a different brand will compromise immunogenicity or safety.
(viii) Post-exposure prophylaxis for hepatitis B Following significant exposure (percutaneous, ocular, or mucous membrane) to blood or potentially blood-contaminated secretions, the source individual should be tested for HBsAg as soon as possible. If the person exposed has not been previously vaccinated against hepatitis B, his/her anti-HBs level and HBsAg should be determined immediately. If the person exposed is anti-HBs negative, and the source is either HBsAg positive, or cannot be identified and tested rapidly, administer a single dose of HBIG of 100 IU for children weighing up to 30 kg (about 5 years of age) and 400 IU for all others, within 72 hours. Also give hepatitis B vaccine (by IM injection into either the deltoid or anterolateral thigh, depending on age) as soon as possible, but within 7 days of exposure. Two further doses of vaccine should be given, 1 and 6 months after the first dose. For previously vaccinated people exposed to either an HBsAg positive source or a source whose hepatitis B status cannot be determined, post-exposure prophylaxis is not necessary if there was a documented protective response (antiHBs level ≥10 mIU/mL) at any time after vaccination. If the response to previous vaccination is unknown, the anti-HBs level should be determined as quickly as possible. If the anti-HBs level is <10 IU/mL and HBsAg is negative, HBIG and vaccine should be administered as above.
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Although vaccine-induced antibody levels decline with time and may become undetectable, booster doses are not recommended in immunocompetent individuals after a primary course, as there is good evidence that a completed primary course of hepatitis B vaccination provides long-lasting protection. This applies to children and adults, including healthcare workers and dentists.33-39 However, booster doses are recommended for individuals with impaired immunity, in particular those with either HIV infection or renal failure. The time for boosting in such individuals should be decided by regular monitoring of antiHBs levels at 6 to 12-monthly intervals.33
In most instances, it is advisable to offer a course of hepatitis B vaccine to a nonimmune healthcare worker sustaining a needle-stick injury or other potential hepatitis B exposure, since the injury or exposure itself is evidence that they work in an area with a significant risk of exposure. Table 3.6.3: Post-exposure prophylaxis for non-immune individuals exposed to an HBsAg positive person Type of exposure
Hepatitis B immunoglobulin
Vaccine
Perinatal (exposure of babies during and after birth)
100 IU by IM injection
Single dose within 12 hours of birth, preferably immediately after birth
0.5 mL by IM injection
Immediately after birth (preferably within 24 hours, no later than 7 days*) then at 2, 4, and either 6 or 12 months of age
Percutaneous/ ocular or mucous membrane
400 IU by IM injection
Single dose within 72 hours
0.5 mL or 1 mL by IM injection depending on age
Within 7 days* and at 1 and 6 months after first dose
Sexual
400 IU by IM injection
100 IU if body weight <30 kg
Single dose 0.5 mL or 1mL within 14 days by IM injection of sexual contact depending on age
Within 14 days* and at 1 and 6 months after first dose
* The first dose can be given at the same time as HBIG, but should be administered at a separate site.
Contraindications The only absolute contraindications to hepatitis B vaccine are: • anaphylaxis following a previous dose of hepatitis B vaccine, or • anaphylaxis following any component of the vaccine.
Adverse events • Adverse events after hepatitis B vaccination are transient and minor, and include soreness at the injection site (5%, common), fever (usually low grade, 2–3%, common), nausea, dizziness, malaise, myalgia and arthralgia. Fever can be expected in neonates immunised with hepatitis B vaccine (0.6–3.7%, common). • Anaphylaxis has been reported very rarely in adults. Although various adverse events such as demyelinating diseases, Guillain-Barré syndrome and arthritis have been reported, there is no evidence of a causal relationship with hepatitis B vaccination.40,41 There have been a few reports of generalised
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febrile reactions attributed to yeast allergy, and exceptional instances of polyarteritis nodosa have been reported. • The World Health Organization Global Advisory Committee on Vaccine Safety states that “multiple studies and review panels have concluded that there is no link between MS [multiple sclerosis] and hepatitis B vaccination”.42 • The vaccine produces neither therapeutic effects nor adverse events in hepatitis B virus carriers. It is safe in those already immune to hepatitis B.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
The product information for both Infanrix hexa and Infanrix Penta states that these vaccines may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 month of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age.
Hepatitis B immunoglobulin (HBIG) Hepatitis B immunoglobulin (HBIG) is prepared from plasma donated through routine blood bank collection. Samples are selected on the basis that they contain high levels of antibody to HBsAg. As stocks of HBIG are very limited, use should be strictly reserved for those who are at high risk, such as babies born to hepatitis B carrier mothers and healthcare workers who are exposed to the blood of HbsAg positive individuals through occupational exposure. Requests should be directed to the Australian Red Cross Blood Service in your State/Territory (see Chapter 3.8, Immunoglobulin preparations ‘Availability of immunoglobulins’). HBIG is given by IM injection. • Hepatitis B Immunoglobulin-VF – CSL Bioplasma (160 mg/mL immunoglobulin (IgG) prepared from human plasma containing high levels of antibody to surface antigen of the hepatitis B virus). 100 IU and 400 IU ampoules, with the actual volume stated on the label on the vial.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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Variations from product information
3.7 Human papillomavirus Virology and HPV classification Human papillomaviruses (HPVs) are small, non-enveloped viruses that have circular double-stranded DNA. HPVs infect and replicate within cutaneous and mucosal epithelial tissues, most commonly involving the skin or anogenital tract. HPVs are designated as specific types according to sequence variation in the major genes. There are 40 distinct HPV genotypes that affect the genital tract; of these, 15 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) are designated as ‘high-risk’ as they are causally associated with the development of cervical cancer. HPV genotypes 16 and 18 are the causative agents in 70 to 80% of all cervical cancers. HPV genotypes 6 and 11 are among the HPV genotypes designated as ‘low-risk’ (for cancer), and are associated with 90% of genital warts and 100% of recurrent respiratory papillomatosis (RRP) cases.1,2 High-risk genital HPV genotypes are associated with a spectrum of other anogenital diseases, including vulval, vaginal, penile and anal cancers, and their precursors. In addition, genital HPV genotypes are associated with extragenital diseases, including some squamous cell carcinomas of the head and neck (highrisk HPV types) and recurrent respiratory papillomatosis (HPV types 6 and 11). Persistent HPV infection is a necessary precursor of cervical cancer, but is not sufficient in itself to cause the disease.3 For pre-cancerous lesions to form and progress to cancer, the crucial event appears to be HPV DNA integration into the host cell genome, which interferes with the expression and regulation of proteins responsible for normal cell growth and repair.4 Malignancy due to build-up of sufficient mutations for cellular transformation usually requires 10 to 20 years, but has been reported to occur in under 2 years.5
Clinical features HPV infection is often subclinical but, dependent upon the infecting HPV genotype, may result in lesions that include cutaneous warts, genital warts, cervical and other anogenital tract dysplasias and cancers, and respiratory papillomatosis. Most genital HPV infections are cleared (no longer detectable) within 12 to 24 months (the median duration for high-risk genotypes is 7 to 10 months).6-9 In a minority of infections, estimated at 3 to 10%, the virus persists.10
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Epidemiology HPV infection Transmission of HPV occurs through contact with infected skin or mucosal surfaces, primarily via sexual contact for the genital HPV genotypes. Transmission may rarely occur by other mechanisms, such as laryngeal infection of infants during birth.11 There is a high probability of transmission following sexual exposure to a person with a productive HPV infection, estimated to be 50 to 80%, after unprotected sexual intercourse.12-14 However, sexually active adolescents and young adults may remain naïve to all 4 vaccine HPV genotypes or be infected with a non-vaccine HPV genotype. HPV infection rates vary greatly between geographic regions, but it is estimated that up to 79% of women worldwide will be infected with at least one genital type of HPV at some point in their lives.15,16 HPV infection rates are highest among young women, usually peaking soon after the age when most young women become sexually active.17 Australian data show that, among women currently aged 16–19 years, the median age of first intercourse is 16 years.18
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Although comprehensive risk-prediction models for HPV exposure are not available, an increasing number of lifetime sex partners is consistently found to be associated with HPV acquisition.19-24 A US population-based study of women aged 18–25 years found genital HPV infection in 14.3% of women with one lifetime sex partner, 22.3% with 2 lifetime sex partners, and 31.5% with more than 3 lifetime partners.25 Australian women aged 16–19 years report a median number of 2 lifetime sexual partners, women aged 20–29 years a median of 4.3 lifetime sexual partners, and those aged 30–39 years a median of 4.7 lifetime sexual partners.26 Although its sensitivity is somewhat limited, HPV seroprevalence measured using serum anti-HPV antibody levels can be used to estimate cumulative lifetime exposure to specific types of HPV infection.27 In a study of women in Finland, Dillner et al (1996) described a linear increase in the risk of HPV16 seropositivity of 4% for every additional sex partner, ranging from 4% for 1 lifetime partner to 35% among those with 6 or more partners.24 Similarly, HPV18 seroprevalence was observed to increase linearly at the rate of 3% per partner from 4% for 1 lifetime partner up to 24% for 6 or more partners. In the US, population data indicate that 25% of women aged 20–29 years are seropositive for HPV16.28 An increasing number of sexual contacts on the part of their male partner is also associated with HPV acquisition in women.29
Cervical abnormalities Cervical infection with HPV causes a range of pathological responses depending on the genotype of HPV. These range from no reaction, carriage of HPV without cytological changes, to a variety of cellular changes in the cervix. Histologically, the cervical abnormalities have been referred to as cervical intraepithelial neoplasia (CIN), with 3 grades of severity: CIN1 (mild dysplasia), CIN2 (moderate dysplasia) and CIN3 (severe dysplasia/carcinoma in situ). CIN3 and AIS (adenocarcinoma in situ) are immediate precursors of cervical cancer. CIN2 represents a mix of low-grade and high-grade lesions (and hence it is treated as a high-grade lesion). Cytologically, under the Australian Modified Bethesda System, the term Low-grade Squamous Intraepithelial Lesion (LSIL) encompasses changes thought to be due to HPV and mild dysplasia, and the term High-grade Squamous Intraepithelial Lesion (HSIL) encompasses the former categories of moderate dysplasia, severe dysplasia and carcinoma in situ. Guidelines for the interpretation and treatment of screen-detected cervical abnormalities are published by the NHMRC.12 Every year in Australia, approximately 90 000 women have an LSIL detected and 15 000 women have an HSIL detected through Pap screening.12 The incidence of both lesions peaks in women aged 20–24 years. In addition, there are approximately 20 000 hospital admissions per year for cervical dysplasia and carcinoma in situ. This is an underestimate of the burden of disease, as the investigation and management of cervical lesions are mostly carried out as outpatient procedures, either in the private or public sector. For procedures in the private sector, Medicare has processed, over the past 10 years, claims for an average of approximately 104 000 examinations of the lower genital tract by colposcopy and 14 600 combined colposcopy procedures per year. As well as physical side effects and complications from treatment for cervical abnormalities, there is consistent evidence that receipt of an abnormal Pap smear result, and the subsequent investigation and management, is associated with a considerable psychosocial burden.30-35 It was originally thought that there was an inevitable progression from lowgrade abnormalities to high-grade abnormalities to cervical cancer. It is now recognised that LSIL cytology is a manifestation of acute HPV infection, and that most LSIL regresses over time.12 The absolute risk of cancer associated with a high-grade abnormality is difficult to determine from available observational data, but is estimated at less than 1% per year.36 Figure 3.7.1 summarises the dynamic relationship between HPV infection and cervical health.
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Figure 3.7.1: The dynamic relationship between HPV infection and cervical health
Cervical cancer Cancer of the uterine cervix is the second most common cause of cancer among women worldwide.37 However, Australia has one of the lowest mortality rates from cervical cancer in the world.38 In 2002, the age standardised incidence rate in Australia was 6.8 per 100 000 and, in 2004, the mortality rate was 1.9 per 100 000, with an estimated 750 cases, 1800 hospitalisations and 250 deaths each year from cervical cancer.39 This low incidence can be attributed to the success of the National Cervical Screening Program, with cervical cancer in Australia now occurring predominantly in unscreened or under-screened women. The largest decline in cervical cancers has been observed for those of squamous origin, with the incidence of adenocarcinomas being essentially unchanged. This has been attributed to sampling difficulties in obtaining cells from the area where adenocarcinoma arises, problems in pathological interpretation, and variations in clinical investigation and treatment.12
Other anogenital cancers High-risk HPV types (predominantly types 16 and 18) are also implicated in 50 to 90% of other anogenital cancers in both women and men, including cancers of the vulva, vagina, anus, and penis, although these types have almost no role in
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(Figure courtesy of the Australian Government Department of Health and Ageing.)
causing non-malignant lesions (see below). In Australia in 2001, there were 252 vulvar cancers (2.6 per 100 000), 62 vaginal cancers (0.6 per 100 000) and 225 anal cancers (1.2 per 100 000) diagnosed.40
Non-malignant lesions Genital warts are a common manifestation of HPV type 6 and 11 infection. Genital warts can cause significant psychological morbidity. In Australia, 4.0% of men and 4.4% of women aged 16–59 years report ever being diagnosed with genital warts.41 These prevalence estimates translate into approximately 36 000 cases in Australia. The cumulative lifetime risk of genital warts has been estimated at 10%.42,43 Peak attack rates occur in young women aged 15–24 years.44 An analysis of data from the BEACH cross-sectional survey of national GP activity found that, between April 2000 and March 2003, consultations for genital warts in women aged 12–49 years occurred at a rate of 0.17 per 100 encounters.45 Severe morbidity from genital warts, as measured by hospitalisation, is uncommon and peaks in women 20–24 years of age (26 per 100 000) (AIHW National Hospital Morbidity Database 2006). Morbidity not causing hospitalisation includes recurrence and a range of local complications. Worldwide, the best epidemiological data on genital wart incidence comes from the United Kingdom.2 Exposure to HPV types 6 and 11 at birth can also cause recurrent respiratory papillomatosis in children. This relatively rare disease, with an estimated incidence of 4 per 100 000 children,46,47 is characterised by repeated growth of warts in the respiratory tract requiring repeated surgery. Adults can also develop recurrent respiratory papillomatosis.
Type-specific HPV epidemiology Worldwide, approximately 50% of cervical cancers contain HPV16 DNA and 16% contain HPV18 DNA.48,49 Among cervical adenocarcinomas, 70% contain HPV 16 or 18 DNA, with HPV18 being relatively more common (37.7%) than HPV16 (31.3%).48 HPV16 has been detected in 48% of HSILs, 19% of LSILs and 2% of cytologically normal women. HPV18 has been detected in 7% of HSILs, 6% of LSILs and 0.7% of cytologically normal women.50-52 The low-risk HPV types 6 and 11 have been detected in 6.2% and 3.2% of LSILs respectively and each type in 0.1% of cytologically normal women.51,52 Australian studies indicate that the 5 most frequent HPV genotypes identified in 553 cervical cancers were HPV16 (60%), HPV18 (20%), HPV45 (5%), and HPV39 and HPV73 (2.3% each).53-57 Best available Australian data indicate that HPV16 and HPV18 are, respectively, responsible for approximately 60%/20% of cervical cancers and 37%/8% of high-grade cervical abnormalities.53,54
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Vaccines HPV vaccines have been developed using recombinant DNA technology based on virus-like particles (VLPs), which are not infectious and do not have any cancer-causing potential. There are 2 HPV vaccines registered for use in Australia. The bivalent vaccine, 2vHPV vaccine (CERVARIX), contains VLPs of HPV genotypes 16 and 18, and is administered as a 3-dose schedule at 0, 1 and 6 months. The quadrivalent vaccine, 4vHPV vaccine (GARDASIL), is administered at 0, 2 and 6 months and contains VLPs of HPV genotypes 16, 18, 6 and 11. • CERVARIX – GlaxoSmithKline (human papillomavirus vaccine – recombinant protein particulate (VLP) vaccine containing the major capsid (L1) protein of HPV types 16 and 18). Each 0.5 mL monodose pre-filled syringe or vial contains 20 µg each of HPV types 16 and 18 adjuvanted with AS04 (AS04 is comprised of 500 µg aluminium hydroxide and 50 µg of 3-O-desacyl-4’-monophosphoryl lipid A [MPL]); 4.4 mg sodium chloride; 624 µg sodium dihydrogen phosphate dihydrate.
It is important to note that HPV vaccines are prophylactic vaccines (ie. designed to prevent initial HPV infection). In women who are already infected with HPV types covered by the vaccines before vaccination (ie. HPV DNA positive), the vaccines do not treat infection or prevent disease caused by that type.58 In women HPV DNA negative and HPV seronegative for relevant types, both vaccines are highly effective at preventing persistent type-specific infection and related cervical disease (~90–100%).59-62 The 4vHPV vaccine also has established efficacy against external genital lesions (warts, and vulval and vaginal dysplasias) in women. Vaccine efficacy against external genital lesions related to HPV 6, 11, 16 or 18 in women who were naïve to vaccine types at the beginning of the trials and who received 3 doses was 99% (95% CI: 95–100%). Compared to HPV DNA negative and HPV seronegative women, vaccine efficacy (VE) in women who received vaccine regardless of HPV status at baseline and may, therefore, have had previous infection, was much lower. Against HPV16/18-related CIN2/3 or worse, VE was 44% (95% CI: 31–55%) at a mean of 3 years follow-up63 and against high-grade CIN caused by any HPV type it
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• GARDASIL – CSL Biotherapies/Merck & Co Inc (human papillomavirus vaccine – recombinant protein particulate (VLP) vaccine containing the major capsid (L1) protein of HPV types 6, 11, 16 and 18). Each 0.5 mL monodose pre-filled syringe or vial contains 20, 40, 40 and 20 µg of HPV types 6, 11, 16 and 18, respectively, adsorbed onto 225 µg aluminium hydroxyphosphate sulphate; 9.65 mg of sodium chloride; 780 µg of L-histidine; 50 µg of polysorbate 80; 35 µg of sodium borate. May also contain yeast proteins.
was 18% (95% CI: 7–29%).63 However, vaccine efficacy is expected to be higher over a longer duration of follow-up, as the proportion of disease due to incident infection (where vaccination has an effect) increases compared to the proportion of disease due to infection/disease at baseline (which is not affected by the vaccine). These data reflect the reduced impact of vaccinating women in whom a proportion will already have been infected with HPV, eg. older women who are/ have been sexually active. Vaccine efficacy estimates in populations including women already infected with HPV at baseline have not yet been published for 2vHPV vaccine, but a similarly reduced impact, compared with an HPV naïve population, can be anticipated. It is possible that HPV vaccines may provide some protective efficacy against disease due to types closely related to types 16 and 18, in particular HPV31 and HPV45, but published data supporting this hypothesis are currently limited to infection endpoints only and are imprecise.60,64-66 When given as a 3-dose series, HPV vaccines elicit neutralising antibody titres many times higher than those observed following natural infection.67-69 Antibody responses peak at month 7 (1 month after dose 3) at titres between 7 and 150 times greater than following natural infection, depending upon the HPV type and vaccine.59,62,70,71 Following an initial decline, they appear to plateau at 18 to 24 months, remaining stable for at least 5 years at levels above or at least equivalent to those seen following natural infection.58,60,62,70 It should be noted that there is no standard serological assay for detecting HPV antibodies and no protective titre has been established. Therefore, absolute titres achieved (as reported in the randomised trials) are not directly comparable between 2vHPV and 4vHPV vaccines. Similarly, differences in methodologies and the populations examined make direct comparisons of published 4vHPV and 2vHPV vaccine efficacy estimates difficult. Overall, seroconversion occurs in 99 to 100% of those vaccinated.58,60,61 The duration of immunity after vaccination is not yet known (but is of at least 5 years’ duration); hence, it is possible that booster doses may be required in the future.58,60,62 There are currently no clinical efficacy data available in males or in pre-adolescent females (as collection of genital specimens is not appropriate). Antibody response to both 4vHPV and 2vHPV vaccination has been evaluated in pre-adolescent and adolescent females (9–15 years of age and 10–14 years of age, respectively). In males, antibody response has only been studied for 4vHPV, and only in the age group 9–15 years, through immunological bridging studies.72,73 Young males and females administered 4vHPV vaccine and females aged 10–14 years administered 2vHPV vaccine produce antibody responses that are at least 2-fold higher compared to women in whom clinical efficacy has been demonstrated. The peak antibody levels achieved following vaccination decrease with age. Immunobridging studies for older women (aged >26 – ≤45 years) administered the 2vHPV demonstrate antibody titres in a comparable range to women in the 15–25 year age group who are in the plateau phase of long-term follow-up.
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These data were current at the time of publishing The Australian Immunisation Handbook.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.74 Store at +2°C to +8°C. Do not freeze. Protect from light.
Dosage and administration The dose of 2vHPV vaccine is 0.5 mL administered by IM injection. The recommended schedule is 0, 1 and 6 months. The second dose of 2vHPV can be administered between 1 and 2.5 months after the first dose. The dose of 4vHPV vaccine is 0.5 mL administered by IM injection. The recommended schedule is 0, 2 and 6 months. In clinical studies, efficacy for 4vHPV vaccine has been demonstrated in individuals who have received all 3 doses within a 1 year period. Where flexibility in the recommended dosing schedule is unavoidable, the second dose should be administered at least 1 month after the first dose and the third dose should be administered at least 3 months after the second. There is no need to repeat earlier doses. Give missing dose(s) as soon as is practicable, making efforts to complete doses within 12 months.
There are no clinical data regarding concomitant administration of either 2vHPV or 4vHPV vaccine with adolescent/adult formulation dTpa or varicella vaccine, but there is no reason to expect any adverse outcomes if they are given simultaneously, using different injection sites.
Recommendations Both vaccines are recommended to provide protection against oncogenic HPV type 16 and/or 18 cervical disease. If protection against genital warts is desired, the 4vHPV vaccine provides protection against HPV types 6 and 11, which are associated with more than 90% of these lesions.67 (See also ‘Vaccines’ above.)
(i) Females aged 10–13 years (Safety-Grade B)(Efficacyno data)(Immunogenicity-Grade B)67 HPV vaccine is recommended for females 10–13 years of age. Currently only the 4vHPV vaccine is on the NIP schedule for females aged 12–13 years. Please refer to your State/Territory health authority for further information (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
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4vHPV vaccine has been administered concomitantly with hepatitis B vaccine in clinical trials, with no reduction in immunogenicity of either vaccine observed.
(ii) Females aged 14–18 years (Safety-Grade B)(EfficacyGrade B)(Immunogenicity-Grade B)67 HPV vaccine is also recommended for females 14–18 years of age. While some females in this age group will already have commenced sexual activity, the majority will not yet be infected with a HPV vaccine type.
(iii) Females aged 19–26 years (Safety-Grade A)(EfficacyGrade A)(Immunogenicity-Grade A)67 HPV vaccine is also recommended for females 19–26 years of age. In females in this age group who have never had sexual intercourse the vaccine efficacy will be comparable to younger women, and HPV vaccination is recommended. In sexually active females 19–26 years of age, the overall benefit from HPV vaccination is likely to be less; however, past or current infection with all HPV types covered by the vaccine is unlikely. NB. The absolute benefit of HPV vaccine to an individual sexually active woman cannot be determined clinically, as appropriate tests to detect both previous and current HPV infection with vaccine types are not available. In all sexually active women, the most important preventive intervention against cervical disease remains regular Pap screening. Vaccination is not an alternative to Pap screening but is complementary. The National Cervical Screening Program recommends routine screening with Pap smears every 2 years for all women between the ages of 18 (or 2 years after first sexual intercourse, if later) and 69 years.
(iv) Females aged ≥27 years (Safety 2vHPV vaccine-Grade B; 4vHPV vaccine-no data)(Efficacy-no data)(Immunogenicity 2vHPV-Grade B; 4vHPV-no data)67 2vHPV vaccine is registered for use in females 27–≤45 years of age on the basis of safety and bridging immunogenicity data. The extent of benefit that can be expected to be derived from the use of HPV vaccine in this age group will depend upon past sexual history and the likelihood of new sexual partners in the future (ie. an assessment of likely past and future HPV exposure) and the sexual behaviour of her male partner(s). HPV-related cervical infection and Pap test abnormalities peak in women aged <30 years in Australia. 4vHPV vaccine is not registered for use in females over the age of 27 years as there are no safety or efficacy data to support its use in this age group. In all sexually active women, the most important preventive intervention against cervical disease remains regular Pap screening. Vaccination is not an alternative to Pap screening but is complementary. The National Cervical Screening Program recommends routine screening with Pap smears every 2 years for all women between the ages of 18 (or 2 years after first sexual intercourse, if later) and 69 years.
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For women who have recently been diagnosed with cervical dysplasia, or have been treated for this in the past, HPV vaccine will have no impact on current disease, but may prevent future dysplasia due to a different HPV vaccine type.
(v) Males [For males aged 9–15 years (Safety 4 vHPV vaccineGrade B; 2vHPV vaccine-no data)(Efficacy-no data)(Immunogenicity 4vHPV vaccine-Grade B; 2vHPV vaccine-no data)]67 4vHPV vaccine is licensed for use in males aged 9–15 years. 4vHPV vaccine produces high antibody titres in pre-adolescent and adolescent males but it is not known whether vaccination of males can either prevent transmission of HPV or provide protection against genital HPV infection, genital warts, anogenital dysplasia or anogenital cancers. 2vHPV vaccine is not registered for use in males. There is no recommendation for vaccination of males at this time due to the lack of clinical efficacy data.
Contraindications The only absolute contraindications to HPV vaccine are: • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis to any vaccine component. The 4vHPV vaccine may contain minute amounts of yeast proteins.
Precautions There are limited clinical trial data available for this group. However, as HPV vaccines are not live vaccines, they can be administered to women who are immunosuppressed as a result of disease or medications. The immune response and vaccine efficacy might be less than in individuals who are immunocompetent (see Chapter 2.3, Subsection 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment).
Adverse events Both the 2vHPV and 4vHPV vaccines are generally safe and well tolerated. A variety of comparators were used in clinical trials of 2vHPV and 4vHPV, but data comparing vaccine adverse events with an aluminium-containing placebo are available for both vaccines and are quoted below for common local adverse reactions. More detailed information about adverse events occurring in the vaccine trials is available from the product information for 2vHPV vaccine and from the US FDA for 4vHPV.75 In clinical trials of the 2vHPV vaccine, the most commonly reported adverse events were injection site pain 78%, swelling ~26% and erythema ~30% compared to ~53%, ~8% and 11% in the aluminium hydroxide placebo group. Incidence of injection site pain decreased across the 3 doses, whereas there was
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People with impaired immunity
a slight increase in the reported proportion with swelling and erythema after successive doses. In clinical trials of the 4vHPV vaccine the most commonly reported adverse events were injection site pain ~81%, swelling ~24% and erythema ~24%, compared to ~75%, ~16% and ~18% in the aluminium-containing placebo group. The incidence of injection site pain was approximately equal across the 3 doses, whereas there was a modest increase in the reported proportion with swelling and erythema after successive doses. HPV vaccines are well tolerated by those who have already been exposed to the HPV types included in the vaccine.
Use in pregnancy HPV vaccine should not be given during pregnancy (see Chapter 2.3, Subsection 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants). It should be noted that there is no evidence from animal studies, or among HPV vaccine trial participants who inadvertently became pregnant, of teratogenicity or of adverse fetal outcomes and, therefore, HPV vaccination during pregnancy is not an indication for termination. Where vaccine has inadvertently been administered during pregnancy, further doses should be deferred until after delivery.
Use during lactation HPV vaccine may be given while lactating (see Chapter 2.3, Subsection 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants). In trials, 995 nursing mothers received 4vHPV vaccine or placebo, and no relation between vaccination and adverse events was observed. The effect on breastfed infants of the administration of 2vHPV vaccine to their mothers has not been evaluated in clinical studies. It is not known whether HPV vaccine antigens or HPV antibodies are excreted in human milk.
Variations from product information None.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.8 Immunoglobulin preparations Introduction Passive immunity can be provided by administration of human immunoglobulin.1-3 The protection afforded is immediate, but is transient and lasts for only a few weeks, as the half-life of IgG, the major constituent, is between 3 and 4 weeks. There are 2 types of immunoglobulin, normal and specific. It is important to recognise that separate immunoglobulin preparations are provided for intramuscular (IM) use and for intravenous (IV) use. These have different properties, and the preparations should be given only by the recommended route. Administration of IM immunoglobulin by the IV route will lead to severe reactions.
• Normal human immunoglobulin (NHIG) This is derived from the pooled plasma of blood donors. It contains antibody to microbial agents which are prevalent in the general population.
• Specific immunoglobulins Specific immunoglobulin preparations are obtained from pooled blood donations from patients convalescing from the relevant infection, donors recently vaccinated with the relevant vaccine, or those who, on screening, have been found to have sufficiently high antibody concentrations. These blood-derived specific immunoglobulins therefore contain concentrations of antibody to an individual organism or toxin at a higher titre than would be present in normal immunoglobulin.
Potential interaction with vaccines Live attenuated virus vaccines • Immunoglobulin preparations can interfere with the response to live attenuated virus vaccines by preventing vaccine strain viral replication after vaccine administration. Therefore, administration of live attenuated virus vaccines, such as measles and varicella vaccines, should be deferred for at
Immunoglobulin preparations 175
3.8 Immunoglobulin preparations
Donors of blood used for the production of NHIG and specific immunoglobulin products are screened and products treated to minimise the risk of the immunoglobulin preparations containing HIV, hepatitis A, hepatitis B or hepatitis C viruses, or parvovirus. Two dedicated pathogen inactivation steps are incorporated into the manufacturing process. A pasteurisation step is usually used during manufacture. The risk of prion transmission remains theoretical.
least 3 months after the IM administration of NHIG, and for at least 9 months after the administration of NHIG (intravenous).4 For the same reason, administration of immunoglobulin products should be deferred if possible until at least 2 weeks after a vaccine has been given, unless it is essential that immunoglobulin be given. However, Rh (D) immunoglobulin (anti-D) does not interfere with the antibody response to MMR vaccines and the two may be given at the same time in different sites with separate syringes or at any time in relation to each other (see Chapter 2.3, Groups with special vaccination requirements, Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination).
Inactivated vaccines • Inactivated vaccines such as tetanus, hepatitis B or rabies may be administered concurrently with immunoglobulin preparations, or at any time after, using separate syringes and separate injection sites to induce passive/ active immunity. This usually would occur when there has been actual or possible acute exposure.
Availability of immunoglobulins CSL Bioplasma supplies NHIG for IM use. Rabies immunoglobulin can be obtained only upon application from State/Territory health authorities. Respiratory syncytial virus (RSV) monoclonal antibody (Synagis; Abbott Australia) is available commercially. The specific immunoglobulins and the CSL Bioplasma NHIG for IV use, which are derived from Australian donated plasma, can be obtained only from the Australian Red Cross Blood Service (ARCBS) with permission from a ARCBS medical officer. The Red Cross Blood Service can be contacted by telephone (ACT 02 6206 6006; NSW 02 9229 4444; NT 08 8927 7855; QLD 07 3835 1333; SA 08 8422 1200; TAS 03 6230 6230; VIC 03 9694 0111; WA 08 9325 3333). The Australian Red Cross Blood Service supplies these products free of charge.
Transport, storage and handling All immunoglobulins must be protected from light and stored at +2°C to +8°C. Do not freeze.
Normal human immunoglobulin (NHIG) – intramuscular use NHIG is prepared by plasma fractionation of blood collected from volunteer donors by the Australian Red Cross Blood Service. It is a sterile solution of immunoglobulin, mainly IgG, and contains those antibodies commonly present in adult human blood. In Australia, NHIG is supplied as a 16% solution, in the United States as a 16.5% solution, and in the United Kingdom as a 10% solution.
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• Normal Immunoglobulin-VF (human) (NHIG) – CSL Bioplasma. A sterile preservative-free solution of immunoglobulin G (IgG) 160 mg/mL prepared from Australian blood donations and made available through the Australian Red Cross Blood Service. It is supplied in 2 mL and 5 mL vials for IM injection.
Administration NHIG should be given by deep IM injection using a large (19 or 20) gauge needle. The NHIG should be introduced slowly into the muscle, to reduce pain. This product should not be administered intravenously because of possible severe adverse events, and hence an attempt to draw back on the syringe after IM insertion of the needle should be made in order to ensure that the needle is not in a small vessel. A special product for IV use (NHIG (intravenous)) has been developed for patients requiring large doses of immunoglobulin.
Recommendations Immunoglobulin preparations may be given to susceptible individuals as either pre-exposure or post-exposure prophylaxis against specific infections. Normal pooled immunoglobulin contains sufficiently high antibody concentrations to be effective against hepatitis A and measles. The duration of effect of NHIG is dose-related. It is estimated that protection is maintained for 3 to 4 weeks with standard recommended doses of NHIG.
(i) Prevention of hepatitis A (see also Chapter 3.5, Hepatitis A) NHIG contains sufficiently high levels of antibody against hepatitis A to be able to prevent or ameliorate infection in susceptible individuals,5 if administered within 2 weeks of exposure.6 Because the hepatitis A vaccine is readily available, there is no place for the routine use of NHIG to prevent hepatitis A in travellers. It should be given (at the same time as a dose of hepatitis A vaccine) only to those, such as nonimmune aid-workers to be deployed within 2 weeks, who will be living in very inadequate circumstances.7,8
(ii) Prevention of hepatitis B
(iii) Prevention of measles (see also Chapter 3.11, Measles) NHIG contains a sufficiently high concentration of antibody against measles to be able to prevent or ameliorate infection in susceptible individuals. NHIG should be given as soon as possible and within 7 days of exposure. Passive protection against measles particularly may be required if the exposed individual has an underlying immunological disorder (HIV/AIDS, immunosuppressive
Immunoglobulin preparations 177
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See Chapter 3.6, Hepatitis B, under ‘Management of infants born to hepatitis B carrier mothers’ and ‘Post-exposure prophylaxis for hepatitis B’.
therapy), or to control an outbreak of measles among non-immunised individuals, eg. in a childcare centre. The use of NHIG should be considered in HIV-positive individuals exposed to a patient with measles.
(iv) Prevention of varicella (see also Chapter 3.24, Varicella) Zoster immunoglobulin (ZIG) is able to prevent or ameliorate varicella in infants <1 month of age, in children who are being treated with immunosuppressive therapy, and in pregnant women.9,10 ZIG should be given as soon as possible, and preferably within 96 hours, after exposure. ZIG is recommended for non-immune HIV-positive individuals up to 7 days after exposure to clinical cases of either varicella or zoster. If ZIG is unavailable, large doses of NHIG can be given intramuscularly. This does not necessarily prevent varicella, but it lessens the severity of the disease. The dose of NHIG is 0.4–1.0 mL per kg body weight given by the IM route.
(v) Immune deficiency Patients with abnormal antibody production (primary hypogammaglobulinaemia, multiple myeloma, chronic lymphoblastic leukaemia) are usually treated with the IV preparation of normal human immunoglobulin (NHIG (intravenous)).2 However, in some cases, NHIG is given by IM injection in a dose of 400–600 mg/ kg (0.4–0.6 g/kg) every 2 to 4 weeks. The aim of therapy is to maintain serum IgG levels above 6 g/L. Some patients may receive the IM (160 mg/mL) preparation subcutaneously. NB. Skin tests with NHIG should not be undertaken. The intradermal injection of concentrated immunoglobulin causes a localised area of inflammation which can be misinterpreted as a positive allergic reaction. True allergic responses to NHIG given by IM injection are extremely rare.
Contraindications Hypersensitivity reactions occur rarely but may be more common in patients receiving repeated injections. It is recommended that NHIG should not be given to individuals with absolute IgA deficiency, as the small amounts of IgA in NHIG could theoretically lead to the development of anti-IgA antibodies in these individuals. NHIG should not be administered to individuals who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
Adverse events and precautions Local tenderness, erythema and muscle stiffness at the site of injection sometimes occurs and may persist for several hours after injection. Systemic adverse events such as mild pyrexia, malaise, drowsiness, urticaria and angioedema may occur occasionally. Skin lesions, headache, dizziness, nausea, general hypersensitivity reactions and convulsions may occur rarely.
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Anaphylaxis following an injection of NHIG is very rare, but has been reported. Anaphylaxis is more likely to occur if NHIG for IM use is inadvertently given intravenously.
Normal human immunoglobulin (NHIG) – intravenous use Normal human immunoglobulin (intravenous) is usually abbreviated as NHIG (intravenous). • Intragam P – CSL Bioplasma. A sterile preservative-free solution of immunoglobulin G (IgG) 60 mg/mL prepared from Australian blood donations and made available through the Australian Red Cross Blood Service. Intragam P contains only trace amounts of IgA, and the final solution contains 100 mg/mL maltose. It is supplied as 3 g in 50 mL and 12 g in 200 mL bottles (for intravenous use). • Sandoglobulin NF liquid – CSL Bioplasma (sterile preservative-free solution of immunoglobulin G (IgG), 120 mg/mL). It is supplied as 6 g in 50 mL and 12 g in 100 mL bottles (for intravenous use). A sterile lyophilised preparation for reconstitution, containing human gammaglobulin. The product is reconstituted with sodium chloride 0.9% solution to a sterile 3% or 6% solution. Available in 6 g vials (for intravenous use). • Octagam – Octapharma. A sterile preservative-free solution of immunoglobulin G (IgG) 50 mg/mL prepared from multiple blood donors. It is supplied as 1 g in 20 mL vials, and as bottles of 2.5 g in 50 mL, 5 g in 100 mL and 10 g in 200 mL (for intravenous use). The available NHIG (intravenous) preparations in Australia have different recommendations for dosage and administration and the product information must be consulted before the use of each individual product. The text below provides an overview of dosage and administration for NHIG (intravenous).
Dosage and administration
The dose for replacement therapy in individuals with immune deficiency is 0.4–0.6 g/kg every 3 to 4 weeks. In Kawasaki disease, a single dose of 2 g/kg given over at least 6 to 8 hours is recommended, repeated once if fever fails to resolve within 48 hours. Doses should be calculated to the nearest (next highest) bottle so as not to waste any immunoglobulin. Giving slightly more than the calculated dose per kilogram will not be harmful.
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The infusion should be commenced slowly and the rate increased gradually. Patients should be closely observed for the duration of the infusion. The patient’s pulse, blood pressure and respiration rate should be recorded at 15-minute intervals, and their temperature every hour. All these observations should also be made and recorded before the commencement of the infusion.
Recommendations (i) Antibody deficiency disorders NHIG (intravenous) is indicated for patients with antibody deficiency disorders requiring large doses of immunoglobulin. Therapy in these patients is usually administered at monthly intervals. NHIG (intravenous) produces higher serum concentrations of IgG after administration than the IM preparation.2
(ii) Kawasaki disease In clinical studies, NHIG (intravenous) has been found to be effective in the acute phase of Kawasaki disease, as it reduces the risk of coronary artery involvement, and is associated with more rapid resolution of other acute phase features of the disease.11-15
(iii) Other uses NHIG (intravenous) has been used in the management of immune thrombocytopenia,16 Guillain-Barré syndrome,17,18 chronic inflammatory demyelinating polyneuropathy,18 toxic shock syndrome,19 post-transfusion purpura, in patients with bacterial infections associated with secondary immunodeficiency, and in other inflammatory and infective disorders.3 (NB. Some recommendations in this section are not included in the current registered indications for Intragam P. Potential users of NHIG (intravenous) in these circumstances should consult the Australian Red Cross Blood Service or the manufacturer.)
Contraindications Individuals who are known to have had an anaphylactic or severe systemic response to NHIG should not receive further immunoglobulin. Individuals with selective IgA deficiency should not receive immunoglobulin preparations.
Adverse events and precautions Adverse events with NHIG (intravenous) consist of shivering, headache, chest and back pains and moderate pyrexia. Severe headache, sometimes attributed to aseptic meningitis, has also been observed with NHIG (intravenous). This can be ameliorated by slowing the infusion or by mixing the 60 mg/mL preparation with an equal volume of normal saline before administration. There have been isolated reports of renal dysfunction and acute renal failure following the administration of NHIG (intravenous). To date, anaphylactic shock has not been experienced with NHIG (intravenous). Subjects with absolute selective IgA deficiency have an increased risk of severe adverse events following NHIG (intravenous).
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Specific immunoglobulins These products are used to protect individuals against specific microbial agents such as hepatitis B,20 rabies and varicella-zoster viruses,9,10 and tetanus toxin. Each of these specific immunoglobulins is described in more detail in this Handbook in the chapter or section relevant to these specific infections. In addition, specific immunoglobulins are available for botulism, cytomegalovirus (CMV) and respiratory syncytial virus (RSV) as described below. Adverse events and storage requirements for these specific immunoglobulins are similar to those for NHIG (IM) and, therefore, are not repeated here.
Botulism antitoxin (formerly known as Botulism Immune Globulin, BIG) Equine antitoxin made in horses has long been used in the treatment of adult botulism, but has not been shown to be effective in infant botulism.21 Equine antitoxin is manufactured by major vaccine producing companies such as Chiron. Use in Australia is governed by the Therapeutic Goods Administration’s Special Access Scheme and physicians wishing to access this stock should initially contact their State/Territory health authority. Hypersensitivity, presenting as fever, serum sickness or anaphylaxis, may follow its use. Skin testing followed by appropriate dosing should be administered according to the manufacturer’s instructions. A new intravenous botulinum antitoxin, produced in the USA, reduced the duration of mechanical ventilation and hospitalisation significantly in infant botulism.22 It is not currently registered in Australia, but is registered by the US FDA. The sponsor is Californian Department of Health Services. Access to this product should be sought through the Special Access Scheme.
CMV immunoglobulin
The product contains no antibacterial agent, and so it must be used immediately after opening. Any unused portion must be discarded. If the solution has been frozen, it must not be used. If the use of CMV immunoglobulin is contemplated, detailed protocols for administration and management of adverse events should be consulted, in addition to the Product Information.
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CMV immunoglobulin is indicated for the prevention of CMV infection in immunodeficient people at high risk of severe CMV infection, such as after bone marrow and renal transplants.23-31 The treatment of established CMV infection is primarily with antivirals such as ganciclovir, and there is scant evidence that the addition of CMV immunoglobulin improves outcome.25,26,28 It would seem most logical to reserve the use of CMV immunoglobulin to treat established CMV infection in those patients with hypogammaglobulinaemia.
• CMV Immunoglobulin-VF (human) – CSL Bioplasma (sterile solution of immunoglobulin prepared from human plasma containing high levels of antibody to CMV). The plasma protein content is approximately 60 mg/mL of which at least 98% is IgG immunoglobulin with a CMV immunoglobulin activity of 1.5 million CMV units per vial. Maltose is added to achieve isotonicity.
RSV immunoglobulin Several clinical studies of immunoglobulin against RSV have been conducted overseas using hyperimmune polyclonal RSV immunoglobulin (RSVIG) derived from blood donations.32-34 It has been shown to reduce the incidence and severity of RSV infections when given prophylactically in some babies and infants at high risk of severe infection. Benefit has been shown for babies and infants with bronchopulmonary dysplasia (BPD), for those with prematurity without BPD, and children with haemodynamically significant congenital heart disease.34,35 RSVIG has caused severe cyanotic episodes and poor outcome after surgery in children with congenital heart disease and is contraindicated in such children.36 RSVIG is not registered in Australia. A humanised mouse monoclonal antibody to RSV produced by cultured cells – palivizumab – is now registered in Australia for prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease. This product is given by IM injection each month during periods of anticipated risk of RSV. Palivizumab was found to reduce the absolute risk of hospitalisation from about 10% to about 5% for babies born prematurely,37 for babies with BPD,37 and also for babies with haemodynamically significant congenital heart disease.35 It has not been shown to reduce the incidence of more severe outcomes such as the need for ventilation, nor has it been shown to reduce mortality.35,37 Palivizumab is more effective and less costly than RSVIG, but its cost is still prohibitive. Cost-effectiveness analyses have not shown palivizumab to be costbeneficial, and even analysis of sub-groups of children at high risk has not shown a single subgroup where prophylaxis results in net savings.38,39 • Synagis – Abbott Australia (palivizumab). Supplied in single-use vials of powder, to be reconstituted with sterile water for injection; 50 mg in 4 mL vial; 100 mg in 10 mL vial.
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Dosage and administration Palivizumab is administered by IM injection preferably in the anterolateral thigh, in a dose of 15 mg/kg once a month. Where possible, the first dose should be administered before commencement of the RSV season.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
3.8 Immunoglobulin preparations
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3.9 Influenza Virology The influenza viruses are orthomyxoviruses. They are classified antigenically as types A, B or C, but only influenza A and B are clinically important in human disease.1 Influenza viruses possess 2 surface glycoprotein antigens, the haemagglutinin (H) which is involved in cell attachment during infection, and the neuraminidase (N) which facilitates the release of newly synthesised virus from the cell. The influenza A viruses can be segregated into subtypes based on differences in these surface antigens, whereas influenza B cannot be segregated into subtypes. Antibody against the surface antigens, particularly the haemagglutinin, reduces infection or severe illness due to influenza. Both influenza A and influenza B viruses undergo frequent changes in their surface antigens. Both influenza A and B undergo stepwise mutations of genes coding for H and N. This results in cumulative changes in influenza antigens, or ‘antigenic drift’. This is responsible for the annual outbreaks and epidemics of influenza and is the reason that the composition of influenza vaccines requires annual review. Antigenic shift, defined as a dramatic change in H antigen with or without a similar change in N, occurs occasionally and unpredictably and can cause pandemic influenza.1 Pandemic subtypes arise spontaneously from antigenic shift or as a result of genetic reassortment (mixing) between bird (avian) or animal viruses and human strains. Three pandemics are recognised in the 20th century, in 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2). These pandemic strains have gone on to circulate in the community, with various subtypes causing seasonal influenza and, since 1977, 2 subtypes of influenza A, A (H1N1) and A (H3N2), co-circulating in the human population together with influenza B. Recently, the avian influenza virus subtypes, A (H5N1) and A (H9N2), have been observed to cause human infections. The most notable of these is the A (H5N1) subtype which has become established in domestic poultry throughout southeast Asia and has spread to Europe and Africa in either wild birds or domestic poultry. Although growing numbers of people have contracted the virus by contact with birds and there is a high mortality rate (of ≥50%), there has been no evidence of ongoing person to person transmission.
Clinical features Influenza is transmitted from person to person via virus-containing respiratory aerosols, droplets produced during coughing or sneezing, or by direct contact with respiratory secretions.1,2 Influenza virus infection causes a wide spectrum of disease from minimal or no symptoms, to respiratory illness with systemic features, to multisystem complications and death from primary viral or
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In adults, the onset of illness due to influenza is usually abrupt, after an incubation period of 1 to 3 days, and includes systemic features such as malaise, feverishness, chills, headache, anorexia, and myalgia. These may be accompanied by a cough, nasal discharge and sneezing. Fever is a prominent sign of infection and peaks at the height of the systemic illness. Symptoms are similar for influenza A and B viruses. However, infections due to influenza A (H3N2) strains are more likely to lead to severe morbidity and increased mortality than influenza B or influenza A (H1N1) strains.1,2 The clinical features of influenza A in infants and children are similar to those in adults. However, temperatures may be higher in children (and may result in febrile convulsions in the susceptible age group) and otitis media and gastrointestinal manifestations are more prominent. Infection in neonates may be associated with more non-specific symptoms. Complications of influenza include acute bronchitis, croup, acute otitis media, pneumonia (both primary viral and secondary bacterial pneumonia), cardiovascular complications including myocarditis and pericarditis, post-infectious encephalitis, Reye syndrome, and various haematological abnormalities. Primary viral pneumonia occurs rarely, but secondary bacterial pneumonia is a frequent complication in individuals whose medical condition makes them vulnerable to the disease. Such individuals are at high risk in epidemics and may die of pneumonia or cardiac decompensation.
Epidemiology In most years, minor or major epidemics of type A or type B influenza occur, usually during the winter months. In Australia, 85 deaths and 4250 hospitalisations are notified, on average, per year, although this is almost certainly an underestimate due to failure to recognise the excess mortality and hospitalisation associated with the disease. Extrapolation from US estimates, based on more detailed surveillance, suggests 2000 deaths and 10 000 hospitalisations are likely to occur annually in Australia. During epidemics, the mortality rises, especially among the elderly and people with chronic diseases, and there is increased morbidity and hospitalisation for pneumonia and exacerbation of chronic diseases.3 Figure 3.9.1 shows the Australian hospitalisation and notification data for the period 2003–2005.
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3.9 Influenza
secondary bacterial pneumonia. Severe disease is more likely with advanced age, lack of previous exposure to antigenically related influenza virus, greater virulence of the viral strain, chronic conditions such as heart or lung disease, renal failure and diabetes, chronic neurological conditions, pregnancy, and smoking. Annual attack rates in the general community are typically 5 to 10%, but may be up to 20% in some years. In households and ‘closed’ populations, attack rates may be 2 to 3 times higher.2
Figure 3.9.1: Influenza notification rates 2003–2005 and hospitalisation rates 2002/2003 to 2004/2005, Australia,* by age group4
Rate per 100,000
90
80
Rate per 100,000 population
70
Notifications Hospitalisations
60
200 180 160 140 120 100 80 60 40 20 0 0
1
2
3
4
Age (years)
50
40
30
20
10
0 0-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
>=85
Age (years)
* Notifications where the month of diagnosis was between January 2003 and December 2005; hospitalisations where the month of separation was between 1 July 2002 and 30 June 2005.
Pandemic influenza It is now recognised that influenza A viruses have evolved in birds and that all 16 subtypes of influenza A persist in the avian reservoir. Occasionally, human infections may occur, with influenza subtypes not currently present in the human population, through close contact with infected poultry or poultry products. These may result, as in the case of recent A (H5N1) infections, in severe or fatal disease. Avian influenza viruses are not naturally transmissible from person to person. However, adaptation to human to human transmission can occur either if an individual is concurrently infected with a human and an avian influenza virus, permitting genetic reassortment to occur, or if the virus acquires this ability via mutation. Genetic studies have shown that avian influenza viruses are the source of new human pandemic strains and that both these processes resulted in pandemic influenza in the 20th century. Vaccines in routine inter-pandemic use will not protect against a pandemic strain which, by definition, is new and unpredictable. If a pandemic occurs, there will be a delay in producing a pandemic vaccine. Once the pandemic vaccine is available, the priority groups and the timing of vaccination may be quite different from those during inter-pandemic periods. In addition, the number of vaccine doses required to confer protection and the optimal interval between doses may differ. The Australian Influenza Pandemic Planning Committee has
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developed guidelines for vaccine use and will advise health authorities about priority groups, dosing schedules and timing of vaccination, should a pandemic occur.
Vaccines The administration of influenza vaccine to individuals at risk of complications of infection is the single most important measure in preventing or attenuating influenza infection and preventing mortality. After vaccination, most adults develop antibody titres that are likely to protect them against the strains of virus represented in the vaccine. In addition, the individual is protected against many related variants. Infants, the very elderly, and patients with impaired immunity may develop lower post-vaccination antibody titres. Under these circumstances, influenza vaccine may be more effective in preventing lower respiratory tract involvement or other complications of influenza than in preventing infection. • Fluad – Delpharm Consultants/Novartis Vaccines (inactivated influenza vaccine). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of the 3 recommended strains, adjuvanted with MF59C; 0.05 mg thiomersal. May contain traces of kanamycin, neomycin, formaldehyde and egg protein. • Fluarix – GlaxoSmithKline (inactivated influenza vaccine). Each 0.5 mL prefilled syringe contains 15 µg haemagglutinin of each of the 3 recommended strains; polysorbate 80/octoxinol 9. May contain traces of thiomersal, formaldehyde, gentamicin and egg protein. • Fluvax – CSL Biotherapies (inactivated influenza vaccine). Each 0.5 mL prefilled syringe contains 15 µg haemagglutinin of each of the 3 recommended strains. May contain traces of neomycin, polymyxin and egg protein. • Fluvirin – Medeva/Ebos Health & Science (inactivated influenza vaccine). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of the 3 recommended strains. May contain traces of neomycin, polymyxin and egg protein. • Influvac – Solvay Pharmaceuticals (inactivated influenza vaccine). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the 3 recommended strains. May contain traces of gentamicin and egg protein. • Vaxigrip – Sanofi Pasteur Pty Ltd (inactivated influenza vaccine). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the 3 recommended strains. May contain traces of formaldehyde, neomycin and egg protein.
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See http://www.health.gov.au/internet/wcms/publishing.nsf/Content/phdpandemic-plan.htm.
• Vaxigrip Junior – Sanofi Pasteur Pty Ltd (inactivated influenza vaccine). Each 0.25 mL pre-filled syringe contains 7.5 µg haemagglutinin of each of the 3 recommended strains. May contain traces of formaldehyde, neomycin and egg protein. Fluvax and Fluarix each have a marking on the syringe to allow preparation of a 0.25 mL dose suitable for paediatric use. All the influenza vaccines currently available in Australia are either split virion or subunit vaccines prepared from purified inactivated influenza virus which has been cultivated in embryonated hens’ eggs. Split virion and subunit vaccines are generally considered to be equivalent with respect to safety and efficacy, and both are substantially free of the systemic reactions sometimes induced by whole virus vaccines. Because the vaccine viruses are cultivated in embryonated hens’ eggs, the vaccine may contain traces of egg-derived proteins. Manufacturing processes vary by manufacturer, and different chemicals (formaldehyde or betapropiolactone) may be used to inactivate the virus. Some influenza vaccines distributed in Australia contain thiomersal, a mercury-containing compound, as preservative, and other antibacterials or antibiotics may be used in the manufacturing process. The product information should be consulted for specific information. Influenza vaccines normally contain the 3 recommended strains of virus, 2 current influenza A subtypes and influenza B, representing recently circulating viruses. The final product contains 15 µg of viral haemagglutinin, the principal surface antigen, for each virus strain. Vaxigrip Junior contains 7.5 µg of viral haemagglutinin of each of the 3 recommended strains found in the adult formulations. The composition of vaccines for use in Australia is determined annually by the Australian Influenza Vaccine Committee. Other forms of influenza vaccines (such as live attenuated intranasal vaccine) have not yet been licensed in Australia.5 The effectiveness of influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient and the degree of similarity between the virus strains in the vaccine and those circulating in the community. In healthy individuals <65 years of age, influenza vaccine is 70 to 90% effective when the antigenic match between vaccine and circulating viruses is close.6 Among elderly people, the vaccine is 30 to 70% effective in preventing all hospitalisation for pneumonia and influenza for those living outside nursing homes or similar chronic-care facilities. For those residing in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications and deaths. In such a population, the vaccine can be 50 to 60% effective in preventing hospitalisation or pneumonia, and 80% effective in preventing death, even though the effectiveness in preventing influenza illness may be lower.7 Currently
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Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.8 Store at +2°C to +8°C. Do not freeze. At the end of each year, vaccine should be appropriately discarded to avoid inadvertently using a product with incorrect formulation in the following year.
Dosage and administration Shake the pre-filled syringe vigorously before injection. Influenza vaccine is administered by either IM or SC injection. The IM route causes fewer local reactions and is preferred.9 Table 3.9.1: Recommended doses of influenza vaccine Age
Dose
Number of doses (first vaccination)
Number of doses* (subsequent years)
6 months–<3 years
0.25 mL
2†
1
3–9 years
0.5 mL
2
1
>9 years
0.5 mL
1
1
†
* If a child 6 months to ≤9 years of age receiving influenza vaccine for the first time inadvertently does not receive the second dose within the same year, he/she should have 2 doses administered the following year.7 † Two doses at least 1 month apart are recommended for children aged ≤9 years who are receiving influenza vaccine for the first time. The same vial should not be re-used for the 2 doses.
Note: (i) Some influenza vaccines available in Australia are packed in syringes graduated for measurement of recommended paediatric doses. Vaxigrip Junior presentation is a 0.25 mL pre-filled syringe ready for use. Fluvax and Fluarix each have a marking on the syringe to allow preparation of a 0.25 mL dose. A tuberculin syringe can be used to measure the dose of vaccine not packed in graduated syringes. Excess vaccine is expelled from the syringe and the remaining volume injected. (ii) All the product information sheets have some differences from Table 3.9.1. Fluvirin does not have a dose recommendation for children <4 years of age. The safety of Fluad, which is adjuvanted with MF59C, has not been established in children and it is registered for use only in people ≥65 years of age.
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available influenza vaccines confer protection for about a year. Low levels of protection may persist for a further year, if the prevalent strain remains the same or undergoes only minor antigenic drift. To provide continuing protection, annual vaccination with vaccine containing the most recent strains is necessary.
Vaccination is best undertaken in autumn, in anticipation of winter outbreaks of influenza. However, vaccination can be given as early as February. In autumn, the opportunities to provide influenza vaccination to individuals at increased risk should not be missed when they present for routine care. As full protection is usually achieved within 10 to 14 days and there is evidence of increased immunity within a few days, vaccination can still be offered to adults and children after influenza virus activity has been documented in a community. Influenza vaccine can be administered concurrently with other vaccines, including pneumococcal polysaccharide vaccine and all the scheduled childhood vaccines.
Recommendations Annual influenza vaccination is recommended for any person ≥6 months of age who wishes to reduce the likelihood of becoming ill with influenza. Influenza vaccination is strongly recommended and should be actively promoted for the following groups:
1. People at increased risk of complications from influenza infection (i) All individuals ≥65 years of age3,10-13 Influenza vaccine has been shown to reduce hospitalisations from pneumonia and all-cause mortality by about half in adults ≥65 years of age.
(ii) All Aboriginal and Torres Strait Islander people ≥15 years of age Annual influenza vaccine is recommended for Aboriginal and Torres Strait Islander people ≥15 years of age in view of the substantially increased risk of hospitalisation and death from influenza and pneumonia (see Chapter 3.15, Pneumococcal disease). In Aboriginal and Torres Strait Islander people ≥50 years of age, routine pneumococcal polysaccharide vaccination is also recommended (see Chapter 2.1, Vaccination for Aboriginal and Torres Strait Islander people and Chapter 3.15, Pneumococcal disease).
(iii) Individuals ≥6 months of age with conditions predisposing to severe influenza • Cardiac disease including cyanotic congenital heart disease, coronary artery disease and congestive heart failure.14,15 Influenza causes increased morbidity and mortality in children with congenital heart disease and adults with coronary artery disease and congestive heart failure.14 • Chronic respiratory conditions including: • Suppurative lung disease, bronchiectasis, and cystic fibrosis.16 Patients with these diseases are at greatly increased risk from influenza, which may cause irreversible deterioration in lung function.
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• Severe asthma. In patients with severe asthma, defined as requiring frequent hospital visits, annual influenza vaccine is an important part of routine care.17-19 There are insufficient data from randomised controlled trials of influenza vaccine to define efficacy across the whole spectrum of asthma,20 but influenza can cause severe exacerbations of wheezing, and about 10% of episodes of virus-induced wheezing are attributable to influenza. • Other chronic illnesses requiring regular medical follow-up or hospitalisation in the preceding year, including: • diabetes mellitus, • chronic metabolic diseases, • chronic renal failure, • haemoglobinopathies, and • impaired immunity (including drug-induced immune impairment).7,21,22 • Chronic neurological conditions (eg. multiple sclerosis, spinal cord injuries, seizure disorders or other neuromuscular disorders) that can compromise respiratory function or the expulsion of respiratory secretions or that can increase the risk for aspiration.7 NB. Because they can experience severe, even fatal, influenza, vaccination is particularly important for children ≥6 months of age with chronic neurological conditions.7 • People with impaired immunity, including HIV infection.23,24 Patients with impaired immunity, including HIV infection, malignancy and chronic steroid use, are at greatly increased risk from influenza, although they also have a reduced immune response to the vaccine. While patients with advanced HIV disease and low CD4 T-lymphocyte counts may not develop protective antibody titres, there is evidence that for those with minimal symptoms and high CD4 T-lymphocyte counts (see Chapter 2.3, Groups with special vaccination requirements, Table 2.3.4), protective antibody titres are obtained after influenza vaccination.24 Influenza vaccine has been shown in a clinical trial to reduce the incidence of influenza in HIV-infected patients,24 and although viral load may increase transiently, there is no impact on CD4 count.23 • Long-term aspirin therapy in children (aged 6 months to 10 years). Such children are at increased risk of Reye syndrome after influenza.
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• Chronic obstructive pulmonary disease and chronic emphysema. There is clinical trial evidence that inactivated influenza vaccination has a clinically important protective effect on influenza-related exacerbations, and probably an effect on the total of exacerbations in COPD patients. There is no evidence that inactivated influenza vaccination causes exacerbations of COPD.16
(iv) Pregnant women It is recommended that influenza vaccine be offered in advance to women planning a pregnancy, and to pregnant women who will be in the second or third trimester during the influenza season, including those in the first trimester at the time of vaccination.25,26 Influenza vaccination is estimated to prevent 1 to 2 hospitalisations per 1000 women vaccinated during the second or third trimester.
(v) Residents of nursing homes and other long-term care facilities This is due to high rates of transmission and complications during outbreaks.3,9-13,27
(vi) Homeless people and those providing care to them The living conditions and prevalence of underlying medical conditions among homeless people will predispose to complications and transmission of influenza.
2. People who may potentially transmit influenza to those at high risk of complications from influenza The following groups of people can potentially transmit influenza to high-risk patients and it has been shown that vaccinating the former protects those at high-risk: • staff of nursing homes, • healthcare providers28 (particularly of patients with impaired immunity), • staff of long-term care facilities, • household contacts (including children ≥6 months of age) of individuals in high-risk groups.
3. People involved in the commercial poultry industry or in culling poultry during confirmed avian influenza activity29 Vaccination using the current influenza season vaccine composition is recommended for poultry workers and others in regular close contact with poultry during an avian influenza outbreak.29 Although routine influenza vaccine does not protect against avian influenza, there is a possibility that a person who was infected at the same time with avian and human strains of influenza virus could allow reassortment of the 2 strains to form a virulent strain that could spread from human to human (ie. initiate a pandemic).
4. People providing essential services Vaccination of those who provide essential community services will minimise disruption of essential activities during influenza outbreaks. Influenza viral infections can place considerable pressure upon both public and private healthcare services (see Chapter 2.3, Groups with special vaccination requirements, Table 2.3.6).
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5. Workers in other industries
6. Travellers Large tourist groups, especially those including elderly people and those travelling on cruises, who are likely to be in confined circumstances for days to weeks, are at risk of influenza, either acquired before departure or from travel to areas of the world where influenza is currently circulating. Influenza vaccination, preferably using the strain prevalent in the areas in which they will be travelling, is recommended if travelling during the influenza season, especially if it is known before travel that there are high rates or epidemics of influenza.7
Contraindications Absolute contraindications to influenza vaccine are: • anaphylaxis following a previous dose of any influenza vaccine, • anaphylaxis following any vaccine component, • individuals with anaphylactic sensitivity to eggs should not be given influenza vaccine. This includes those who, soon after ingesting eggs, develop swelling of the lips or tongue, or experience acute respiratory distress or collapse.
Precautions Patients with a history of Guillain-Barré Syndrome (GBS) with an onset related in time to influenza vaccination may be at increased risk of again developing GBS if given influenza vaccine. The risk should be weighed against the benefits to the individual patient of influenza vaccination. Because patients with a history of GBS have an increased likelihood of developing the syndrome again, the chance of them coincidentally developing the syndrome following influenza vaccination may be higher than in individuals with no history of GBS.
Adverse events27,30 Local adverse events (induration, swelling, redness and pain) are very common (>10%). Fever, malaise and myalgia occur commonly (1–10%). These adverse events may commence within a few hours of vaccination and may last for 1 to 2 days. In children <5 years of age, these adverse events may be more pronounced. Postvaccination symptoms may mimic influenza infection but current influenza vaccines do not contain live virus and cannot cause influenza.
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The cost-effectiveness of influenza vaccination in industry varies from year to year, depending on the amount of circulating influenza, but the overall impact over time is judged to be cost-saving in several settings.6,7 Individual industries should consider the benefits of offering influenza vaccine in the workplace.
Immediate adverse events (such as hives, angioedema, or anaphylaxis) are a rare consequence of influenza vaccination. They probably represent an allergic response to a residual component of the manufacturing process, most likely egg protein. Individuals with a history of anaphylaxis after eating eggs or a history of a severe allergic reaction following occupational exposure to egg protein should not be given influenza vaccine. An association was shown between influenza vaccine used in the northern hemisphere from 1992 to 1994 and Guillain-Barré syndrome (GBS), with 1 to 2 cases of GBS occurring per million vaccinated. There has not been an excess number of cases of GBS reported in Australia in association with influenza vaccine.31
Use in pregnancy Influenza vaccine is recommended for pregnant women who will be in the second or third trimester during the influenza season, including those in the first trimester at the time of vaccination. See ‘Recommendations’ above.
Variations from product information The product information lists allergy to chicken feathers and some food proteins as a contraindication, whereas NHMRC recommends that patients with allergies other than anaphylaxis can be vaccinated. The product information for Fluarix states the influenza vaccine may be used in children from 3 months of age. NHMRC recommends influenza vaccine in children ≥6 months of age. The product information for some vaccines gives a dose of 0.125 mL for children 3 or 6 months to 2 years old. NHMRC recommends that the lowest dose for any influenza vaccine is 0.25 mL. This is because influenza vaccine is relatively poorly immunogenic in infants, and 0.25 mL is the dose recommended in the USA for children aged ≥6 months where it has been shown to be safe.32 The product information for Fluvirin states that the product should not be given to children <4 years of age. Although the NHMRC recommends that children as young as 6 months of age can be vaccinated if they are at risk of complications of influenza, the suitability of the vaccine formulation for accurate preparation of 0.25 mL doses should be taken into account.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.10 Japanese encephalitis Virology Japanese encephalitis (JE) is caused by a mosquito-borne flavivirus.
Clinical features
Epidemiology JE is a significant public health problem in many parts of Asia including the Indian subcontinent, southeast Asia and China.1 In recent years, however, the disease has extended beyond its traditionally recognised boundaries with, for example, outbreaks occurring in the Torres Strait and north Queensland in 1995 and 1998.2,3 The JE virus is essentially a zoonosis of pigs and wading birds, and is transmitted between these animals by Culicine mosquitoes.1 The virus replicates, leading to a transient high-level viraemia, within these so-called ‘amplifying’ hosts but not within other large vertebrates such as horses and humans. Indeed, humans are an incidental host infected when living in close proximity to the enzootic cycle; this usually occurs in rural areas where there is prolific breeding of the vectors in flooded rice fields.1 There are two recognised epidemiological patterns of JE.1 In the temperate or subtropical regions of Asia (northern Thailand, northern Vietnam, Korea, Japan, Taiwan, China, Nepal and northern India), the disease occurs in epidemics during the summer or wet season months (April to May until September to October). In the tropical regions (most of southeast Asia, Sri Lanka, southern India), the disease is endemic, occurring throughout the year, but particularly during the wet season.1 In some countries (Japan, Taiwan, South Korea, and some provinces of China), the incidence of JE has declined considerably in recent decades, and it has been eradicated from Singapore. Immunisation, changes in pig husbandry, a reduction in land utilised for rice farming, and improved socioeconomic circumstances have all contributed to these changes.1
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The disease is typically an acute neurological illness characterised by headache, fever, convulsions, focal neurological signs and depressed level of consciousness. It has a high case-fatality rate and there is a high prevalence of neurological sequelae (up to 50%) in those who survive the acute illness.1 Less commonly, the disease may present as an acute flaccid paralysis.1 Milder forms include febrile illness with headache, and aseptic meningitis. It is recognised, however, that most infections are asymptomatic; published estimates of the symptomatic to asymptomatic infection ratio vary in different populations from 1:25 to 1:1000.1
In early 1995, 3 cases of JE, 2 of them fatal, occurred on Badu island in the Torres Strait.2 Subsequent serological surveys showed that JE virus activity was widespread in many other remote ‘outer’ islands of the Torres Strait (see Figure 3.10.1) at or about that time.2 Although the 1995 outbreak was the first known incursion of JE virus into Australia, surveillance using sentinel pigs has shown incursions into the Torres Strait in virtually every wet season (December to May) since then. In early 1998, a further case of JE occurred in an unvaccinated Badu resident and the first ever mainland case of JE occurred in a person working on the west coast of Cape York.3 However, serological surveys revealed no evidence of JE virus infection in people in several nearby communities.3 To date, there have been 5 cases of JE acquired in Australia. An investigation subsequent to the 1995 outbreak of JE in the Torres Strait documented the presence of the JE virus in the Western Province of Papua New Guinea.4 A severe case of JE acquired near Port Moresby occurred in early 2004,5 indicating that the JE virus is now probably widespread in Papua New Guinea. Figure 3.10.1: Map of the Torres Strait. The outer islands are north of the dotted line
Vaccine • JE-VAX – Sanofi Pasteur Pty Ltd (Japanese encephalitis virus vaccine inactivated). Each 1.0 mL reconstituted monodose vial contains formaldehyde inactivated Japanese encephalitis virus; 0.007% thiomersal; 470 µg gelatin; <100 µg formaldehyde; 5 mg monosodium glutamate; <50 ng mouse brain serum protein.
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The JE vaccine available in Australia is an inactivated mouse brain-derived vaccine manufactured in Japan. However, the manufacturer has recently discontinued its production and, although the Australian distributor has access to a stockpile, shortages of the vaccine could occur over the next few years. New generation JE vaccines are expected in the mid to longer term. The vaccine is prepared by inoculating mice intracerebrally with NakayamaNIH strain JE virus. Infected brains are harvested, homogenised, then centrifuged. The supernatant is inactivated with formaldehyde and purified by ultracentrifugation; the suspension is then lyophilised. No myelin basic protein can be detected at the threshold of the assay (<2 ng/mL).
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.8 Store at +2°C to +8°C. Do not freeze. Reconstituted vaccine should be used immediately, but it can be stored at +2°C to +8°C and used within 8 hours.
Dosage and administration JE vaccine is administered by the subcutaneous route. The volume injected is 0.5 mL in 1–3-year-old children and 1.0 mL for all individuals >3 years of age. In those from non-endemic regions, including Australia, a 3-dose regimen (ie. days 0, 7 and 28) over a month is required. An accelerated schedule of 0, 7 and 14 days can be used, but this is likely to result in lower antibody levels than the standard schedule.7 If the accelerated schedule is used, a further dose should, if possible, be administered 1 to 3 months later. NB. The volume of the reconstituted vaccine is greater than 1.0 mL. Because the dose of JE vaccine is 1.0 mL (0.5 mL in 1–3-year-old children) this means a small portion of the total reconstituted vaccine should be discarded.
Recommendations (i) Travellers Although the risk of travellers in Asia acquiring JE is extremely low, there have been instances of even short-term travellers developing the disease.9 Therefore, all travellers to Asia (and other tropical regions) must be fully aware of the need to take appropriate measures to avoid mosquito bites. The risk of JE to travellers to Asia is determined by the season of travel, the regions visited, the duration of travel, the extent of outdoors activity and the extent to which mosquito-avoidance measures are taken.1 Clearly the risk is
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A randomised clinical trial in Thailand in the early 1980s determined that 2 doses of the inactivated mouse brain-derived vaccine, administered to children 7 days apart, had a protective efficacy of 91%.6 However, immunogenicity studies have demonstrated that 3 doses of the vaccine are required to ensure adequate immunity in vaccinees from JE non-endemic areas.7
greater during prolonged travel to rural areas of Asia during the wet season; it is probably negligible during short business trips to urban areas. NB. A recent study has shown that the JE virus is hyperendemic in Bali, that it causes substantial human illness, and that it circulates year round.10 Therefore JE vaccination is recommended for: • travellers spending 1 month or more in rural areas of Asia. However, as JE has occurred in travellers after shorter periods of travel, JE vaccination should be considered for shorter-term travellers, particularly if the travel is during the wet season, and/or there is considerable outdoor activity, and/or the accommodation is not mosquito-proof,9 • for all other travellers spending a year or more in Asia (except Singapore), even if much of the stay is in urban areas, and • travellers intending to spend a month or more in Papua New Guinea, particularly if the travel is during the wet season.
(ii) Residents of Far North Queensland JE vaccination is recommended for: • all residents (>1 year of age) of the outer islands in the Torres Strait, and • all non-residents who will be living or working on the outer islands of the Torres Strait for a cumulative total of 30 days or more during the wet season (December to May). NB. The period of greatest risk is from February to March and the vaccination course should be completed before February. Those arriving in the outer islands late in the wet season (ie. in May) have arrived after the risk period and do not require vaccination. Those visiting the outer islands in the dry season (June to November) do not require vaccination. Those visiting only the inner islands, including Thursday Island, do not require vaccination.
(iii) Laboratory personnel JE vaccination is recommended for all research laboratory personnel who potentially might be exposed to the virus.
(iv) Booster doses Single booster doses are recommended at 3-yearly intervals.
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Contraindications • Anaphylaxis following a previous dose of JE vaccine or a significant allergic reaction, such as generalised urticaria, to a previous dose. • Anaphylaxis following any component of the vaccine. A past history of allergic disorders (including urticaria, angioedema, anaphylaxis) following bee-stings, medications, foods etc. must be considered as possible contraindications to vaccination. • The inactivated mouse brain-derived JE vaccine is contraindicated in those <1 year of age.
There are few data on the safety and efficacy of JE vaccine in people with impaired immunity. A small study undertaken in Thailand has documented that HIVinfected infants respond less well to 2 doses of JE vaccine than do non-infected infants;11 the response to further doses was not studied.
Adverse events • Local reactions and minor systemic reactions are common to very common following vaccination against JE.1 About 20% experience tenderness, redness and/or swelling at the injection site, and 10% experience systemic reactions such as fever, headache, being ‘off-colour’, chills, dizziness, aching muscles, nausea and/or vomiting. • Although the manufacturing process purifies the infected mouse brain suspension so that no myelin basic protein can be detected in the vaccine, serious neurological events following immunisation have been reported. In 1994, 4 cases of severe neurological illness, 2 of which were fatal, were reported from South Korea, and surveillance in Japan indicates the rate of severe neurological adverse events following JE vaccination is 1.8 cases per 1 million doses of vaccine.7 • Hypersensitivity (allergic) reactions are uncommon and occur in about 0.5% (ie. 1 in 200) vaccinees. These reactions include urticaria that is often widely distributed over the body, angioedema of the limbs, face and throat, and generalised pruritus (sometimes without a rash). In the early 1990s, apparently severe allergic reactions to the inactivated mouse brain-derived JE vaccine were reported from several industrialised countries, including Australia.7 In a few cases, upper airway swelling with respiratory distress and hypotension occurred; some had to be hospitalised. An important feature of the hypersensitivity reactions to JE vaccine is that they may be delayed for several days, in some cases up to 10 days, after the actual time of vaccine administration. The risk of these delayed reactions seems to be increased after the first and second doses, and they appear to be more likely to occur in those with a history of allergic reactions, especially urticaria.7 Although
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Precautions
the pathogenesis of the more severe hypersensitivity reactions remains uncertain, there is some evidence that gelatin, added to stabilise the vaccine, may be the provoking agent.7 As a precaution, vaccinees should ideally remain within access to medical care for 10 days after vaccination.
Use in pregnancy Although JE vaccine might pose a theoretical risk to the developing fetus, no adverse outcomes of pregnancy have ever been attributed to vaccination against JE. Because JE virus infection during the first and second trimester is also associated with miscarriage, pregnant women at risk of acquiring JE should be offered JE vaccine.
Variations from product information The product information states that ‘definitive recommendations cannot be given on the timing of booster doses at this time’ and that ‘a booster dose may be given after 2 years’. The NHMRC recommends that single booster doses be given at 3-yearly intervals.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.11 Measles Virology Measles is a paramyxovirus, genus Morbillivirus. It is an RNA virus with 6 structural proteins, 3 complexed to the RNA and 3 associated with the viral envelope. Two of the envelope proteins, the F (fusion) protein and the H (haemagglutinin) protein, are the most important in pathogenesis. The measles virus can survive up to 2 hours in air, but is rapidly inactivated by heat, light and extremes of pH.1,2
Clinical features Measles is a highly infectious, acute viral illness spread by respiratory secretions, including air-borne transmission via aerosolised droplets.2 It is infectious from the beginning of the prodromal period and up to 4 days after the appearance of the rash. The incubation period is usually 10 to 14 days. The prodrome, lasting 2 to 4 days, is characterised by fever and malaise followed by a cough, coryza and conjunctivitis. The maculopapular rash typically begins on the face and upper neck, and then becomes generalised.
Epidemiology Evidence suggests that endemic measles has been eliminated from Australia, an indigenous measles strain being absent for several years.4 Although measles outbreaks of limited duration continue to occur, they have usually been linked to imported cases.5-7 In a recent measles outbreak, linked to an imported case, 25% of notified cases were in children aged 1–4 years, most of whom were not vaccinated.8 Measles notifications and hospitalisations for the 5 years 2001–2005 have been the lowest recorded in Australia.9,10 In the 30 years (1976–2005) since measles vaccination was recommended in Australia, there have been 95 deaths
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Measles is often a severe disease, frequently complicated by otitis media (in ~9%), pneumonia (in ~6%) and diarrhoea (in ~8%).1,2 Acute encephalitis occurs in 1 per 1000 cases, and has a mortality rate of 10 to 15%, with 15 to 40% of survivors suffering permanent brain damage.3 Subacute sclerosing panencephalitis (SSPE) is a late complication of measles, occurring on average 7 years after infection in approximately 0.5 to 1 per 100 000 measles cases.2 SSPE causes progressive brain damage and is always fatal. Complications from measles are more common and more severe in the chronically ill, in children <5 years of age, and in adults.1 Approximately 60% of deaths from measles are attributed to pneumonia, especially in the young, while complications from encephalitis are more frequently seen in adults.1,2 Measles infection during pregnancy can result in miscarriage and premature delivery but has not been associated with congenital malformation.1
recorded from measles, 1 death in 2004 being the only one recorded since 1995.9-11 High-level vaccination coverage is imperative to maintain measles elimination, requiring rates for each new birth cohort of >95% for a single dose and >90% for 2 doses.12 In 2004, the Australian Childhood Immunisation Register (ACIR) recorded that 93.6% of children aged 2 years (born in 2002) had received at least 1 dose of measles-containing vaccine and 84.8% of children aged 6 years (born in 1998) had received both doses.13 It is likely that, when corrected for underreporting, the target of 95% coverage for 1 dose of measles vaccine is reached at 2 years, but, if the second dose is not given until 4 years of age, 95% 2-dose coverage is not achieved.14 Scheduling of the second dose of measles-containing vaccine at 18 months of age (see ‘Recommendations’ below) will provide 2-dose protection at an earlier age and may also improve second dose coverage. Following the National Measles Control Campaign (which took place in 1998 and resulted in 1.7 million primary school children being vaccinated), a national serosurvey in the first quarter of 1999 showed that 89% of children aged 2–5 years, 94% of those aged 6–11 years, and 91% of those aged 12–18 years, were immune to measles.15,16 The serosurvey evaluating the young adult MMR campaign in 2000 showed that those most at risk of measles infection in Australia were infants <12 months of age, 1–<2-year-olds due to delayed vaccine uptake, and individuals born in the late 1960s to mid 1980s (especially the 1978–1982 birth cohort).17 Young adults are recognised to be at a greater risk of measles infection. Many missed being vaccinated as infants (when coverage was low), while during their childhood a second dose was not yet recommended and disease exposure was decreasing.18 Worldwide, measles is thought to be the fifth leading cause of childhood morbidity and mortality with 770 000 deaths estimated to have occurred in 2000. More than half these deaths occurred in Africa.1,19 Following extensive vaccination campaigns, measles accounted for approximately 454 000 deaths worldwide in 2004.20 The WHO is overseeing efforts to eliminate measles worldwide through immunisation and surveillance strategies that aim to interrupt the circulation of the virus.21
Vaccines One measles-mumps-rubella (MMR) vaccine is currently available in Australia. It is anticipated that measles-mumps-rubella-varicella (MMRV) vaccines will become available in the near future. A monovalent vaccine is available for rubella where this is specifically required (see Chapter 3.19, Rubella). Separate administration of measles, mumps or rubella vaccine is not recommended as an alternative to MMR vaccine and no monovalent vaccines for mumps or measles are licensed in Australia. Measles immunity induced by single-dose vaccination provides long-term immunity in most recipients.1,22 However, approximately 5% of recipients fail to develop immunity to measles after 1 dose.23 Following a second vaccine dose,
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approximately 99% of subjects overall will be immune to measles. Combination MMRV vaccines have been shown, in clinical trials, to produce similar rates of seroconversion to all 4 vaccine components compared with MMR and monovalent varicella vaccines administered at separate injection sites.24,25 Data on the use of MMRV vaccines are not available for people >12 years of age. • Priorix (MMR) – GlaxoSmithKline (live attenuated measles virus (Schwarz strain), RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 103.0 CCID50 (cell culture infectious dose 50%) of the Schwarz measles, not less than 103.7 CCID50 of the RIT 4385 mumps and not less than 103.0 CCID50 of the Wistar RA 27/3 rubella virus strains; lactose; neomycin; amino acids; sorbitol and mannitol as stabilisers.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.26 Store at +2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine should be used immediately, but can be stored at +2°C to +8°C for up to 8 hours before use.
Dosage and administration For both children and adults, the dose of MMR is 0.5 mL, administered by either SC or IM injection.
Recommendations (i) Routine vaccination of children Two doses of MMR are recommended for all children. The first dose should be given at 12 months of age and the second dose at 18 months of age. The minimum interval between doses is 4 weeks. When MMRV vaccines are available, the 12 month and 18 month doses may be given as MMRV. The scheduled age at administration of the second dose of measles-containing vaccine has been moved from 4 years of age to 18 months of age to provide earlier 2-dose protection against measles and to improve vaccine uptake (see ‘Epidemiology’ above). The second dose of measles-containing vaccine at 18 months of age can be given as either MMR or, when available, MMRV. Receipt of 2 doses of varicella vaccine (VV) provides increased protection against
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MMR can be given at the same time as other vaccines (including DTPa, hepatitis B, MenCCV and varicella), using separate syringes and injection sites. If MMR is not given simultaneously with other live viral parenteral vaccines (eg. varicella vaccine), they should be given at least 4 weeks apart (see ‘Precautions’ below).27,28
varicella, and MMRV, when available, should be preferred over MMR for the second dose of measles-containing vaccine at 18 months of age. (For further information, see also Chapter 3.24, Varicella.)
(ii) Vaccination of adults and adolescents Those born before 1966: No vaccination is required (unless serological evidence indicates otherwise) as circulating virus and disease were prevalent before this time suggesting most people would have acquired immunity from natural infection. However, recent confirmed cases of measles have occurred in individuals born before 1966 and, if doubt exists, it may be more expedient to offer vaccination than serological testing.8 Those born during or since 1966: Infants ≥12 months up to 18 months of age should have documented evidence of 1 dose of MMR (or MMRV when available), or serological evidence of protection for measles. Those ≥18 months of age should have documented evidence of 2 doses of MMR (administered at least 4 weeks apart with both doses administered at 12 months of age or over), or serological evidence of protection for measles, mumps and rubella. Catch-up vaccination of children who have not received MMR or MMRV at 18 months of age should occur at the 4-year-old schedule point, until all the relevant children have reached 4 years of age. It is also acceptable to use MMRV in place of MMR at the 4-year-old schedule point. This would have the added benefit of providing a 2-dose VV schedule to an additional 2.5 birth cohorts of infants who had received single-dose monovalent VV at 18 months. There are no increased adverse events from vaccinating those with pre-existing immunity to 1 or more of the vaccine components.
(iii) Healthcare workers and those who work with children All workers in these categories who were born during or since 1966 and are non-immune or who have only received 1 dose of MMR, should be vaccinated with MMR, and have documented evidence of 2 doses or serological evidence of protection for measles, mumps and rubella (see ‘Vaccination of adults and adolescents’ above). (See also Section 2.3, Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases.)
(iv) Travellers Those born during or since 1966 should be encouraged to complete the MMR vaccination schedule (using MMR or MMRV, when appropriate) before embarking on international travel if they do not have evidence of receipt of 2 doses of MMR (see ‘Vaccination of adults and adolescents’ above).
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Infants travelling to endemic countries may be vaccinated with MMR between 9 and 12 months of age. In these cases, another dose of MMR (or MMRV) should be given at 12 months of age or 4 weeks after the first dose, whichever is later. This should be followed by the routine administration of the next dose of MMR or MMRV at 18 months of age. This is because maternal antibodies to measles are known to persist in many infants until 11 months of age and may interfere with active immunisation before 12 months of age1 (see ‘Vaccination during an outbreak’ below).
Contraindications If using MMRV vaccine, additional contraindications relating to the varicella vaccine component are outlined in Chapter 3.24, Varicella.
(i) Allergy to vaccine components Vaccination is contraindicated where there has been: • anaphylaxis following a previous dose of MMR or MMRV, or • anaphylaxis following any component of the vaccine. Providers should consult the product information regarding vaccine components when MMRV vaccines are available.
(ii) People with impaired immunity
• those with primary or acquired cellular immunodeficiency states, including impaired immunity due to HIV/AIDS or conditions in which normal immunological mechanisms may be impaired. MMR (but not MMRV) vaccine can be given to HIV-positive children who do not have impaired immunity (see ‘Precautions’ below), • those taking high-dose oral corticosteroids (in children equivalent to either >2 mg/kg per day prednisolone (≥20 mg per day total) for >1 week or >1 mg/kg per day for >4 weeks) (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment), • those receiving high-dose systemic immunosuppressive treatment, general radiation or x-ray therapy, • those suffering from malignant conditions of the reticuloendothelial system (such as lymphoma, leukaemia, Hodgkin’s disease).
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Measles-, mumps-, rubella- and varicella-containing vaccines are contraindicated in individuals with impaired immunity. In addition, there are no clinical trials or post-licensure data to address the safety and immunogenicity of MMRV in children or adults with impaired immunity. However, based on recommendations for the component live attenuated vaccine viruses, both MMR and MMRV are contraindicated in the following groups:
(iii) Recent administration of antibody-containing blood product • The expected immune response to measles, mumps, rubella and varicella vaccination may be impaired after receipt of antibody-containing blood products.23,27,29 The duration of interference with the response to measles vaccination depends on the amount of immunoglobulin contained in each product, and ranges from 3 to 11 months.27 Vaccination with MMR or MMRV should be delayed after administration of antibody-containing products as indicated in Table 2.3.5 (see Section 2.3.5, Vaccination of patients following receipt of other blood products including blood transfusions). • After vaccination with MMR or MMRV, immunoglobulin-containing products should not be administered for 3 weeks unless the benefits exceed those of vaccination. If immunoglobulin-containing products are administered within this interval, the vaccinee should either be revaccinated later at the appropriate time following the product as indicated in Table 2.3.5, or tested for immunity 6 months later and then revaccinated if seronegative. • Blood transfusion with washed red blood cells is not a contraindication to MMR or MMRV vaccinations. • Rh (D) immunoglobulin (anti-D) does not interfere with the antibody response to MMR vaccine and may be given at the same time in different sites with separate syringes or at any time in relation to each other.
(iv) Pregnant women • If MMR vaccines are given to women of child-bearing age, pregnancy should be avoided for 28 days30 (see Chapter 3.19, Rubella). Data on the use of MMRV vaccines in individuals >12 years of age are not available.
Precautions • MMR can be administered on the same day as other live viral parenteral vaccines, such as monovalent varicella vaccine. However, if this is not possible, MMR should be deferred for at least 4 weeks after vaccination with other live viral parenteral vaccines. • MMR can be given to asymptomatic or mildly symptomatic HIV-positive individuals providing they do not have severely impaired immunity.23 (see Section 2.3.3, Table 2.3.4, Immunological categories based on age-specific CD4 counts and percentage of total lymphocytes). This is because the risk posed by measles infection is considered to be greater than the likelihood of adverse events from vaccination.31 As there are no data available on the safety, immunogenicity or efficacy of MMRV vaccine in HIV-infected children, MMRV vaccine should not be administered as a substitute for MMR when vaccinating these children.23,29
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• Children on daily doses of ≤2 mg/kg per day of systemic corticosteroids for <1 week, and those on lower doses of 1 mg/kg per day or alternate-day regimens for longer periods, may be given live viral vaccines. • Children receiving >2 mg/kg per day or ≥20 mg per day in total of prednisolone (or equivalent) for >14 days can receive live viral vaccines after corticosteroid therapy has been discontinued for at least 1 month.31 Some experts suggest withholding lower doses of steroids 2 to 3 weeks before vaccination with live viral vaccines if this is possible29,31 (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment). • Use of salicylates (aspirin) is not recommended for 6 weeks following MMRV vaccination. This is because of the association between use of salicylates during natural varicella infection and Reye syndrome (see Chapter 3.24, Varicella). There is no need to avoid salicylates (aspirin) after MMR vaccination. • Thrombocytopenia is a rare adverse event following vaccination with MMR.2,32,33 Authorities differ in their opinion about whether the risk of vaccine-associated thrombocytopenia is increased in those who have previously had immune thrombocytopenia.23,33 Post-marketing experience of live MMR vaccine in the USA indicates that individuals with current thrombocytopenia may develop more severe thrombocytopenia after vaccination. Recent studies found that children with immune thrombocytopenia before MMR had no vaccine-associated recurrences.32,33 There are no systematic studies of the outcome of a second dose of MMR in children who developed thrombocytopenia after a first dose.33
• Measles virus inhibits the response to tuberculin, so tuberculin-positive individuals may become tuberculin-negative for up to a month after measles infection or administration of measles-containing vaccines.23 Mantoux testing is therefore unreliable for at least 4 weeks after the administration of MMR or MMRV. As measles infection may cause exacerbation of tuberculosis, there is a theoretical concern that measles-containing vaccine may exacerbate tuberculosis. Patients with tuberculosis should be under treatment when vaccinated. • Children with egg allergy, even anaphylactic egg allergy, can be safely given MMR or MMRV vaccine.2,34 Skin testing has been shown to be of no value in the management of these cases.2 Although measles and mumps (but not rubella or varicella) vaccine viruses are grown in chick embryo tissue cultures,
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• Children with a personal or close family history of seizures or convulsions should be given MMR or MMRV vaccine, provided the parents understand that there may be a febrile response 5 to 12 days after vaccination.23 Advice for reducing fever with paracetamol and other measures should be given. Specialist advice should be sought rather than refusing to provide MMR or MMRV vaccination.
it is now recognised that MMR (and MMRV) vaccine contains negligible amounts of egg protein (see ‘Variations from product information’ below). • MMR and MMRV vaccines can be administered to susceptible children who have mild illnesses (eg. diarrhoea or upper respiratory infection), with or without low-grade fever (<38.5°C).
Adverse events (If using MMRV vaccine, additional adverse events relating to the varicella vaccine component are outlined in Chapter 3.24, Varicella.) • Malaise, fever and/or a rash may occur after MMR vaccination, most commonly 7 to 10 days (range 5–12 days) after vaccination and lasting about 2 to 3 days. High fever (>39.4°C) occurs in approximately 5 to 15% (common to very common), and rash occurs in approximately 5% (common) of MMR vaccinees.1,23 The risk for febrile seizures is approximately 1 case per 3000 doses of MMR vaccine administered.23 Slightly higher rates of fever were observed in clinical trials of MMRV vaccines, as compared with giving MMR and monovalent varicella vaccine at the same time but at separate sites.24,25 • A varicelliform rash may occur after vaccination with MMRV (see Chapter 3.24, Varicella ‘Adverse events’). The appearance of a rash after monovalent varicella vaccine occurs in <5% (common) of vaccinees, and similar rates are observed with the use of MMRV.35 • Adverse events are much less common after the second dose of MMR and MMRV than after the first dose. • Anaphylaxis following the administration of MMR is very rare (less than 1 in 1 million doses distributed).23 Although no cases of anaphylaxis were reported in MMRV clinical trials, the incidence is likely to be similar to that occurring with use of MMR. Anaphylaxis after vaccination is likely due to gelatin or neomycin anaphylactic sensitivity, not egg allergies (see ‘Precautions’ above). • It is uncertain whether encephalopathy occurs after measles vaccination. If it does, it is at least 1000 times less frequent than as a complication from natural infection.1,23 • Other rare adverse events attributed to MMR vaccine include transient lymphadenopathy and arthralgia (see Chapter 3.19, Rubella). Parotitis has been reported rarely.23 • Thrombocytopenia (usually self-limiting) has been very rarely associated with the rubella or measles component of MMR occurring in 3 to 5 per 100 000 doses of MMR vaccine administered.2,23,32,33 This is considerably less than after natural measles, mumps and rubella infections33 (see also Chapter 3.19, Rubella). Any association with MMRV vaccine is expected to be similar.
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• It is recommended that parents/vaccine recipients be advised about possible symptoms, and given advice for reducing fever, including the use of paracetamol for fever in the period 5 to 12 days after vaccination. The use of aspirin after MMRV vaccination is not recommended for 6 weeks (see Chapter 3.24, Varicella). • It had been hypothesised that the measles component of the MMR vaccine may be causally linked with autism, autistic spectrum disorder and inflammatory bowel disease.36 There has been no credible scientific evidence to support this claim. Most proponents of the hypothesis have retracted this claim37 and there is now good evidence to refute it38 (see Appendix 5, Commonly asked questions about vaccination).
Transmissibility of MMR vaccine viruses Measles, mumps and rubella vaccine viruses are not transmissible to contacts.23 It is, therefore, safe to vaccinate the healthy siblings of children with impaired immunity and safe for children with impaired immunity to go to school with children recently vaccinated with the MMR vaccine. If using MMRV, see Chapter 3.24, Varicella for information about varicella vaccine virus transmission.
The public health management of measles (i) Definition of a person who is considered not susceptible to measles A person is considered not susceptible to measles if he/she meets 1 of the following criteria:
• born before 1966 (unless serological evidence indicates otherwise), • documented evidence of immunity, • documented evidence of laboratory confirmed measles infection. NB. These criteria have been revised since publication of the Guidelines for the control of measles outbreaks in Australia in 2000.39
(ii) Vaccination of measles contacts As vaccine-induced measles antibody develops more rapidly than that after natural infection, MMR vaccine can be used to protect susceptible contacts.23 The incubation period of the vaccine strain (4 to 6 days) is shorter than the incubation period of wild measles virus (10 to 14 days). To be effective, the vaccine must be administered within 72 hours of exposure. If there is doubt about a person’s immunity, vaccine should be given, since there are no ill effects from vaccinating individuals who are already immune. It must be noted that antibody responses
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• born during or since 1966 with documented evidence of receiving 2 doses of a measles-containing vaccine, with both doses of vaccine having been given at ≥12 months of age and at least 4 weeks apart. This applies unless serological evidence indicates otherwise,
to the rubella and mumps components are too slow for effective use of vaccine as prophylaxis after exposure to these infections. Alternatively, MMRV vaccine, when available, could also be used in this setting if varicella vaccination is indicated. However, there are no data on the use of MMRV vaccines in individuals >12 years of age. Immunoglobulin is available for contacts for whom measles-containing vaccine is contraindicated (see ‘Use of immunoglobulin to prevent measles’ below), for infants aged 6–9 months, and for susceptible individuals who did not receive a measles-containing vaccine within 72 hours of contact (see Table 3.11.1 below). Isolation of susceptible close contacts by exclusion from school or the workplace should occur until 14 days after their last exposure39 unless they receive either the MMR vaccine within 72 hours or immunoglobulin within 7 days of their first exposure. If they do not receive MMR vaccine or immunoglobulin within these specified timeframes, they should be excluded.
(iii) Vaccination during an outbreak During a confirmed measles outbreak, MMR vaccine may be given (on the direction of public health authorities) to infants between 9 and 12 months of age, and even to those between 6 and 9 months of age.39 In these cases, another dose of MMR (or MMRV when available) should be given at 12 months of age or 4 weeks after the first dose, whichever is later. This should be followed by the routine administration of the next dose of measles-containing vaccine at 18 months of age. This is because maternal antibodies to measles are known to persist in many infants until 11 months of age and may interfere with active immunisation before 12 months of age.1 Children between 12 and 18 months of age who have received 1 dose of measlescontaining vaccine can be offered their second dose early (ie. at least 4 weeks after the first dose) if they are considered at risk of coming in contact with measles39 (see ‘Recommendations (i)’ above). If a child receives the second dose early, he/she is considered to have completed the vaccination schedule and, therefore, does not require another dose at 18 months of age or beyond, provided 2 doses were given at ≥12 months of age and at least 4 weeks apart. Any older children, adolescents or adults who are considered susceptible to measles (see (i) above) during an outbreak should receive MMR (or MMRV if appropriate).
(iv) Use of immunoglobulin to prevent measles Normal human immunoglobulin (NHIG) should be considered for contacts of patients with confirmed or suspected measles39 (see Table 3.11.1). If NHIG is administered by IM injection within 7 days of exposure, it can prevent or modify measles in non-immune individuals. The dose of NHIG is 0.2 mL/kg by deep IM injection for healthy children, adolescents and adults (including pregnant women), and 0.5 mL/kg by deep IM injection for people with impaired immunity. The maximum dose is 15 mL.
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NHIG should be given to exposed individuals if contact was within the previous 7 days in the following instances: • infants <6 months of age where the infant’s mother is the measles case, or the infant was born before 28 weeks’ gestation, • infants 6–9 months of age (see ‘Vaccination during an outbreak’ above), • all those ≥9 months of age in whom administration of MMR vaccine would be contraindicated, • non-immune pregnant women, • those exposed to measles who have impaired immunity, • those who have never received a measles-containing vaccine, and who did not receive a MMR or MMRV vaccine within 72 hours of contact. Children with impaired immunity, where MMR is contraindicated, should be given NHIG as soon as possible (within 7 days) after exposure. Testing for measles antibody does not assist with the decision to use immunoglobulin, since neither previous vaccination nor demonstrated low-level serum antibody guarantees immunity to measles in individuals with significantly impaired immunity.23,39 Testing for measles antibody may delay the appropriate use of NHIG. However, testing may be of value in making a definitive diagnosis of measles.
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Infants 6–9 months of age who have direct contact with a person with measles are at risk of developing complications from the disease, and should be offered NHIG within 7 days of contact.39 MMR vaccine should then be given as close as possible to 12 months of age, after an interval of at least 5 months following the administration of immunoglobulin (see Chapter 2.3, Groups with special vaccination requirements, Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination). NHIG is not usually given to babies <6 months of age, who are protected by passive maternal antibodies. However, if the mother of an infant <6 months of age does not have documented evidence of having received 2 doses of MMR, or is the measles case, the infant should be given NHIG. Similarly, premature infants (<28 weeks’ gestation) have little or no acquisition of transplacental maternal antibody, irrespective of the number of doses of MMR the mother has received, and should also be offered NHIG (see Table 3.11.1).
Table 3.11.1: Management of significant measles exposure using vaccination or normal human immunoglobulin (NHIG) Age
Action
<6 months
NHIG 0.2 mL/kg* IM injection if mother has not received 2 documented doses of MMR, or the mother is the measles case, or the infant was premature (<28 weeks’ gestation)
≥6–≤9 months
NHIG 0.2 mL/kg IM injection*
≥10 months
MMR or MMRV vaccine within 72 hours of exposure OR NHIG 0.2 mL/kg IM injection* if 3–7 days after exposure†
* The dose of NHIG is 0.2 mL/kg in immunocompetent individuals and 0.5 mL/kg in those with impaired immunity. † Immunoglobulin is not required if the person has received at least 1 measles-containing vaccine at ≥12 months of age or is assessed as being not susceptible (see (i) ‘Definition of a person who is considered not susceptible to measles’ above), unless the person has impaired immunity.
Use in pregnancy MMR vaccine is not recommended in pregnancy due to the theoretical risk of transmission of the rubella component of the vaccine to a susceptible fetus. Pregnancy should be avoided for 28 days after vaccination30 (see Chapter 3.19, Rubella and Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy).
Variations from product information The product information recommends that women of child-bearing age should be advised not to become pregnant for 3 months after vaccination with MMR or MMRV vaccines, whereas the NHMRC recommends 28 days.30 The product information for Priorix states that people with a history of anaphylactic or anaphylactoid reactions should not be vaccinated with Priorix, but it is established that MMR vaccine can be given in this situation.23
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.12 Meningococcal disease Bacteriology Meningococcal disease is caused by the bacterium Neisseria meningitidis (N. meningitidis or the meningococcus), a Gram-negative diplococcus. There are 13 known serogroups distinguished by differences in surface polysaccharides of the outer membrane capsule. Meningococcal serogroups are designated by letters of the alphabet. Globally, serogroups A, B, C, W135 and Y most commonly cause disease. Meningococci can be further differentiated by differences in their outer membrane proteins, which are referred to as serotypes and serosubtypes.1 More recently, molecular typing has been used to further differentiate meningococci. In Australia, serogroups B and C occur most frequently. There is no consistent relationship between serogroup or type and virulence.2,3
Clinical features Neisseria meningitidis can cause meningitis, septicaemia or a combination of the two. Other localised infections, including pneumonia, arthritis and conjunctivitis, may also occur but are uncommon. Septicaemia, with or without meningitis, can be particularly severe. The overall mortality risk is high (about 10%) despite appropriate antibiotic therapy. N. meningitidis is carried and transmitted only by humans. There are no known animal reservoirs. Asymptomatic respiratory tract carriage of meningococci is present in about 10% of the population, and the prevalence may be higher when groups of people occupy small areas of living space.2-8 Recent studies indicate that there may be a number of factors which contribute to the increased risk of contracting meningococcal disease, including exposure to smokers, recent illness, living in crowded conditions and multiple intimate kissing partners.4-8 People with inherited disorders of phagocytosis associated with properdin deficiency or absence of the terminal components of complement, as well as individuals with functional or anatomical asplenia, have an increased risk of meningococcal infection.1
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The disease is transmitted via respiratory droplets, and has an incubation period of between 1 and 10 days, but commonly 3 to 4 days.4 The capacity of meningococcal disease to have a fulminant and rapidly fatal course in previously healthy (and usually young) individuals causes it to be greatly feared. Intensive public health follow-up is required after each single case to conduct contact tracing and to institute appropriate public health measures for contacts. As a result of all these factors, this disease causes widespread community alarm and generates significant media interest.9
Epidemiology Meningococci cause both sporadic and epidemic disease throughout the world. Serogroup A disease occurs predominantly in developing populations such as those in Africa and Asia, while serogroup B is the major cause of sporadic meningococcal disease in most developed countries. Serogroup C disease has a more cyclic pattern of occurrence, and increased in incidence in the 1990s in some developed countries such as Australia and the United Kingdom.4 Serogroup C meningococci have also been occasionally associated with small clusters of meningococcal disease cases in schools, universities and nightclubs in Australia over the past 10 years.10-15 As in other temperate climates, meningococcal disease cases occurring in Australia tend to follow a seasonal trend, the majority of cases being reported during late winter and early spring. The overall notification rate of meningococcal disease to the National Notifiable Diseases Surveillance System increased gradually from 1.8 per 100 000 in 1991, to a peak of 3.5 per 100 000 in 2001, but declined to 1.8 per 100 000 in 2005.16 There are considerable differences noted in the incidence of meningococcal disease between States and Territories, with 5.4 cases per 100 000 notified from the Northern Territory to 1.9 per 100 000 reported for Queensland during 2005.16 These figures include meningococcal disease cases which were diagnosed on clinical grounds alone, and those cases that were confirmed by laboratory methods such as culture, serology or nucleic acid testing of clinical material. In 2005, 369 cases were reported nationally, of which 345 were laboratory confirmed.16,17 The majority of laboratory-confirmed meningococcal cases were serogroup B (73%) and serogroup C (14.5%).17 There has been a steady decline in serogroup C meningococcal disease among the 0–18 years age group since the 2003 introduction of routine meningococcal C vaccination and catch-up programs in this age group.18 Meningococcal disease can occur in any age group, but the majority of cases occur in those <5 years of age, with a secondary peak seen in the 15–24 years age group. In Australia, meningococcal disease in the <5 years age group is due predominantly to infection with serogroup B meningococci; very few cases of serogroup C meningococcal disease are now seen in this age group.17 In the 15–19 years age group, both serogroup B and C disease were seen before the introduction of the meningococcal C conjugate vaccine in 2003. In contrast to Australia, New Zealand has, over the past 14 years, experienced an epidemic of meningococcal disease which has been almost exclusively associated with a particular strain of serogroup B (B:4:P1.7b,4).19,20 Meningococcal disease rates in NZ rose from 1.5 cases per 100 000 during 1989–1990 to 14.5 cases per 100 000 in 2003.19 A meningococcal B outer membrane vesicle vaccine (MeNZB™), currently being used in New Zealand, is only effective against the serotype and serosubtype of the New Zealand serogroup B strain and is not available in Australia.20
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Vaccines There are 2 different types of meningococcal vaccine: the meningococcal C conjugate vaccines (MenCCV) and the tetravalent meningococcal polysaccharide vaccines (4vMenPV). The differences between these 2 types of vaccines lie in the different way that each vaccine stimulates an immune response. Other than the New Zealand specific vaccine, there is currently no vaccine effective against serogroup B meningococcal disease although extensive research is being undertaken in this area.
CONJUGATE VACCINES Meningococcal C conjugate vaccines (MenCCV) • Meningitec – Wyeth Australia Pty Ltd (meningococcal serogroup C–CRM197 conjugate vaccine). Each 0.5 mL monodose vial contains 10 µg N. meningitidis serogroup C oligosaccharide conjugated to approximately 15 µg of a non-toxic Corynebacterium diphtheriae CRM197 protein; aluminium phosphate. • Menjugate Syringe – CSL Biotherapies/Novartis Vaccines (meningococcal serogroup C–CRM197 conjugate vaccine). Lyophilised powder in a monodose vial with a pre-filled diluent syringe. Each 0.5 mL dose of reconstituted vaccine contains 10 µg N. meningitidis serogroup C polysaccharide conjugated to 12.5–25 µg of a non-toxic Corynebacterium diphtheriae CRM197 protein; 1.0 mg aluminium hydroxide. 5 or 10 monodose packs also available. • NeisVac-C – Baxter Healthcare (meningococcal serogroup C–tetanus toxoid protein conjugate vaccine). Each 0.5 mL pre-filled syringe contains 10 µg N. meningitidis serogroup C polysaccharide conjugated to 10–20 µg of tetanus toxoid protein; 0.5 mg aluminium hydroxide. 10 or 20 monodose packs available.
MenCCVs confer protection only against serogroup C disease. In these vaccines, an oligo- or polysaccharide antigen is chemically linked (ie. ‘conjugated’) to a carrier protein. Conjugation changes the nature of the antibody response from a T cell-independent to a T cell-dependent response. The T cell help results in improved antibody responses, especially in young children, greater functional activity, and induction of immunological memory, probably resulting in longterm protection.
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In January 2003, the Australian Government commenced the National Meningococcal C Vaccination Program which provided free MenCCV to all children who turned 1 to 19 years of age during 2003. MenCCV was also added to the National Immunisation Program (NIP) schedule at 12 months of age at that time.
In the United Kingdom, 98 to 100% of infants given 3 doses of MenCCV in a 2, 3 and 4 month schedule developed protective antibody titres after the third dose,21,22 but evidence of waning immunity and vaccine failures led to a booster dose being recommended for children vaccinated according to the 2, 3 and 4 month schedule of MenCCV,23 which has now been altered to a 3-dose schedule at 3, 4 and 12 months of age.24 In Australia, although some children have received MenCCV before 12 months of age, this was according to a 2, 4, 6 month schedule and there is no evidence of vaccine failure. NHMRC, therefore, does not recommend recall for a booster dose in children previously vaccinated before 12 months of age (unless they have inherited defects of properdin or complement, or functional or anatomical asplenia – see ‘Recommendations’ below). In children >12 months of age, a single dose of MenCCV appears sufficient to induce protective antibody responses. In children 12–18 months of age receiving a single dose of MenCCV, 91 to 100% achieved serum bactericidal antibodies (SBA) titres ≥1:8.25 In older children, seroconversion rates increase with age: 96% of 3-year-olds, 98% of 4–5-year-olds, and 98% of 14–17-year-olds achieved SBA titres ≥1:8 after a single dose.25 In those children aged ≥1 year who have received only a single dose of the meningococcal C conjugate vaccine, the duration of immunity and the need for booster doses is not yet known. The Netherlands routinely vaccinates with MenCCV at 14 months of age, and data from 2002 onwards currently indicates that vaccination after the 1st birthday results in longer protection than multiple doses in infancy.26
POLYSACCHARIDE VACCINES Meningococcal polysaccharide vaccines (4vMenPV) • Mencevax ACWY – GlaxoSmithKline (serogroup A, C, W135 and Y meningococcal polysaccharide vaccine). Each 0.5 mL monodose of the reconstituted lyophilised vaccine contains 50 µg of each polysaccharide; lactose. 10-dose vials in packs of 50 contain 0.25% phenol as a preservative. Saline diluent for each vial. • Menomune – Sanofi Pasteur Pty Ltd (serogroup A, C, W135 and Y meningococcal polysaccharide vaccine). Each 0.5 mL monodose of the reconstituted lyophilised vaccine contains 50 µg of each polysaccharide; lactose. 4vMenPVs provide protection against serogroups A, C, W135 and Y. The vaccine induces antibodies in 10 to 14 days in 90% of recipients >2 years of age. Immunity decreases markedly during the first 3 years following a single dose of vaccine, particularly in infants and young children. However, clinical protection persists for at least 3 years in school children and adults.
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The duration of immunity is further complicated by the induction of immunological hyporesponsiveness to the serogroup C component following repeated vaccination with 4vMenPV, as revaccination results in a reduced antibody response compared with the primary immunisation.27 This phenomenon has been noted in both children and adults.28-31 The demonstration of subsequent hyporesponsiveness has led to the concern that vaccinating lowrisk individuals may reduce the effectiveness of revaccination in a subsequent high-risk situation, although this has not been clinically demonstrated. This hyporesponsiveness can be overcome with MenCCV, although additional doses of the conjugate vaccine may be required in young children.32,33 There is little response to the serogroup C component of the 4vMenPV before 18 months of age and little response to serogroup A before 3 months of age.34,35
Transport, storage and handling Meningococcal C conjugate vaccines Transport according to National Vaccine Storage Guidelines: Strive for 5.36 Storage of all MenCCVs should be at +2°C to +8°C. Do not freeze. Protect from light. The product information for NeisVac-C states that this vaccine can be stored at +25°C for a period of up to 9 months but must not be returned to the refrigerator.
Meningococcal polysaccharide vaccines Transport according to National Vaccine Storage Guidelines: Strive for 5.36 Store at +2°C to +8°C. Do not freeze. Protect from light. Reconstituted vaccine should be used immediately but may be stored in the refrigerator at +2°C to +8°C, and must be discarded if not used within 8 hours.
Dosage and administration Meningococcal C conjugate vaccines
Meningococcal polysaccharide vaccines The 4vMenPV dose is 0.5 mL, administered by SC injection. 4vMenPVs are approved for use in Australia in children ≥2 years of age, adolescents and adults.
Administration of MenCCV after administration of 4vMenPV There are limited data available on the length of time that should lapse before administration of MenCCV after giving 4vMenPV. The NHMRC recommends a period of 6 months before the conjugate vaccine is given.21,37
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The MenCCV dose is 0.5 mL given by IM injection. Do not mix MenCCV with other vaccines in the same syringe. Experience from the use of the conjugate Hib vaccines suggests that the different brands of the MenCCVs are interchangeable. MenCCVs may be administered simultaneously with other vaccines in the NIP (see ‘Variations from product information’ below). MenCCVs are registered for use in Australia from 6 weeks of age.
Administration of 4vMenPV after administration of MenCCV On occasion, both MenCCV and 4vMenPV are recommended (eg. asplenia). If MenCCV is given first, a period of ≥2 weeks should lapse before 4vMenPV is given.
Recommendations Meningococcal C conjugate vaccines (i) Routine vaccination It is recommended that a single dose be given to all children at the age of 12 months. Vaccination before 12 months of age is not recommended, except in infants with inherited defects of properdin or complement, or functional or anatomical asplenia (see (ii) below). Infants, other than those described in the circumstances below, who receive dose(s) of vaccine at <12 months of age, should be given a further dose at 12 months of age or 4 weeks after the last dose, whichever is later. However, it is not necessary to recall older children who received 3 doses of MenCCV before 12 months of age, as there has been no evidence to date of vaccine failure in infants vaccinated according to a 2, 4, 6 month schedule (see ‘Vaccines’ above).
(ii) Vaccination of people at high risk for meningococcal disease The vaccine is also recommended for: • close (household or household-like) contacts of meningococcal disease cases due to serogroup C, >2 months of age, who have not previously been vaccinated (refer to ‘The early clinical and public health management of meningococcal disease’ below), • control of outbreaks caused by serogroup C (refer to ‘The early clinical and public health management of meningococcal disease’ below), • laboratory personnel who frequently handle N. meningitidis, who should also receive 4vMenPV, • those >6 weeks of age with inherited defects of properdin or complement, or functional or anatomical asplenia. When MenCCV is given to these individuals at <12 months of age, in addition to a booster dose of MenCCV at 12 months of age, a dose of 4vMenPV is recommended at ≥2 years of age. Under the circumstances as described above, a child under the recommended age of 12 months requiring vaccination should receive doses as follows: • Infants <6 months of age require 2 doses of 0.5 mL, given at least 8 weeks apart, followed by a booster dose at 12 months of age. • Children 6–11 months of age require 1 dose of 0.5 mL, followed by a booster dose at 12 months of age or 8 weeks after the first dose, whichever is later.
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Meningococcal polysaccharide vaccines Routine vaccination with 4vMenPV is not recommended. However, it is recommended in the following situations: • people who intend travelling to parts of the world where epidemics of group A, W135 or Y disease are frequent (a current list of those countries is available from the World Health Organization at either http://www.who.int/ith or http://www.who.int/disease-outbreak-news/), • close (household or household-like) contacts, ≥2 years of age, of cases of serogroup A, W135 or Y meningococcal disease, • control of outbreaks caused by serogroup A, W135 or Y. A Cochrane review examined the use of polysaccharide vaccine for the prevention of serogroup A meningococcal meningitis. The review assessed 8 randomised controlled trials and the protective effect from the vaccine was consistent across all the trials with a vaccine efficacy of around 95%,38 • laboratory personnel who frequently handle N. meningitidis, who should also receive MenCCV, • those ≥2 years of age with inherited defects of properdin or complement, or functional or anatomical asplenia, who should also receive MenCCV, and • pilgrims attending the annual Hajj (Saudi Arabian authorities require a valid certificate of vaccination as a condition to enter the country). A single revaccination with 4vMenPV is indicated for people at continued high risk of infection (such as those living in epidemic areas, and those with impaired immunity as defined above), particularly children first vaccinated before 4 years of age. As antibody levels decline rapidly over 2 to 3 years, revaccination should be given 3 to 5 years later. Data regarding the benefit of subsequent revaccinations with 4vMenPV are unavailable at this time.
Contraindications Meningococcal C conjugate vaccines The only absolute contraindications to MenCCV are: • anaphylaxis following a previous dose, or Previous serogroup C disease is not a contraindication to administration of MenCCV.
Meningococcal polysaccharide vaccines The only absolute contraindications to 4vMenPV are: • anaphylaxis following a previous dose, or • anaphylaxis following any vaccine component.
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• anaphylaxis following any component of the vaccine
Adverse events Meningococcal C conjugate vaccines Very common (>10%) adverse events caused by MenCCVs are pain, redness and swelling at the site of injection, fever, irritability, anorexia and headaches. There are some age-related differences in the type of adverse event following vaccination, with systemic adverse events tending to decrease with increasing age, and local adverse events tending to increase with increasing age. Headache is more likely to be reported in the adolescent age group. Serious general adverse events are rare.37
Meningococcal polysaccharide vaccines Local reactions to 4vMenPV include erythema, induration, tenderness, pain and local axillary lymphadenopathy. However, they are usually mild and infrequent. Fever and chills occur in approximately 2% (common) of young children, and may persist for 48 hours or longer, but significant general adverse events are rare.
The early clinical and public health management of meningococcal disease Prompt diagnosis and emergency treatment of cases of suspected meningococcal disease are life-saving. If a diagnosis of meningococcal disease is suspected, the patient should be immediately given parenteral (usually IM) penicillin and transferred to hospital. The relevant Public Health Unit must be contacted as soon as possible.4 Table 3.12.1: Early clinical management of suspected meningococcal disease The patient should receive immediate benzylpenicillin (usually IM).
Age <1 year
300 mg benzylpenicillin
Age 1–9 years
600 mg benzylpenicillin
Age ≥10 years
1200 mg benzylpenicillin
The patient should be transferred to hospital urgently. The relevant Public Health Unit should be notified promptly, so that appropriate public health management can be initiated.
Guidance on the early clinical and public health management of cases of invasive meningococcal disease has been developed by the Communicable Diseases Network of Australia, and is available at http://www.health.gov.au/pubhlth/cdi/pubs/pdf/mening_guide.pdf.4 Contrary to popular belief, a patient with meningococcal disease is not a good transmitter of the disease. Rather, it is carrier(s) passing on the bacteria to other susceptible individuals who may cause further cases of meningococcal disease. Further cases may develop in household contacts in particular. The risk of secondary cases is greatest in the first 7 days, and may persist for many weeks after contact. The public health management of close contacts includes
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information, clearance antibiotics and vaccination. Clearance antibiotics should be offered to all identified close contacts regardless of previous vaccination history. Clearance antibiotics are not recommended for healthcare workers unless they were engaged in either mouth-to-mouth resuscitation or were not wearing a mask while intubating a case. Non-vaccinated close contacts of a proven vaccine-preventable strain of invasive meningococcal disease should be advised in writing by their local Public Health Unit to visit their usual healthcare provider at the next available opportunity to receive the appropriate vaccine.4 Antibiotics that reduce or eliminate nasopharyngeal carriage of N. meningitidis include ceftriaxone, ciprofloxacin and rifampicin. • Ceftriaxone is administered as a single IM dose of 250 mg for adults and 125 mg for children <12 years of age. Although it is considerably more expensive, ceftriaxone has a number of advantages over rifampicin: it is more likely to eradicate pharyngeal carriage, it eliminates problems with compliance and it is the preferred chemoprophylaxis for pregnant women. • Ciprofloxacin in a single oral dose of 500 mg is effective and safe, but it should not be given to children <12 years of age, or to pregnant women. • Rifampicin is given to children and adults in an oral dose of 10 mg/kg (maximum dose of 600 mg) twice daily for 2 days. The recommended dose for infants <1 month of age is 5 mg/kg twice daily for 2 days. Pharyngeal carriage will be eliminated in 75 to 90% of recipients unless the strain is resistant to rifampicin. The side effects of rifampicin should be explained, including orange-red discolouration of contact lenses, urine and tears, possible interference with the contraceptive pill, and interference with the metabolism of many other drugs including warfarin, phenobarbitone and phenytoin. Rifampicin is not recommended for use in pregnant women.
Use in pregnancy Meningococcal C conjugate vaccines Although no clinical study data are available on the use of MenCCV in pregnant women, it is unlikely that it would have any deleterious effect on the pregnancy. Routine pregnancy testing before vaccination is not justified.
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A potential outbreak of meningococcal disease in an institutional or community setting is a public health emergency needing a rapid response from clinicians and public health practitioners. The decision to control an outbreak with a vaccination program should be made by the appropriate Public Health Unit, following the Guidelines for the early clinical and public health management of meningococcal disease in Australia.4 If vaccination is indicated and the organism responsible is serogroup C, MenCCV should be used in preference to 4vMenPV.
Meningococcal polysaccharide vaccines Studies of vaccination with meningococcal and other polysaccharide vaccines during pregnancy have not documented adverse events in either pregnant women or newborns.1,39,40 The number of pregnant vaccinees who received 4vMenPV as reported in the literature is small. A North American study of 109 women who received the 4vMenPV vaccine between 30 and 38 weeks’ gestation reported no birth defects.39 A further study of 34 pregnant women in the US who received 4vMenPV during their second and third trimester revealed no teratogenicity and the infants were assessed for 2 years after birth. No developmental abnormalities were detected.40
Variations from product information Meningococcal C conjugate vaccines The product information for meningococcal C conjugate vaccines state that, under the age of 12 months, either 2 (NeisVac-C) or 3 (Meningitec and Menjugate) doses of vaccine are required. The NHMRC recommends that meningococcal C vaccination is not required before 12 months of age (unless specifically indicated). The NeisVac-C product information states that the vaccine should not be administered with pneumococcal conjugate vaccine, hepatitis B vaccine and PRP-OMP Haemophilus influenzae type b vaccine unless ‘medically important’. However, the NHMRC states that the vaccine may be administered simultaneously with other vaccines in the NIP. There have been recent publications citing the coadministration of MenCCV with other combination vaccines and it was found to be immunogenic and safe.41,42 The product information for all 3 conjugate vaccines states that there are no data on the use of MenCCVs in lactating women, whereas the NHMRC does not consider breastfeeding in a healthy woman a reason for not vaccinating. The Meningitec product information states that an allergic reaction following a previous dose is a contraindication to further doses, whereas the NHMRC states that only an anaphylactic adverse event following a previous dose is a contraindication.
Meningococcal polysaccharide vaccines The NHMRC recommends revaccination with 4vMenPV within 3 to 5 years of a previous dose in the situations detailed in ‘Recommendations’ above. The Mencevax ACWY product information states within 2 to 3 years, and the Menomune product information gives no recommended interval before revaccination.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.13 Mumps
Mumps is a paramyxovirus, genus Rubulavirus, with a single-stranded RNA genome. It is rapidly inactivated by heat, formalin, ether, chloroform and ultraviolet light.1
Clinical features Mumps is an acute viral illness with an incubation period of 14 to 25 days.2 Asymptomatic infection occurs in one-third of cases.3 Symptomatic disease ranges from mild upper respiratory symptoms to widespread systemic involvement.3 A high proportion of mumps infections involve non-specific symptoms including fever, headache, malaise, myalgia and anorexia.4 The characteristic bilateral, or occasionally unilateral, parotid swelling occurs in 60 to 70% of clinical cases.4 Benign meningeal signs appear in up to 15% of cases, but permanent sequelae are rare. Nerve deafness is one of the most serious of the rare complications (1 in 500 hospitalised cases). Orchitis (usually unilateral) has been reported in up to 20% of clinical mumps cases in post-pubertal males, but subsequent sterility is rare. Symptomatic involvement of other glands and organs has been observed less frequently (pancreatitis, oophoritis, hepatitis, myocarditis, thyroiditis, mastitis).1,4 Patients may be infectious from 6 days before parotid swelling to 9 days after.2 Mumps encephalitis has been reported to range as high as 1 in 200 cases, with a case-fatality rate of around 1.0%. Mumps infection during the first trimester of pregnancy may result in spontaneous abortion.3,4 Maternal infection is not associated with an increased risk of congenital malformation.3,4
Epidemiology Mumps is reported worldwide, and is a human disease. Transmission is by the respiratory route in the form of air-borne droplets or by direct contact with saliva or possibly urine.2 Before universal vaccination, mumps was primarily a disease of childhood, the peak incidence being in the 5–9 year age group. However, since 2000, peak rates have been reported in older adolescents and young adults, especially the 20–24 year age group.5-7 Between 2001 and 2005, the average notification rate for mumps in Australia was 0.6 per 100 000.8 There have been recent outbreaks of mumps in the USA, and also in the United Kingdom, where the peak rates of disease have been in the 18–24 year age group.9,10 Approximately 2000 cases were reported in the USA in a 2006 outbreak, parotitis being reported in 66% of clinical cases.11 Mumps attack rates in outbreaks are lowest in individuals who have received 2 doses of mumps-containing vaccines, as this provides optimal long-term protection.10,11 In Australia, over the 10-year
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Virology
period from 1996 to 2005, mumps has been reported as the underlying cause of death in 4 subjects, all adults aged over 80 years.5-7
Vaccines Monovalent mumps vaccine is no longer available in Australia. Mumps vaccination is provided using either MMR vaccine or MMRV vaccine when available. Clinical trials of mumps vaccine indicate 95% seroconversion after a single dose of MMR.4 However, outbreak investigations and post-marketing studies have reported 1-dose vaccine effectiveness to be between 60 and 90%.10 Protection is greater in 2-dose vaccine recipients, who have seroconversion rates of up to 100%.4,10,12 • Priorix (MMR) – GlaxoSmithKline (live attenuated measles virus (Schwarz strain), RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 103.0 CCID50 (cell culture infectious dose 50%) of the Schwarz measles, not less than 103.7 CCID50 of the RIT 4385 mumps and not less than 103.0 CCID50 of the Wistar RA 27/3 rubella virus strains; lactose; neomycin; amino acids; sorbitol and mannitol as stabilisers.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.13 Store at +2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine should be used immediately, but can be stored at +2°C to +8°C for up to 8 hours before use.
Dosage and administration For both children and adults, the dose of MMR is 0.5 mL, administered by either SC or IM injection. MMR can be given at the same time as other vaccines (including DTPa, hepatitis B, MenCCV and varicella), using separate syringes and injection sites. If MMR is not given simultaneously with other live viral parenteral vaccines (eg. varicella vaccine), they should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations All children should receive 2 doses of MMR vaccine (or MMRV vaccine, when available, if ≤12 years of age). Routine administration of MMR (or MMRV) is now recommended at 12 months and 18 months of age in order to maximise protection at an early age. The minimum interval between doses is 4 weeks. In older individuals, who have received only 1 dose of mumps-containing vaccine, a second dose can be given, as MMR, at any age.
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For further information on the recommendations for MMR (and MMRV when available) see Chapter 3.11, Measles and Chapter 3.24, Varicella.
See information on MMR and MMRV vaccines in Chapter 3.11, Measles and Chapter 3.24, Varicella.
Precautions If MMR is not given simultaneously with other live viral parenteral vaccines (eg. varicella vaccine), they should be given at least 4 weeks apart. See further information on MMR and MMRV vaccines in Chapter 3.11, Measles and Chapter 3.24, Varicella.
Adverse events In Australia, vaccine-associated aseptic meningitis is not considered a problem. Post-licensure surveillance of mumps vaccine recipients in Germany, over a 2-year period, found no increase in cases of aseptic meningitis. However, other estimates in countries using mumps vaccines with different vaccine virus strains suggest 1 case occurs per 800 000–1 million doses.4,14 Vaccineassociated meningoencephalitis is invariably mild or asymptomatic and resolves spontaneously. When mumps virus is isolated from the cerebrospinal fluid in such cases, laboratory tests can be undertaken to distinguish between wild and vaccine strains. The assistance of State virology laboratories should be sought in such cases. Re-vaccination with mumps-containing vaccines is not associated with an increased incidence of adverse events. For further information on the adverse events associated with MMR and MMRV, see Chapter 3.11, Measles and Chapter 3.24, Varicella.
Use of immunoglobulin to prevent mumps Normal human immunoglobulin (NHIG) has not been shown to be of value in post-exposure prophylaxis for mumps.1,15 Live mumps-containing vaccine does not provide protection if given after an individual has been exposed to mumps.1,15 However, if the exposure did not result in infection, the vaccine would induce protection against subsequent infection.
Use in pregnancy MMR vaccine is not recommended in pregnancy due to the theoretical risk of transmission of the rubella component of the vaccine to a susceptible fetus (see Chapter 3.19, Rubella). Pregnancy should be avoided for 28 days after vaccination.16 Data on the use of MMRV vaccines in individuals >12 years of age are not available.
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Contraindications
Variations from product information See information on MMR vaccines in Chapter 3.11, Measles.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.14 Pertussis Bacteriology Pertussis (whooping cough) is caused by Bordetella pertussis, a fastidious, Gramnegative, pleomorphic bacillus. There are other organisms (such as Bordetella parapertussis, Mycoplasma pneumoniae and Chlamydia pneumoniae) which can cause a pertussis-like syndrome.1 Identification of pertussis is limited by patient and physician awareness and the limited sensitivity of diagnostic tests; it is generally believed to be significantly under-diagnosed.
Clinical features
Death due to pertussis is rare in people >10 years of age. However, the case fatality rate in unvaccinated infants <6 months of age is estimated to be 0.8%.5,6 The most common cause of death in pertussis infection is pertussis pneumonia, sometimes complicated by seizures and hypoxic encephalopathy.2 Both hospitalisations and deaths are likely to be under-estimated.7 In Australia between 1993 and 2005, there were 18 deaths attributed to pertussis, all but 2 in infants <12 months of age.8-11
Epidemiology Epidemics occur every 3 to 4 years. In unvaccinated populations, these outbreaks can be very large. In vaccinated populations, outbreaks are smaller, with greatly reduced mortality and morbidity, and may continue to occur every 3 to 4 years or be more widely spaced. Maternal antibody does not provide reliable protection against pertussis, and the maximal risk of infection and severe morbidity is before infants are old enough to have received at least 2 vaccine doses.7 In recent years, among highly immunised communities, many cases of pertussis in adults and adolescents, due to waning immunity, have been recognised due to the increased availability of serological testing.6,12 These individuals are a significant reservoir of infection. From 1993 to 2005, 4 epidemics of pertussis
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Pertussis is an epidemic respiratory infection with an incubation period of 7 to 20 days. In unvaccinated individuals, B. pertussis is highly infectious, spreading by respiratory droplets to 80% of susceptible household contacts.2 The characteristic paroxysmal cough with inspiratory whoop seen in unvaccinated children is less common in older children and adults who have varying degrees of immunity acquired from vaccination or infection. It has been estimated that B. pertussis accounts for up to 7% of cough illness per year in adults and, each year, more than 25% of adults experience a coughing illness of at least 5 days’ duration.2,3 Even in adults, pertussis can be associated with significant morbidity, with cough persisting for up to 3 months, and other significant symptoms, such as sleep disturbance or, rarely, rib fracture.4
occurred in Australia. A total of more than 84 000 cases was reported in this time, an annual incidence of 22.8 to 57.4 cases per 100 000 population.13 Introduction of a fifth dose of diphtheria, tetanus and pertussis vaccine (DTP) for 4–5-year-old children in August 1994 was followed by a pattern of decrease in notifications consistent with a vaccine effect, occurring first among children aged 5 and 6 years, followed by those in the 7–9-year age group.14,15 Subsequently, the average age of those notified with pertussis has continued to increase. In 2004–2005, more than 70% of pertussis notifications were in individuals >15 years of age13,16 compared with 40 to 50% in the early 1990s. This supports the need for booster doses in those >10 years of age, both to reduce individual morbidity, and to reduce transmission to those most at risk (infants <6 months of age).17 Vaccination of adolescents, who have a high risk of pertussis infection, and adults in contact with very young infants, is expected to result in the greatest health benefits. A single booster dose using an adolescent/adult formulation acellular pertussis-containing vaccine (dTpa) has been included in the National Immunisation Program (NIP) for 15–17-year-olds since January 2004. Figure 3.14.1: Pertussis notifications by year of onset, Australia 1993–2005. The percentage of notifications in those aged ≥15 years is shown (- -)
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Vaccines Acellular pertussis-containing vaccines have been used for both primary and booster vaccination of children in Australia since 1999. There are a number of acellular pertussis vaccines, which contain 3 or more purified components of B. pertussis. In the 3 component vaccines, these are pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). In the 5 component vaccines, fimbrial antigens or agglutinogens are also included. Acellular pertussis vaccines with 3 or more antigens have similar efficacy to good quality wholecell vaccines18 and are immunogenic and safe. Although serious adverse events such as hypotonic-hyporesponsive episodes can still occur, they are much less common than with whole-cell vaccines.18 Vaccines containing DTPa are also available in various combinations with inactivated polio, hepatitis B and Haemophilus influenzae type b vaccines.
The adolescent/adult formulation dTpa vaccines are immunogenic, safe and well tolerated in adults.19-21 Formulations for children aged <8 years • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine-Haemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins. • Infanrix-IPV – GlaxoSmithKline (DTPa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin.
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The acronym DTPa, using capital letters, signifies child formulations of diphtheria, tetanus and acellular pertussis-containing vaccines. The acronym dTpa is used for adolescent/adult formulations which contain substantially lesser amounts of diphtheria toxoid and pertussis antigens (see formulations).
• Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. May also contain yeast proteins. Formulations for people aged ≥8 years Combination vaccines • Adacel – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg pertussis fimbriae (FIM) 2+3; 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde. • Adacel Polio – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg FIM 2+3, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett); 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin, neomycin and streptomycin. • Boostrix – GlaxoSmithKline (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial or pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, adsorbed onto 0.5 mg aluminium hydroxide/phosphate; 2.5 mg phenoxyethanol as preservative. May contain traces of formaldehyde. • Boostrix-IPV – GlaxoSmithKline (dTpa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde, polymyxin and neomycin.
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Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.22 Store at +2°C to +8°C. Do not freeze. Protect from light.
Dosage and administration The dose of DTPa-combinations, dTpa and dTpa-IPV is 0.5 mL by IM injection. Do not mix DTPa-containing vaccines with any other vaccine in the same syringe, unless specifically registered for use in this way.
Recommendations (i) Vaccination of children and adolescents
For the booster dose of DTPa given at 4 years of age, all brands of DTPacontaining vaccines are considered interchangeable. In view of the prolonged immunity now known to result from a primary course of DTPa at 2, 4 and 6 months of age,23 the 18-month dose was omitted in 2003. It is expected that postponing receipt of a fourth dose of DTPa until 4 years of age will reduce the proportion of children experiencing extensive local reactions, which occurred in 2% of children following a fourth dose at 18 months of age.24,25 A second booster, between 12 and 17 years of age, using the adolescent/adult formulation dTpa, is essential for maintaining immunity to pertussis through the adolescent period and into early adulthood. By the age of 17 years, young adults should have received 5 doses of a pertussis-containing vaccine. Most adolescents would have either had at least 3 previous doses of a pertussis-containing vaccine or been exposed to the pertussis bacterium. Therefore, if documentation of previous vaccinations is not readily available, it can be safely assumed that a dose of dTpa at 12–17 years is indeed a booster dose. For details on the management of children who have missed doses in the NIP schedule, see Section 1.3.5, Catch-up.
(ii) Vaccination of adults dTpa vaccines are recommended in Australia for booster vaccination of individuals ≥8 years of age who have previously had a primary course of
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Acellular pertussis antigens are given in combination with diphtheria and tetanus toxoids (DTPa) in a primary course of vaccination at 2, 4 and 6 months of age. In view of the high morbidity and occasional mortality associated with pertussis under the age of 6 months, receipt of the first dose of vaccine as soon as possible after 2 months of age should be strongly emphasised. If the primary course is interrupted, it should be resumed but not repeated; catch-up doses may be given as little as 4 weeks apart. The same formulation of vaccine should be used for each of the 3 doses. If it is not known which brand was used, vaccination should be provided using any available brand.
diphtheria-tetanus-pertussis vaccine. dTpa vaccines have a lower content of diphtheria and pertussis antigens than DTPa formulations for young children. Primary vaccination If a 3-dose primary course of diphtheria/tetanus toxoids is given to an adolescent/adult without a previous history of having received pertussiscontaining vaccine, the preferred option is that dTpa replace the first dose of dT, to provide pertussis immunity as early as possible,26 with subsequent doses as dT. In the event that dT is not available, dTpa can be used for all primary doses, but this is not routinely recommended as there are no data on the safety, immunogenicity or efficacy of dTpa for primary vaccination. For detailed recommendations regarding a primary dT course in adults, see Chapter 3.21, Tetanus. Duration of protection and spacing of booster doses A single booster dose of dTpa is recommended for the following groups provided that no documented dTpa booster dose has been previously received: • Adults planning a pregnancy, or for both parents as soon as possible after delivery of an infant (preferably before hospital discharge), unless contraindicated.17 Other adult household members, grandparents and carers of young children should also be vaccinated. This recommendation is based on evidence from several studies of infant pertussis cases, which indicated that family members, particularly parents, were identified as the source of infection in more than 50% of cases and were the presumed source in a higher proportion.27-29 • Adults working with young children. Vaccination is especially recommended for childcare workers (see Chapter 2.3, Groups with special vaccination requirements, Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases).30,31 • All healthcare workers (see also Chapter 2.3, Groups with special vaccination requirements, Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases). Several case reports have documented nosocomial infection in young infants acquired from healthcare workers.30,31 • Any adult expressing an interest in receiving a booster dose of dT vaccine should be encouraged to do so with dTpa vaccine. At the age routinely recommended for tetanus and diphtheria booster (50 years), dTpa produces immune responses to tetanus and diphtheria antigens equivalent to dT vaccine, and would also provide protection against pertussis.32 Data on the duration of immunity to pertussis following a single booster dose of dTpa are limited in adults and adolescents.20,33 Although subsequent doses of dTpa may prove beneficial, especially in high-risk groups such as healthcare workers, such boosters are unlikely to be required before 10 years and recommendations must await further data.
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Minimum interval between dTpa and other tetanus/ diphtheria-containing vaccines A single dose of dTpa can be administered at any time after a dose of a vaccine containing tetanus and diphtheria toxoids. Recent studies from Canada have shown that a single dose of dTpa can be safely administered as soon as 18 months after a previous dose of a vaccine containing tetanus or diphtheria toxoids.34-36 Where a tetanus- or diphtheria-containing vaccine has been given even less than 18 months previously, the benefits of protection against pertussis are likely to outweigh the risk of an adverse event,37 and justify vaccination with dTpa or dTpa-IPV.
Special considerations Previous pertussis infection
Pre-existing neurological disease and pertussis vaccination Infants and children known to have active or progressive neurological disease can be safely vaccinated with DTPa-containing vaccines. A large Canadian study found no evidence of encephalopathy following acellular pertussis vaccines.38 For infants and children with stable neurological disease (including cerebral palsy), or a family history of idiopathic epilepsy or other familial neurological disorder, the risk of adverse events following DTPa-containing vaccines are essentially the same as for other infants of the same age.
Contraindications The only true contraindications to acellular pertussis vaccines are: • anaphylaxis following a previous dose of an acellular pertussis vaccine, or • anaphylaxis following any vaccine component.
Precautions Children who have a hypotonic-hyporesponsive episode (defined in ‘Adverse events’ below) following DTPa-containing vaccines should receive further doses as scheduled in the National Immunisation Program. Supervision may be required under some circumstances and specialist advice can be obtained from a clinic specialising in the assessment and management of putative adverse events
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Vaccination with pertussis vaccine in children, adolescents or adults who have had laboratory-confirmed pertussis infection is safe but will not confer any additional protection. If there is any uncertainty about a previous diagnosis of pertussis, then vaccinate. In particular, incompletely vaccinated infants <6 months of age who develop pertussis may not mount an adequate immune response following infection and should receive all routinely scheduled vaccines, including pertussis.
following vaccination (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control). A history of extensive limb swelling after a booster dose of DTPa is not a contraindication to adolescent/adult formulation dTpa at 12–17 years of age (or older).24 Parents of children about to receive the booster dose of a DTPacontaining vaccine (at 4 years of age) should be informed of the small but welldefined risk of this adverse event which, even when extensive, is usually not associated with significant pain or limitation of movement.
Adverse events Significant adverse events following pertussis vaccination should be reported as set out in Section 1.5.2, Adverse events following immunisation. • Acellular pertussis vaccines are associated with a much lower incidence of fever (approximately 20%, very common) and local adverse events (approximately 10%, common) than whole-cell pertussis vaccines (approximately 45% and 40%, respectively) which are no longer used in Australia).18,39 • Following the introduction of DTPa in Australia, there was an increase in the incidence of extensive local adverse events in children receiving booster doses at 18 months and 4 years of age.40 Extensive limb swelling, defined by swelling and/or redness involving at least half the circumference of the limb, and the joints both above and below the injection site, was common (occurring in 2% of vaccinees) following a booster dose of DTPa given at 18 months of age; this was 1 reason for ceasing this booster dose in 2003. Although it is still too early to assess the effect that removing the 18-month booster dose has had on the incidence of local adverse events following the booster dose at 4 years of age, recent anecdotal reports of much less extensive swelling are encouraging.41 Such reactions commence within 48 hours of vaccination, last for 1 to 7 days and resolve completely without sequelae.25 The pathogenesis of extensive limb swelling is poorly understood. In an analysis of fourth and fifth dose follow-up studies that examined 12 different DTPa vaccines, 2% (common) of 1015 children who received consecutive doses of the same DTPa vaccine reported entire thigh swelling, which resolved completely.25 • Children who experience a febrile convulsion after a dose of DTPa-containing vaccines are at increased risk (albeit low) of further febrile convulsion following a subsequent dose of DTPa-containing vaccines. These risks can be minimised by appropriate measures to prevent fever, so vaccination is still recommended. Febrile convulsions are very infrequently reported following DTPacontaining vaccines. The risk is even lower in infants who complete their primary course at 6 months of age, as febrile convulsions are uncommon under 6 months of age.
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• Hypotonic-hyporesponsive episodes (HHE), defined by an episode of pallor, limpness and unresponsiveness 1 to 48 hours after vaccination, often preceded by irritability and fever, occur rarely following DTPa. Shallow respiration and cyanosis may also occur in an HHE. The whole episode lasts from a few minutes to 36 hours. In Australia during 2005, 1.33 cases of HHE were reported per 100 000 doses of DTPa or DTPa-hepB vaccines given.41 Follow-up of children with HHE shows no long-term neurological or other sequelae and they can receive further doses of DTPa-containing vaccines.42 • Pertussis vaccine does not cause infantile spasms or epilepsy. • Sudden infant death syndrome (SIDS) is not associated with either DTPa or any pertussis-containing vaccine.43 Some studies suggest a decreased risk of SIDS in children who have been vaccinated (see Appendix 5, Commonly asked questions about vaccination).
(i) Management of cases The clinical case definition of pertussis is either (i) an acute cough lasting ≥14 days with at least one of post-tussive vomiting, apnoea or whoop, or (ii) a cough of any duration in a person epidemiologically linked to a laboratoryconfirmed case. The diagnosis can be definitively confirmed by either culture or PCR of a per-nasal swab or nasopharyngeal aspirate. The serological tests available in most areas of Australia are based on detection of IgA antibodies to B. pertussis antigens and are insensitive, so that false negative results are a problem, especially if performed on only one occasion.44 In those who have not received a pertussis-containing vaccine within the previous 5 years, detection of IgA to pertussis antigens is highly specific in the presence of appropriate symptoms. If pertussis is suspected in someone who has received a pertussiscontaining vaccine within 5 years, PCR is the diagnostic method of choice, but has progressively decreasing sensitivity with increased duration of symptoms. In a research setting, an IgG PT level of at least 125 EU/mL has been shown to be indicative of a recent or active pertussis infection; however, this assay is not available in routine pathology laboratories.45,46 A detailed history is required when a case of pertussis is suspected, including date of onset, vaccination status and details of household contacts. To reduce the risk of transmission, cases should be commenced on antibiotic therapy on clinical suspicion, but only if commenced within 21 days of the onset of coryza. There is no evidence of any reduction in pertussis transmission following antibiotic treatment if the case has had symptoms for more than 21 days. Appropriate macrolide antibiotics for treatment of pertussis are azithromycin, clarithromycin and erythromycin. An alternative for those unable to take macrolides is trimethoprim-sulfmethoxazole. Table 3.14.1 shows the dose regimens for each of these antibiotics. (See also ‘Variations from product information’ below.)
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The public health management of pertussis
Table 3.14.1: Recommended antimicrobial therapy and chemoprophylaxis regimens for pertussis in infants, children and adults47-54 Age group
Azithromycin
Clarithromycin
Erythromycin
TMP-SMX*
<1 month
10 mg/kg single dose for 5 days†
Not recommended
If azithromycin is unavailable;
Not recommended in infants <2 months of age unless macrolides cannot be used
≤7 days old: 10 mg/kg/ dose 12-hourly for 7 days;‡ 8–28 days old: 10 mg/kg/ dose 8-hourly for 7 days 1–5 months
10 mg/kg single dose for 5 days
7.5 mg/kg/ dose twice daily for 7 days
10 mg/kg/ dose 6-hourly for 7 days
≥2 months of age; TMP: 4 mg/ kg twice daily, SMX: 20 mg/ kg twice daily for 7 days
Infants (≥6 months) and children
10 mg/kg single dose on day 1, then 5 mg/ kg single dose for days 2–5
7.5 mg/kg/ dose (up to a maximum dose of 500 mg) twice daily for 7 days
(maximum 250 mg/day)
(maximum 1 g/day)
10 mg/kg/ dose (up to a maximum dose of 250 mg) 6-hourly for 7 days
TMP: 4 mg/kg, SMX: 20 mg/kg twice daily for 7 days (maximum 160 mg TMP and 800 mg SMX 12-hourly)
500 mg single dose on day 1, then 250 mg single dose for days 2–5
500 mg twice daily for 7 days
Adults
(maximum 1 g/day) Erythromycin: 250 mg 6-hourly for 7 days;
TMP: 160 mg twice daily, SMX: 800 mg twice daily for 7 days
Erythromycin ethyl succinate (EES): 400 mg 6-hourly for 7 days
* Trimethoprim-sulfmethoxazole † Preferred for this age; refer to ‘(c) Pertussis in pregnancy’ and ‘(d) Use in infants and infantile hypertrophic pyloric stenosis’ below. ‡ Please refer to ‘(d) Use in infants and infantile hypertrophic pyloric stenosis’ below.
Cases should be excluded from, for example, childcare facilities and school, until they have taken 5 days of antibiotic treatment. All cases, both suspect and confirmed, should be notified to the State/Territory public health authorities (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
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(ii) Management of contacts of cases (a) Vaccination Since a primary course of 3 or more injections is required to protect against pertussis, infant vaccination cannot be effectively used to control an outbreak. However, unvaccinated or partially vaccinated contacts up to their 8th birthday should be offered DTPa-containing vaccines and older individuals a single dose of dTpa (see Section 1.3.5, Catch-up). Passive immunisation with normal human immunoglobulin has not been shown to be effective in the prevention of pertussis. (b) Chemoprophylaxis
Based on these principles, prophylaxis is recommended for the following ‘highrisk’ contacts of pertussis cases: • All household members when the household includes any child <24 months of age who has received fewer than 3 effective doses of pertussis vaccine (ie. commenced after 6 weeks of age with at least a 4-week interval between doses, and the last dose given at least 14 days previously). • Any woman in the last month of pregnancy, regardless of vaccination status (see ‘Pertussis in pregnancy’ below). • All other children and adults in the same care group if the case, regardless of his/her vaccination status, attended childcare for more than 1 hour while infectious and that care group includes 1 or more children <24 months of age who have received fewer than 3 effective doses of pertussis vaccine. • Healthcare staff, regardless of vaccination status, working in a maternity hospital or newborn nursery. Chemoprophylaxis is not recommended routinely for healthcare staff caring for older infected children or adults. • Where a case worked in a maternity ward or newborn nursery for more than an hour while infectious, then all babies in that ward should receive antibiotics.
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3.14 Pertussis
In the usual clinical setting of delayed presentation and imperfect compliance, the benefit of chemoprophylaxis in preventing the secondary transmission of pertussis is likely to be limited.49,55 In view of this, the well established (mainly gastrointestinal) side effects of erythromycin and the cost of the newer macrolides, the use of chemoprophylaxis for prevention of secondary cases should be reserved for those settings where the benefit is greatest. These settings are best defined by the chance of transmission and the high risk of severe complications should transmission occur. Close contacts can be defined as those who either live in the same household (but not occasional ‘sleepover’ contacts unless they too are at increased risk of severe disease), or work in or attend the same institutional setting (eg. maternity hospital ward, newborn nursery, childcare centre) as a case.
Antibiotic regimens for chemoprophylaxis are the same as for cases (Table 3.14.1 above). Antibiotics should be given only if commenced either within 21 days of the onset of any symptoms, or within 14 days of the onset of the paroxysmal cough in the case. Childcare contacts in the same room as the case, who are not age-appropriately vaccinated, should be excluded from childcare until the expiry of 14 days from their last exposure to the infectious case, unless they have already completed 5 days of a recommended antibiotic treatment, in which case they may return. (c) Pertussis in pregnancy Treatment of pregnant women with pertussis onset within a month of delivery is important for the prevention of neonatal pertussis and, if the onset is within 3 weeks of delivery, their newborn babies should also be given antibiotic therapy (Table 3.14.1). Erythyromycin use earlier in pregnancy has well documented safety (Category A). There are only limited data on the use of azithromycin in pregnancy (Category B1). (d) Use in infants and infantile hypertrophic pyloric stenosis Several studies have shown an increased risk of infantile hypertrophic pyloric stenosis (IHPS) when erythromycin is given for prophylaxis following exposure to pertussis, especially in the first 2 weeks of life.56,57 While there are, as yet, no data available on the effectiveness of azithromycin use in infants <1 month of age, published case series report fewer adverse events following azithromycin use when compared with erythromycin and, to date, there have been no reports of IHPS in infants following use of azithromycin, although the size and number of these studies is limited.58,59 Therefore, on currently available evidence, and because of the risks of severe pertussis in this age group, azithromycin is preferred to erythromycin for treatment and prophylaxis in infants aged <1 month by US authorities. Azithromycin is available as a suspension and approved for use in Australia, but treatment and prophylaxis of pertussis are not currently referred to in the product information. Parents of newborns prescribed either erythromycin or azithromycin should be informed about the possible risks for IHPS and counselled about signs of developing IHPS.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information The product information for both Infanrix hexa and Infanrix Penta states that these vaccines may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 months of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age.
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The product information for Infanrix-IPV states that this vaccine may be used as a booster dose for children ≤6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis. NHMRC recommends that booster doses of DTPa and IPV be given at 4 years of age; however, this product may be used for catch-up of the primary schedule or as a booster in children <8 years of age. The product information for adolescent/adult formulations of dTpa-containing vaccines states that these vaccines are indicated for booster doses only. NHMRC recommends that, when a 3-dose primary course of diphtheria/tetanus toxoids is given to an adolescent/adult, that dTpa replace the first dose of dT, with 2 subsequent doses of dT. If dT is not available, dTpa can be used for all 3 primary doses, but this is not routinely recommended.
The product information for both clarithromycin and azithromycin do not list the treatment or prophylaxis of pertussis as an approved indication for either antibiotic. NHMRC recommends that these antibiotics may be used for the treatment or prophylaxis of pertussis as per Table 3.14.1 above.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.14 Pertussis
The product information for Adacel and Boostrix (adolescent/adult formulations of dTpa) states that these vaccines are recommended for use in those aged >10 years. However, NHMRC recommends that they may be used in people aged ≥8 years. The product information also states that dTpa should not be given within 5 years of a tetanus toxoid-containing vaccine. However, NHMRC recommends that a single dose of dTpa vaccine can be administered at any time following receipt of a diphtheria and tetanus toxoid-containing vaccine.
3.15 Pneumococcal disease Bacteriology Streptococcus pneumoniae are lancet shaped Gram-positive streptococci. To date, 90 capsular antigenic types have been recognised, each eliciting type-specific immunity. Some of these types are commonly carried in the upper respiratory tract, and some are more frequently associated with invasive disease. The emergence of antibiotic-resistant strains of this organism has become an increasing challenge with 2004 Australian data indicating that up to 18% of invasive strains are resistant to 2 or more classes of antibiotics.1
Clinical features Invasive pneumococcal disease (IPD) is defined as isolation of S. pneumoniae from a normally sterile site, most commonly blood. The major clinical syndromes of IPD include pneumonia, meningitis and bacteraemia without focus. In adults, pneumococcal pneumonia is the most common clinical presentation of IPD, while, in children, bacteraemia accounts for more than two-thirds of cases.2-4 The risk of IPD is highest in patients who cannot mount an adequate immune response to pneumococcal capsular antigens, including those with functional or anatomical asplenia, immunoglobulin deficiency, acute nephrotic syndrome, multiple myeloma, HIV/AIDS, chronic renal failure, organ transplantation and lymphoid malignancies.3,4 Other groups of patients, although generally immunocompetent, develop IPD of higher incidence and/or severity. These include people with chronic cardiovascular or pulmonary disease, diabetes mellitus, alcohol-related problems, cirrhosis, or CSF leak after cranial trauma or surgery, and those who smoke.3,5 In those without predisposing medical conditions, both frequent otitis media and recently commencing childcare are associated with increased risk of IPD in children,6 and tobacco smoking with increased risk in adults.
Epidemiology The highest rates of IPD are seen in children <2 years of age and adults >85 years of age. In 2004, 2375 cases of IPD were notified to the National Notifiable Diseases Surveillance System, a notification rate of 11.8 per 100 000 population.1 The overall rate of IPD in Indigenous Australians was 3.2 times that in nonIndigenous Australians.1 In 2004, after implementation of the pneumococcal conjugate vaccine program for high-risk children in 2001, the rate of IPD in children <2 years of age had decreased in Indigenous children (91.5 cases per 100 000) to become similar to their non-Indigenous peers (93.6 cases per 100 000).1 In the less-developed world and in some groups of Aboriginal and Torres Strait Islander people, the incidence of IPD is as high as 200 per 100 000 per year.
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However, mortality rates among Indigenous Australian people are comparable to those in non-Indigenous people, even in remote areas. Most non-Indigenous adults who develop IPD have at least 1 risk factor, while most cases occurring in Indigenous adults are associated with multiple risk factors. In adults, most IPD isolates belong to serotypes contained in the 23-valent pneumococcal polysaccharide vaccine.7-9 Among Indigenous children in northern Australia, before the introduction of the 7-valent pneumococcal conjugate vaccine, only about one-half to two-thirds of IPD was caused by serotypes in the 7-valent pneumococcal conjugate vaccine compared with 85% or more among non-Indigenous children.7,8,10 Nevertheless, in north Queensland, a decrease in the annual incidence of IPD in the <5 years age group from 170 to 78 cases per 100 000 was documented in the 3 years after introduction of the 7-valent pneumococcal conjugate vaccine.11 Similarly, the annual incidence of vaccine-preventable IPD in Indigenous adults has declined by 86% since the 23-valent pneumococcal polysaccharide vaccine was introduced to north Queensland in 1986.11
Vaccines
Pneumococcal conjugate vaccine, 7-valent (7vPCV) • Prevenar – Wyeth (7-valent pneumococcal conjugate vaccine; 7vPCV). Each 0.5 mL monodose pre-filled syringe contains 2 µg of pneumococcal serotypes 4, 9V, 14, 18C, 19F, 23F and 4 µg of serotype 6B, conjugated to a mutant non-toxic diphtheria toxin (CRM197) carrier protein, adsorbed onto 0.5 mg aluminium phosphate. Available in packs of 10 monodose pre-filled syringes. 7vPCV is approved for use in infants and children aged 6 weeks to 9 years. Efficacy data from a pivotal trial in California found greater than 95% protective efficacy against IPD due to the serotypes contained in the vaccine.12 A Cochrane review of 4 trials assessing the efficacy of 7vPCV in children <2 years of age found 7vPCV to be effective in reducing the incidence of IPD due to all serotypes, the greater effect being seen in the reduction of IPD due to vaccine-related serotypes.13
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3.15 Pneumococcal disease
There are currently 2 different types of pneumococcal vaccine available in Australia. A 7-valent pneumococcal conjugate vaccine (7vPCV) became available in 2001 for immunisation of infants and children aged from 6 weeks to 9 years. 7vPCV was added to the NIP for high-risk children in 2001 and for all children up to 2 years of age from January 2005. The 23-valent pneumococcal polysaccharide vaccine (23vPPV) has been available since 1983. A funded program with 23vPPV for Indigenous Australians aged ≥50 years began in 1999. Non-Indigenous Australians aged 65 years became eligible to receive the vaccine under the NIP from January 2005. In addition, people aged <65 years with underlying chronic conditions predisposing them to IPD can access 23vPPV through the PBS.
Other pneumococcal infections in children (pneumonia and otitis media), not associated with a positive sterile site culture, are also reduced by 7vPCV, but the estimated reduction varies with case definition and severity. For clinically defined otitis media or pneumonia, the reduction is similar at approximately 5%.14,15 A post-licensure study of 157 471 children in California showed evidence of disease reduction in unimmunised people, confirmed by a larger US study showing a decline in the incidence of IPD of 52% in those 20–39 years of age and 26% in those ≥60 years of age.16-18
Pneumococcal polysaccharide vaccine, 23-valent (23vPPV) • Pneumovax 23 – CSL Biotherapies/Merck & Co Inc (23-valent pneumococcal polysaccharide vaccine; 23vPPV). Each 0.5 mL monodose vial contains 25 µg of each of pneumococcal serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F; 0.25% phenol. 23vPPV contains polysaccharides derived from the 23 most frequent or most virulent capsular types of S. pneumoniae in the USA. These same serotypes are responsible for most IPD cases in adults in Australia. At least 90% of healthy adults respond to the vaccine, with a 4-fold rise in type-specific antibody within 2 to 3 weeks. Response to vaccine is diminished in patients with impaired immunity and, in children <2 years of age, is limited to a small number of serotypes unless there has been previous 7vPCV vaccination.19 In developing countries with high attack rates, controlled trials have shown that pneumococcal polysaccharide vaccine reduces mortality from pneumonia in younger adults which, in this setting, is very likely to be pneumococcal. Among at-risk individuals in developed countries with much lower attack rates, a Cochrane review examining vaccines for preventing pneumococcal disease reported that 23vPPV was effective in reducing the incidence of IPD, but not non-bacteraemic pneumonia, among adults and the immunocompetent elderly.20 Similarly, a recent retrospective study in a managed care setting in the USA studied 47 365 adults >65 years of age over 3 years, of whom 1428 were hospitalised with community-acquired pneumonia and 61 developed documented pneumococcal bacteraemia. Receipt of 23vPPV vaccine was associated with a significant reduction in pneumococcal bacteraemia but not in hospitalisation for non-bacteraemic pneumonia.21 In Australia, Victoria introduced a publicly funded 23vPPV program for the >65 years age group in 1998, resulting in an estimated 36% reduction in the incidence of IPD and vaccine effectiveness of 71% (95% CI: 54–82%).22
Transport, storage and handling 7-valent pneumococcal conjugate vaccine Transport according to National Vaccine Storage Guidelines: Strive for 5.23 Store at +2°C to +8°C. Do not freeze. Protect from light.
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23-valent pneumococcal polysaccharide vaccine Transport according to National Vaccine Storage Guidelines: Strive for 5.23 Store at +2°C to +8°C. Do not freeze. Protect from light.
Dosage and administration 7-valent pneumococcal conjugate vaccine The dose is 0.5 mL by IM injection in the opposite limb to other injectable vaccines if possible.
23-valent pneumococcal polysaccharide vaccine The dose is 0.5 mL as a single dose, by either SC or IM injection, in the opposite limb to other injectable vaccines if possible.
Recommendations 7-valent pneumococcal conjugate vaccine Vaccination of children 7vPCV is recommended in the NIP for all infants from 2 months of age with a catch-up for children up to 2 years of age. 7vPCV may be safely given at the same time as other vaccines listed on the NIP but must be administered using a separate injection site and limb. 7vPCV should be administered in a primary series of 3 doses at 2, 4 and 6 months of age. Unless there is an increased risk of IPD (see below), the additional benefits are not considered sufficient to justify a routine (fourth) booster dose. This recommendation is based on data from the pivotal randomised controlled trial suggesting similar efficacy against type-specific IPD with either 3 or 4 doses.12 Subsequent studies from the UK examining immunogenicity data24 and the US examining vaccine effectiveness25 were consistent with significant protection after 2 or more doses. The US study found higher vaccine effectiveness among those who had received a fourth dose at 12 months of age, but this was not statistically significant.25 The current Australian dosing regimen will be regularly reviewed in the light of trends in Australian IPD data and emerging international experience.
(ii) Aboriginal and Torres Strait Islander children living in the Northern Territory, Queensland, South Australia and Western Australia 7vPCV should be administered at 2, 4 and 6 months of age, followed at 18–24 months of age by a dose of 23vPPV. This recommendation is based on: (i) data from several Australian studies which showed lower serotype coverage from the 7vPCV in similar populations;7,8,10 (ii) 2 large studies which demonstrated adequate boosting responses to serotypes contained in the 7vPCV following 23vPPV;26,27 and (iii) 2 large studies which demonstrated adequate primary responses to some serotypes in 23vPPV, but not in 7vPCV, from 18–24 months of age.28,29
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3.15 Pneumococcal disease
(i) Healthy children
(iii) Children with underlying medical conditions (listed in Table 3.15.2) associated with greater risk or severity of IPD 7vPCV should be administered at 2, 4 and 6 months of age, followed by a fourth dose of 7vPCV at 12 months of age and a booster dose of 23vPPV at 4–5 years of age. This is based on data showing lower immune responses in these children to certain serotypes in 7vPCV which can be enhanced by an additional dose, and their continuing susceptibility to IPD at older ages, with a higher prevalence of serotypes not contained in the 7vPCV.30
(iv) Children with asplenia (functional or anatomical) ≤9 years of age (ie. before their 10th birthday) • with no previous history of pneumococcal vaccination with 7vPCV or 23vPPV • 2 doses of 7vPCV given 2 months apart, followed by 23vPPV at least 2 months after the last dose of 7vPCV. This is based on an inadequate response to 1 dose of 7vPCV among some asplenic individuals which is enhanced by a second dose.27 • with previous history of pneumococcal vaccination with 7vPCV or 23vPPV • where a dose of 23vPPV was given more than 6 months ago but no doses of 7vPCV have been administered, give 2 doses of 7vPCV at least 2 months apart. This is based on inadequate response to 1 dose of 7vPCV in some asplenic individuals which seems unlikely to be influenced by previous receipt of 23vPPV, although no specific data are available. • where previous doses of 7vPCV have been administered but no 23vPPV, give 23vPPV at least 2 months after the last 7vPCV dose. This is based on similar considerations to those above. NB. Children with asplenia should also be considered for other interventions (see Chapter 2.3, Subsection 2.3.3.5, Individuals with functional or anatomical asplenia).
(v) Children ≤9 years of age (ie. before their 10th birthday) who have been diagnosed with an underlying medical condition (listed in Table 3.15.2 below) after they received the infant schedule of 7vPCV at 2, 4 and 6 months of age Where a previously healthy child, currently aged >12 months, was vaccinated according to the NIP schedule and received 7vPCV at 2, 4 and 6 months of age but has since developed or been diagnosed with a condition listed in Table 3.15.2 below, he/she should receive a further dose of 7vPCV followed 2 months later by a dose of 23vPPV.
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Table 3.15.1: Summary table – pneumococcal vaccination schedule for children ≤9 years of age (see also Section 1.3.5, Catch-up) For childhood immunisation schedule (children ≤5 years of age) 7vPCV
23vPPV
Comments
All healthy children (including Indigenous children residing in ACT, NSW, TAS and VIC)
2, 4 and 6 months of age (up to 2 years of age)*
No
If delays in start of schedule after 2 months, refer Section 1.3.5, Catch-up, Table 1.3.9.
Indigenous children residing in NT, QLD, SA and WA only
2, 4 and 6 months of age (up to 2 years of age)
18–24 months
If delays in start of schedule after 2 months, refer Section 1.3.5, Catch-up, Table 1.3.10.
Children with underlying medical conditions (refer Table 3.15.2)
2, 4, 6 and 12 months of age
4–5 years
If delays in start of schedule after 2 months, refer Section 1.3.5, Catch-up, Table 1.3.11.
For children 6–≤9 years of age with underlying medical conditions as listed in Table 3.15.2 7vPCV
23vPPV
Comments
2 doses, at least Give 1 dose at least 2 months apart 2 months after last dose of 7vPCV
For revaccination schedules for children ≥10 years, refer to Table 3.15.3 below.
Has received 7vPCV primary course at 2, 4 and 6 months of age
1 dose
Give 1 dose at least 2 months after last dose of 7vPCV
For revaccination schedules for children ≥10 years, refer to Table 3.15.3 below.
History of at least 2 7vPCV doses, and no 23vPPV
1 dose
Give 1 dose at least 2 months after last dose of 7vPCV
For revaccination schedules for children ≥10 years, refer to Table 3.15.3 below.
History of 23vPPV, but no 7vPCV
Give 2 doses at Refer revaccination least 2 months schedule Table 3.15.3 apart, starting for further schedules at least 6 months after dose of 23vPPV
For revaccination schedules for children ≥10 years, refer to Table 3.15.3 below.
* Immunisation of healthy children (including Indigenous children residing in ACT, NSW, VIC, and TAS) only up to 2 years of age.
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3.15 Pneumococcal disease
No history of any pneumococcal vaccination
Booster doses of 7vPCV With the exception of children with underlying medical conditions (see above), booster doses of 7vPCV are not required. For details of catch-up schedules, please refer to Section 1.3.5, Catch up. Table 3.15.2: Underlying medical conditions predisposing children ≤9 years of age to IPD Diseases compromising immune response to pneumococcal infection: • congenital immune deficiency including symptomatic IgG subclass or isolated IgA deficiency (but children who require monthly immunoglobulin infusion are unlikely to benefit from vaccination), • immunosuppressive therapy (including corticosteroid therapy ≥2 mg/kg per day of prednisolone or equivalent for more than 2 weeks) or radiation therapy, where there is sufficient immune reconstitution for vaccine response to be expected, • compromised splenic function due to sickle haemoglobinopathies, or congenital or acquired asplenia, • haematological malignancies, • HIV infection, before and after development of AIDS, • renal failure, or relapsing or persistent nephrotic syndrome, • Down syndrome. Anatomical or metabolic abnormalities associated with higher rates or severity of IPD: • cardiac disease associated with cyanosis or cardiac failure, • all premature infants with chronic lung disease, • all infants born at less than 28 weeks’ gestation, • cystic fibrosis, • insulin-dependent diabetes mellitus, • proven or presumptive cerebrospinal fluid (CSF) leak, • intracranial shunts and cochlear implants.
23-valent pneumococcal polysaccharide vaccine 23vPPV may be safely given at the same time as other vaccines listed on the NIP but must be administered using a separate injection site and limb.
(i) 23vPPV is recommended for: • All people aged ≥65 years. • Aboriginal and Torres Strait Islander people ≥50 years of age and those 15–49 years of age who have underlying conditions placing them at risk of IPD. • People aged ≥10 years who have underlying chronic illnesses predisposing them to IPD including:
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• asplenia either functional (including sickle-cell disease) or anatomical; where possible, the vaccine should be given at least 14 days before splenectomy, • conditions associated with increased risk of IPD due to impaired immunity, eg. HIV infection before the development of AIDS, acute nephrotic syndrome, multiple myeloma, lymphoma, Hodgkin’s disease and organ transplantation, • chronic illness associated with increased risk of IPD including chronic cardiac, renal or pulmonary disease, diabetes, alcohol-related problems, • CSF leak. • Tobacco smokers.
(ii) 23vPPV ‘booster’ dose is recommended following previous 7vPCV • At 18–24 months of age, after a primary series of 7vPCV, in Aboriginal and Torres Strait Islander children in the Northern Territory, Queensland, South Australia and Western Australia (see Section 1.3.5, Catch up, Table 1.3.10). • At 4–5 years of age in children at risk of either high incidence or severity of IPD because of underlying medical conditions (see Table 3.15.2), following a primary series of 7vPCV (see Section 1.3.5, Catch up, Table 1.3.11).
iii) Revaccination with 23vPPV
Although an early study raised concerns about extensive local adverse events following revaccination with 23vPPV,31 several recent studies have shown that 3 doses (ie. 2 revaccinations) of 23vPPV are not associated with more local adverse events compared to 1 or 2 doses.32,33 Less clear, however, is the adequacy of the immune response after revaccination with 23vPPV. Although an earlier study reported that there was an immune hyporesponsiveness after a first revaccination, more recent studies suggest that the immune responses to revaccination may be adequate.31,34
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A maximum of 3 doses (ie. 2 revaccinations) of 23vPPV are recommended, based on data concerning adverse events and effectiveness.
Table 3.15.3: Revaccination with 23vPPV for people ≥10 years of age Primary dose 23vPPV given to
First 23vPPV revaccination
Second 23vPPV revaccination
Non-Indigenous adults ≥65 years
5 years after first dose
No
Non-Indigenous adults <65 years with underlying chronic medical condition or smoker
5 years after first dose
Either 5 years after first revaccination or at 65 years of age (whichever is later)
Indigenous adults aged ≥50 years
5 years after first dose
No
Indigenous adults aged <50 years with underlying chronic medical condition or smoker
5 years after first dose
Either 5 years after first revaccination or at 50 years of age (whichever is later)
Asplenic individuals
5 years after first dose
Either 5 years after first revaccination or at 50 years of age (for Indigenous adults) or 65 years of age (for non-Indigenous adults), whichever is later
NB. Indigenous children in the Northern Territory, Queensland, South Australia and Western Australia receive 23vPPV at 18–24 months of age (see ‘Recommendations’, point (ii) above). This childhood dose is not relevant to the recommendations concerning revaccination given in Table 3.15.3.
Contraindications 7-valent pneumococcal conjugate vaccine The only absolute contraindications to 7vPCV are: • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis following any vaccine component.
23-valent pneumococcal polysaccharide vaccine The only absolute contraindications to 23vPPV are: • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis following any vaccine component.
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Relative contraindications include the following: • Age <2 years – the immune response in young children is restricted to a few serotypes (so benefits of immunisation are limited) unless previously given 1 or more doses of 7vPCV. • Recent use of immunosuppressive therapy or radiation of lymph nodes. However, once it is considered that these patients are immunologically ‘stabilised’, they should be promptly vaccinated.
Adverse events 7-valent pneumococcal conjugate vaccine Among the most commonly reported are injection site adverse events and fever. 7vPCV is more commonly associated with local adverse events, with rates of erythema ranging from 10.0 to 11.6% (very common) for 7vPCV, compared with 6.7 to 11.4% (common to very common) for DTPa. There is no pattern of increasing local reactogenicity with subsequent doses.12 A higher rate of local adverse events has been observed in older children after a single dose. Prophylactic antipyretic medication is recommended in children who have seizure disorders or a previous history of febrile seizures.
23-valent pneumococcal polysaccharide vaccine
Previously, there were concerns about extensive local adverse events following revaccination with 23vPPV31 but recent studies indicate that revaccination is not associated with more local adverse events compared to 1 or 2 doses.32,33 Revaccination is not associated with an increase in systemic adverse events such as fever or headache.32-34
Use in pregnancy 7-valent pneumococcal conjugate vaccine Vaccination during pregnancy has not been evaluated for potential harmful effects in animals or humans. Although unlikely to result in adverse effects to mother or fetus, it is neither indicated nor recommended.
23-valent pneumococcal polysaccharide vaccine Although 23vPPV has been administered in pregnancy in the context of clinical trials with no evidence of adverse effects, data are limited and deferral of vaccination is recommended unless there is an increased risk of IPD.35,36 Women of reproductive age with known risk factors for IPD should be vaccinated before planned pregnancy.
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About half the recipients of 23vPPV will experience some soreness after the first dose, but pain or swelling severe enough to limit arm movement occurs in less than 5% (common) of recipients.31 Low-grade fever occurs occasionally, but fever above 39°C occurs in less than 0.5% (uncommon) of recipients.31
Variations from product information 7-valent pneumococcal conjugate vaccine The product information recommends a 4-dose 7vPCV schedule for vaccination commencing at 2 months of age with doses at 2, 4, 6 and 12 months of age, 3 doses for vaccination commencing between 7 and 12 months of age, and 2 doses for vaccination commencing between 13 and 23 months of age. However, NHMRC recommends 1 dose less than that stated in the product information for healthy children who are not at increased risk of IPD.
23-valent pneumococcal polysaccharide vaccine 23vPPV is licensed for use only in children >24 months of age, but NHMRC considers that it can be used from 18 months of age in children who have previously received 7vPCV.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.16 Poliomyelitis Virology Polioviruses are classified as enteroviruses in the family Picornaviridae.1 They have an RNA genome, and are transient inhabitants of the gastrointestinal tract (GIT). There are 3 poliovirus serotypes, PV1, PV2 and PV3. The virus enters through the mouth, multiplies in the pharynx and GIT and is excreted in the stools for several weeks. The virus invades local lymphoid tissue, enters the blood stream and may then infect and replicate in cells of the central nervous system.2
Clinical features Poliomyelitis is an acute illness following gastrointestinal infection by one of the 3 types of poliovirus. Transmission is through faecal-oral and, occasionally, oraloral spread.3 The infection may be clinically inapparent. If symptoms occur, they may include headache, gastrointestinal disturbance, malaise and stiffness of the neck and back, with or without paralysis. Paralysis is classically asymmetrical. Paralytic polio is a complication of poliovirus aseptic meningitis, and may be spinal (79%), bulbar (2%) or bulbospinal (19%). The case-fatality rate in paralytic polio is 2 to 5% in children, 15 to 30% in adults and up to 75% in bulbar polio. The infection rate in households with susceptible young children can reach 100%. The proportion of inapparent or asymptomatic infection to paralytic infection may be as high as 1000:1 in children and 75:1 in adults, depending on the poliovirus type and social and environmental conditions.2 The incubation period ranges from 3 to 21 days. Infected individuals are most infectious from 7 to 10 days before to 7 to 10 days after the onset of symptoms. The oral vaccine virus may be shed in the faeces for 6 weeks or more,2 and for up to several years in people with impaired immunity. Oral vaccine strains shed for many years may mutate into potentially neurovirulent strains.4-9
Epidemiology
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The incidence of poliomyelitis has been dramatically reduced worldwide, but cases still occur in developing countries in the Indian subcontinent, the eastern Mediterranean and Africa.10,11 The World Health Organization (WHO) aimed to eradicate poliomyelitis by the year 2005 and, although not successful, is still hopeful this will be achieved by 2010 or soon after.12 In 1994, the continents of North and South America were certified to be free of polio,13 followed by the Western Pacific region (including Australia) in 2000 and the European region in 2002.14,15 In countries where the disease incidence is low but transmission is still occurring, poliomyelitis cases are seen sporadically or as outbreaks among non-vaccinated individuals. In 2005, 12 countries previously declared polio-
free, including Indonesia, experienced outbreaks due to importations of wild poliovirus from one of the remaining endemic countries: Afghanistan, India, Nigeria and Pakistan.11 In Australia, the peak incidence of poliomyelitis was 39.1/100 000 in 1938. There has been a dramatic fall in incidence since 1952, but epidemics occurred in 1956 and 1961–62. The last notified case of wild poliomyelitis in Australia occurred in 1977 due to an importation from Turkey, but 2 vaccine-associated cases were notified in 1986 and 1995.16,17 Because of the rapid progress in global polio eradication and diminished risk of wild virus associated disease, inactivated poliomyelitis vaccine (IPV) is now used for all doses of polio vaccine in Australia.3,18 This change was implemented because of concern about the risk of causing vaccine-associated paralytic poliomyelitis (VAPP), which is about 1 case for every 2.4 million doses of oral poliomyelitis vaccine (OPV) distributed.19 The advantage of using IPV is that it cannot cause VAPP.
Global eradication of polio The WHO strongly supports the use of OPV to achieve global eradication of poliomyelitis, especially in countries with continued or recent circulation of wildtype poliovirus.20 However, most countries which can afford IPV now use IPV in preference to OPV, in order to eliminate the risk of VAPP and also to reduce the risk of prolonged shedding of potentially neurovirulent strains of poliovirus by individuals with impaired immunity.3 A vaccine-derived poliovirus (VDPV) is derived from OPV but has a number of significant mutations due to longterm replication in an individual with impaired immunity (iVDPV) or through person-to-person transmission in areas of low polio vaccine coverage (circulating VDPV or cVDPV). Outbreaks of poliomyelitis due to cVDPV have been reported worldwide.6 People travelling to countries still using OPV are at risk of VAPP, as was reported for an unimmunised adult from the USA who travelled to Costa Rica in 2005.21 The WHO is planning for global OPV cessation, once the interruption of wild poliovirus transmission has been certified, to remove the incidence of VAPP and VDPVs.22 Further information is available from the WHO Polio Eradication website http://www.polioeradication.org.
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Vaccines • IPOL – Sanofi Pasteur Pty Ltd (IPV; inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains poliovirus 40D antigen units of type 1, 8D antigen units of type 2 and 32D antigen units of type 3 grown on monkey kidney cells, inactivated with formaldehyde; traces of phenoxyethanol as preservative, neomycin, streptomycin and polymyxin B. Combination vaccines that include IPV Formulations for children aged <8 years • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheriatetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccineHaemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/ phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins. • Infanrix-IPV – GlaxoSmithKline (DTPa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin.
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• Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. May also contain yeast proteins.
Formulations for people aged ≥8 years • Adacel Polio – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis- inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg pertussis fimbriae (FIM) 2+3; 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett); 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin, neomycin and streptomycin. • Boostrix-IPV – GlaxoSmithKline (dTpa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde, polymyxin and neomycin. IPV (IPOL) and IPV-containing combination vaccines contain polioviruses of types 1, 2 and 3 inactivated by formaldehyde. A course of 3 injections with an interval of 2 months between each dose produces long-lasting immunity (both mucosal and humoral) to all 3 poliovirus types. IPV produces considerably lower levels of intestinal immunity than OPV.
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.23 Store at +2°C to +8°C. Do not freeze. Protect from light.
Dosage and administration The dose of IPV (IPOL) and of the IPV-containing combination vaccines is 0.5 mL. IPV is given by SC injection, whereas the IPV-containing vaccines are administered by IM injection. If IPV (IPOL) is inadvertently given intramuscularly, there is no need to repeat the dose.
Recommendations Primary vaccination of infants and children (i) IPV (IPOL) or IPV-containing vaccines are recommended for infants from 2 months of age. An open, randomised, multi-centre trial comparing the hexavalent and pentavalent IPV-containing vaccines found that infants receiving either vaccine at 2, 4 and 6 months of age had seroprotective levels of antibody to polio virus types 1, 2 and 3.24
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Extra doses of IPV (IPOL) or IPV-containing vaccines are not needed for babies born prematurely. (ii) The primary course consists of 3 separate doses of vaccine. An interval of 2 months between each dose is recommended, but the minimum interval can be as short as 1 month for catch-up. (iii) Interchangeability of OPV and IPV: Oral poliomyelitis vaccine (OPV) is no longer in use in Australia. OPV and IPV are interchangeable. Children commenced on OPV should complete their polio vaccination schedule using IPV (IPOL) or IPV-containing vaccines.
Primary vaccination of adults A course of 3 doses of IPV (IPOL) or IPV-containing vaccines at intervals of 1 to 2 months is recommended for the primary vaccination of adults. No adult should remain unvaccinated against poliomyelitis.
Booster doses Children A booster dose of IPV (IPOL) or IPV-containing vaccine should be given at 4 years of age. A fifth dose of IPV is no longer recommended as Australia has been declared polio free since 200014 and, as in the US, a completed poliomyelitis vaccination schedule for children is 3 primary doses and 1 booster dose of IPV (IPOL) or an IPV-containing vaccine.25 Adults Booster doses for adults are not necessary unless they are at special risk, such as: • travellers to areas or countries where poliomyelitis is epidemic or endemic (see http://www.polioeradication.org for more information on affected countries), or • healthcare workers, including laboratory workers, in possible contact with poliomyelitis cases. For those exposed to a continuing risk of infection, booster doses are desirable every 10 years. dTpa-IPV combination vaccines can be used where otherwise indicated.
Contraindications • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis following any component of the vaccine.
Adverse events IPV-containing vaccines cause erythema (33%, very common), pain (13%, very common), and induration (1%, uncommon) at the injection site. Other symptoms reported in young babies are: fever, crying and decreased appetite (5–10%, common).
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The only absolute contraindications to IPV (IPOL) or IPV-containing vaccines are:
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information The product information for IPV suggests that the fourth dose be given 12 months after the third dose for both adults and children, followed by a fifth dose for children at 4 years of age. NHMRC recommends the fourth dose for children at 4 years of age and no fourth dose for adults unless they are at special risk. The product information suggests that any sensitivity to vaccine components is a contraindication, whereas NHMRC recommends that the only contraindication is a history of anaphylaxis to a previous dose or to any of the vaccine components. The product information for both Infanrix hexa and Infanrix Penta states that these vaccines may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 months of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age. The product information for Infanrix-IPV states that this vaccine may be used as a booster dose for children ≤6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis. NHMRC recommends that booster doses of DTPa and IPV be given at 4 years of age; however, this product may be used for catch-up of the primary schedule or as a booster in children <8 years of age.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.17 Q fever
Q fever is caused by Coxiella burnetii, an obligate intracellular bacterium, classified in a separate genus, Coxiella. A near relative is Legionella pneumophilia.1 The organism is slightly more resistant to heat than other vegetative bacteria, but nevertheless is inactivated at pasteurisation temperatures. It survives well in air, soil, water and dust and may also be disseminated on fomites such as wool, hides, clothing, straw and packing materials.2,3
Clinical features Q fever can be acute or chronic, and there is increasing recognition of long-term sequelae. However, in many instances, infection can be asymptomatic.4,5 Acute Q fever usually has an incubation period of 2 to 3½ weeks, depending on the inoculum size and other variables6 (range from 4 days up to 6 weeks). Clinical symptoms vary by country but in Australia it commonly presents with rapid onset of high fever, rigors, profuse sweats, extreme fatigue, muscle and joint pain, severe headache and photophobia.4,5 As the attack progresses there is usually evidence of hepatitis, occasionally with frank jaundice; a proportion of patients may have pneumonia which is usually mild but can require mechanical ventilation. If untreated, the acute illness lasts 1 to 3 weeks and may be accompanied by substantial weight loss in the more severe cases.4,5 C. burnetii may cause chronic manifestations, the most commonly reported being subacute endocarditis. Less common presentations include granulomatous lesions in bone, joints, liver, lung, testis and soft tissues. Infection in early pregnancy, or even before conception, may recrudesce at term and cause fetal damage.7-9 Recent studies have also identified a late sequel to infection, post Q fever fatigue syndrome (QFS), which occurs in about 10 to 15% of patients with acute Q fever.10-13 Laboratory research suggests that C. burnetii persists in most instances of acute Q fever, regardless of clinical status, and that immunogenic variation in the response to persistent infection leads to cytokine dysregulation and determines whether QFS occurs.11,14,15
Epidemiology C. burnetii infects both wild and domestic animals and their ticks, with cattle, sheep and goats being the main source of human infection. Companion animals such as cats and dogs may also be infected. The animals shed C. burnetii into the environment through their products of conception (especially high numbers of coxiellas) but also in their milk, urine, and faeces. C. burnetii is highly infectious16 and can survive in the environment. The organism is transmitted to humans via
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Bacteriology
the inhalation of infected aerosols or dust. Those most at risk include workers from the meat and livestock industries and shearers, with non-immune new employees or visitors being at highest risk of infection. Nevertheless, Q fever is not confined to occupationally exposed groups; there are numerous reports of sporadic cases or outbreaks in the general population in proximity to infected animals in stockyards, feedlots, processing plants or farms. Use of Q fever vaccine in Australia can be considered in 3 periods. First, from 1991 to 1993 when vaccine was used in a limited number of abattoirs, then from 1994 to 2000 when vaccination steadily increased to cover large abattoirs in most states,17 and finally from 2001 to 2006 during the period of the Australian Government sponsored Q fever Management Program.18 This program extended vaccination to farmers, their families and employees in the livestock-rearing industry. With respect to abattoir workers, there has been a clear reduction in Q fever cases and associated insurance claims since 1994.17,19 More widely, the numbers of Q fever cases reported to the National Notifiable Diseases Surveillance System (NNDSS) have declined over the period 1994 to 2005, during which there has been an increasing use of vaccine (see Figure 3.17.1). This decline is suggestive of an impact from vaccination among people not working in abbatoirs but, as there are substantial variations in total numbers of cases from year to year, requires confirmation over a longer period.20 Figure 3.17.1: Q fever notifications and hospitalisations, Australia, 1993 to 2005,* by month of diagnosis or admission20 100
90
Notifications Hospitalisations
80
70
Number
60
50
40
30
20
10
0 Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul Jan Jul 1993 1993 1994 1994 1995 1995 1996 1996 1997 1997 1998 1998 1999 1999 2000 2000 2001 2001 2002 2002 2003 2003 2004 2004 2005 2005
* Notifications where the month of diagnosis was between January 1993 and December 2005; hospitalisations where the month of admission was between 1 July 1993 and 30 June 2005.
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Vaccine4,21
• Q-VAX Skin Test – CSL Biotherapies (Q fever skin test). Each 0.5 mL liquid vial when diluted in 15 mL of sodium chloride contains 16.6 ng of purified killed suspension of Coxiella burnetii in each diluted 0.1 mL dose; thiomersal 0.01% w/v before dilution. May contain egg proteins. Q fever vaccine and skin test consist of a purified killed suspension of C. burnetii. It is prepared from the Phase I Henzerling strain of C. burnetii grown in the yolk sacs of embryonated eggs. The organisms are extracted, inactivated with formalin, and freed from excess egg proteins by fractionation and ultracentrifugation. Thiomersal 0.01% w/v is added as a preservative. Phase I whole-cell vaccines have been shown to be highly antigenic and protective against challenge both in laboratory animals and in volunteer trials.22 Serological response to the vaccine is chiefly IgM antibody to C. burnetii Phase I antigen. In subjects weakly seropositive before vaccination, the response is mainly IgG antibody to Phase I and Phase II antigens.23 Although the seroconversion rate may be low, long-term cell-mediated immunity develops24 and the vaccine has been shown to be protective in open and placebo-controlled trials, and in 2 post-licensing trials, to have a vaccine efficacy of 100%.25-28 Lack of seroconversion is not a reliable marker of lack of vaccination.22 During recent years, with much larger numbers vaccinated, a few instances of laboratory proven Q fever have been observed in vaccinated subjects.21 It is important that these apparent vaccine failures are fully investigated and that vaccination status is reported for all notified cases. It should be noted that vaccination during the incubation period of a natural attack of Q fever does not prevent the development of the disease.22 A useful website for Q fever vaccine providers is http://www.qfever.org/vaclist.php.
Transport, storage and handling Transport the vaccine according to National Vaccine Storage Guidelines: Strive for 5.29 Store at +2°C to +8°C, and do not freeze or store in direct contact with ice packs. If vaccine has been exposed to temperatures less than 0°C, do not use. Protect from light.
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• Q-VAX – CSL Biotherapies (Q fever vaccine). Each 0.5 mL pre-filled syringe contains 25 µg purified killed suspension of Coxiella burnetii; thiomersal 0.01% w/v. May contain egg proteins.
Dosage and administration A single dose of 0.5 mL of Q-VAX is given by SC injection after ascertaining that serological and skin testing have been performed and that both tests are negative (see ‘Pre-vaccination testing’ below).
Recommendations Q fever vaccine is recommended for those at risk of infection with C. burnetii. This includes abattoir workers, farmers, stockyard workers, shearers, animal transporters, and others exposed to cattle, camels, sheep, goats and kangaroos or their products (including products of conception). It also includes veterinarians, veterinary nurses, veterinary students, agricultural college staff and students (working with high-risk animals) and laboratory personnel handling veterinary specimens or working with the organism (see also Chapter 2.3, Groups with special vaccination requirements, Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases). Workers at pig abattoirs do not require Q fever vaccination.
Pre-vaccination testing (i) Before vaccination, people with a negative history of previous Q fever must have serum antibody estimations and skin tests to exclude those likely to have hypersensitivity reactions to the vaccine resulting from previous (possibly unrecognised) exposure to the organism. (ii) If the person has a positive history of previous infection with Q fever, or has already been vaccinated for Q fever, skin testing and serology are not required and vaccination is contraindicated. (iii) Note that a few subjects who have had verified Q fever in the past show no response to serological or skin testing. However, such subjects may experience serious reactions to administration of Q fever vaccine. Thus, it is vital to take a detailed history and to obtain documentation of previous Q fever vaccination or laboratory results confirming Q fever disease in all potential vaccinees; those who have worked for more than 10 years in the livestock or meat industries should be questioned particularly carefully. If there is any doubt about serological results or skin testing, they should be repeated 2 to 3 weeks later (see (vi) below for interpretation). (iv) Antibody studies were originally done by complement fixation (CF) tests at serum dilutions of 1 in 2.5, 5 and 10 against the Phase II antigen of C. burnetii. Although this is generally satisfactory, many testing laboratories now use enzyme immunoassay (EIA) or immunofluorescent antibody (IFA) to detect IgG antibody to C. burnetii as an indicator of past exposure. Subjects CF antibody positive at 1 in 2.5, IFA positive at 1 in 10 or more, or with a definite positive absorbance value in the EIA, should not be vaccinated (see Table 3.17.1).
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Table 3.17.1: Interpretation and action for serological and skin test results (with modifications from Q fever. Your questions answered (CSL, 1999)4) Serology
Skin test
Interpretation/Action
Positive antibody test*
Positive
Sensitised: do not vaccinate
Equivocal antibody test^
Negative antibody test
#
†
Borderline‡
Sensitised: do not vaccinate
Negative§
Sensitised: do not vaccinate
Positive
Sensitised: do not vaccinate
Borderline
Indeterminate (see (vi) below)
Negative
Indeterminate (see (vi) below)
Positive
Sensitised: do not vaccinate
Borderline
Indeterminate (see (vi) below)
Negative
Non-immune: vaccinate
* Positive antibody test: CF antibody or IFA positive (according to criteria used by diagnosing laboratory); or definite positive EIA absorbance value (according to manufacturer’s instructions). † Positive skin test: induration present. ‡ Borderline skin test: induration just palpable. § Negative skin test: no induration. ^ Equivocal antibody test: CF antibody or IFA equivocal (according to criteria used by diagnosing laboratory); or equivocal EIA absorbance value (according to manufacturer’s instructions). # Negative antibody test: CF antibody or IFA negative (according to criteria used by diagnosing laboratory); or definite negative EIA absorbance value (according to manufacturer’s instructions).
(vi) Test results are indeterminate when skin test induration is just palpable and/ or there is an equivocal level of antibodies in one or other of the serological tests.
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(v) Skin testing and interpretation should only be carried out by experienced personnel. For further information on training and accredited Q fever immunisation service providers, contact your State or Territory Health Department (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control). Skin testing is performed by diluting 0.5 mL of the Q-VAX Skin Test in 15 mL of sodium chloride (injection grade). Diluted Q-VAX Skin Test should be freshly prepared, stored at +2°C to +8°C and used within 6 hours. 0.1 mL of the diluted Q-VAX Skin Test is injected intradermally into the volar surface of the forearm. Commercial isopropyl alcohol skin wipes should not be used. If the skin is not visibly clean, then methylated spirits may be used. A positive reaction is indicated by any induration at the site of injection after 7 days. Individuals giving such a reaction must not be vaccinated, because they may develop severe local reactions.
An indeterminate result, which occurs in only a small proportion of subjects, may be the consequence of past infection with Q fever. It may also merely indicate the presence in the subject of antibodies to antigens shared between C. burnetii and other bacteria. Australian Q fever vaccine users have dealt with this finding in one of two ways: (a) Repeat the skin test and interpret as per the guidelines for initial testing. Collect serum 2 to 3 weeks later to look for a rise in titre of C. burnetii antibodies in the IFA test, using Phase I and Phase II antigens, and immunoglobulin class analysis. A significant increase (defined as a 4-fold rise in titre of paired sera) indicates previous Q fever infection and vaccination is then contraindicated. (b) Vaccinate the subject using SC injection of a 5 µg (0.1 mL) dose instead of a 25 µg (0.5 mL) dose of the vaccine. If there are no adverse effects (severe local induration or severe systemic effects, perhaps accompanied by fever) 48 hours after the injection, a further 0.4 mL (20 µg) dose of the vaccine is given within the next 2 to 3 weeks, ie. before the development of cell-mediated immunity to the first dose.
Booster doses Immunity produced by the vaccine appears to be long lasting (in excess of 5 years). Until further information becomes available, revaccination or booster doses of the vaccine are not recommended because of the risk of accentuated local adverse events.
Contraindications Q fever vaccine is contraindicated in the following: • individuals with a history of an illness suggestive of or proved to be Q fever, • those shown to be immune by either serological testing or sensitivity to the organism by skin testing, • those who have been previously vaccinated against Q fever, • those with known hypersensitivity to egg proteins or any component of the vaccine (Q-VAX may contain traces of egg protein, formalin, and sucrose).21 There is no information available on the accuracy of skin testing or the efficacy and safety of Q fever vaccine use in individuals with impaired immunity. In general, skin testing and Q fever vaccine should be avoided in such people. The lower age limit for Q fever vaccine is not known. However, it is not recommended for use in those aged <15 years.
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Precautions
Adverse events Non-immune subjects very commonly show local tenderness (48%) and erythema (33%) at the vaccination site. Local induration or oedema is uncommon (<1%). General symptoms occur commonly in about 10% of vaccinees and may include mild influenza-like symptoms such as headache (9%), fever (up to 2%), chills and minor sweating.4,21 There are also 2 patterns of more significant adverse events among the estimated more than 130 000 individuals vaccinated from 1989–2004.5,17 The first and familiar pattern is the intensified local reaction at the injection site which may occur shortly after inoculation in individuals sensitised immunologically by previous infection or repeated vaccination. Rarely, an immune abscess develops and requires excision and drainage. The acute reactions may be accompanied by short-term systemic symptoms resembling the post Q fever fatigue syndrome. Note, however, that not all those with positive pre-vaccination skin and/or serological tests develop severe reactions. The introduction of the pre-vaccination skin test at NIH/NIAID Rocky Mountain Laboratory,30 later combined with antibody testing in Australia, has largely eliminated reactions due to previous immune sensitisation. Despite this, the adverse experience from the earlier American trials22 in which subjects were not pre-tested, were vaccinated repeatedly or were inoculated with vaccines of a different composition and larger bacterial mass, are still quoted in the general Q fever literature as representative of a whole cell vaccine. The second, much less frequent, pattern has been reported in people who were skin and antibody test negative at the time of vaccination who did not have any immediate reaction. Some 1 to 8 months after vaccination, some vaccinees, predominately women, developed an indurated lesion at the inoculation site. At the time when the indurated lesion developed, the original skin test site often became positive, presumably indicating a late developing cellular immune response. These lesions were not fluctuant and did not progress to an abscess. Most gradually declined in size and resolved over some months without treatment. A few lesions were biopsied or excised and showed accumulations of macrophages and lymphocytes.31,32
Use in pregnancy Not recommended. Q fever vaccine contains inactivated products and inactivated bacterial vaccines are not considered to be harmful in pregnancy. However, safety of the vaccine in pregnancy has not been established. No information is available on the use of Q fever vaccine during breastfeeding.
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Vaccination of subjects already immune to C. burnetii, as a result of either previous infection or subjects being rendered hyperimmune by repeated vaccination, may result in severe local or systemic adverse events.
Variations from product information The product information for Q-VAX does not include the use of the reduced dose of vaccine in individuals who have indeterminate results on either serological or skin testing. However, this option has been used successfully by experienced Q fever vaccinators.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.18 Rotavirus Virology
Rotaviruses are shed in high concentrations in the stools of infected children and are transmitted by the faecal-oral route, both through close person-to-person contact and via fomites.6 Rotaviruses are probably also transmitted by other modes, such as faecally contaminated food, water and respiratory droplets.7,8
Clinical features Rotavirus is the predominant agent of severe dehydrating gastroenteritis in infants and young children in both developed and developing countries.1,2 The spectrum of rotavirus illness ranges from asymptomatic infection, to mild, watery diarrhoea of limited duration, to severe dehydrating diarrhoea with vomiting, fever, electrolyte imbalance, shock and death. Rotavirus infections are often more severe than other common causes of diarrhoea, and are more likely to be associated with dehydration and hospitalisation.1,7 The incubation period is 1 to 3 days, after which illness can begin abruptly with vomiting often preceding the onset of diarrhoea.7 Up to one-third of patients have a temperature of >39°C in the first few days of illness. Symptoms generally resolve in 3 to 7 days.
Epidemiology Although individuals can be infected with rotavirus several times during their lives, the first infection, typically between 3 and 36 months of age, is most likely to cause severe diarrhoea and dehydration.9,10 After a single natural infection, 40% of children are protected against any subsequent infection with rotavirus, 75% are protected against diarrhoea from a subsequent rotavirus infection, and 88% are protected against severe diarrhoea.10 Repeat infections provide even greater protection. Disease is also less likely when reinfection occurs with a serotype (G type) to which an individual has already been exposed.
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Rotaviruses are non-enveloped RNA viruses in the family Reoviridae. Rotaviruses are classified according to the 2 surface proteins they contain: VP7, the glycoprotein (G protein), and VP4, the protease-cleaved protein (P protein). The G and P proteins are targets for neutralising antibodies thought to be necessary for protection.1,2 Because the 2 gene segments that encode these proteins can segregate independently, a typing system consisting of both P and G types has been developed. Rotavirus strains are most commonly referred to by their G serotype, with G1, G2, G3, G4 and G9 accounting for around 90% of serotypes both globally and in Australia.3,4 The most common P types found in combination with these G types are P1a[8] (found with all common G-types except G2) or P1b[4], usually found in combination with G2.5
In Australia, the best available estimates are that approximately 10 000 hospitalisations due to rotavirus in children <5 years of age occur each year.11 As such, rotavirus accounts for around half the hospitalisations for acute gastroenteritis of any cause in this age group.11,12 This translates to 3.8% of children (1 in 27) being hospitalised with rotavirus gastroenteritis by the age of 5 years. In addition to hospitalised children, an estimated 115 000 children <5 years of age visit a GP, and 22 000 children require an Emergency Department visit.11,13 On average, there is 1 death attributed to rotavirus each year in Australia, but this is likely to be a minimum estimate.13 In temperate Australia, rotavirus infections follow a seasonal pattern, the peak incidence being in mid to late winter. In the northern tropical and arid regions, there is no consistent seasonal pattern and disease peaks are unpredictable.14 Epidemics of rotavirus gastroenteritis have occurred in Central Australia, causing severe strain on healthcare services.15,16 Overall, Indigenous Australian infants and children are hospitalised with rotavirus gastroenteritis about 3 to 5 times more commonly than their non-Indigenous peers, have a younger age at hospitalisation, and longer duration of hospital stay (an average of 5 days compared with 2 days for non-Indigenous infants).12,14,15,17 Children and adults with impaired immunity, such as those with congenital immunodeficiency, or post haematopoietic or solid organ transplantation, are at increased risk of severe, prolonged, and even fatal rotavirus gastroenteritis.1,18,19 Rotavirus is an important cause of nosocomial gastroenteritis,20-24 and can also cause disease in adults, especially those caring for children, and outbreaks of gastroenteritis in aged care facilities.1,25,26
Vaccines Two oral rotavirus vaccines are available in Australia, and data on their immunogenicity, safety and efficacy has been systematically reviewed.27 Both vaccines are live attenuated vaccines administered orally to infants, but the component vaccine viruses differ. Rotarix (GlaxoSmithKline) is a live attenuated vaccine containing 1 strain of attenuated human rotavirus (G1P1[8] strain). The human live attenuated strain protects against non G1 serotypes on the basis of their common P[8] antigen and other epitopes involved in heterotypic immunity. RotaTeq (CSL Biotherapies/Merck & Co Inc) is a pentavalent vaccine containing 5 human-bovine rotavirus reassortants with the human serotypes G1, G2, G3, G4, and P1[8] and the bovine serotypes G6 and P7. The vaccine viruses replicate in the intestinal mucosa and can be shed in the stool of vaccine recipients, particularly after the first dose. Vaccine virus shedding is more common with Rotarix and is detected in the stool a week after vaccination in up to 80% of first dose recipients, and in up to 30% of second dose recipients.27-29 RotaTeq is only shed after the first dose (in up to 13% of recipients).30 There have been no studies to assess the implications of shedding for horizontal spread to contacts.
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• Rotarix – GlaxoSmithKline (live attenuated RIX4414 human rotavirus strain expressing G1P1[8] outer capsid proteins). Each 1.0 mL monodose of the reconstituted vaccine contains not less than 106.0 CCID50 (cell culture infectious dose 50%) of the RIX4414 strain; sucrose; dextran 40; sorbitol; amino acids; Dulbecco’s Modified Eagle Medium; calcium carbonate; xanthan gum. Calcium carbonate buffer solvent (diluent) supplied for reconstitution. • RotaTeq – CSL Biotherapies/Merck & Co Inc (live, oral pentavalent vaccine). Each 2.0 mL monodose pre-filled dosing tube contains rotavirus reassortants G1, G2, G3, G4 and P1[8] each with a minimum dose level of at least 2.0 x 106 infectious units; sucrose; sodium citrate; sodium phosphate monobasic monohydrate; sodium hydroxide; polysorbate 80; cell culture media; trace amounts of fetal bovine serum. Also available in packs of 10 monodose pre-filled dosing tubes.
Transport, storage and handling Transport both vaccines according to National Vaccine Storage Guidelines: Strive for 5.34 Store at +2°C to +8°C. Do not freeze. Protect from light.
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Current oral rotavirus vaccines are underpinned by decades of developmental work.31 Randomised placebo-controlled studies of both vaccines have documented their efficacy and safety in the prevention of gastroenteritis caused by rotavirus.27,30,32 A vaccination course prevents rotavirus gastroenteritis of any severity in approximately 70% of recipients over the following 1 to 2 years. The efficacy against severe rotavirus gastroenteritis and against hospitalisation for rotavirus gastroenteritis is higher, ranging from 85 to 100% in clinical trials in many different countries.27,30,32,33 Efficacy in the prevention of hospitalisation from rotavirus gastroenteritis ranged from 85 to 100%.27,30,32,33 Vaccination was also highly effective in preventing Emergency Department and clinic/GP visits.30,33 Overall, rotavirus vaccination prevented around half (42–58%) of hospital admissions for acute gastroenteritis of any cause in young children, suggesting that rotavirus is responsible for more gastroenteritis than detected using routine testing and admission practices.30,32,33 In randomised control trials, a degree of protection against rotavirus gastroenteritis was also observed in infants who received fewer than the recommended number of doses of rotavirus vaccines. In the available clinical trials, no statistically significant differences were found between the 2 vaccines with regard to protective efficacy by serotype.27,30,32 The efficacy and safety of both rotavirus vaccines have been evaluated only in clinical trials in which infants received vaccine within specified age limits. There are no data on the use of rotavirus vaccines outside these age ranges (see ‘Recommendations’ and ‘Adverse events’ below).
Dosage and administration Rotavirus vaccines are for oral administration only. Under no circumstances should rotavirus vaccines be injected. There are no restrictions on the infant’s consumption of food or liquid, including breast milk, either before or after vaccination with either rotavirus vaccine.7,35 Rotarix is recommended for use in a 2-dose course (at 2 and 4 months of age). It is presented as a white powder for reconstitution with a separately supplied diluent, and a transfer adapter. The syringe/oral plunger containing the diluent is attached to the vial of lyophilised powder via the transfer adapter, and following reconstitution the 1 mL dose of vaccine should be administered orally via the syringe/oral plunger onto the inside of the infant’s cheek. RotaTeq is recommended for use in a 3-dose course (at 2, 4, and 6 months of age). It is supplied in a container consisting of a squeezable plastic, latex-free dosing tube with a twist-off cap, allowing for direct oral administration of the 2 mL dose onto the inside of the infant’s cheek. RotaTeq does not require reconstitution or dilution. RotaTeq is a pale yellow, clear liquid that may have a pink tint. Rotavirus vaccines can be co-administered with other vaccines included on the NIP schedule at 2 and 4 months of age (Rotarix) or 2, 4 and 6 months of age (RotaTeq). The available evidence from clinical trials suggests co-administration of oral rotavirus vaccines is safe and effective and does not interfere with the immune response to the other vaccine antigens (DTPa, Hib, IPV, hepB, and 7vPCV).28,29,35
Recommendations (i) Routine infant vaccination (Safety-Grade B)(EfficacyGrade B)(Immunogenicity-not assessed)27 Administration of a course of oral rotavirus vaccination is recommended for all infants in the first half of the first year of life. Vaccination of older infants and children is not recommended as there are theoretical concerns regarding use in older age groups (see ‘Adverse events’ below). Vaccination should occur at either 2 and 4 months of age (Rotarix), or 2, 4 and 6 months of age (RotaTeq), according to the following schedules (see also Table 3.18.1): • Rotarix (human monovalent rotavirus vaccine) The vaccination course of Rotarix consists of 2 doses at approximately 2 and 4 months of age. The first dose should be given between 6 and 14 weeks of age, and the second dose should be given by the end of the 24th week of age (6 months). The interval between the 2 doses should not be less than 4 weeks. • RotaTeq (pentavalent human-bovine reassortant rotavirus vaccine) The vaccination course of RotaTeq consists of 3 doses at approximately 2, 4, and 6 months of age. The first dose should be given between 6 and 12 weeks of age,
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and all doses should be given by the end of the 32nd week of age (~7.5 months). The interval between doses should be 4 to 10 weeks. Table 3.18.1: Age limits for dosing of oral rotavirus vaccines Doses
Age of routine oral administration
Age limits for dosing 1st dose
2nd dose
3rd dose
Minimum interval between doses
Rotarix (GlaxoSmithKline)
2 oral doses (1 mL/ dose)
2 and 4 months
6–14* weeks
10–24* weeks
None
4 weeks
RotaTeq (CSL Biotherapies/ Merck & Co Inc)
3 oral doses (2 mL/ dose)
2, 4 and 6 months
6–12† weeks
10–32† weeks
14–32† weeks
4 weeks
† The upper age limit for receipt of the first dose of RotaTeq is 12.9 weeks, that is up to the anniversary of the 13th week of age. The second dose of vaccine should preferably be given by 28 weeks of age to allow for a minimum interval of 4 weeks before receipt of the third dose, and the upper age limit for either the second or third doses is 32.9 weeks, that is by the anniversary of the 33rd week of age.
For infants in whom the first dose of rotavirus vaccine is inadvertently administered at an age greater than the suggested cut-off (14 weeks for Rotarix or 12 weeks for RotaTeq), the remaining vaccine doses should be administered as per the schedule, providing the minimum interval between doses can be maintained, and the course completed within the recommended age limits. The timing of the first dose should not affect the safety and efficacy of the second and third dose.7 Infants who develop rotavirus gastroenteritis before receiving the full course of rotavirus vaccinations should still complete the full 2- or 3-dose schedule (dependent on the brand of vaccine) because one rotavirus infection only provides partial immunity.7
(ii) Catch-up (no studies) Routine ‘catch-up’ or primary vaccination of older children is not recommended. Infants should commence the course of rotavirus vaccination within the recommended age limits for the first dose. It is also necessary to ensure that doses are not given beyond the upper age limits for the final dose of the vaccine course (see (i) above). This is based on theoretical concerns regarding possible adverse events in older age groups (see ‘Adverse events’ below), and because the safety of rotavirus vaccination in older infants and children has not been established.
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* The upper age limit for receipt of the first dose of Rotarix is 14.9 weeks, that is up to the anniversary of the 15th week of age and the upper age limit for receipt of the second dose of Rotarix is 24.9 weeks, that is up to the anniversary of the 25th week of age.
(iii) Premature infants (Safety-Grade C) (Efficacy-Grade C)(Immunogenicity-not assessed)27 Vaccination of preterm infants using either available rotavirus vaccine is indicated at a chronologic age of at least 6 weeks if clinically stable. Premature infants (<37 weeks’ gestation) appear to be at increased risk of hospitalisation from viral gastroenteritis.36 In clinical trials, RotaTeq or placebo was administered to 2070 preterm infants (25–36 weeks’ gestational age; median 34 weeks) who experienced rates of adverse events after vaccination similar to matched placebo recipients.7,27 Efficacy against rotavirus gastroenteritis of any severity was evaluated in only a small subset of premature infants and appeared comparable to efficacy in term infants (70%; 95% CI: -15%–95%). These conclusions would also be expected to apply to Rotarix vaccine. If standard infection control precautions are maintained, administration of rotavirus vaccine to hospitalised infants, including hospitalised premature infants, would be expected to carry a low risk for transmission of vaccine viruses (see ‘Precautions’ below).
Contraindications The only absolute contraindications to rotavirus vaccines are: • anaphylaxis following a previous dose of either rotavirus vaccine, or • anaphylaxis following any vaccine component.
Precautions (i) Acute gastroenteritis Infants with moderate to severe acute gastroenteritis should not be vaccinated until after recovery from their acute illness. Infants with mild gastroenteritis (including mild diarrhoea) can be vaccinated. The use of rotavirus vaccines has not been studied in infants with acute gastroenteritis.
(ii) Moderate to severe illness As with other vaccines, infants with a moderate to severe illness should be vaccinated after recovery. In addition to the factors mentioned above in (i), this avoids superimposing potential adverse events related to vaccination with the concurrent illness.
(iii) Underlying conditions predisposing to severe rotavirus gastroenteritis Conditions predisposing to severe or complicated rotavirus gastroenteritis include metabolic disorders or chronic gastrointestinal disease, such as Hirschsprung’s disease, malabsorption syndromes or short gut syndrome.1 Although the safety and efficacy of rotavirus vaccines have not been studied in such infants, because they are at greater risk of serious rotavirus disease over an extended age range, the potential benefits of vaccination at an age older than the upper limits recommended in Table 3.18.1 are likely to be substantial. Vaccination of such children at an older age may be judged by clinicians to warrant
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discussion with parents on a case by case basis (see ‘Variations from product information’ below).
(iv) Infants with impaired immunity There are no studies of the safety or efficacy of the currently available rotavirus vaccines in infants with impaired immunity. As with other live viral vaccines, there are theoretical concerns that vaccine virus-associated gastrointestinal disease could occur in infants with severely impaired immunity who receive rotavirus vaccines. However, the theoretical risk for vaccine virus-associated disease in immune-impaired vaccinated infants is likely to be less than their risk from being exposed to disease from natural infection. Risks and benefits of vaccination should be considered in the context of the infant’s specific immune impairment with appropriate specialist advice7 (see (v) below, and Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment). Infants living in households with people who have impaired immunity should be vaccinated. In general, household members with impaired immunity are afforded protection by vaccination of young children in the household. This outweighs the small risk for transmitting vaccine virus shed in stool to the household member with impaired immunity. The theoretical risk for vaccine virus-associated disease in contacts with impaired immunity is considered less than their risk of being exposed to disease from natural infection. However, there have been no studies to specifically address this question.7 (See also Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment.)
(vi) Recent administration of antibody-containing blood products Infants who have recently received antibody-containing blood products and are at an eligible age should be vaccinated. The interval between vaccination and receipt of the blood product should be as long as possible, but without delaying administration of vaccine beyond the suggested age limits for dosing (as per Table 3.18.1 above). This recommendation for maximising the interval is based on theoretical concern that passively acquired antibody to rotavirus may interfere with vaccine immunogenicity.7
(vii) Hospitalised infants If a recently vaccinated child is hospitalised for any reason, no precautions other than routine standard precautions need be taken to prevent the spread of vaccine virus in the hospital setting. Administration of rotavirus vaccine to hospitalised infants, including hospitalised premature infants, is likely to carry a low risk for transmission of vaccine viruses if standard infection control precautions are maintained (see ‘Vaccines’ above).
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(v) Infants living in households with people with impaired immunity
(viii) Exposure of pregnant women to vaccinated infants Infants living in households of pregnant women can receive rotavirus vaccines. Most pregnant women will have pre-existing immunity to rotavirus but avoidance of wild-type infection through the vaccination of infant contacts may benefit adults, including pregnant women, and outweighs any theoretical concern regarding exposure to vaccine viruses.
(ix) Regurgitation of vaccine dose Readministration of the vaccine is not necessary after regurgitation, spitting out, or vomiting of a rotavirus vaccine. This is because there are limited data available on the safety of administering higher than the recommended dose of rotavirus vaccines. There are no studies of the efficacy of a partially administered dose(s).
Adverse events (i) Intussusception (IS) Current evidence indicates that intussusception (IS, a form of bowel obstruction) is not associated with either Rotarix or RotaTeq vaccines, especially when given to infants within the age limits studied in clinical trials.27,30,32 Post-licensure data in larger numbers of children will monitor if there is an increased risk of IS following rotavirus vaccination, particularly among those inadvertently receiving doses outside the recommended age limits. Concern about association between IS and rotavirus vaccines arose because a tetravalent rhesus-reassortant vaccine, called RotaShield, licensed in the United States (but not elsewhere) in 1998–99, was associated with IS in approximately 1 in 10 000 vaccine recipients.37 The greatest risk of IS occurred within 3 to 14 days after the first dose, with a smaller risk after the second dose.37,38 There is evidence that when the first dose of RotaShield was given at >3 months of age, the risk of intussusception was increased.38 The pathogenesis of RotaShield-associated intussusception has not been determined. However, the current rotavirus vaccines (RotaTeq and Rotarix) differ in composition to RotaShield, which was also more reactogenic.39-41 The large-scale safety studies of the 2 current rotavirus vaccines included approximately 140 000 infants, and found the risk of IS in vaccine recipients to be similar to that of placebo recipients, and less than that estimated for RotaShield.27,30,32 To minimise background rates of IS, the clinical trials of Rotarix and RotaTeq limited administration of the first dose of vaccine to infants under 14 and 12 weeks of age, respectively, and did not give subsequent doses to infants beyond a certain age (24 weeks for Rotarix and 32 weeks for RotaTeq).27,30,32 As such, data on safety of these vaccines in older infants is not currently available (see ‘Recommendations’ above).
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(ii) Other adverse events Vaccine recipients developed gastrointestinal symptoms such as diarrhoea or vomiting in the week after rotavirus vaccination more commonly than placebo recipients (increased risk of up to 3%).27,30,32 Fever was not significantly more common in rotavirus vaccine recipients compared with placebo recipients in clinical trials of both available vaccines.27,30,32
Interchangeability of rotavirus vaccines
Variations from product information The product information for Rotarix states that the vaccine should not be administered to subjects with chronic gastrointestinal disease. NHMRC recommends that pre-existing chronic gastrointestinal disease is not considered to be a contraindication to rotavirus vaccination (see ‘Precautions’ above).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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Completion of a course of rotavirus vaccine should be with vaccine from the same manufacturer whenever possible. There are no studies that address the interchangeability of the 2 available rotavirus vaccines. However, if either dose 1 or 2 of vaccine is given as RotaTeq, a third dose of either rotavirus vaccine should be given, provided that the upper age limit and inter-vaccine interval, as defined above in ‘Recommendations’, Table 3.18.1, are met.
3.19 Rubella Virology Rubella is an enveloped togavirus, genus Rubivirus. The virus has an RNA genome and is closely related to group A arboviruses, but does not require a vector for transmission. It is relatively unstable, and is inactivated by lipid solvents, trypsin, formalin, extremes of heat and pH, amantadine and UV light.1
Clinical features Rubella is generally a mild and self-limiting infectious disease.2 It causes a transient, generalised, erythematous, maculopapular rash, lymphadenopathy involving the post-auricular and sub-occipital glands, and, occasionally, arthritis and arthralgia. Other complications, such as neurological disorders and thrombocytopenia, may occur but are rare. Clinical diagnosis is unreliable since the symptoms are often fleeting and can be caused by other viruses; in particular, the rash is not unique to rubella and may be absent.1,2 Up to 50% of rubella virus infections are subclinical or asymptomatic.1 A history of rubella should, therefore, not be accepted without serological evidence of previous infection.1 The incubation period is 14 to 21 days, and the period of infectivity is from 1 week before until 4 days after the onset of the rash.2 Rubella infection in pregnancy can result in fetal infection resulting in congenital rubella syndrome (CRS) in a high proportion of cases (see ‘Rubella infection in pregnancy’ below).
Epidemiology Rubella occurs worldwide and is spread from person to person by droplet contact and possibly air-borne transmission of infectious respiratory secretions.1 In temperate climates, the incidence is highest in late winter and early spring.3 The incidence of rubella has fallen rapidly since vaccine licensure, and there has been a shift in the age distribution of cases, with comparatively more cases being seen in older age groups, particularly the 20–24 year age group.4 In the early 1990s, rubella epidemics were reported in those States where rubella was notifiable.5 Over 3000 cases per year were reported between 1992 and 1995.5 In 2004–2005, rubella notifications were the lowest yet recorded with 31 confirmed cases being reported in each year (0.15 per 100 000 per year).4 This low notification rate most likely reflects the high vaccine coverage achieved and sustained with the National Measles Control Campaign in late 1998.3,6,7 The number of cases of congenital rubella syndrome has also fallen rapidly since rubella vaccine licensure in Australia. Successful vaccination campaigns and high vaccination coverage resulted in no cases of congenital rubella syndrome occurring in infants of Australian-born mothers between 1998 and 2002. However, 5 cases resulting from infection acquired outside of Australia
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were reported during this time.8,9 Between 2003 and 2005, an additional 5 cases were reported from infection that occurred in Australia9-11 which reinforces the need for high vaccination coverage of women of child-bearing age (see ‘Rubella infection in pregnancy’ below). The rubella virus was isolated in cell culture in 1962, and vaccines prepared from strains of attenuated virus have been approved for use in Australia since 1970. Mass vaccination of schoolgirls commenced in 1971.1,12 Non-pregnant, seronegative adult women were also vaccinated. These programs were successful and there was a significant reduction in the incidence of congenital rubella syndrome from 1977.13-15 There has also been a significant increase in the percentage of pregnant women immune to rubella (in NSW from 82% in 1971 to 96% in 1983). Based on a recent study in Melbourne, it was estimated that, in 2000, only 2.5% of all women in Australia of child-bearing age were seronegative. However, susceptibility was higher among overseas-born women, and has been reported as higher among some Indigenous women.16,17
Rubella infection in pregnancy Maternal rubella infection in the first 8 to 10 weeks of pregnancy results in fetal damage in up to 90% of affected pregnancies, and multiple defects are common.19-21 The risk of damage declines to 10 to 20% by 16 weeks’ gestation. After this stage of pregnancy, fetal damage is rare but has been reported up to 20 weeks’ gestation.19 The characteristics of congenital rubella syndrome include intellectual disabilities, cataracts, deafness, cardiac abnormalities, intrauterine growth retardation and inflammatory lesions of the brain, liver, lungs and bone marrow.19 Any combination of these defects may occur, but defects which commonly occur alone following infection after the first 8 weeks of pregnancy are perceptive deafness and pigmentary retinopathy. Some infected infants may appear normal at birth, but defects, especially sensorineural deafness, may be detected later.22 Rubella reinfection can occur in individuals who have both natural and vaccineinduced antibody.19 Occasional cases of congenital rubella syndrome after reinfection in pregnancy have been reported. However, fetal damage is very rare in cases of infection in women in whom antibody has previously been detected.20,23-25
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Many adolescent and young adult males are not immune to rubella because they did not receive an MMR vaccine.18 The MMR vaccination program for all adolescents replaced the rubella program for girls in 1993/94.12 A serosurvey conducted in 1999 showed that only 84% of males aged 14–18 years (compared to 95% of females) and 89% of males aged 19–49 years (compared to 98% of females) were immune to rubella.18 For this reason, adolescent and young adult males, as well as females, who do not have a documented history of receipt of 2 doses of MMR, should receive MMR vaccine (see ‘Recommendations’ below). This is both for their own protection and to prevent transmission of the infection in the community (see ‘The public health management of rubella’ below).
All pregnant women with suspected rubella or exposure to rubella should be serologically tested, irrespective of a history of previous vaccination, clinical rubella or a previous positive rubella antibody result (see ‘Serological testing for rubella’ below). This is because the rash of rubella is not diagnostic, asymptomatic infection can occur, and acute rubella can be confirmed only by laboratory tests.19,23,24 Pregnant women should be counselled to restrict contact with individuals with confirmed, probable or suspected rubella for 6 weeks (2 incubation periods).26 Counselling of pregnant women with confirmed rubella regarding the risk to the fetus should be given in conjunction with the woman’s obstetric service.
Serological testing for rubella A number of commercial assays for testing immunity to rubella are available. These vary according to the method used to determine the positive cut-off value (the WHO cut-off is 10 IU/mL but, at present, there is no recommended Australian minimal level). Available data support the presumption that an antibody level found by use of a licensed assay to be above the standard positive cut-off for that assay can be considered evidence of past exposure to rubella virus.23 Antibody levels below the cut-off are likely not to be protective, particularly if the antibodies have been generated by vaccination rather than by natural infection, and MMR vaccine (or MMRV if protection against varicella is required in children 12 months to 12 years of age) should be administered according to the ‘Recommendations’ below. Expert consultation and referral of sera to a reference laboratory are recommended if there is a difficulty interpreting results. Acute rubella infection is indicated by presence of rubella IgM or 4-fold or greater increase in rubella IgG. Rubella IgM may not appear until a week after clinical symptoms. Sera for IgG testing should be taken 7 to 10 days after onset of illness and repeated 2 to 3 weeks later. The most recent date of potential exposure should be obtained, if possible, to calculate the potential incubation period. As some patients may have more than 1 exposure to a person with a rubella-like illness, and because exposure may occur over a prolonged period, it is important to ascertain the dates of the first and last exposures.26 Seronegative women of child-bearing age should be vaccinated (see ‘Recommendations’ below) and tested for seroconversion 8 weeks after vaccination. All women should be informed in writing of the result of their antibody test. Women should be screened for rubella antibodies shortly before every pregnancy, or early in the pregnancy, or if pregnancy is contemplated, irrespective of a previous positive rubella antibody result.15,19 Very occasionally, errors may result in patients who are seronegative being reported as seropositive. Where possible, specimens from pregnant women should be stored until the completion of the pregnancy. Serological testing of pregnant women exposed to rubella should always be performed (see ‘Rubella infection in pregnancy’ above). A blood sample
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should be taken and sent to the laboratory with the date of the last menstrual period and the date of presumed exposure (or date of onset of symptoms).26 If the woman has an antibody titre below the protective level, or a low level of antibodies and remains asymptomatic, a second blood specimen should be collected 28 days after the exposure (or onset of symptoms) and tested in parallel with the first. If the woman develops symptoms, the specimen should be collected and tested as soon as possible. A third blood specimen may be required in some circumstances.24
Vaccines Rubella vaccine is available as either MMR vaccine or as a monovalent rubella vaccine. It is anticipated that combination measles-mumps-rubella-varicella (MMRV) vaccines will become available in the near future. A single dose of rubella vaccine produces an antibody response in more than 95% of vaccinees, but antibody levels are lower than after natural infection.19,23,24 Vaccine-induced antibodies have been shown to persist for at least 16 years in the absence of endemic disease.23,24,27,28 Protection against clinical rubella appears to be longterm in those who seroconvert.19 Monovalent rubella vaccine
Combination measles-mumps-rubella vaccine • Priorix (MMR) – GlaxoSmithKline (live attenuated measles virus (Schwarz strain), RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 103.0 CCID50 (cell culture infectious dose 50%) of the Schwarz measles, not less than 103.7 CCID50 of the RIT 4385 mumps and not less than 103.0 CCID50 of the Wistar RA 27/3 rubella virus strains; lactose; neomycin; amino acids; sorbitol and mannitol as stabilisers.
Transport, storage and handling Transport both vaccines according to National Vaccine Storage Guidelines: Strive for 5.29 Store at +2°C to +8°C. Protect from light. Do not freeze. Reconstituted vaccine should be used immediately, but can be stored at +2°C to +8°C for up to 8 hours before use.
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• Meruvax II – CSL Biotherapies/Merck & Co Inc (rubella virus vaccine). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 1000 TCID50 (tissue culture infectious dose 50%) of attenuated rubella virus (Wistar RA 27/3 strain); 25 µg neomycin; 3 mg human serum albumin; sorbitol and gelatin as stabilisers.
Dosage and administration For both children and adults, the dose of MMR and monovalent rubella vaccine is 0.5 mL, administered by either SC or IM injection. MMR and monovalent rubella vaccine can be given at the same time as other vaccines (including DTPa, hepatitis B, MenCCV and varicella), using separate syringes and injection sites. If MMR or monovalent rubella vaccine is not given simultaneously with other live viral parenteral vaccines (eg. varicella vaccine), they should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations The principal aim of rubella vaccination is to prevent congenital rubella syndrome by stopping the circulation of rubella virus in the community. Susceptible pregnant women will continue to be at risk of rubella infection in pregnancy until the transmission of rubella virus is interrupted by a sufficiently high uptake of rubella-containing vaccine in children and adults of both sexes.
(i) Routine vaccination of children Two doses of rubella-containing vaccine are recommended for all children. The first dose should be given at 12 months of age and the second dose at 18 months of age (MMR or MMRV when available). The minimum interval between the first and second doses of MMR or MMRV is 4 weeks. A history of rubella is not a contraindication to vaccination. Individuals who are already immune to rubella have no increased risk of side effects from vaccination.19,23
(ii) Vaccination of women of child-bearing age Every effort should be made to identify non-pregnant seronegative women of child-bearing age. The following women are more likely to be seronegative to rubella: women born overseas (especially in Asia, Pacific islands, sub-Saharan Africa and South America) who have entered Australia after the age of routine vaccination; non-English speaking women; women over the age of 35; and Muslim women.5,13,14,16,30 Seronegative women should be given MMR vaccine and advised not to become pregnant for 28 days after vaccination. Monovalent rubella vaccine can be used where there is a contraindication to the measles or mumps components of MMR. Vaccinated women should be tested for seroconversion 6 to 8 weeks after vaccination (see ‘Serological testing for rubella’ above). Women who have negative or very low antibody levels after vaccination should be revaccinated. If their antibody levels remain low after a second vaccination, it is unlikely that further vaccinations will improve this.19 Although 2 doses of MMR vaccine are routinely recommended, if rubella immunity is demonstrated after receipt of 1 dose of a rubella-containing vaccine, no further dose is required, unless indicated by subsequent serological testing (see ‘Serological testing for rubella’ above).
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(iii) Vaccination of adolescent and adult males All males born during or after 1966 require 2 doses of MMR at least 4 weeks apart if they have no record of receiving the vaccine, as they are especially likely to be non-immune to rubella (see ‘Epidemiology’ above).
(iv) Vaccination post-partum Women found to be seronegative on antenatal rubella immunity testing should be vaccinated after delivery and before discharge from the maternity unit. MMR vaccine is recommended, although monovalent rubella vaccine can also be used for this purpose. These women should be tested for rubella immunity 6 to 8 weeks after vaccination (see ‘Vaccination of women of child-bearing age’ above). Anti-D immunoglobulin does not interfere with the antibody response to vaccine.1,19 If anti-D immunoglobulin is also required, the two may be given at the same time in different sites with separate syringes, or at any time in relation to each other24 (see ‘Contraindications’ below).
(v) Vaccination of healthcare workers and people working with children
For further recommendations related to MMR vaccination, see Chapter 3.11, Measles.
Contraindications Vaccination is contraindicated in the following circumstances:
(i) Allergy to vaccine components • anaphylaxis following a previous dose of rubella, MMR or MMRV, or • anaphylaxis following any vaccine component.
(ii) People with impaired immunity Rubella-containing vaccine should not be administered to patients with congenital or acquired impaired immunity (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment). This includes those receiving high-dose corticosteroid or immunosuppressive treatment, general radiation, malignant conditions of the reticuloendothelial system (such as lymphoma, leukaemia, Hodgkin’s disease), or in cases where the normal
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All healthcare staff and people working with children, born during or since 1966, including medical, nursing, and other health professional students, either without vaccination records or seronegative upon screening, should receive 2 doses of MMR vaccine, both for their own protection and to avoid the risk of transmitting rubella to pregnant patients and/or colleagues31 (see Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases). Preferably, MMR should be used. Where necessary, those vaccinated can be tested for seroconversion 8 weeks after vaccination and revaccinated if seronegative (see ‘Vaccination of women of child-bearing age’ above).
immunological mechanism may be impaired, as in hypogammaglobulinaemia.1,23 Rubella vaccine or MMR may be given to HIV-positive individuals unless they have severely impaired immunity.23 (For further information on MMR and MMRV vaccines, see Chapter 3.11, Measles and Chapter 3.24, Varicella).
(iii) Recent administration of antibody-containing blood product Rubella-containing vaccine should not be given within at least 3 months after an injection of immunoglobulin, other antibody-containing blood product, or wholeblood transfusion, because the expected immune response may be impaired.19,24 The recommended intervals for receipt of rubella-containing vaccines after receipt of blood products are given in Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination. Rubellacontaining vaccines may be administered concomitantly with, or at any time in relation to, anti-D immunoglobulin, but at a separate injection site. However, women who have received anti-D immunoglobulin should be serologically tested 8 weeks after vaccination to ensure that seroconversion has occurred.1,23
(iv) Pregnant women MMR and monovalent rubella vaccines should not be given to a woman known to be pregnant, and pregnancy should be avoided for 28 days after vaccination (see ‘Use in pregnancy’ below).1,32 Data on the use of MMRV vaccines in individuals >12 years of age are not available.
Precautions • If MMR or monovalent rubella vaccine is not given simultaneously with other live viral parenteral vaccines (eg. varicella vaccine), they should be given at least 4 weeks apart. • Breastfeeding is not a contraindication to rubella vaccination. The rubella vaccine virus may be secreted in human breast milk, and there have been rare cases of transmission of vaccine virus through breast milk reported. However, these infections have been mild.1 • There is no risk to pregnant women from contact with recently vaccinated individuals. The vaccine virus is not transmitted from vaccinees to susceptible contacts.1 For precautions related to MMR and MMRV vaccines, see Chapter 3.11, Measles and Chapter 3.24, Varicella.
Adverse events Mild adverse events such as fever, sore throat, lymphadenopathy, rash, arthralgia and arthritis may occur after vaccination.1,23 Symptoms most often begin 1 to 3 weeks after vaccination and are usually transient. Joint symptoms are more common in adults, especially women (10 to 25%, very common) than in children (0.3%, uncommon).1,23 Thrombocytopenia, that is usually self limiting, has been
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reported rarely after rubella vaccine.23 Very rarely, neurological symptoms have been reported, but a causal relationship has not been established.23 For adverse events related to MMR and MMRV vaccines, see Chapter 3.11, Measles and Chapter 3.24, Varicella.
The public health management of rubella All cases of suspected rubella infection should be laboratory tested and false positive results excluded. Infected individuals should be excluded from school/ work/institution and should avoid contact with women of child-bearing age for at least 4 days after the onset of the rash.26 All contacts should be identified, especially those who are pregnant. If a contact is pregnant, see ‘Rubella infection in pregnancy’ above. All contacts >12 months of age without adequate proof of immunity should receive 1 dose of MMR (or MMRV, when available, in those 12 months to 12 years of age). This will not prevent rubella disease if already exposed. If vaccination is refused, the contact should avoid further contact with cases until at least 4 days after onset of the rash in the case. Exposed healthcare workers without adequate proof of immunity should be excluded from work for 21 days from exposure or for at least 4 days after the onset of a rash.26
Use in pregnancy
Use of normal human immunoglobulin (NHIG) to prevent rubella Post-exposure prophylaxis with NHIG does not prevent infection in non-immune contacts and is, therefore, of little value for protection of pregnant women exposed to rubella.23 It may, however, prolong the incubation period, which may marginally reduce the risk to the fetus. It may also reduce the likelihood of clinical symptoms in the mother. NHIG should only be used if termination
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Vaccination should be avoided in early pregnancy.1 However, active surveillance in the USA, UK and Germany indicates that no case of vaccineinduced congenital rubella syndrome occurred among more than 500 women inadvertently vaccinated with rubella vaccine during pregnancy, whose pregnancies continued.33 In a recent Iranian study performed after mass vaccination with a measles-rubella vaccine, 117 susceptible women were inadvertently vaccinated while pregnant or became pregnant ≤3 months after vaccination. There were no CRS-related abnormalities among the infants born to these women.34 Based on this evidence, the vaccine cannot be considered to be teratogenic, and termination of pregnancy following inadvertent vaccination is not indicated1,24 (see Section 2.3.2, Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants).
for confirmed rubella would be unacceptable under any circumstances. In such cases, IM administration of 20 mL of NHIG within 72 hours of rubella exposure might reduce – but will not eliminate – the risk for rubella.23 Serological followup of recipients is essential, and should continue for up to 2 months. There is some evidence to suggest that, in outbreak situations, pre-exposure NHIG may be effective in preventing infection in women who are likely to be pregnant, and its use may be indicated for such women with low antibody titres in high-risk occupations.35
Variations from product information The product information recommends that women of child-bearing age should be advised not to become pregnant for 3 months after vaccination with rubella, MMR or MMRV vaccines, whereas NHMRC recommends 28 days.32 The product information for Meruvax II recommends the vaccine be given by SC injection, but NHMRC recommends administration by either SC or IM injection. The product information for Meruvax II states that there is no reason to revaccinate individuals who were vaccinated originally when 12 months of age or older. However, NHMRC recommends routine administration of a second dose of rubella vaccine when given as MMR or MMRV to children.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.20 Smallpox Virology The smallpox or variola virus is one of the poxviruses, a group characterised by large brick-shaped virus particles, which includes the agents vaccinia, monkeypox, mousepox and cowpox. The virus is inhaled into the respiratory tract, multiplies in local lymph nodes and then seeds to the reticuloendothelial system. During the clinical prodrome the virus then circulates to the skin and mucous membranes where the cell destruction produces the characteristic vesicular lesions.1
Clinical features An incubation period of about 12 days is abruptly followed by the prodrome, a 2 to 5 day period of high fever, malaise and severe headache. Then follows the pharyngeal enanthum and, a day later, the skin rash begins as small red macules before progressing to papules, vesicles and finally pustules over the next 4 to 7 days.1 Death follows in about 20% of cases. The diagnosis is made by collecting vesicular fluid for examination by electron microscopy, or for detection of viral nucleic acids by amplification techniques. Diseases that are most likely to mimic smallpox in Australian populations are varicella and drug eruptions.
Epidemiology Smallpox, a disease only of humans, was declared eradicated in 1979 after an intense international campaign of detection and vaccination. The disease would now be of only historical interest if not for concerns that illicit laboratory stocks of the virus may exist and may be used as biological weapons.2 In the days of endemic disease in rural areas, each case of smallpox would generate several more cases among family and friends attending the victim, who was usually bed-bound from the onset of the prodromal illness. The epidemiology of disease spread by bioterrorists may be quite different. Patients hospitalised in the prodromal period may widely transmit the virus during coughing, as demonstrated in an outbreak in a German hospital after admission of one patient with unrecognised smallpox.3
Little is known of the origin of vaccinia virus, the poxvirus used to immunise humans against smallpox. Despite its name, which has been given generally to compounds (vaccines) which induce artificial immunity, it is not cowpox.4-6 Australia has stocks of smallpox vaccine for use in an emergency situation only.4-6 The USA smallpox vaccine Dryvax, has been used to vaccinate Australian laboratory personnel working with poxviruses. This vaccine contains vaccinia which produces cross-immunity against variola. Dryvax is a freeze-dried formulation.
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Vaccines
The duration of immunity is uncertain. A recent review, examining the frequency of adverse events after vaccination with different vaccinia strains, reported that the Lister strain vaccine is associated with a higher risk of severe adverse events, in particular postvaccinal encephalopathy.7
Transport, storage and handling Transport according to Guidelines for smallpox outbreak, preparedness, response and management.4 Smallpox vaccine should be kept frozen at –30°C. The shelf life of the vaccine is 24 hours once thawed and, once thawed, the vaccine should be stored at +2°C to +8°C.
Dosage and administration Only trained healthcare workers should perform smallpox vaccination. One of several techniques can be used to place a tiny volume of the reconstituted vaccine on the skin of the lateral surface of the upper arm. Most commonly, a bifurcated needle is dipped into a multidose container and then positioned vertically over the skin, which is then punctured repeatedly with sufficient vigour to produce no more than a trace of blood at the site.4-6,8 Personal protective equipment must be used while performing smallpox vaccination. Smallpox vaccines must not be injected subcutaneously, intramuscularly or intravenously. Intradermal inoculation with smallpox vaccine results in the formation of an erythematous papule within 3 to 5 days. It becomes a vesicle, then a pustule reaching a maximum size of 1 to 2 cm in 8 to 12 days, then scabs and separates by 14 to 21 days. When the procedure results in this circumscribed infection, vaccination provides long-term protection against fatal disease. Furthermore, vaccination very soon after exposure to smallpox markedly attenuates or prevents clinical disease.4-6
Recommendations The only current indication for vaccination in Australia is for workers using live pox virus in recombinant gene research, in order to prevent infection at sites of accidental inoculation. Currently, no vaccine is licensed for use in Australia; however, information about sources of vaccines and their use should be obtained from the Therapeutic Goods Administration, Canberra.4 Australian guidelines for smallpox outbreak, preparedness, response and management may be found at http://www.health.gov.au/internet/wcms/ publishing.nsf/Content/health-pubhlth-publicat-others.htm.4
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Contraindications The vaccine is contraindicated in:4,5 • people with diseases that cause impaired immunity such as human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma, generalised malignancy, agammaglobulinaemia, • those undergoing therapy with alkylating agents, antimetabolites, radiation or large doses of steroids, • those who have ever been diagnosed with eczema, even if the condition is mild or not presently active, • those with a history of neurological disorder, • women who are either pregnant or trying to become pregnant, • women who are breastfeeding, • children aged <1 year, • anyone living in a household with a member who has any of the conditions listed above, • people with serious, life-threatening allergies to the antibiotics polymyxin B, streptomycin, tetracycline or neomycin (this may depend on brand of vaccine used), • those vaccinated in the past 30 days with a live vaccine, • those with a history of cardiac disease, including: • previous myocardial infarction, • angina, • congestive heart failure, • cardiomyopathy, • valvular disease, including rheumatic heart disease, • stroke or transient ischaemic attack, • chest pain or shortness of breath with activity, • other heart conditions under the care of a doctor.
Individuals with acute or chronic skin conditions, such as atopic dermatitis, impetigo and varicella-zoster (chickenpox and shingles), should not be vaccinated until the condition resolves. Individuals with eczema should live apart from recently vaccinated family members who may have skin lesions.
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Precautions4-6
Women should be advised to avoid pregnancy for 3 months after smallpox vaccination. Anyone who receives a smallpox vaccination should not receive another live vaccine for 1 month afterwards.
Adverse events4-6,8 Smallpox vaccines have well described adverse events, which vary in frequency according to the virus present in the seed stock. They include: • postvaccinal encephalitis (PVE) or encephalomyelitis (PVEM), a demyelinating disease which occurs at a rate of 1 per 300 000 vaccinations; PVE is generally seen in those aged <1 year and PVEM in those aged >2 years; • progressive vaccinia (vaccinia gangrenosa) at the site of inoculation, in vaccinees with immune impairment; • eczema vaccinatum, being vaccinial skin disease at sites of previous or current eczema; occurs at a rate of about 1 in 26 000 vaccinations; • generalised vaccinia, a self-limiting condition resulting from blood-borne dissemination of the virus to other skin sites; more serious in people with impaired immunity; occurs at a rate of 1 in 5000 vaccinations; • inadvertent inoculation of either the vaccinee or vaccinator in sites such as the face, eyes or hands; occurs at a rate of 1 in 20 000 primary vaccinations; • various skin rashes, usually self-limiting but can progress to Stevens-Johnson Syndrome; • fetal vaccinia is rare (<50 reported cases), greatest risk occurs during the third trimester; • cardiac adverse events including myocarditis, pericarditis and, possibly, dilated cardiomyopathy.
Use in pregnancy Smallpox vaccine is contraindicated in women who are either pregnant or trying to become pregnant. Women should be advised to avoid pregnancy for 3 months after vaccination.
Vaccinia immune globulin4,5 Vaccinia immune globulin (VIG) is a sterile solution of the immunoglobulin fraction of plasma containing antibodies to the vaccinia virus, from individuals who were previously vaccinated with smallpox vaccine. VIG and the nucleoside analogue active against poxviruses, cidofovir, may be used to treat vaccine complications such as inadvertent inoculation of the eye or eyelid without vaccinal keratitis, severe generalised vaccinia if patient is toxic, eczema
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vaccinatum and progressive vaccinia. VIG is not indicated for treatment of vaccinal keratitis or postvaccinal encephalitis. VIG is contraindicated in those with a history of anaphylactic sensitivity to thiomersal or to other humanised monoclonal antibodies. There are currently limited stocks of VIG and cidofovir available in Australia. Contact the Australian Government Department of Health and Ageing or your State/Territory Health Department for further information regarding these products (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
3.20 Smallpox
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3.21 Tetanus Bacteriology Tetanus is caused by Clostridium tetani, a motile, non-capsulated, Gram-positive rod that forms endospores. Spores of the bacillus are found in manured soil and can enter wounds. Once in a wound site, the bacillus can grow anaerobically. C. tetani produces a potent protein toxin which has 2 components, tetanospasmin (a neurotoxin) and tetanolysin (a haemolysin).
Clinical features Tetanus is an acute, often fatal, disease caused by the toxin produced by C. tetani. The neurotoxin acts on the central nervous system to cause muscle rigidity with painful spasms. The disease usually occurs after an incubation period of 3 to 21 days (range 1 day to several months), with a median time of onset after injury of 10 days. Generally, a shorter incubation period is associated with a more heavily contaminated wound, more severe disease and a worse prognosis. Generalised tetanus, the most common form of the disease, is characterised by increased muscle tone and generalised spasms. Early symptoms and signs include increased tone in the masseter muscles (trismus, or lockjaw), dysphagia, stiffness or pain in the neck, shoulder and back muscles. Some patients develop paroxysmal, violent, painful, generalised muscle spasms. A constant threat during generalised spasms is reduced ventilation or apnoea or laryngospasm. The patient may be febrile, although many have no fever; mental state is unimpaired. Sudden cardiac arrest sometimes occurs, but its basis is unknown. Other complications include pneumonia, fractures, muscle rupture, deep vein thrombophlebitis, pulmonary emboli, decubitus ulcers and rhabdomyolysis. Death results from respiratory failure, hypertension, hypotension or cardiac arrhythmia. Tetanus is rare in people who have received 5 doses of a tetanus-containing vaccine (1 in 90 cases in the United Kingdom from 1984–2000).1 However, individual cases have been reported2,3 and clinicians should consider tetanus when there are appropriate symptoms and signs, irrespective of the person’s vaccination record. A high level of diagnostic awareness of tetanus is particularly important in the elderly in industrialised countries, including Australia, as most deaths occur in people over 70 years of age, especially women, and may be associated with apparently minor injury.1,4 Neonatal tetanus usually occurs as the generalised form and is usually fatal if left untreated. It develops in children born to inadequately immunised mothers, frequently after unsterile treatment of the umbilical cord stump. Its onset generally occurs during the first 2 weeks of life. Poor feeding, rigidity, and spasms are typical features of neonatal tetanus.
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Epidemiology
Effective protection against tetanus can be provided only by active immunisation. Tetanus vaccine was introduced progressively into the childhood vaccination schedule after World War II. The effectiveness of the vaccine was demonstrated in that war; all Australian servicemen were vaccinated against tetanus and none contracted the disease. As tetanus can follow apparently trivial, even unnoticed wounds, active immunisation is the only certain protection.1 A completed course of vaccination provides protection for many years.
Vaccines The acronym DTPa, using capital letters, signifies child formulations of diphtheria, tetanus and acellular pertussis-containing vaccines. The acronym dTpa is used for adolescent/adult formulations which contain substantially lesser amounts of diphtheria toxoid and pertussis antigens (see formulations). Formulations for children aged <8 years • Infanrix hexa – GlaxoSmithKline (DTPa-hepB-IPV-Hib; diphtheriatetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis vaccineHaemophilus influenzae type b (Hib)). The vaccine consists of both a 0.5 mL pre-filled syringe containing 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg pertussis toxoid (PT), 25 µg filamentous haemagglutinin (FHA), 8 µg pertactin (PRN), 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/ phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin and a vial containing a lyophilised pellet of 10 µg purified Hib capsular polysaccharide (PRP) conjugated to 20–40 µg tetanus toxoid. The vaccine must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. May also contain yeast proteins.
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In Australia, tetanus is rare, occurring primarily in older adults who have never been vaccinated or were vaccinated in the remote past. There were 18 notified cases of tetanus during 2001–2005, but 120 hospitalisations (July 2000–June 2005) where tetanus was the principal diagnosis.4,5 This discrepancy suggests under-notification. During 2001–2005, there were 2 deaths from tetanus.4,5 The case-fatality rate in Australia is about 3%. Neonatal tetanus is a frequent cause of infant mortality in parts of Asia, Africa and Latin America.
• Infanrix-IPV – GlaxoSmithKline (DTPa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. • Infanrix Penta – GlaxoSmithKline (DTPa-hepB-IPV; diphtheria-tetanusacellular pertussis-hepatitis B-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains 30 IU diphtheria toxoid, 40 IU tetanus toxoid, 25 µg PT, 25 µg FHA, 8 µg PRN, 10 µg recombinant HBsAg, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin and neomycin. May also contain yeast proteins. Formulations for people aged ≥8 years Adsorbed diphtheria-tetanus vaccine • ADT Booster – Statens Serum Institut/CSL Biotherapies (dT; diphtheriatetanus, adult formulation). Each 0.5 mL pre-filled syringe or monodose vial contains ≥2 IU diphtheria toxoid and ≥20 IU tetanus toxoid adsorbed onto 0.5 mg aluminium hydroxide. Combination vaccines • Adacel – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg pertussis fimbriae (FIM) 2+3; 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde. • Adacel Polio – Sanofi Pasteur Pty Ltd (dTpa; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL monodose vial contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 2.5 µg PT, 5 µg FHA, 3 µg PRN, 5 µg FIM 2+3, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett); 1.5 mg aluminium phosphate; phenoxyethanol as preservative; traces of formaldehyde, polymyxin, neomycin and streptomycin.
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• Boostrix-IPV – GlaxoSmithKline (dTpa-IPV; diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine). Each 0.5 mL pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, 40 D-antigen units inactivated polioviruses type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett) adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde, polymyxin and neomycin. Tetanus vaccination stimulates the production of antitoxin, which protects against the toxin produced by the organism. The immunogen is prepared by treating a cell-free preparation of toxin with formaldehyde, thereby converting it into the innocuous tetanus toxoid. Tetanus toxoid is usually adsorbed onto an adjuvant, either aluminium phosphate or aluminium hydroxide, to increase its immunogenicity. Antigens from Bordetella pertussis, in combination vaccines, also act as an effective adjuvant. Complete immunisation (5 doses) induces protective levels of antitoxin lasting throughout childhood but, by middle age, about 50% of vaccinees have low or undetectable levels.6-8 A single dose of tetanus toxoid produces a rapid anamnestic response in such vaccinees.9-11 Tetanus toxoid is available in combination with other antigens. Production of the previously available tetanus toxoid vaccine was discontinued by the manufacturer in February 2006. Production of the previous DT (CDT vaccine), registered for use in children <8 years of age, ceased in June 2005. ADT Booster can be used for the booster dose of dT in people aged ≥8 years or, if necessary, for the primary dT course (see ‘Variations from product information’ below).
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.12 Store at +2°C to +8°C. Protect from light. Do not freeze.
Dosage and administration The dose of tetanus-containing vaccine is 0.5mL by IM injection. Do not mix DTPa-containing vaccines, dTpa or dT vaccine with any other vaccine in the same syringe, unless specifically registered for use in this way.
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• Boostrix – GlaxoSmithKline (dTpa; diphtheria-tetanus-acellular pertussis). Each 0.5 mL monodose vial or pre-filled syringe contains ≥2 IU diphtheria toxoid, ≥20 IU tetanus toxoid, 8 µg PT, 8 µg FHA, 2.5 µg PRN, adsorbed onto 0.5 mg aluminium hydroxide/phosphate; 2.5 mg phenoxyethanol as preservative. May contain traces of formaldehyde.
Recommendations (i) Vaccination in childhood Vaccination against tetanus is part of the National Immunisation Program (NIP) schedule, with tetanus toxoid being given in combination with diphtheria toxoid and acellular pertussis as DTPa vaccine. The recommended primary course of vaccination is at 2, 4 and 6 months of age. A booster dose of DTPa is given at 4 years of age. Immunity to tetanus will not be compromised before the booster dose, as the serological response to the primary course of vaccination is usually sufficient for those years. A second booster, using the adolescent/adult formulation, dTpa, at 12–17 years of age, is essential for maintaining immunity to tetanus in adults. By the age of 17 years, young adults should have received 5 doses of a tetanus toxoid-containing vaccine, and may have received an extra dose if they have experienced a tetanus-prone wound during childhood. For details on the management of children who have missed doses in the NIP schedule, see Section 1.3.5, Catch-up.
(ii) Vaccination of adults Booster vaccination Routine 10-yearly booster doses in adults who have previously received 5 doses of a tetanus-containing vaccine have not been recommended in Australia since 2000. All adults who reach the age of 50 years and have not received a booster dose of a tetanus-containing vaccine in the previous 10 years should be given dT or dTpa vaccine. This stimulates further production of circulating tetanus antibodies at an age when waning of diphtheria and tetanus immunity is commencing in the Australian population.6 The adolescent/adult formulation dTpa is preferred, if not given previously, as it provides additional protection against pertussis (see Chapter 3.14, Pertussis). Primary vaccination Where an adult has not received a primary course of tetanus toxoid previously, 3 doses of dT should be given, at minimum intervals of 4 weeks, followed by booster doses at 10 and 20 years after the primary course. Give the first of these doses as dTpa, to provide boosting to natural immunity from exposure to pertussis, which is almost universal in unvaccinated adults. In the event that dT vaccine is not available, dTpa can be used for all primary doses. However, this is not recommended routinely because there are no data on the safety, immunogenicity or efficacy of dTpa in multiple doses for primary vaccination. Tetanus-prone wounds Adults who have sustained injuries deemed to be tetanus prone should receive a booster dose of dT, if more than 5 years have elapsed since the last dose. In the event that dT vaccine is not available, dTpa can be used (see Table 3.21.1 below).
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(iii) Other people at special risk
Travellers to countries where health services are difficult to access should be adequately protected against tetanus before departure. They should receive a booster dose of dT, if more than 10 years have elapsed since the last dose, or dTpa if not given previously.
Tetanus-prone wounds In the event of a tetanus-prone injury (defined below), a booster dose of vaccine should be given if more than 5 years have elapsed since the last dose. If there is any doubt about the adequacy of previous tetanus immunisation, tetanus immunoglobulin (see below) should be given as well as tetanus toxoid (see Table 3.21.1). In children <8 years of age, this dose of vaccine should be given as DTPa or a DTPa-combination vaccine, consistent with the child’s vaccination history and the NIP schedule. For details on the management of children who have missed doses in the NIP schedule, see Section 1.3.5, Catch-up. The definition of a tetanus-prone injury is not straightforward, as tetanus may occur after apparently trivial injury, such as from a rose thorn, or with no history of injury. However, there are certain types of wounds likely to favour the growth of tetanus organisms. These include compound fractures, bite wounds, deep penetrating wounds, wounds containing foreign bodies (especially wood splinters), wounds complicated by pyogenic infections, wounds with extensive tissue damage (eg. contusions or burns) and any superficial wound obviously contaminated with soil, dust or horse manure (especially if topical disinfection is delayed more than 4 hours). Reimplantation of an avulsed tooth is also a tetanus-prone event, as minimal washing and cleaning of the tooth is conducted to increase the likelihood of successful reimplantation.
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Adults who were born in countries without adequate vaccination programs may never have received primary vaccination against tetanus. Older adults may have inadequate antitoxin levels, due to incomplete primary vaccination against tetanus. Injecting drug users are at risk of tetanus, particularly if skin ‘popping’ is practised.13
General measures for treatment of tetanus-prone wounds14-19 Table 3.21.1: Guide to tetanus prophylaxis in wound management History of tetanus vaccination
Time since last dose
Type of wound
DTPa, DTPacombinations, dT, dTpa, as appropriate
Tetanus immunoglobulin* (TIG)
≥3 doses
<5 years
All wounds
NO
NO
≥3 doses
5–10 years
Clean minor wounds
NO
NO
≥3 doses
5–10 years
All other wounds
YES
NO
≥3 doses
>10 years
All wounds
YES
NO
<3 doses or uncertain†
Clean minor wounds
YES
NO
<3 doses or uncertain†
All other wounds
YES
YES
* The recommended dose for TIG is 250 IU, given by IM injection using a 21 gauge needle, as soon as practicable after the injury. If more than 24 hours has elapsed, 500 IU should be given. † Individuals who have no documented history of a primary vaccination course (3 doses) with a tetanus toxoid-containing vaccine should receive all missing doses. See Section 1.3.5, Catch-up.
As an alternative to dT vaccine after a tetanus-prone wound, adults can receive a single dose of dTpa vaccine to provide additional protection against pertussis (providing they have not received a dose of dTpa previously).20 Whatever the immune status of an individual with a tetanus-prone wound, local disinfection and, where appropriate, surgical treatment of tetanus-prone wounds, must never be omitted. The use of antibiotics (such as penicillin or metronidazole) for preventing infection is a matter for clinical judgement. The recommended use of booster tetanus vaccines and the use of human tetanus immunoglobulin are set out in Table 3.21.1. These should be administered as soon as possible after the injury.
Tetanus immunoglobulin Tetanus immunoglobulin (human) for intramuscular use • Tetanus Immunoglobulin-VF (TIG) – CSL Bioplasma. 160 mg/mL solution of immunoglobulin from selected human plasma with high concentration of antibodies to tetanus toxin, 250 IU.
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(ii) The recommended dose for TIG is 250 IU by IM injection, to be given as soon as practicable after the injury. If more than 24 hours have elapsed, 500 IU should be given. A tetanus toxoid-containing vaccine should be given at the same time in the opposite limb with a separate syringe, and arrangements should be made to complete the full course of tetanus toxoid-containing vaccinations. (iii) Because of its viscosity, TIG should be given to adults using a 21 gauge needle. For children, it can be given slowly, using a 23 gauge needle. (iv) For wounds not categorised as tetanus-prone, such as clean cuts that have been treated appropriately, TIG is unnecessary.
Tetanus immunoglobulin (human) for intravenous use • Tetanus Immunoglobulin-VF (human, for intravenous use) – CSL Bioplasma. 60 mg/mL solution of immunoglobulin fraction of selected human plasma with high concentration of antibodies to tetanus toxin, 4000 IU. This product is used in the management of clinical tetanus. The recommended dose is 4000 IU given by slow intravenous infusion. Detailed protocols for administration of this product and management of adverse events should be consulted if its use is contemplated.
Contraindications The only absolute contraindications to tetanus vaccine are: • anaphylaxis following a previous dose of the vaccine, or • anaphylaxis following any vaccine component. If an individual has a tetanus-prone wound and has previously had a severe adverse event following tetanus vaccination, alternative measures, including the use of human tetanus immunoglobulin, can be considered.
Precautions In previously vaccinated people, administration of more than 1 dose of a tetanuscontaining vaccine in a 5-year period may provoke adverse events.
Adverse events Mild discomfort or pain at the injection site persisting for up to a few days is common. Uncommon general adverse events following dT vaccine include headache, lethargy, malaise, myalgia and fever. Anaphylaxis, urticaria and peripheral neuropathy very rarely occur (brachial neuritis occurs in 0.001% of
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(i) TIG should be used for passive protection of individuals who have sustained a tetanus-prone wound, where the person has not received 3 or more doses of a tetanus toxoid-containing vaccine or where there is doubt about their tetanus vaccination status. TIG provides immediate protection, for a period of 3 to 4 weeks.
cases). For specific adverse events following combination vaccines containing both tetanus and pertussis antigens, see Chapter 3.14, Pertussis.
Use in pregnancy Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information The product information for both Infanrix hexa and Infanrix Penta states that these vaccines may be given as a booster dose at 18 months of age. NHMRC recommends that a booster dose of DTPa (or DTPa-containing vaccines) is not necessary at 18 months of age. However, DTPa-containing vaccine may be used for catch-up of the primary schedule in children <8 years of age. The product information for Infanrix-IPV states that this vaccine may be used as a booster dose for children ≤6 years of age who have previously been vaccinated against diphtheria, tetanus, pertussis and poliomyelitis. NHMRC recommends that booster doses of DTPa and IPV be given at 4 years of age; however, this product may be used for catch-up of the primary schedule or as a booster in children <8 years of age. The product information for ADT Booster states that this vaccine is indicated for a booster dose only in children aged ≥5 years and adults who have previously received at least 3 doses of diphtheria and tetanus vaccines. NHMRC recommends that, where a dT vaccine is required for any person ≥8 years of age, ADT Booster can be used, including for primary immunisation against diphtheria and tetanus. The product information for adolescent/adult formulations of dTpa-containing vaccines states that these vaccines are indicated for booster doses only. NHMRC recommends that, where dT is unavailable for the primary course, dTpa can be used. The product information for Adacel and Boostrix (adolescent/adult formulations of dTpa) states that these vaccines are recommended for use in those aged >10 years. However, NHMRC recommends that they may be used in people aged ≥8 years. The product information also states that dTpa should not be given within 5 years of a tetanus toxoid-containing vaccine. However, NHMRC recommends that dTpa vaccines can be administered at any time following receipt of a diphtheria and tetanus toxoid-containing vaccine.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.22 Tuberculosis Bacteriology Tuberculosis (TB) is caused by organisms of the Mycobacterium tuberculosis complex (M.TB complex), that are slow-growing, aerobic, acid-fast bacilli. The M.TB complex consists of Mycobacterium tuberculosis, M. bovis, M. microti, M. canetti and M. africanum.1 M. tuberculosis is the cause of almost all TB in Australia, whereas M. bovis, M.canetti and M. africanum are rare.2
Clinical features
Most individuals infected with M. tuberculosis remain asymptomatic, but there is a 10% lifetime risk of developing clinical illness, sometimes many years after the original infection. Infants, the elderly and patients with impaired immunity due to drugs or disease or as a result of adverse socioenvironmental circumstances (eg. malnutrition, alcoholism) are more prone to rapidly progressive or generalised infection.1,4
Epidemiology The World Health Organization (WHO) declared tuberculosis a global emergency in 1993, and recent reports have reaffirmed the threat to human health.5 About 1000 cases of TB are notified to Australian health authorities each year. The annual notification rate for TB has been relatively stable at approximately 5 to 6 cases per 100 000 population since 1985, and multi-drug resistance remains rare, occurring in less than 2% of notified cases.2 Tuberculosis in animals (M. bovis) has been eradicated by screening and culling programs. In Australia, most TB cases (greater than 80%) occur in people born overseas, particularly in Asia, southern and eastern European countries, the Pacific Islands, and north and subSaharan Africa. The rates of TB in the overseas-born population have been slowly increasing over the past decade.3 High TB rates seen in people from Ethiopia, Somalia and the Sudan reflect recent changes in the composition of Australia’s migrant and refugee intake.3,6 Rates of TB are also high in Aboriginal and Torres Strait Islander people and in Papua New Guineans living in some parts of Australia.3,7
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As infection is usually air-borne, lung disease is the most common form of tuberculosis, accounting for approximately 60% of notified TB cases in Australia.3 Cough, fever, sweats, weight loss and haemoptysis are common symptoms of pulmonary TB. TB lymphadenitis is the most common extrapulmonary manifestation, but the disease can occur in any part of the body, including the meninges, bone and kidneys. Disseminated disease (miliary TB) and meningeal TB are the most serious forms, particularly in children.1
Patients with impaired immunity are at high risk of developing active TB if they are infected with M. tuberculosis.4,5 Screening programs in Australia now concentrate on those at high risk, including contacts of notified patients.
Vaccine • BCG vaccine – Sanofi Pasteur Pty Ltd (freeze-dried live vaccine prepared from an attenuated strain of Mycobacterium bovis). When reconstituted with accompanying buffered saline diluent, vaccine contains between 8–32 x 106 colony forming units per mL and monosodium glutamate 1.5% w/v. Reconstituted vaccine provides about 10 adult or 20 infant doses. BCG (Bacille Calmette-Guérin) vaccine is a suspension of live attenuated M. bovis. Worldwide, there are many BCG vaccines available but they are all derived from the strain propagated by the Institut Pasteur and first tested in humans in 1921.8 Protective efficacy ranges from 0 to 80% in controlled trials. The variation has been attributed to differences in vaccine strains, local prevalence of (protective) environmental mycobacteria, and host factors such as age at vaccination and nutritional status. Geographic latitude and vaccine strains explain most of the variation in efficacy. However, it should be noted that BCG is highly effective in children, particularly those <5 years of age, for whom it is primarily intended. The efficacy of BCG in adolescents and adults is less. BCG is primarily intended for children as meta-analyses have found the protective efficacy for preventing serious forms of TB in this group is over 80%.9 Protective efficacy in all age groups is about 50%.10,11 An Australian study reported a protective efficacy of 30%, at best, in school-aged children.12 Protective efficacy is difficult to quantify and may vary from 10 years to 50 years.13,14 The WHO does not recommend repeat vaccination. In some studies, BCG has been shown to offer some protection against leprosy.15
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.16 Store reconstituted vaccine at +2°C to +8°C or unreconstituted (freeze-dried) vaccine in a freezer at –20°C. Protect vaccine from light (sunlight or fluorescent). Store diluent at +2°C to +8°C and do not freeze. Reconstituted BCG vaccine is very unstable and should be discarded after one working session of 8 hours. Do not freeze reconstituted BCG vaccine.
Dosage and administration BCG vaccine is administered as a single dose by intradermal injection. It should be given only by specially trained medical or nursing staff who are fully conversant with the following procedures:
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Tuberculin test all individuals, except infants <6 months of age, before vaccination. Read the test 48 to 72 hours later and, where 5 tuberculin units has been given, give BCG only to those who have <5 mm of induration. • Give 0.1 mL of BCG to children and adults, and 0.05 mL to infants <12 months of age. • Use a short (10 mm) 26–27 gauge needle with a short bevel. The risk of spillage can be minimised by using an insulin syringe to which the needle is already attached. • Wear protective eye-wear. The patient and parent holding the patient (if patient is a small child requiring restraint) should also wear protective eyewear. Eye splashes may ulcerate, so if an eye splash occurs, wash the eye with saline or water immediately.
• Stretch the skin between a finger and thumb and insert the bevel into the dermis, bevel uppermost, to a distance of about 2 mm. The bevel should be visible through the transparent epidermis. • If the injection is not intradermal, withdraw the needle and try again at a new site. A truly intradermal injection should raise a blanched bleb of about 7 mm in diameter with the features of peau d’orange. Considerable resistance will be felt as the injection is given. If this resistance is not felt, the needle may be in the subcutaneous tissues. • Advise the subject of adverse events which may follow the injection. A tuberculin reaction induced by BCG usually ranges from 0 to 15 mm, but clinical trials have not shown a consistent relationship between the size of tuberculin reactions and the protection provided. For this reason, tuberculin skin testing of BCG vaccinees is not routinely recommended. Because of waning hypersensitivity, most adults who were vaccinated with BCG in early childhood will have a negative tuberculin test. BCG is available from State/Territory tuberculosis services.
Response to BCG vaccination A small red papule forms and eventually ulcerates, usually within 2 to 3 weeks of vaccination. The ulcer heals with minimal scarring over several weeks. There may be swelling and tenderness in local lymph nodes. Subjects who are given BCG despite previous tuberculosis infection will experience an accelerated response characterised by induration within 24 to 48 hours, pustule formation in 5 to 7 days and healing within 10 to 15 days.
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• Inject BCG into the skin over the region of the insertion of the deltoid muscle into the humerus. This is just above the mid-point of the upper arm. This site is recommended to minimise the risk of keloid formation. By convention, the left upper arm is used wherever possible to assist those who subsequently look for evidence of BCG vaccination.
Recommendations (i) Given the low incidence of TB in Australia and the variable efficacy in adults, BCG is not used in the general population. (ii) BCG is recommended for the following:17 • Aboriginal and Torres Strait Island neonates living in regions of high TB incidence, • neonates born to parents with leprosy or a family history of leprosy, • children <5 years of age who will be travelling to live in countries of high TB prevalence for longer than 3 months (WHO defines ‘high-risk’ countries as those with an annual incidence of TB in excess of 100 per 100 000 population – see http://www.who.int/tb/en/), • embalmers, • healthcare workers involved in conducting autopsies. (iii) State and Territory guidelines should be consulted for advice on vaccination of the following groups of individuals:17 • healthcare workers who may be at high risk of exposure to drug-resistant cases, • neonates weighing <2.5 kg, • children ≥5 years and <16 years of age who will be travelling or living for extended periods in countries with a high prevalence of tuberculosis.
Contraindications The use of BCG vaccine is contraindicated in the following: • individuals with impaired immunity due to HIV infection, corticosteroids or other immunosuppressive agents, congenital immunodeficiencies and malignancies involving bone marrow or lymphoid systems (because of the risk of disseminated BCG infection) (see also Chapter 2.3, Groups with special vaccination requirements), • individuals with a high risk of HIV infection where HIV antibody status is unknown, • individuals with any serious illness including the malnourished, • individuals with generalised septic skin diseases and skin conditions such as eczema, dermatitis and psoriasis, • pregnant women (BCG has never been shown to cause fetal damage, but use of live vaccines in pregnancy is not recommended), • individuals who have previously had TB or a large (≥5 mm) tuberculin (Mantoux) reaction, • individuals with significant febrile illness (administer 1 month from the time of recovery).
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Precautions BCG should be deferred in the following: • neonates with a birth weight <2.5 kg or those who may be relatively malnourished, • neonates of mothers who are HIV-positive, • children who are currently on isoniazid preventive therapy for latent TB infection (as the therapy can inactivate the BCG), • a 4-week interval should be allowed after administration of another live vaccine (MMR, varicella [and MMRV when available], yellow fever vaccine) unless given concurrently with the BCG.
About 5% (common) of vaccinees experience adverse events. 2.5% develop injection site abscesses and 1% lymphadenitis. About 1% (uncommon) may need medical attention including surgery as a result of the adverse event.18 Anaphylactoid reactions have also been reported. Gross local or generalised infection can be treated with antituberculous drugs. Keloid formation can occur, but the risk is minimised if the injection is not given higher than the level of the insertion of the deltoid muscle into the humerus.
Use in pregnancy Use of BCG in pregnancy is not recommended. BCG has never been shown to cause fetal damage, but use of live vaccines in pregnancy is contraindicated.
The tuberculin skin test (TST) (i) Hypersensitivity to tuberculin Purified Protein Derivative (PPD) follows either natural infection with either M. tuberculosis or with other mycobacteria that induce cross-reactivity, or BCG vaccination. The skin test is used (a) to detect past infection for epidemiological purposes, (b) to detect latent TB infection (LTBI), especially in contacts of TB patients, (c) as an aid in diagnosing disease due to TB, and (d) as a pre-vaccination screen before BCG to prevent vaccine reactions. (ii) Most tuberculin testing in Australia is performed using the Mantoux technique. The PPD preparation for this test is currently supplied by Sanofi Pasteur Pty Ltd. The product, Tubersol, comes in multidose vials and has 5 Tuberculin units (TU)/0.1 mL (10 doses per 1 mL vial). For routine testing, 0.1 mL of PPD (ie. a dose of 5 TU) is injected intradermally into the skin of the upper third of the flexor surface of the left forearm, producing a peau d’orange bleb 4 to 10 mm in diameter. The reaction is examined 48 to 72 hours later, and the diameter of the palpably indurated skin is measured across the long axis of the forearm and recorded in millimetres. In certain circumstances, 2-step skin testing may be required. It is used to detect individuals previously infected who may
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Adverse events
test negative to tuberculin testing initially, but who show a strong reaction to tuberculin if the same procedure is repeated 1 to 2 weeks later. The 2-step test is important to establish the baseline reaction when future tuberculin testing is required as part of contact tracing or monitoring of high-risk groups. Detailed information can be accessed in the Tubersol product information and relevant State/Territory guidelines. (iii) Erythema without induration should be disregarded. Strongly positive reactions may be accompanied by skin necrosis, lymphangitis and regional adenitis. Patients with a history of such strongly positive reactions to previous testing should not be retested. (iv) The reaction to PPD may be suppressed by recent surgery, sarcoidosis, immunosuppressant drugs and illnesses, such as Hodgkin’s disease, lymphoma and HIV infection that result in impaired immunity. The reaction also wanes with increasing age, so that most adults vaccinated with BCG in childhood have negative tuberculin reactions. (v) The reaction to PPD may be unreliable for 4 weeks after administration of other live vaccines including MMR, varicella and yellow fever vaccines unless given concurrently. The tuberculin skin test should be deferred for patients with major viral infections or live-virus vaccination in the past month. Oral typhoid and oral polio (OPV is no longer used in Australia but may have been received overseas) vaccines do not necessitate a delay in testing. (vi) The use of the Heaf gun, a multiple puncture apparatus primed with highly concentrated PPD, is not recommended. (vii) Although BCG is not routinely recommended, it may be offered by some States and Territories to their healthcare staff who should be made aware that subsequent tuberculin skin testing may be difficult to interpret. (viii) New interferon-gamma release assays (blood tests) using specific antigens for M. tuberculosis are now available in some laboratories. Interferon-gamma based assays are increasingly being used to diagnose latent TB and, particularly, to distinguish latent TB from post-BCG vaccine skin reactivity. There are relatively few data on the sensitivity and specificity of these tests in children, particularly those <2 years of age, or in people with impaired immunity.19
Variations from product information The product information states that BCG should not be frozen. NHMRC advises that BCG can be stored unreconstituted (freeze-dried) in a freezer at –20°C.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.23 Typhoid Bacteriology Typhoid fever is a clinical syndrome caused by a systemic infection with Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). Paratyphoid fever, caused by infection with S. enterica serovar Paratyphi A or B, is similar to, and often indistinguishable from, typhoid fever. The two infections are collectively known as enteric fever; there is no vaccine against paratyphoid fever. NB. S. Paratyphi B biovar Java does not cause typhoid-like enteric fever but rather causes a typical gastroenteritis; it can be acquired through handling aquarium fish.1
Clinical features Typhoid fever has a usual incubation period of 7 to 14 days (range 3 to 60 days).2 Although clinical presentations of typhoid fever can be quite variable, a typical case presents with a low-grade fever, dull frontal headache, malaise, myalgia, anorexia and a dry cough.2 The fever tends to increase as the disease progresses; constipation (more typically diarrhoea in young children), abdominal tenderness, relative bradycardia and splenomegaly are common. Complications occur in 10 to 15% of patients and tend to occur in patients who have been ill for >2 weeks. The more important complications include gastrointestinal bleeding, intestinal perforation and typhoid encephalopathy.2
Because travellers are likely to seek medical advice relatively early in the illness, severe typhoid fever with complications is rarely seen in this group of patients. Nevertheless, travellers can still become chronic carriers of S. Typhi.
Epidemiology Humans are the sole reservoir of S. Typhi. It is shed in the faeces of those acutely ill and those who are chronic asymptomatic carriers of the organism; transmission usually occurs via the ingestion of faecally-contaminated food or water. The vast majority of typhoid fever cases occur in less-developed countries where poor sanitation, poor food hygiene and untreated drinking water all contribute to endemic disease with moderate to high incidence and considerable mortality.3 Geographic regions with high incidence (>100 cases per 100 000 population
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Relapse occurs in 5 to 10% of patients, usually 2 to 3 weeks after the initial fever resolves. Chronic asymptomatic biliary carriage of S. Typhi occurs in up to 5% of patients with typhoid fever, even after treatment. Chronic carriage is defined by the continued shedding of the organism for >1 year, and is a public health risk (eg. if a carrier works in the food industry).2
per year) include the Indian subcontinent, most southeast Asian countries and several south Pacific nations, including Papua New Guinea. In developed countries, typhoid fever is predominantly a travel-related disease, with a considerably greater risk following travel to the Indian subcontinent than to other regions.4,5 Those who travel to endemic regions to visit friends and relatives (ie. immigrants who travel to their former homelands) appear to be at considerably greater risk of acquiring typhoid fever than other travellers.4,5 There are approximately 50 to 80 cases of typhoid fever reported in Australia each year, with most following travel to regions with endemic disease.
Vaccines • Vivotif Oral – CSL Biotherapies/Berna Biotech Ltd (oral live attenuated typhoid vaccine). Each enteric-coated capsule contains not less than 2 x 109 viable organisms of attenuated S. Typhi strain Ty21a Berna. 3 capsules in a blister pack. • Typherix – GlaxoSmithKline (purified Vi capsular polysaccharide vaccine). Each 0.5 mL pre-filled syringe contains 25 µg Vi polysaccharide of S. Typhi; phenol as preservative; phosphate buffer. 10 dose packs are also available. • Typhim Vi – Sanofi Pasteur Pty Ltd (purified Vi capsular polysaccharide vaccine). Each 0.5 mL pre-filled syringe contains 25 µg Vi polysaccharide of S. Typhi; phenol as preservative; phosphate buffer. Combination vaccine that includes both typhoid and hepatitis A (see Chapter 3.5, Hepatitis A) • Vivaxim – Sanofi Pasteur Pty Ltd (inactivated hepatitis A virus and typhoid Vi capsular polysaccharide). Supplied in a unique dual-chamber syringe which enables the 2 vaccines to be mixed just before administration. Each 1.0 mL dose of mixed vaccine contains 160 ELISA units of inactivated hepatitis A virus antigens, 25 µg purified typhoid capsular polysaccharide; 0.3 mg aluminium hydroxide; 2.5 μL phenoxyethanol; formaldehyde; traces of neomycin and bovine serum albumin. The attenuated non-pathogenic S. Typhi strain Ty21a was derived by chemical treatment attenuation of a wild-type strain. Attenuated features of Ty21a include the absence of the enzyme, UDP-galactose-4-epimerase, and the Vi capsular polysaccharide antigen (an important virulence determinant of S. Typhi). These features partially contribute to the non-pathogenicity and, therefore, the safety of the oral live vaccine.6 The oral vaccine Ty21a strain cannot be detected in faeces more than 3 days after administration of the vaccine. It stimulates vigorous secretory intestinal IgA and cell-mediated immune responses.6 Clinical trials, with different formulations of
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the vaccine and with a variety of schedules, have been undertaken in several countries (Egypt, Chile, Indonesia) with endemic typhoid fever. These have documented varying degrees of protection against the disease.2,6 The parenteral Vi polysaccharide vaccine is produced by fermentation of the Ty2 strain followed by inactivation with formaldehyde, and then extraction of the polysaccharide from the supernatant using a detergent.6 The vaccine elicits prompt serum IgG anti-Vi responses in 85 to 95% of adults and children >2 years of age. The vaccine has also been used in clinical trials in endemic regions (Nepal, South Africa, China), indicating moderate protection against typhoid fever.2,6 Neither the oral nor the parenteral vaccines have been studied in prospective clinical trials in travellers to endemic regions. Because many travellers do not have any naturally-acquired immunity, the protection conferred through typhoid vaccination may be less than that documented in the clinical trials mentioned above. However, there is circumstantial evidence that the vaccines do provide protection to travellers to endemic regions,4,5 and that 3-yearly revaccination is necessary to prolong the protection.7
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.8 Store all typhoid vaccines at +2°C to +8°C. Protect from light. Do not freeze. Because the vaccinee will be responsible for looking after the course of the oral live attenuated vaccine, details of how it should be transported (from the pharmacy to the home) and stored in the refrigerator (at home) must be carefully explained.
Oral live attenuated vaccine The vaccine is registered for use in individuals ≥6 years of age; it is presented in a pack of 3 capsules. The dose (a whole capsule) is the same for both adults and children. It may be administered at the same time as either OPV (no longer used in Australia), or yellow fever vaccine.6 It may also be given concurrently with mefloquine or with atovaquone/proguanil combination (Malarone). The vaccination schedule consists of 1 capsule of vaccine on days 1, 3, and 5, taken 1 hour before food. The capsule must be swallowed whole with water and must not be chewed since the organisms can be killed by gastric acid. Do not give the vaccine concurrently with antibiotics, or other drugs that are active against Salmonellae. If possible, antibiotics and other relevant drugs should be delayed for 3 days after the last dose of the vaccine. A fourth capsule taken on day 7 has been shown (in a single study9) to result in a lower incidence of typhoid fever than 3 doses. However, the use of a fourth dose requires partial use of a second pack and, therefore, may involve considerable extra expense.
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Dosage and administration
Oral live attenuated typhoid vaccine should be separated from the administration of inactivated oral cholera vaccine by an interval of at least 8 hours (see ‘Precautions’ below).
Parenteral Vi polysaccharide vaccines Both vaccines (Typherix and Typhim Vi) are registered for use in individuals ≥2 years of age; the dose (0.5 mL) is the same for both adults and children. (The dose of the combined Vi polysaccharide and hepatitis A vaccine is 1 mL.) The vaccines are given by IM injection.
Booster doses The optimal timing of revaccination against typhoid fever is uncertain and, therefore, international recommendations can vary considerably.2,5,6 However, if continued exposure to S. Typhi exists (such as occurs with either prolonged travel or residence in an endemic region) it is reasonable to recommend a dose of the parenteral vaccine 3 years after the initial primary parenteral vaccination. If a 3-dose schedule of the oral live attenuated vaccine was used initially, a repeat 3-dose course can be given after 3 years; if a 4-dose schedule of the oral vaccine was used initially, a repeat 4-dose course can be given after 5 years.6
Recommendations Typhoid vaccination is recommended for all travellers ≥2 years of age going to endemic regions, where food hygiene may be suboptimal and drinking water may not be adequately treated. Travellers include the military. Vaccination should be completed at least 2 weeks before travel. Individuals travelling to endemic regions to visit friends and relatives are probably at considerable risk of acquiring typhoid fever, and vaccination is strongly recommended for them. NB. Travellers must also be advised about personal hygiene, food safety and about drinking boiled or bottled water only. They should be advised that raw (or undercooked) shellfish, salads, cold meats, untreated water and ice (in drinks) are all potentially ‘high-risk’, as are short (day) trips away from higher quality accommodation venues. Laboratory personnel routinely working with S. Typhi should also be considered for vaccination.
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Contraindications The only absolute contraindications to typhoid vaccines are: • anaphylaxis following a previous dose of a typhoid vaccine, or • anaphylaxis following any component of a particular typhoid vaccine.
Oral live attenuated vaccine The oral live attenuated vaccine should not be administered • to pregnant women; parenteral Vi polysaccharide vaccine should be used instead; • to individuals with impaired immunity, including those known to be infected with HIV; parenteral Vi polysaccharide vaccine should be used instead; or • to individuals taking antibiotics; parenteral Vi polysaccharide vaccine should be used instead.
Parenteral Vi polysaccharide vaccines There are no other contraindications to these vaccines.
Precautions There should be an interval of at least 8 hours between the administration of the inactivated oral cholera and oral typhoid vaccines, as the buffer in the cholera vaccine may affect the transit of the capsules of oral typhoid vaccine through the gastrointestinal tract.
The oral live attenuated vaccine should not be administered to children <6 years of age; parenteral Vi polysaccharide vaccine should be used instead in children 2–5 years of age.
Adverse events Typhoid vaccines, both oral and parenteral, are associated with very few adverse events and, when adverse events do occur, they tend to be mild and transient.10
Oral live attenuated vaccine Abdominal discomfort, diarrhoea, nausea, vomiting and rashes have occasionally been reported.
Parenteral Vi polysaccharide vaccines Local adverse events such as erythema, swelling and pain at the injection site are very common (10 to 20%). Systemic adverse events are common and include fever (3%), malaise and nausea.
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The Vi polysaccharide vaccines should not be administered to children <2 years of age.
Public health management of typhoid fever Typhoid fever is a notifiable disease in all States and Territories in Australia. Upon notification, the relevant public health authority should ascertain the likely source of infection, and determine if the case has an occupation (eg. as a food handler or carer of children, the elderly or of those with impaired immunity) where there might be the potential for the spread of S. Typhi.11 Cases in such occupations should be excluded from work until 2 consecutive faecal samples, collected a week apart after the completion of antibiotic treatment, are negative for S. Typhi.11 Cases not in such occupations should also be proved to have cleared the organism from 2 consecutive faecal samples, but they can return to work once they have recovered and any diarrhoea has ceased. All those who have been in close contact with a case of typhoid fever in the 30 days before the clearance of S. Typhi from the case’s faeces should have their occupation assessed (as above). Contacts in ‘risk’ occupations should be excluded from work until 2 faecal samples, collected at least 24 hours apart, have proved negative for S. Typhi.11 Contacts not in such occupations can remain at work, but should have at least 1 faecal sample collected. Further instructions about the management of cases of typhoid fever, and their contacts, should be obtained from State/Territory public health authorities (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
Use in pregnancy The oral live attenuated vaccine should not be given in pregnancy. However, pregnancy is not a contraindication to vaccination with a parenteral Vi polysaccharide vaccine. Refer to Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy.
Variations from product information The product information for the oral live attenuated vaccine does not mention the use of a 4-dose course of the vaccine for either primary or booster vaccination. Although NHMRC considers pregnancy a contraindication to the oral live attenuated typhoid vaccine, the product information does not include pregnancy among the listed contraindications. The Typhim Vi product information recommends a booster dose every 2 to 3 years. However, revaccination with a dose of Vi polysaccharide vaccine 3 years after an initial dose is recommended by NHMRC.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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3.24 Varicella Virology Varicella-zoster virus (VZV) is a DNA virus within the herpes virus family.1 Primary infection with VZV causes varicella (chickenpox). Following primary infection, VZV establishes latency in the dorsal root ganglia. Reactivation of the latent virus manifests as herpes zoster (shingles)2 (see Chapter 3.26, Zoster).
Clinical features Varicella is a highly contagious infection spread by air-borne transmission of droplets from the upper respiratory tract or from the vesicle fluid of the skin lesions of varicella or zoster infection.1 Varicella is usually a mild disease of childhood. However, complications occur in approximately 1% of cases.3 It is more severe in adults and in individuals of any age with impaired immunity, in whom complications, disseminated disease, and fatal illness can occur.1 The average incubation period is 14 to 16 days (range 10–21 days), but may be longer in those with impaired immunity, especially after receipt of zoster immunoglobulin (ZIG).2 The period of infectivity is from 48 hours before the onset of rash until crusting of all lesions has occurred. A short prodromal period of 1 to 2 days may precede the onset of the rash, especially in adults.1,2 In otherwise healthy children, skin lesions usually number between 200 and 500.1,2 Acute varicella may be complicated by secondary bacterial skin infection, pneumonia, acute cerebellar ataxia (1 in 4000 cases), aseptic meningitis, transverse myelitis, encephalitis (1 in 100 000 cases), and thrombocytopenia. In rare cases, it involves the viscera and joints.1
Reactivation of latent VZV as a result of waning cellular immunity results in herpes zoster (HZ), a localised vesicular rash. HZ can occur at any age, but is more common in older adults and individuals with impaired immunity. Complications may include post-herpetic neuralgia, and disseminated zoster with visceral, central nervous system and pulmonary involvement1 (see Chapter 3.26, Zoster).
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Congenital varicella syndrome has been reported after varicella infection in pregnancy and may result in skin scarring, limb defects, ocular anomalies, and neurologic malformations.1,4 There is a higher risk to the fetus if maternal infection occurs in the second trimester compared with infection in the first trimester (1.4% vs 0.55%).5 Infants with intrauterine exposure also risk developing herpes zoster in infancy (0.8–1.7%) with the greatest risk following exposure in the third trimester.4 Severe neonatal varicella infection can result from perinatal maternal varicella.6 The onset of varicella in pregnant women from 5 days before delivery to 2 days after delivery is estimated to result in severe varicella in 17 to 30% of their newborn infants.7
There is no specific therapy for uncomplicated varicella infection. Antiviral therapy is used in the treatment of complicated or severe disease or varicella in people with impaired immunity. An increased risk of Reye syndrome following varicella infection has been reported in association with aspirin or other salicylate use8-12 (see ‘Precautions’ below). Aspirin or other salicylates should not be used in the management of varicella infection.
Epidemiology In an unimmunised population in temperate climates, the annual number of cases of varicella approximates the birth cohort.13 Tropical regions have a higher proportion of cases in adults. Approximately 5% of cases are subclinical. A serosurvey conducted in 1997–1999 found that 83% of the Australian population were seropositive by 10–14 years of age.14 Before the introduction of a varicella vaccination program in Australia there were about 240 000 cases, 1500 hospitalisations and an average of 7 to 8 deaths each year from varicella in Australia.15-17 The highest rates of hospitalisation occur in children <4 years of age.18 In the USA, universal varicella vaccination since 1995 has resulted in a decline in varicella disease by 85% and hospitalisations have declined by 70 to 88%.19-21 The greatest decline in hospitalisation rates has been in 0–4-year-olds, who were most likely to be vaccinated. However, a reduction in hospitalisation rates also occurred in older children and adults, due to herd immunity.19 Surveillance of varicella and HZ in the USA, conducted between 1992 and 2002, demonstrated that, as vaccination coverage increased to 65% in 2002, the incidence of varicella decreased by 65% across all age groups, and the incidence of HZ remained stable.22
Vaccines Live attenuated varicella vaccine (VV) is currently available as a monovalent vaccine. It is anticipated that quadrivalent combination vaccines containing measles, mumps, rubella and varicella vaccines (MMRV) will be available in the near future (see Chapter 3.11, Measles for information on MMRV vaccines). All available varicella-containing vaccines are derived from the Oka VZV strain, but have some genetic differences.23 Monovalent VVs have been available in Australia since 2000, and from November 2005, a single dose of VV has been funded under the NIP for all children at 18 months of age, with a catch-up dose funded for children 10–<14 years of age.24 At the time of implementation of a universal varicella vaccination program in Australia, a single dose was considered adequate for protection of infants and children <14 years of age. However, recent data from the USA suggests that a second dose of varicella-containing vaccine in children is optimal to provide an immune response more like natural infection, reducing the risk of vaccine failure and increasing population immunity.7 Vaccine failure is known as ‘breakthrough varicella’ and is defined as a case of wild-type varicella ≥42 days post vaccination. A majority of cases of breakthrough varicella are
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mild with fewer lesions than natural infection. However, breakthrough varicella infections can be contagious.25 Post-licensure studies in the USA have estimated the effectiveness of 1 dose of VV in children to be 80 to 85% against any disease and 95 to 98% against severe varicella.25-29 Although earlier data suggested persistence of immunity in most healthy vaccinees,1 recent long-term data from the United States has shown that, >5 years after vaccination, rates of vaccine failure increased by 2.6 times in children who received only 1 dose of vaccine, compared with those who had received the vaccine within 5 years.30 Data from a randomised controlled trial in varicella-negative children 12 months to 12 years of age, comparing 1 with 2 doses of VV over a 10-year period, showed significantly higher protection with 2 doses (94.4% vs 98.3%).31 Based on current evidence, 2 doses of a varicellacontaining vaccine in children from 12 months of age will minimise the risk of breakthrough varicella (see ‘Recommendations’ below). Healthy adolescents (≥14 years of age ) and adults require 2 doses of varicella vaccine, 1 to 2 months apart, as the response to a single dose of VV decreases progressively as age increases and is insufficient to provide adequate protection.32 Monovalent varicella vaccines • Varilrix – GlaxoSmithKline (lyophilised preparation of live attenuated Oka strain of varicella-zoster virus). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 103.3 plaque-forming units of attenuated varicella-zoster virus; human serum albumin; lactose; neomycin; polyalcohols. Single and 10 pack of monodose vials also available. • Varivax Refrigerated – CSL Biotherapies/Merck & Co Inc (lyophilised preparation of live attenuated Oka/Merck strain of varicella-zoster virus). Each 0.5 mL monodose of the reconstituted, lyophilised vaccine contains not less than 1350 plaque-forming units; 18 mg sucrose; 8.9 mg gelatin; 3.6 mg urea; 0.36 mg monosodium glutamate; residual components of MRC-5 cells; trace amounts of neomycin and fetal bovine serum from MRC-5 culture media. Single and 10 pack of monodose vials also available.
Transport, storage and handling
Varilrix – store at +2°C to +8°C. Protect from light. Do not freeze. After reconstitution, use within 90 minutes at ambient temperature or for up to 8 hours at +2°C to +8°C.
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Varicella vaccines are less stable than other commonly used live viral vaccines, and the storage temperature requirements are critical. Available monovalent VVs have different storage requirements.
Varivax Refrigerated – store at +2°C to +8°C. Protect from light. Do not freeze. After reconstitution, use within 30 minutes at ambient temperature (+20°C to +25°C) to maintain potency. Transport according to National Vaccine Storage Guidelines: Strive for 5.33
Dosage and administration The dose of monovalent VV is 0.5 mL, administered by SC injection. If VV is given at the same time as MMR, it should be given using separate syringes and injection sites. MMR and monovalent VV should not be mixed before injection. VV can be given at the same time as other vaccines (including MMR, DTPa, hepatitis B and MenCCV), using separate syringes and injection sites. If VV is not given simultaneously with other live viral parenteral vaccines (eg. MMR), they should be given at least 4 weeks apart (see ‘Precautions’ below).
Recommendations (i) Children It is recommended that at least 1 dose of a varicella-containing vaccine be given to all non-immune children from the 2nd year of life to <14 years of age. Children in this age group with a reliable history of varicella infection, either by confident clinical diagnosis or with laboratory confirmation, may be considered immune and do not require vaccination. Routine varicella-containing vaccine should be administered as follows (and as per Table 3.24.1): • One dose of monovalent VV at 18 months of age. • When MMRV vaccines become available, 1 dose of varicella-containing vaccine should be given as MMRV at 12 months of age. The change in the recommended age of administration of varicella vaccine is influenced by moving the second dose of MMR to 18 months of age, and the anticipated availability of MMRV vaccines in the near future. The available evidence now suggests that the administration of varicella vaccine at the earlier age of 12 months, compared with 18 months, does not reduce vaccine effectiveness or lead to increased rates of breakthrough varicella.34 Administration of varicella vaccine at 12 months of age will provide earlier protection from varicella. However, until MMRV vaccines are available in Australia, it is recommended that administration of monovalent VV at 18 months of age continue to avoid schedule crowding (4 injections) at 12 months of age. Receipt of 2 doses of varicella-containing vaccine provides increased protection and minimises the chance of breakthrough varicella in children.31 However, at this time, routine administration of 2 doses of varicella-containing vaccine at <14 years of age is not included on the NIP schedule. If parents/carers wish to
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minimise the risk of breakthrough varicella, a second dose of varicella-containing vaccine to children <14 years of age is recommended (see ‘Vaccines’ above). When available, use of MMRV at 18 months of age is a suitable means to provide a second dose of varicella-containing vaccine. (For further information, see also Chapter 3.11, Measles.) The minimum approved interval between doses of varicella-containing vaccine in children <14 years of age is 4 weeks. Table 3.24.1: Recommendations for varicella vaccination with monovalent VV (currently available), and once MMRV vaccines are available Monovalent varicella vaccine
12 months
18 months
MMR
MMR + VV
MMRV when available MMRV
Catch-up requirements* †
MMR‡
No requirement for varicella catch-up Use MMRV at 18 months for children who have not yet received at least 1 dose of varicella vaccine
* If catch-up is required for MMR, see Chapter 3.11, Measles. † Give in separate syringes and at separate injection sites (preferably the other arm). ‡ When available, use of MMRV at 18 months of age is a suitable means to provide a second dose of varicella-containing vaccine.
(ii) Adolescents (≥14 years of age) and adults Vaccination is recommended in non-immune adolescents (≥14 years of age) and adults. Immune responses are reduced in adolescents and adults compared with young children.32,35 Therefore, adolescents and adults must receive 2 doses of VV to achieve adequate protection from varicella. The 2 doses should be administered at least 4 weeks apart. However, a longer interval between vaccine doses is acceptable. Lack of immunity to varicella should be based on a negative history of previous varicella infection and can be supplemented by serological testing (see ‘Serological testing before varicella vaccination’ below). VV is particularly indicated for those in the following categories: • non-immune people in high-risk occupations where exposure to varicella is likely (such as healthcare workers, teachers and workers in childcare centres) (see Section 2.3, Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases),36
• seronegative women immediately after delivery, • non-immune parents of young children, and • non-immune household contacts of all ages of people with impaired immunity.
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• non-immune women before pregnancy to avoid congenital or neonatal varicella,
MMRV vaccines are not recommended for use in adolescents and adults because data are currently available only for children ≤12 years of age.
(iii) Serological testing before varicella vaccination Vaccination is well tolerated in previously infected individuals and can be administered if there is uncertainty regarding immunity. Serological testing before varicella vaccination of children with a reliable history of varicella infection, either by confident clinical diagnosis or with laboratory confirmation, is not warranted. Reliable history of varicella infection correlates highly with serological evidence of immunity.37,38 Those who have an uncertain history should be considered susceptible and offered vaccination. In adolescents and adults with a negative history of varicella infection, serological testing before vaccination is more likely to be cost-effective, as a majority of those with a negative history may be immune.36,39 However, vaccination can proceed without testing (provided there are no contraindications), as the vaccine is well tolerated in seropositive people.
(iv) Serological testing after varicella vaccination Testing to check for seroconversion after varicella vaccination is not recommended. Commercially available laboratory tests are not always sufficiently sensitive to detect low antibody levels following vaccination and, in addition, the presence of detectable antibody shortly after vaccination does not necessarily indicate complete immunity to varicella.40,41
(v) Post-exposure prophylaxis and outbreak control Several studies have shown that VV is effective in preventing varicella infection, particularly moderate to severe disease, following exposure. This is generally successful when given within 3 days, and up to 5 days, after exposure, with earlier administration being preferable.42-46 Vaccination of exposed individuals during outbreaks has also been shown to prevent further cases and control outbreaks (see also ‘The public health management of varicella’ below). When available, vaccination with MMRV in children 12 months to 12 years of age could be used for vaccination in this setting if MMR vaccination is also indicated. In the event of an outbreak, seek advice from local public health authorities before proceeding with vaccination of a large number of individuals (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
(vi) Household contacts of people with impaired immunity Vaccination of household contacts of people with impaired immunity is strongly recommended. This recommendation is based upon evidence that transmission of varicella vaccine virus strain is extremely rare and it is likely to cause only mild disease that can be treated with acyclovir. This compares with the relatively high risk of severe disease in people with impaired immunity following
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exposure to wild-type varicella-zoster virus.41,47 If vaccinees develop a rash, they should cover the rash and avoid contact with people with impaired immunity for the duration of the rash. Zoster immunoglobulin (ZIG) need not be given to an immune impaired contact of a vaccinee with a rash because the disease associated with this type of transmission (should it occur) would be expected to be mild.
(vii) Vaccination of healthcare workers (HCW) (Refer to Table 2.3.6 Recommended vaccinations for those at risk of occupationally acquired vaccine-preventable diseases) Pre-exposure vaccination of HCWs: • A HCW with a negative or uncertain history of varicella infection should undergo serological testing. If seronegative, vaccination should be offered in a 2-dose schedule48 (see ‘Recommendations (ii)’ above). • If a rash develops during the 6 weeks after administration of the vaccine, the HCW should cover the rash and be reassigned to duties that require no patient contact, or placed on sick leave.48 Reassignment or leave should be only for the duration of the rash48 (see ‘Variations from product information’ below). • VV-associated rash may be atypical and may not be vesicular (see ‘Adverse events’ below). A VV-associated rash is likely to occur in less than 5% of vaccinees, and to last for less than 1 week.49,50 • Testing to check for seroconversion after VV is not recommended (see ‘Serological testing after varicella vaccination’ above). Post-exposure management of HCWs: • If a previously vaccinated HCW is exposed to varicella, assume immunity and report exposure. A vaccinated HCW should watch for a rash for 3 weeks after exposure and report to the nominated infection control officer should a rash develop. If HCW vaccinees develop a rash, cover the rash, reassign duties (no patient contact) or place on sick leave until no new lesions appear and all lesions have crusted.
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• If a HCW is exposed to varicella and is unvaccinated and has a negative or uncertain history of varicella infection, offer vaccination. This is usually effective in preventing the development of varicella if given within 3 days, and up to 5 days, after exposure. In situations where facilities for rapid testing are available, it may be possible to identify those with pre-existing immunity before vaccination. However, serological testing should not delay vaccination beyond the recommended 3 to 5 days after exposure. Vaccination in the absence of serological results is acceptable (see ‘Serological testing after varicella vaccination’ above).
• If the HCW is vaccinated after exposure, as above, he/she can work but should watch daily for any rash for 6 weeks after exposure. Note that the VV-associated rash may be atypical, maculopapular and non-vesicular. If a varicella-exposed and vaccinated HCW develops a rash following vaccination, this may be due to either wild-virus or vaccine-strain varicellazoster virus (see ‘Adverse events’ below). In the event of a rash after vaccination, cover the rash, reassign duties (no patient contact) or place on sick leave until no new lesions appear and all lesions have crusted. • If an exposed non-immune HCW does not accept vaccination, reassign duties or place on sick leave from days 10 to 21 from the time of first exposure.
Contraindications (i) Allergy to vaccine components Varicella vaccination is contraindicated where there has been: • anaphylaxis following a previous dose of any of the varicella vaccines, or • anaphylaxis following any vaccine component.
(ii) Pregnant women VV should not be given during pregnancy and vaccinees should not become pregnant for 28 days after vaccination. Since wild-type VZV poses only a very small risk to the fetus, the risk to the fetus of the attenuated VV virus, if any, should be even lower. Data from a registry, established in the USA to monitor the maternal-fetal outcomes of pregnant women who were inadvertently administered VV 3 months before or at any time during pregnancy, revealed that no birth defects compatible with congenital varicella syndrome occurred in 254 known pregnancy outcomes.51,52 The rate of occurrence of congenital anomalies from prospective reports in the registry was similar to what is reported in the general USA population (3.2%) and the anomalies showed no specific pattern or target organ. A non-immune pregnant household contact is not a contraindication to vaccination with VV of a healthy child or adult in the same household. The benefit of reducing the exposure to varicella by vaccinating healthy contacts of non-immune pregnant women outweighs any theoretical risks of transmission of vaccine virus to these women. Data on the use of MMRV vaccines in individuals >12 years of age are not available.
(iii) People with impaired immunity Varicella-containing vaccines are contraindicated in subjects with primary or acquired impaired immunity, including: • people with impaired immunity due to HIV/AIDS. Vaccination with live attenuated vaccine can result in a more extensive vaccine-associated rash or disseminated infection in individuals with AIDS.53 However, varicella vaccination of asymptomatic or mildly symptomatic HIV-infected children
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may be considered (see Table 2.3.4 Immunological categories based on age-specific CD4 counts and percentage of total lymphocytes). Since studies have not been performed using combination MMRV vaccines in asymptomatic or mildly symptomatic HIV-infected children, it is recommended that only MMR and monovalent VV be considered for use in such children;54 • people with conditions in which normal immunological mechanisms may be impaired; • people suffering from malignant conditions of the reticuloendothelial system (such as lymphoma, leukaemia, Hodgkin’s disease); and • people receiving high-dose systemic immunosuppressive treatment, such as general radiation, x-ray therapy or oral corticosteroids. Varicella-containing vaccines are contraindicated in those taking high-dose oral corticosteroids (in children equivalent to either >2 mg/kg per day prednisolone (≥20 mg per day total) for >1 week or >1 mg/kg per day for >4 weeks) (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment). NHMRC also recommends that children who have been receiving high-dose systemic steroids for 2 weeks or more may be vaccinated after steroid therapy has ceased for at least 1 month.55 (See also Chapter 2.3, Groups with special vaccination requirements and Chapter 3.11, Measles).
Precautions (i) Vaccination with MMR If VV is not given simultaneously with other live viral parenteral vaccines (eg. MMR), they should be given at least 4 weeks apart.
(ii) Vaccination after immunoglobulin or blood products NHMRC recommends that varicella-containing vaccines should not be given for between 3 and 9 months after the administration of immunoglobulincontaining blood products. The interval between receipt of the blood product and vaccination depends on the amount of antibody in each product, and is indicated in Table 2.3.5 Recommended intervals between either immunoglobulins or blood products and MMR, MMRV or varicella vaccination. For further information, see Section 2.3.5, Vaccination of patients following receipt of other blood products including blood transfusions, and ‘Variations from product information’ below.
After vaccination with varicella-containing vaccines, immunoglobulin-containing products should not be administered for 3 weeks unless the benefits exceed those of vaccination. If immunoglobulin-containing products are administered within this interval, the vaccinee should either be revaccinated later at the appropriate time following the product, as indicated in Table 2.3.5, or tested for immunity 6 months later and then revaccinated if seronegative.
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(iii) Administration of immunoglobulin or bloodderived products after vaccination
(iv) Long-term aspirin or salicylate therapy Individuals receiving long-term salicylate therapy should be vaccinated if indicated, as the benefit is likely to outweigh any possible risk of Reye syndrome occurring after vaccination. Natural varicella infection and salicylate use has been associated with an increased risk of developing Reye syndrome. However, there have been no reports of an association between Reye syndrome and varicella vaccination (see ‘Variations from product information’ below).
Adverse events • Adverse events following administration of VV are generally mild and well tolerated.56 Fever >39°C has been observed in 15% (common) of healthy children, but this was comparable to that seen in children receiving placebo.55 In adults and adolescents, fever has been reported in 10% (common) of VV vaccinees. Injection site adverse events (pain, redness or swelling) are the most common adverse events reported after varicella vaccination, occurring in 7 to 30% (common to very common) of vaccinees, but are generally well tolerated.2,56 Slightly higher rates of fever were observed in the clinical trials of MMRV vaccines, as compared with giving MMR and monovalent varicella vaccine at the same time but at separate sites.57,58 It is recommended that parents/vaccine recipients be advised about possible symptoms, and given advice for reducing fever, including the use of paracetamol for fever in the period 5 to 12 days after vaccination. • A maculopapular or papulovesicular rash may develop after vaccination (usually within 5 to 26 days). Rashes typically consist of 2 to 5 lesions and may be generalised (3–5%, common), or occur at the injection site (3–5%, common).55 Most varicelliform rashes that occur within the first 2 weeks after vaccination are due to wild-type VZV, with median onset 8 days after vaccination (range 1–24 days), while vaccine-strain VZV rashes occur at a median of 21 days after vaccination (range 5–42 days).59 (See also ‘Transmission of vaccine virus…’ below.) • No serious adverse events were reported from pre-licensure trials of VV.1 A post-licensure study reported that serious adverse events, such as encephalitis, ataxia, thrombocytopenia and anaphylaxis, were reported following vaccination at a rate of 2.9 per 100 000 doses distributed. However, this does not necessarily imply a causal relationship.41 • Transmission of vaccine virus to contacts of vaccinated individuals is rare. In the USA, where more than 56 million doses of VV were distributed between 1995 and 2005, there have been only 6 well documented cases of transmission of the vaccine-type virus from 5 healthy vaccinees.55,60 Contact cases have been mild and associated with a rash in the vaccinee.55,60-62
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Risk of herpes zoster (shingles) Herpes zoster (HZ) has been reported rarely in vaccine recipients and has been attributed to both the vaccine strain and to wild-type varicella virus reactivation.59 The risk of developing HZ is currently thought to be lower after vaccination than after natural varicella virus infection, and reported cases have been mild.2 HZ is uncommon before the age of 45 years, and incidence increases with age.63 Rates of herpes zoster in children 0–9 years of age after natural VZV infection were estimated to be 30 to 74 per 100 000 per year.64,65 Vaccination results in a lower rate of zoster with a rate of 22 per 100 000 person-years reported in a 9-year follow-up of 7000 varicella vaccinated children (Jane Seward, US Centers for Disease Control and Prevention (CDC), personal communication) (see Chapter 3.26, Zoster).
Zoster immunoglobulin High-titre zoster immunoglobulin (ZIG) is available from the Australian Red Cross Blood Service on a restricted basis for the prevention of varicella in highrisk subjects. ZIG has no proven use in the treatment of established varicella or zoster infection. ZIG must be given early in the incubation period (within 96 hours of exposure). ZIG is highly efficacious, but is often in short supply. Normal human immunoglobulin (NHIG) can be used for the prevention of varicella if ZIG is unavailable. Zoster immunoglobulin should be given only by IM injection. • Zoster Immunoglobulin-VF (human) – CSL Bioplasma (160 mg/mL immunoglobulin (IgG) preparation from human plasma containing high levels of antibody to the varicella-zoster virus). Vials contain 200 IU, with the actual volume stated on the label on the vial. Also contains glycine.
The public health management of varicella ‘Significant exposure’ is defined as living in the same household as a person with active varicella or HZ, or direct face-to-face contact with a person with varicella or HZ for at least 5 minutes, or being in the same room for at least 1 hour. In the case of varicella infection, the period of infectivity is from 48 hours before the onset of rash until crusting of all lesions has occurred.
ZIG should be given to individuals in the following categories within 96 hours of significant exposure to either varicella or HZ: • Pregnant women who are presumed to be susceptible to varicella infection. If practicable, they should be tested for varicella-zoster antibodies before ZIG is given.4
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Immunocompetent varicella contacts should be tested for varicella-zoster antibodies. However, this should not delay ZIG administration after initial contact with a case.
• ZIG must be given to neonates whose mothers develop varicella from 7 or fewer days before delivery to 2 days after delivery, as the neonatal mortality without ZIG is up to 30% in this setting. ZIG must be given as early as possible in the incubation period. • ZIG should be given to neonates exposed to varicella in the first month of life, if the mother has no personal history of infection with VZV and is seronegative. • Premature infants (born at <28 weeks’ gestation or <1000 g birth weight) exposed to VZV while still hospitalised should be given ZIG regardless of maternal history of varicella. • Patients suffering from primary or acquired diseases associated with cellular immune deficiency, and those receiving immunosuppressive therapy. While it is recommended that varicella contacts with impaired immunity be tested for varicella-zoster antibodies, this should not delay ZIG administration, preferably within 96 hours and up to 10 days after initial contact with a case.66,67 NB. If a contact with impaired immunity is shown to have recent evidence of detectable antibodies, it is not necessary to give ZIG, as its administration will not significantly increase varicella-zoster antibody titres in those who are already positive. Note that varicella-zoster antibodies detected in patients who have been transfused or who have received intravenous immunoglobulin in the previous 3 months may be passively acquired and transient. The following dose schedule is recommended for ZIG administration: Table 3.24.2: Zoster immunoglobulin-VF (ZIG) dose based on weight Weight of patient (kg)
Dose (IU)
0–10
200
11–30
400
>30
600
A dose of ZIG may be repeated if a second exposure occurs more than 3 weeks after the first dose of ZIG. However, testing for varicella antibodies is also recommended (see above). Normal human immunoglobulin can be used for the prevention of varicella if ZIG is unavailable (see Chapter 3.8, Immunoglobulin preparations). Patients receiving monthly high-dose intravenous NHIG are likely to be protected and probably do not require ZIG if the last dose of NHIG was given 3 weeks or less before exposure.
Use in pregnancy Varicella vaccine is contraindicated during pregnancy (see ‘Contraindications (ii) Pregnant women’ above, and Chapter 2.3, Groups with special vaccination requirements, Table 2.3.1 Vaccinations in pregnancy). Pregnancy should be avoided for at least 28 days after vaccination.
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Variations from product information Varilrix vaccine is approved for use in healthy children from 9 months of age. NHMRC recommends that routine vaccination of children against varicella should occur at ≥12 months of age. Varilrix and Varivax Refrigerated are registered for use as 2 doses of 0.5 mL (1–2 months apart) in adolescents ≥13 years of age and adults. NHMRC recommends a single dose of varicella vaccine for children <14 years of age. In adults and adolescents where 2 doses of vaccine are required, the product information for Varilrix states that the second dose should be given at least 6 weeks after the first. NHMRC recommends that the second dose may be given at least 4 weeks after the first dose. For both varicella vaccines, the product information states that pregnancy should be avoided for 3 months after vaccination. NHMRC recommends that pregnancy be avoided for at least 28 days after vaccination. For both varicella vaccines, the product information recommends that vaccinees should avoid contact with people with impaired immunity for up to 6 weeks after vaccination. NHMRC recommends that healthcare worker vaccinees should be reassigned to duties that involve no direct patient contact or be placed on sick leave only if a rash develops, and that the period of leave or reassignment should be only for the duration of the rash (not for the 4 to 6 weeks stated in the product information) (see also ‘Vaccination of healthcare workers (HCW)’ above). For both varicella vaccines, the product information states that salicylates should be avoided for 6 weeks after varicella vaccination, as Reye syndrome has been reported following the use of salicylates during natural varicella infection. NHMRC recommends that non-immune individuals receiving long-term salicylate therapy should receive VV as the benefit is likely to outweigh any possible risk of Reye syndrome occurring after vaccination. The product information for Varivax Refrigerated recommends delaying vaccination for 5 months after receipt of NHIG by IM injection or blood transfusion. The NHMRC recommends that VV should not be given for at least 3 months in subjects who have received immunoglobulin-containing blood products according to the intervals contained in Table 2.3.5.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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The dosage of ZIG recommended in the product information differs with that in Table 3.24.2, which has been revised in order to minimise wastage of ZIG.
3.25 Yellow fever Virology Yellow fever is a viral haemorrhagic fever caused by a flavivirus that is transmitted by mosquitoes. Aedes aegypti, a highly domesticated mosquito found throughout the tropics, is the vector responsible for person-to-person transmission of the yellow fever virus in urban and inhabited rural areas in endemic countries.
Clinical features The clinical spectrum of yellow fever varies from a non-specific febrile illness to a fatal haemorrhagic fever.1 After an incubation period of 3 to 6 days, the disease begins abruptly with fever, prostration, myalgia and headache. The patient appears acutely ill with congestion of the conjunctivae; there is an intense viraemia during this ‘period of infection’ which lasts 3 to 4 days.1 This may be followed by the ‘period of remission’ in which the fever and symptoms settle over 24 to 48 hours during which the virus is cleared by immune responses.1 Approximately 15 to 25% of patients may then relapse with a high fever, vomiting, epigastric pain, jaundice, renal failure and haemorrhage: ‘the period of intoxication’.1 These complications can be severe, and reflect the viscerotropic nature of the yellow fever virus (its ability to infect the liver, heart and kidneys). The case-fatality rate varies widely, but can be as high as 20% in local populations.
Epidemiology Yellow fever occurs in tropical regions of Africa and Central and South America. In both regions the virus is enzootic in rainforest monkeys and canopy mosquito species; sporadic human cases occur when people venture into these forests (‘sylvatic or jungle yellow fever’).1 In moist savannah regions in Africa, especially those adjacent to rainforests, tree hole-breeding Aedes mosquito species are able to transfer yellow fever virus from monkeys to people and then between people, leading to small-scale outbreaks (‘intermediate yellow fever’). Aedes aegypti occurs in both heavily urbanised areas and settled rural areas in tropical Africa and the Americas.1 Epidemics of ‘urban yellow fever’ occur when a viraemic individual (with yellow fever) infects local populations of Ae. aegypti; such epidemics can be large and very difficult to control. Although Ae. aegypti also occurs throughout much of tropical Asia and Oceania (including north Queensland), yellow fever has never been reported from these regions.
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The risk of susceptible travellers acquiring yellow fever varies considerably with season, location, duration of travel and utilisation of mosquito avoidance measures. There have been at least 6 reported cases of yellow fever, all fatal, in unvaccinated travellers to Africa and South America since 1996.3
Vaccine • Stamaril – Sanofi Pasteur Pty Ltd (live attenuated yellow fever virus (17D-204 strain) lyophilised vaccine). Each 0.5 mL monodose of reconstituted, lyophilised vaccine contains not less than 1000 mouse LD50 units; lactose; sorbitol. May contain traces of egg proteins. The vaccine is supplied as a single dose ampoule with 0.5 mL diluent syringe. Yellow fever vaccine is a live, freeze-dried preparation of the 17D attenuated strain of yellow fever virus cultured in, and harvested from, embryonated chicken eggs. The vaccine contains neither antibiotics nor preservatives, and does not contain gelatin. Vaccination elicits protective levels of neutralising antibodies in approximately 90% of adult vaccinees by day 14, and in virtually all by day 28.4 Immunity is long-lasting and perhaps life-long; regardless, revaccination is required after 10 years under International Health Regulations for a valid International Certificate of Vaccination. Because the vaccine produces a transient very low level viraemia in healthy adult recipients, they cannot serve as a source of infection for mosquitoes.4 Although the efficacy of the yellow fever vaccine has never been determined in prospective clinical trials, there is considerable observational evidence that it is very effective in preventing the disease.4
Transport, storage and handling Transport according to National Vaccine Storage Guidelines: Strive for 5.5 The vaccine and diluent should be stored at +2°C to +8°C. Do not freeze. Protect from light. The vaccine should be used within 1 hour of reconstitution.
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3.25 Yellow fever
Although yellow fever is undoubtedly markedly under-reported, it is clear that there has been a considerable increase in the reported number of outbreaks, and therefore cases, of yellow fever in recent decades.2 Most of this increase has been in Africa, particularly in West African countries.2,3 Between 2000 and 2004, 18 of the 25 countries at risk in Africa reported cases of yellow fever, with 13 of the 14 countries at risk in West Africa reporting cases.3 During this time, West Africa experienced 5 epidemics of urban yellow fever, 3 of which affected capital cities (Abidjan (Côte d’Ivoire, 2001), Conakry (Guinea, 2002), Dakar and Touba (Senegal, 2002) and Bobo-Dioulasso (Burkina Faso, 2004)).3
Dosage and administration The vaccine can be given to those ≥9 months of age. The dose is 0.5 mL of reconstituted vaccine regardless of age, given by either IM or SC injection.
Recommendations Yellow fever is considered to be endemic in 32 African and 11 Central and South American countries (Table 3.25.1). Of these, 25 African and 9 South American countries are currently considered at risk because they have reported cases since 1950; of particular concern are the countries in West Africa (Table 3.25.1).3,6 Table 3.25.1: Yellow fever endemic countries West African countries
Other endemic countries
Benin *
Angola*
Guyana*
Burkina Faso *
Bolivia*
Kenya*
Côte d’Ivoire *
Brazil*
Niger
Gambia *
Burundi
Panama
Ghana *
Cameroon*
Peru*†
Guinea *
Central African Republic*
Rwanda
Guinea-Bissau *
Chad
Sao Tome and Principe
Liberia *
Colombia*
Somalia
Mali *
Congo*
Sudan*
Mauritania *
Democratic Republic of the Congo*
Suriname*
Nigeria *
Ecuador*
Trinidad and Tobago
Senegal *
Equatorial Guinea*
Uganda*
Sierra Leone *
Ethiopia*
United Republic of Tanzania
Togo *
French Guiana*
Venezuela*
Gabon* * Countries with cases reported since 1950. † Travellers who will visit only the cities of Cuzco and Machu Picchu do not need vaccination.
The yellow fever vaccine is recommended for: • those ≥9 months of age travelling or living in any country in West Africa (see Table 3.25.1), regardless of where they will be in that country, • those ≥9 months of age travelling or living outside urban areas of all other yellow fever endemic countries (see Table 3.25.1), and • laboratory personnel who routinely work with yellow fever virus.
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As well as the above recommendations, many countries outside the endemic regions require evidence of vaccination for those travellers arriving from endemic countries. Because Ae. aegypti exists in many of these non-endemic countries, there is a potential for yellow fever virus transmission; a listing of these countries is available in an annex at www.who.int/ith/en/. Travellers >1 year of age arriving into Australia within 6 days of leaving a yellow fever endemic country are required to have a valid International Certificate of Vaccination against Yellow Fever (see below). Such travellers who do not have a valid certificate are placed under quarantine surveillance until 6 days have passed after leaving the endemic country. Quarantine surveillance does not place restrictions on the traveller’s movements, but does require prompt medical assessment should the traveller develop relevant symptoms. Yellow fever vaccine can be administered only by Yellow Fever Vaccination Centres approved by the relevant State or Territory health authorities. Each yellow fever vaccination is to be recorded in an International Certificate of Vaccination against Yellow Fever; the certificate must include the vaccinee’s name and signature (or the signature of a parent or guardian if the vaccinee is a child), and the signature of a person approved by the relevant health authority. The date of the vaccination must be recorded in day-month-year sequence with the month written in letters, and the official stamp provided by the State or Territory health authority must be used. The certificate becomes valid 10 days after vaccination, and remains valid for 10 years. NB. People with a true contraindication to yellow fever vaccine (see below) who intend to travel to endemic countries (as recommended above) should obtain a letter from a doctor, clearly stating the reason for withholding the vaccine. The letter should be formal, signed and dated, and on the practice’s letterhead.
Contraindications (i) Known anaphylactic sensitivity The yellow fever vaccine is contraindicated in those who have had either: • anaphylaxis following a previous dose, or • anaphylaxis following any of the vaccine components. In particular, the vaccine is contraindicated if there is a known anaphylaxis to eggs.
Yellow fever 325
3.25 Yellow fever
All those travelling or living in endemic countries should be informed that the mosquito vectors of yellow fever usually bite during the day, and they should be advised of the necessary mosquito avoidance measures. These include the use of insect repellents, coils and sprays, the use of mosquito nets (preferably those that have been treated with an insecticide), and adequate screening of residential (and work) premises.
(ii) Infants Yellow fever vaccine is contraindicated in infants <9 months of age.
(iii) Altered immune status As with all live virus vaccines, the yellow fever vaccine should not be given to people with impaired immunity due to either disease or medical treatment (see Chapter 2.3, Groups with special vaccination requirements).
(iv) Thymus disorders People with a history of any thymus disorder, including myasthenia gravis, thymoma, thymectomy and DiGeorge syndrome, should not be given the yellow fever vaccine.
Precautions (i) Adults ≥60 years of age The risk of severe adverse events following yellow fever vaccine is considerably greater in those aged ≥60 years than in younger adults.7,8 Adults ≥60 years of age should be given yellow fever vaccine only if they intend to travel to endemic countries (as recommended above) and they have been informed about the (albeit very low) risks of developing a severe complication.
(ii) Pregnancy As with all live virus vaccines, unless there is a risk of exposure to the virus, yellow fever vaccine should not be given to pregnant women. Pregnant women should be advised against going to the rural areas of yellow fever endemic areas (and to urban areas of West African countries as well). However, pregnant women who insist on travelling, against medical advice, to endemic countries should be vaccinated. The yellow fever vaccine has been given to considerable numbers of pregnant women4,9 with no evidence of any adverse outcomes. Therefore, women vaccinated in early pregnancy can be reassured that there is no evidence of risk to themselves and very low (if any) risk to the fetus; there are no grounds for a termination of pregnancy.4
(iii) Administration of other vaccines on the same day The administration of other live virus vaccines (MMR, varicella vaccine [and MMRV when available]) should be on the same day as yellow fever vaccine, or separated by a 4-week interval. Other vaccines relevant to travel can be given with, or at any time before or after, yellow fever vaccine.
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Adverse events (i) Common adverse events
(ii) Immediate hypersensitivity reactions Immediate hypersensitivity reactions, including anaphylaxis, following yellow fever vaccine are very rare with an incidence of less than 1 in 1 million and occur principally in people with anaphylactic sensitivity to eggs.4 Although it has been suggested that an anaphylactic sensitivity to gelatin (added as a stabiliser to some yellow fever vaccines) may also precipitate anaphylaxis following vaccination,11 Stamaril does not contain gelatin.
(iii) Vaccine-associated neurotropic adverse events At least 25 cases of meningoencephalitis following yellow fever vaccination have been reported.4 However, 15 of these cases occurred in the 1950s in infants ≤7 months of age; following recommendations in the early 1960s not to vaccinate young infants, the incidence of vaccine-associated meningoencephalitis declined considerably.4 Nevertheless, these adverse events, albeit very rare, still occur in adults; the risk is greater in vaccinees ≥60 years of age.7,8
(iv) Vaccine-associated viscerotropic adverse events Recently, an apparently very rare (and often fatal) complication, characterised by multiorgan system failure, has been recognised following yellow fever vaccination; it appears that overwhelming infection with the 17D vaccine-virus is responsible for these viscerotropic adverse events.4 Up to October 2004, 25 such cases had been reported worldwide; the exact incidence is unknown but may be less than 1 in 400 000 doses of vaccine.4 Vaccine-associated viscerotropic adverse events do not appear to be caused by altered virulence of the vaccine-virus, but rather appear to be related to host factors. Although cases have occurred in younger people, it is apparent that the risk is increased with advanced age, in particular in those aged ≥60 years.7,8 Another host factor associated with an increased risk of a viscerotropic adverse event is pre-existing thymus disease. Four of the 25 reported cases had a history of thymic tumour and thymectomy, both uncommon conditions.12
Use in pregnancy Pregnant women, who insist on travelling to either a West African country, or outside urban areas of any other endemic country, should be vaccinated (see ‘Precautions’ above).
Yellow fever 327
3.25 Yellow fever
Adverse events following yellow fever vaccine are generally mild. Vaccinees often report mild headaches, myalgia and low-grade fevers or other minor symptoms for 5 to 10 days post vaccination. In clinical trials in which symptoms are actively elicited, up to 25% of vaccinees report mild adverse events and up to 1% curtail regular activities.4,10
Variations from product information The product information states that pregnancy is a contraindication to the yellow fever vaccine. However, NHMRC recommends that pregnant women who insist on travelling, against medical advice, to endemic countries, should be vaccinated. The product information suggests that a 0.1 mL test dose of yellow fever vaccine can be used intradermally to assess an individual with suspected allergy to the vaccine. However, NHMRC states that (with the exception of Q fever vaccine) test doses should never be used.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
328 The Australian Immunisation Handbook 9th Edition
3.26 Zoster (herpes zoster) Virology Varicella-zoster virus (VZV) is a DNA virus that is a member of the herpesvirus family. Herpes zoster (HZ) or ‘shingles’ is caused by reactivation of latent VZV which typically resides in the dorsal root or trigeminal ganglia following primary infection with VZV.1 Primary infection with VZV is known as varicella or ‘chickenpox’.1
Clinical features
Post-herpetic neuralgia (PHN), the most frequent debilitating complication of HZ, is a neuropathic pain syndrome that persists or develops after the dermatomal rash has healed or persists longer than 3 months after the onset of the rash.5,6 Other complications associated with HZ, such as ophthalmic disease and neurological complications, may occur depending on the site of reactivation. Rarely, disseminated HZ may develop with visceral, central nervous system, and pulmonary involvement. Disseminated disease is more common in people with impaired immunity.4 Dermatomal pain without the appearance of rash is also documented (zoster siné herpéte). Antiviral therapy, intiated within 3 days after the onset of HZ, reduces the severity and duration of HZ and may reduce the risk of developing PHN.7-11 However, in many cases, PHN may persist for years, and may be refractory to treatment.12
Epidemiology HZ occurs most commonly with increasing age (>50 years), impaired immunity, and a history of varicella in the first year of life. The lifetime risk of reactivation of VZV causing HZ is estimated to be approximately 20 to 30%, and it affects half of those who live to 85 years.1,13-15 Second attacks of HZ occur in less than 5% of immunocompetent individuals, but are more frequent in individuals with impaired immunity.2,16 Internationally, average incidence rates of HZ in the total population vary from 130 to 405 per 100 000 person-years depending on the study population.17,18 Australian data on the incidence of HZ in the community are limited. However, using general practice and other data, approximately
Zoster (herpes zoster) 329
3.26 Zoster (herpes zoster)
Reactivation of VZV causing HZ is thought to be due to a decline in cellular immunity to the virus, and presents clinically as a unilateral vesicular rash in a dermatomal distribution in the majority of cases. It is often painful and lasts 10 to 15 days.1,2 A prodromal phase occurs 48 to 72 hours before the appearance of the lesions in 80% of cases.3 Associated symptoms may include headache, photophobia, malaise, and an itching, tingling, or severe pain in the affected dermatome.2,4 In the majority of patients, HZ is an acute and self-limiting disease. However, complications can occur, especially with increasing age.
5 cases per 1000 population (range 3.3–8.3 per 1000) are estimated to occur annually.19-21 Overall, an estimated 13 to 26% of HZ patients develop complications. Complications occur more frequently with increasing age, and with impaired immunity.22,23 PHN occurs infrequently in young people but, in patients >50 years of age, it complicates HZ in 25 to 50% of cases.1 Modelling the outcomes of the introduction of a universal infant vaccination schedule for varicella has predicted a rise in the incidence of HZ based on the assumption that exposure to VZV boosts immunity.24 It has been suggested that an increase in HZ incidence rates (in the population previously infected with wild-type VZV) will occur for approximately 40 years, based on a varicella vaccine coverage rate of 90% and boosting preventing HZ for an average of 20 years.21,24 Surveillance in the USA has not suggested a change in the incidence of HZ since the introduction of a universal varicella vaccination program in 1995.18 The incidence of HZ in children vaccinated with varicella vaccine is less than in those infected with wild-type virus.1,25 In most states of Australia, surveillance for varicella and HZ is currently being implemented in order to track the burden of disease from VZV before and after the introduction of the varicella vaccination program.26 South Australia has conducted passive surveillance of varicella and HZ since January 2002.
Vaccine A frozen formulation of a live attenuated zoster vaccine is currently registered in Australia but is not marketed. The zoster vaccine is formulated from the same VZV strain (Oka/Merck) as the licensed varicella (chickenpox) vaccine, Varivax, but is of higher potency (at least 14 times greater). The higher viral titre in the zoster vaccine is required in order to elicit a sufficient cellular immune response in adults who usually remain seropositive to VZV but have declining cellular immunity with increasing age. The licensed varicella vaccines are not suitable for use in the prevention of zoster in older people. Several randomised placebo-controlled trials conducted during the clinical development of the zoster vaccine confirmed that a vaccine at potencies above 19 400 plaque forming units (PFU) stimulated both VZV-specific antibodies and a cell-mediated immune response.27,28 A large randomised, double-blind, placebocontrolled efficacy and safety trial of the zoster vaccine (known as the “Shingles Prevention Study”) was conducted among 38 546 primarily healthy adults aged ≥60 years, and demonstrated that the zoster vaccine was safe and generally well tolerated. Vaccination significantly reduced the burden of both HZ and PHN.27 Overall, compared with placebo, vaccination reduced the incidence of HZ by 51.3% (95% CI: 44.2–57.6%), the incidence of PHN by 66.5% (95% CI: 47.5–79.2%), and the burden of illness associated with pain from HZ by 61.1% (95% CI: 51.1–69.1%) over a median of 3.12 years of follow-up.27
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No product is currently marketed in Australia (see Appendix 3, Products registered in Australia but not currently available).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
3.26 Zoster (herpes zoster)
Zoster (herpes zoster) 331
Appendix 1: Contact details for Australian, State and Territory Government health authorities and communicable disease control Australian Government health authorities Australian Government Health
02 6289 1555
Australian Childhood Immunisation Register enquiries (ACIR)
1800 653 809 (This phone number can also be used by vaccination providers to obtain information on the vaccination history of individual children). ACIR email:
[email protected] ACIR Internet site: www.medicareaustralia.gov.au; click on Health Care Providers, then Programs & Services, then Australian Childhood Immunisation Register ACIR Internet Helpline: 1300 650 039
Quarterly Outcomes Payment & GPII Practice Report (ACIR020A):
1800 246 101 Email:
[email protected] Website: www.medicareaustralia.gov.au; click on Health Care Providers, then Incentives & Allowances, then General Practice Immunisation Incentive Scheme
State and Territory Government health authorities Australian Capital Territory (02) 6205 2300 Immunisation Enquiry Line New South Wales
Contact your local Public Health Unit, found under ‘Health’ in the White Pages
Northern Territory
(08) 8922 8044
Queensland
(07) 3234 1500
South Australia Immunisation Coordination Unit
(08) 8226 7177
Tasmania
(03) 6222 7724 or 1800 671 738
http://www.dh.sa.gov.au/pehs/
http://www.dhhs.tas.gov.au/publichealth/ immunisation/index.html Victoria
1300 882 008 http://www.health.vic.gov.au/immunisation
Western Australia
(08) 9321 1312
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Contact details for communicable disease control Australian Capital Territory 24-hour Communicable Disease Control Section: (02) 6205 2155 New South Wales
Contact your local Public Health Unit, found under ‘Health’ in the White Pages
Northern Territory
0830–1700 hrs: (08) 8922 8044 (After hours Royal Darwin Hospital (08) 8922 8888 for CDC on-call doctor)
Queensland
Contact your local Public/Population Health Unit, phone number listed in the White Pages
South Australia
24 hour general enquiries line: (08) 8226 7177
Tasmania
24 hour Hotline: 1800 671 738
Victoria
24 hour contact number: 1300 651 160
Western Australia
0830–1700hrs: (08) 9388 4999. After hours: (08) 9382 0553
Appendices
Appendix 1 333
Appendix 2: Handbook development Introduction The Handbook has been developed by the Australian Technical Advisory Group on Immunisation (ATAGI), which provides advice to the Federal Minister for Health and Ageing on the Immunise Australia Program and other related issues. In addition to technical experts, ATAGI’s membership includes a consumer representative and general practitioners. ATAGI consulted with other expert bodies, and with the National Health and Medical Research Council throughout the development of the 9th edition of the Handbook. The Handbook does not address the cost-effectiveness of different vaccines or different regimens; since January 2006, the cost-effectiveness of vaccines has been assessed by the Pharmaceutical Benefits Advisory Committee (PBAC), which advises government on the funding of vaccines.1 The Handbook is designed as a general guide to inform clinicians on the safest and most effective vaccination strategies, using the highest quality evidence available in peer-reviewed literature, according to NHMRC guidelines.2-5 In the absence of evidence at the highest level (well conducted randomised trials and meta-analyses), recommendations were based on lower levels of evidence such as case series. Where clinical guidelines were available on specific topics, these were used to frame recommendations, if relevant, in the Australian setting. Immunisation handbooks produced by comparable countries were also consulted. If published sources were inadequate, recommendations were based on expert opinion. The draft of the 9th edition of the Handbook was available for public consultation over a 6-week period from February to April 2007. The public comments received were reviewed during an extraordinary meeting of ATAGI and, where necessary, changes to the Handbook were incorporated. The 9th edition of the Handbook is disseminated directly to all registered medical practitioners. Additional hard copies are distributed to other immunisation service providers via their State or Territory health authority. An electronic version of the Handbook is accessible on the Immunise Australia Program website http://immunise.health.gov.au/. Implementation of the recommendations as stated in the Handbook is undertaken by immunisation providers in conjunction with their State or Territory health authority, and the Immunise Australia Program of the Australian Government Department of Health and Ageing.
Handbook literature search methodology For each chapter, broad literature searches were conducted for the years since the last Handbook searches were performed using up to 18 databases, listed in Table 1. The purpose of these searches was to ensure that technical writers and chapter
334 The Australian Immunisation Handbook 9th Edition
sponsors had access to all relevant information from the latest medical literature in identifying important issues relating to the updating of all Handbook chapters. Table 1: Electronic databases searched Electronic database
Time period
MEDLINE
2002–2006
PREMEDLINE (when required)
2002–2006
Cochrane Library—including Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (CENTRAL), the Health Technology Assessment Database, the NHS Economic Evaluation Database
2002–2006
Cumulated Index Nursing & Allied Health Literature (CINAHL) (when required)
2002–2006
EMBASE
2002–2006
Australian focused Informit databases (AMI, APA-FT, APAIS, APAIS – Health, ATSIhealth, Ausport Med, CINCH – Health, DRUG, Informit e-library, Health and Society, HIV A, Meditext, RURAL).
2002–2006
For specific questions arising in individual chapters, other databases and additional resources such as Clinical Evidence were searched as necessary. The scope and nature of the review differed for updating of existing chapters in the Handbook and new chapters for the 9th edition. • Existing chapters in the Handbook
Various search methods were tested, including ‘explode’ and ‘focus’ options. ‘Exploded’ terms retrieve citations containing the term being searched and all the narrower related terms in the database. ‘Focus’ searches retrieve citations that have the search term as the major focus of the item. In the trial searches, some items of interest were missed using the ‘focus’ method, thus ‘exploded’ searches were utilised. All subheadings assigned to the subject headings were generally included. In general, the search strategy consisted of the disease topic combined with the terms immunisation/preventive health. Boolean operators AND, OR, and NOT were used.
Appendix 2 335
Appendices
The medical and health literature was searched to identify relevant studies and reviews regarding individual diseases and the vaccines available using the electronic databases in Table 1. The search period was from 2002 to September 2006. The scope of the searches was broad, to ensure maximum retrieval and minimise the exclusion of items of interest. Previous Handbook searches were examined to determine the scope required for the new searches, and similar search strategies were employed to ensure consistency of information retrieval.
To ensure relevant and accurate retrieval, thesaurus terms (the controlled vocabulary terms used in the database) were used whenever possible. Keyword searching was used only in the absence of an appropriate thesaurus term or if the database did not have thesaurus terms. To facilitate relevant retrieval and to limit what, in some instances, are very large search result sets, the following limits were applied to the disease topic searches: • Publication year – searches were generally limited to items published from 2002–2006, in order to retrieve items published since the searches completed for the 8th edition of the Handbook. • Language – searches were limited to items in English. • Human – items discussing only animals were removed. • In vitro – items discussing only in vitro studies were removed. • Abstracts – search results restricted to items containing abstracts. The search limits were slightly modified for some of the other searches. For example, the Australian-specific searches did not have search results limited to abstract only, to ensure that all Australian items were retrieved, including items such as letters to the editor and editorials. In addition, the search result files were edited to remove irrelevant items. Files were edited, where possible, to remove duplication across the databases. There was often substantial duplication across databases, as databases index some of the same journals. More specific searches were undertaken when requested by chapter sponsors or technical writers to provide additional information on a particular aspect of a topic. • New vaccine chapters For the new vaccine chapters, Chapter 3.7 Human papillomavirus and Chapter 3.18 Rotavirus, search strategies employed for the existing chapters (as above) were used. In addition, recommendations were formulated using a structured clinical question using the PICO (Patient/population, Intervention, Comparison and Outcome) format as per the NHMRC guidelines.3 Where possible, these structured clinical questions informed both the searching and subsequent data extraction processes. Search limits used for the new vaccine chapters differed from those used for the existing chapters. To maximise retrieval and minimise publication or other potential biases, no limitation by date, language or abstract was applied. All papers identified as relevant from the PICO literature review were critiqued using a standard proforma, according to whether they were classified as studies of an intervention, diagnostic tests, prognosis, aetiology or related to screening. Completion of a separate detailed data extraction form was undertaken for each included study considered in the body of evidence for each recommendation. These processes were completed in consultation with the NHMRC-appointed Guideline Assessment Register consultant.
336 The Australian Immunisation Handbook 9th Edition
Complete details of the systematic literature review for the new vaccine chapters in the Handbook may be found on the Immunise Australia website www.immunise.health.gov.au. The evidence presented in the included studies was assessed and classified as described by the NHMRC.3 The consideration of important aspects of the evidence supporting the intervention or recommendations included three main domains: • strength of the evidence (level, quality and statistical precision), • size of the effect (including clinical importance), and • relevance of the evidence. Grades of evidence were assigned to the recommendations in the new vaccine chapters using the NHMRC considered judgment approach for assessing a body of evidence (see Table 2). Grade A and B recommendations are generally based on a body of evidence which can be trusted to guide clinical practice, whereas Grade C and D recommendations must be applied carefully to individual clinical and organisational circumstances and should be followed with care. Table 2: Grades of recommendations4 Description
A
Body of evidence can be trusted to guide practice
B
Body of evidence can be trusted to guide practice in most situations
C
Body of evidence provides some support for recommendation(s) but care should be taken in its application
D
Body of evidence is weak and recommendation must be applied with caution
The level of evidence for the included studies for each recommendation is also given, according to the NHMRC additional levels of evidence. Table 3 shows the levels that apply to intervention studies (for other study types, such as aetiology, prognosis or diagnosis, see http://www.nhmrc.gov.au/consult/index.htm). The level of evidence indicates the study design used by the investigators to assess the effectiveness of an intervention. The level assigned to a study reflects the degree to which bias has been eliminated by the study design.3
Appendix 2 337
Appendices
Grade of recommendation
Table 3: NHMRC Levels of evidence for intervention studies4 Intervention
Level of evidence
A systematic review of level II studies A randomised controlled trial (RCT)
I II
A pseudo-randomised controlled trial (eg. alternate allocation or some other method)
III-1
A comparative study with concurrent controls:
III-2
Non-randomised, experimental trial Cohort study Case-control study Interrupted time series with a control group A comparative study without concurrent controls:
III-3
Historical control study Two or more single arm study Interrupted time series without a parallel control group Case series with either post-test or pre-test/post-test outcomes
IV
Further information of how these grades were applied is given in the detailed description of the systematic literature reviews for the new vaccine chapters, which is available on the Immunise Australia website, www.immunise.health.gov.au.
Establishing Selected Dissemination Information (SDI) searches Selected Dissemination Information (SDI) searches were established to enable the ongoing collection of new relevant items on the search topics. This process used the same search strategies as the previous searches. Search results are automatically generated each time the databases (MEDLINE, EMBASE) are updated, and a report is automatically sent to a nominated e-mail address. This allowed inclusion of the most recent literature to be evaluated and referenced throughout the revision and updating of the Handbook, where applicable.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
338 The Australian Immunisation Handbook 9th Edition
Appendix 3: Products registered in Australia but not currently available Products registered but not currently available Arilvax
CSL Biotherapies/Novartis Vaccines (live attenuated yellow fever virus (17D strain) vaccine)
Gamunex
Bayer Australia Pty Ltd (normal human immunoglobulin for IV use)
Pediacel
Sanofi Pasteur Pty Ltd (diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine-Hib)
Priorix-Tetra
GlaxoSmithKline (live measles-mumps-rubella-varicella vaccine)
ProQuad Frozen
CSL Biotherapies/Merck & Co Inc (live measlesmumps-rubella-varicella vaccine)
ProQuad
CSL Biotherapies/Merck & Co Inc (live measlesmumps-rubella-varicella vaccine)
Zostavax
CSL Biotherapies/Merck & Co Inc (live varicellazoster vaccine, frozen vaccine formulation)
Products previously available CSL Biotherapies (diphtheria-tetanus vaccine, adult)
CDT
CSL Biotherapies (diphtheria-tetanus vaccine, child)
Diphtheria antitoxin
CSL Biotherapies
Diphtheria
CSL Biotherapies (vaccine, adult)
Diphtheria
CSL Biotherapies (vaccine, child)
Infanrix
GlaxoSmithKline (diphtheria-tetanusacellular pertussis vaccine, child)
Infanrix Hep B
GlaxoSmithKline (diphtheria-tetanus-acellular pertussis-hepatitis B vaccine, child)
M-M-R II
CSL Biotherapies/Merck & Co Inc (measles-mumps-rubella vaccine)
Orochol
CSL Biotherapies (oral live recombinant Vibrio cholerae CVD 103-HgR)
Quadracel
Sanofi Pasteur Pty Ltd (diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine, child)
Tet-Tox
CSL Biotherapies (tetanus vaccine)
Tripacel
Sanofi Pasteur Pty Ltd (diphtheria-tetanusacellular pertussis vaccine, child)
Typh-Vax (Oral)
CSL Biotherapies (live attenuated typhoid vaccine)
Tuberculin PPD
CSL Biotherapies (1000 units/mL)
Appendices
ADT
Appendix 3 339
Appendix 4: Components of vaccines used in the National Immunisation Program*† For vaccines not listed in the National Immunisation Program, please refer to individual product information leaflet as supplied with the vaccine, or the Handbook chapter pertinent to that vaccine. Vaccine component (possible cause of an allergy)‡
Vaccine brand§
Antigen
Aluminium hydroxide
Avaxim
Hepatitis A (HAV)
COMVAX
Haemophilus influenzae type b-hepatitis B (Hib-hepB)
Engerix-B
Hepatitis B (HBV) adult
Engerix-B
Hepatitis B (HBV) paediatric
Havrix Junior
Hepatitis A (HAV) paediatric
H-B-VAX II
Hepatitis B (HBV) adult
H-B-VAX II
Hepatitis B (HBV) paediatric
Infanrix-IPV
Diphtheria-tetanus-acellular pertussisinactivated poliomyelitis (DTPa-IPV)
Liquid PedvaxHIB
Haemophilus influenzae type b (Hib)
Menjugate Syringe
Serogroup C meningococcal conjugate
NeisVac-C
Serogroup C meningococcal conjugate
Vaqta
Hepatitis A (HAV) paediatric/adolescent
Boostrix
Diphtheria-tetanus-acellular pertussis (dTpa) adult
GARDASIL
Human papillomavirus (HPV)
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Adacel
Diphtheria-tetanus-acellular pertussis (dTpa) adult
Meningitec
Serogroup C meningococcal conjugate
Prevenar
7-valent pneumococcal conjugate
COMVAX
Haemophilus influenzae type b-hepatitis B (Hib-hepB)
GARDASIL
Human papillomavirus (HPV)
Liquid PedvaxHIB
Haemophilus influenzae type b (Hib)
Vaqta
Hepatitis A (HAV) paediatric/adolescent
Aluminium hydroxide/ phosphate
Aluminium phosphate
Borax
340 The Australian Immunisation Handbook 9th Edition
Vaccine component (possible cause of an allergy)‡
Vaccine brand§
Egg protein
All influenza vaccines
Antigen
Influenza
Fluarix
Influenza
Fluvax
Influenza
Fluvirin
Influenza
Influvac
Influenza
Vaxigrip
Influenza
Adacel
Diphtheria-tetanus-acellular pertussis (dTpa) adult
Avaxim
Hepatitis A (HAV)
Boostrix
Diphtheria-tetanus-acellular pertussis (dTpa) adult
Fluad
Influenza
Fluarix
Influenza
Havrix Junior
Hepatitis A (HAV) paediatric
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix-IPV
Diphtheria-tetanus-acellular pertussisinactivated poliomyelitis (DTPa-IPV)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Vaqta
Hepatitis A (HAV) paediatric/adolescent
Vaxigrip
Influenza
Gelatin
Varivax Refrigerated
Varicella-zoster (VZV)
Gentamicin
Fluarix
Influenza
Formaldehyde
Influvac
Influenza
Kanamycin
Fluad
Influenza
Monosodium glutamate (MSG)
Varivax Refrigerated
Varicella-zoster (VZV)
Appendix 4 341
Appendices
Fluad
Vaccine component (possible cause of an allergy)‡
Vaccine brand§
Antigen
Neomycin
Avaxim
Hepatitis A (HAV)
Fluad
Influenza
Fluvax
Influenza
Fluvirin
Influenza
Havrix Junior
Hepatitis A (HAV) paediatric
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix-IPV
Diphtheria-tetanus-acellular pertussisinactivated poliomyelitis (DTPa-IPV)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Priorix
Measles-mumps-rubella (MMR)
Varilrix
Varicella-zoster (VZV)
Varivax Refrigerated
Varicella-zoster (VZV)
Vaxigrip
Influenza
Phenol
Pneumovax 23
23-valent pneumococcal polysaccharide
Phenoxyethanol
Adacel
Diphtheria-tetanus-acellular pertussis (dTpa) adult
Avaxim
Hepatitis A (HAV)
Boostrix
Diphtheria-tetanus-acellular pertussis (dTpa) adult
Havrix Junior
Hepatitis A (HAV) paediatric
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix-IPV
Diphtheria-tetanus-acellular pertussisinactivated poliomyelitis (DTPa-IPV)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Fluvax
Influenza
Fluvirin
Influenza
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix-IPV
Diphtheria-tetanus-acellular pertussisinactivated poliomyelitis (DTPa-IPV)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Polymyxin
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Vaccine component (possible cause of an allergy)‡
Vaccine brand§
Antigen
Thiomersal
Engerix-B
Hepatitis B (HBV) adult (contains trace <2 µg/mL)
Engerix-B
Hepatitis B (HBV) paediatric (contains trace <2 µg/mL)
Fluad
Influenza
Fluarix
Influenza
COMVAX
Haemophilus influenzae type b-hepatitis B (Hib-hepB)
Engerix-B
Hepatitis B (HBV) adult
Engerix-B
Hepatitis B (HBV) paediatric
GARDASIL
Human papillomavirus (HPV)
H-B-VAX II
Hepatitis B (HBV) adult
H-B-VAX II
Hepatitis B (HBV) paediatric
Infanrix hexa
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b (DTPa-hepB-IPV-Hib)
Infanrix Penta
Diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis (DTPa-hepB-IPV)
Yeast
* Please note that vaccine manufacture is subject to ongoing refinement and change. Therefore, the following information may change. This information was current at the time of preparation. † This table has been adapted with permission from Dr T. McGuire.1
§ Please also refer to Appendix 5, Commonly asked questions about vaccination for more specific information about these various constituents.
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
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‡ If the person to be vaccinated has had an anaphylactic reaction to any of the vaccine components, administration of that vaccine is contraindicated.
Appendix 5: Commonly asked questions about vaccination This chapter contains information for providers to refer to when responding to questions and concerns about immunisation. It covers general questions on adult and childhood vaccination, including contraindications and precautions. In addition, a discussion on some of the more recent concerns about vaccination is included, covering issues relating to vaccine safety, vaccine content, immunisation as a possible cause of some illnesses of uncertain origin, and the need for vaccination. This appendix is divided into 4 sections:
1. General questions
2. Contraindication and precautions
3. Responding to questions and concerns about immunisation
4. Where can I get more information about vaccination?
1. General questions (i) How does vaccination work? When a healthy person becomes infected with a virus, eg. measles, the body recognises the virus as an invader, produces antibodies which eventually destroy the virus and recovery occurs. If contact with the measles virus occurs again in the future, the body’s immune system ‘remembers’ the measles virus and produces an increase in antibodies to destroy the virus. Vaccination is the process that is used to stimulate the body’s immune system in the same way as the real disease would, but without causing the symptoms of the disease. Most vaccines provide the body with ‘memory’ so that an individual doesn’t get the disease if exposed to it. Vaccination conveys immunity to diseases by a process called active immunity, which can be achieved by administration of either inactivated (ie. not live) or live attenuated organisms or their products. Live vaccines are attenuated, or weakened, by growing the organism through serial culturing (or passaging) steps in various tissue culture media. Inactivation is usually done using heat or formalin (sometimes both). Inactivated vaccines may include the whole organism (such as oral cholera vaccine), the toxin produced by the organism (such as tetanus and diphtheria vaccines), or specific antigens (such as Hib and pneumococcal vaccines). In some cases, the antigen is conjugated (ie. chemically linked) with proteins to facilitate the immune response. Inactivated viral vaccines may include whole viruses (such as IPV and hepatitis A vaccines) or specific antigens (such as influenza and hepatitis B vaccines). Live attenuated viral vaccines include MMR, rubella, varicella and yellow fever vaccines.
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Immunity can also be acquired passively by the administration of immunoglobulins. Such immunity is immediate and is dose-related and transient. For example, measles or hepatitis B immunoglobulin can be used promptly after exposure in an unimmunised person to help reduce the chance of catching measles or hepatitis B from the exposure.
(ii) What is the correct site for vaccination of children? The top, outer part of the thigh (the vastus lateralis muscle) is the recommended site for injections for infants <12 months of age. The deltoid region of the upper arm is the recommended site for vaccination of children ≥12 months of age because it is associated with fewer local reactions and has sufficient muscle bulk to facilitate the injection. However, the vastus lateralis muscle can also be used. The ventrogluteal area is an alternative site. (See Section 1.4.6, Recommended injection sites and Section 1.4.8, Identifying the injection site). Rotavirus vaccines are administered by the oral route and must never be injected.
(iii) How many injections can be given into the same limb in a child aged <12 months?
(iv) When should preterm infants be vaccinated? Babies born at <32 weeks’ gestation or <2000 g birth weight should receive their first dose of hepatitis B vaccine either at birth (within the first few days of life) or at 2 months of age. Immunisation schedules differ in different areas of Australia according to which combination vaccines are routinely used in that State or Territory. The routine 2-month vaccines containing the antigens DTPaIPV-Hib-hepB, 7vPCV and rotavirus should be given 2 months after birth as normal, unless an infant is very unwell. ‘Very unwell’ can be interpreted in many ways but, in general, reflects that the premature neonate is particularly unstable. Delaying the 2-month vaccines is rarely required. If any preterm infant has the 2-month vaccines delayed, it should be remembered that the infant doses can be given 1 month apart rather than 2 months. Hence, if an infant receives the 2-month vaccines at 3 months then the 4 month vaccines should still be given at 4 months of age.
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More than 1 vaccine can be safely given into a limb at the same immunisation visit. Most States and Territories have routine immunisation schedules that include 3 injections during the primary course for children <12 months of age. In this case, 2 injections can be given into the same leg into the vastus lateralis muscle and the third injection in the other vastus lateralis muscle (or an alternative is the ventrogluteal site). The injections should be given at least 25 mm (2.5 cm) apart. Use separate sterile injection equipment for each vaccine administered. The accompanying documentation should indicate clearly which vaccines were given into which site (eg. left leg upper/left leg lower).
When Liquid PedvaxHIB is used in an extremely preterm baby (<28 weeks’ gestation or <1500 g birth weight), an additional dose should be given at 6 months of age. Further explanation of the special immunisation needs of premature babies is provided in Section 2.3.2 Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants.
(v) Do elderly people (>65 years) who have no chronic illnesses need the influenza vaccine? Yes. Age is an independent risk factor for influenza. Vaccination of those aged >65 years, regardless of the presence or absence of chronic illness, reduces mortality by up to 50% in the winter period in this age group (see Chapter 3.9, Influenza).1,2 The healthy elderly should also receive the 23-valent pneumococcal polysaccharide vaccine (see Chapter 3.15, Pneumococcal disease).
(vi) Should adults receive pertussis (whooping cough) vaccine boosters? Yes. Two brands of acellular pertussis vaccines, both combined with tetanus and diphtheria antigens, are now available for adolescents and adults. dTpa vaccines are recommended in Australia for booster vaccination of individuals ≥8 years of age who have previously had a primary course of diphtheria-tetanus-pertussis vaccine. dTpa vaccines have a lower content of diphtheria and pertussis antigens than DTPa formulations for young children. A recent study showed that adults can be protected against pertussis after a single dose of dTpa. No recommendations about the need for further boosters using adolescent/adult formulation dTpa have been made at this time. A single dose of dTpa is recommended for the following groups (unless contraindicated or they have already received a previous dose of dTpa): • adults working with young children. Vaccination is especially recommended for childcare workers; • all healthcare workers; • adults planning a pregnancy, or for both parents as soon as possible after delivery of an infant (preferably before hospital discharge), unless contraindicated.3 Other adult household members, grandparents and carers of young children should also be vaccinated. This recommendation is based on evidence from several studies of infant pertussis cases, which indicated that family members, particularly parents, were identified as the source of infection in more than 50% of cases and were the presumed source in a higher proportion; • any adult expressing an interest in receiving a booster dose of dTpa. Adults ≥50 years of age who have not previously received dTpa vaccine should also be offered vaccination. See Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus in this Handbook.
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Contraindications to adolescent/adult formulation dTpa are discussed in Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis and Chapter 3.21, Tetanus in this Handbook and include previous anaphylactic reaction to any vaccine component. If the patient has never received a primary course of dT, see Chapter 3.3, Diphtheria, Chapter 3.14, Pertussis or Chapter 3.21, Tetanus in this Handbook.
(vii) A parent wants a child to receive his/her vaccines separately. Why can’t they do this? There is no scientific evidence or data to suggest that there are any benefits in receiving vaccines such as MMR or DTPa as separate monovalent vaccines. Using the example of MMR vaccine, there is no individual mumps or measles vaccine licensed for use in Australia. If these vaccines were to be administered individually it would require 3 separate vaccines which would unnecessarily increase discomfort for the child. In addition, if these monovalent vaccines were not given on the same day, they would need to be spaced 1 month or more apart which would increase the risk of that child being exposed to serious vaccinepreventable diseases. A policy of providing separate vaccines would cause some children to not receive the entire course, and combination vaccines can offer a reduced amount of vaccine stabiliser and adjuvant compared to 3 individual vaccine doses.
(viii) Is vaccination compulsory? What happens if children do not get vaccinated? Vaccination is not compulsory in Australia.
If a parent decides not to have a child vaccinated and, if cases of certain vaccinepreventable diseases occur at that child’s day-care centre or school, the parent may, in some circumstances, be required to keep the unvaccinated child at home until the incubation period for that particular disease has passed or no further cases have occurred in that setting.
2. Contraindications and precautions If you have any concerns about whether to proceed with vaccination, please seek expert advice. See Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control.
(i) What are the absolute contraindications to childhood vaccination? True contraindications to the childhood vaccines are extremely rare (see relevant chapters), and include only anaphylaxis to any of the particular vaccine’s components, and anaphylaxis following a previous dose of that vaccine.
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The Maternity Immunisation Allowance and Child Care Benefit are parent incentive payments that are paid where a child is up-to-date with his/ her immunisations or the parent has obtained an appropriate medical or philosophical exemption.
NB. Anaphylaxis following ingestion of eggs does not contraindicate MMR vaccine, as the vaccine viruses are not grown in eggs and the vaccine does not contain any egg protein4 (see Chapter 3.11, Measles).
(ii) What are the contraindications to further doses of pertussis-containing vaccines? Further doses of DTPa are contraindicated in those who have had a previous immediate severe allergic or anaphylactic reaction to vaccination with DTPa. A previous simple febrile convulsion or pre-existing neurological disease is not a contraindication to pertussis-containing vaccines.
(iii) What are the precautions to childhood vaccination? In general, children with impaired immunity or on immunosuppressive therapy should not be given live vaccines (see (vii) to (ix) below).
(iv) Should a child with an intercurrent illness be vaccinated? A child with a minor illness (without systemic illness and with a temperature <38.5°C) may be safely vaccinated. Infants and children with minor coughs and colds without fever, or those receiving antibiotics in the recovery phase of an acute illness, can be vaccinated safely and effectively. In a child with a major illness or high fever ≥38.5°C, vaccination should be postponed until the child is well. If vaccination were to be carried out during such an illness, the fever might be confused with vaccine side effects and might also increase discomfort to the child. In such cases, it is advisable to defer vaccination and arrange for the child to return for vaccination when well again.
(v) Should children with epilepsy be vaccinated? Yes. Stable neurological disease (such as epilepsy) is not a reason to avoid giving vaccines like pertussis (whooping cough). Children who are prone to fits should have paracetamol before and for 48 hours after vaccination to reduce the chance of a fever after vaccination bringing on a convulsion. A family history of fits or epilepsy is not a reason to avoid vaccination.
(vi) Should children with neurological disease receive the normal vaccination schedule? Yes. Children with neurological disease are often at increased risk of complications from diseases like measles, influenza and whooping cough, as they can be more prone to respiratory infections and chest problems. It is important that these children be immunised, on time, as recommended in the National Immunisation Program schedule.
(vii) Are steroids a contraindication to vaccination? Live vaccines such as MMR, BCG and varicella-zoster vaccines, should not be given to children or adults receiving high dose oral or parenteral corticosteroid therapy for more than 2 weeks. High dose oral corticosteroid
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therapy is defined as more than 2 mg/kg per day prednisolone for more than 1 week. This is because steroids, in large doses, greatly suppress the immune system which means that, not only is the vaccine unlikely to be effective, but there is an increased chance of an adverse event occurring as a result of the immunosuppression. Inactivated vaccines, eg. DTPa-hepB-IPV, may be less effective in this group but are not contraindicated. Therapy with inhaled steroids is not a contraindication to vaccination.
(viii) Should vaccines be given to children who have problems with their immune systems? Children with impaired immunity or those on immunosuppressive therapy should not be given live viral vaccines such as MMR, varicella, and rotavirus vaccines.5 HIV-infected children may be given MMR vaccine provided they do not have severely impaired immunity (see Table 2.3.4 Immunological categories based on age-specific CD4 counts and percentage of total lymphocytes). The contacts of children with impaired immunity can be given MMR without any risk of transmission. The rash seen in a small percentage of MMR vaccine recipients, usually between days 5 to 12 post vaccination, is not infectious.
Live viral vaccines can be given to children with leukaemia and other malignancies who have been on chemotherapy at least 3 months after they have completed chemotherapy, provided there are no concerns about their immune status. Such measures would normally be carried out under the supervision of the child’s oncologist (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment).
(ix) What vaccines should children with HIV infection receive? Children with HIV (human immunodeficiency virus) infection should have all routine inactivated vaccines on the National Immunisation Program schedule. Varicella vaccine is generally contraindicated in children with HIV, as it can cause disseminated varicella infection. However, it may be considered for asymptomatic or mildly symptomatic HIV-infected children, after weighing up the potential risks and benefits. This should be discussed with the child’s specialist.
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It is highly recommended that non-immune household contacts of children with impaired immunity receive varicella vaccine. There is an almost negligible risk of transmitting varicella vaccine virus from a vaccine-related vesicular rash to contacts. However, vaccine-related rash occurs in 3 to 5% of vaccinees either locally at the injection site or generalised, with a median of only 25 lesions. This small infection risk of the less virulent attenuated vaccine strain is far outweighed by the high risk of non-immune contacts catching wild varicella infection and transmitting the virus to the household member with impaired immunity via respiratory droplets or from the large number of skin lesions that occur with wild varicella infection (a median of 300 to 500 lesions).
MMR vaccine can be given to children with HIV, depending on their CD4 counts (see point (viii) above). Children with HIV infection should also be vaccinated against pneumococcal disease (see Chapter 3.15, Pneumococcal disease). Influenza vaccine is also recommended for HIV-infected children. They should not be given BCG, due to the risk of disseminated infection (see Section 2.3.3, Vaccination of individuals with impaired immunity due to disease or treatment).
(x) Should chronically ill children be vaccinated? In general, children with chronic diseases should be vaccinated as a matter of priority because they are often more at risk from complications from vaccinepreventable diseases. Annual influenza vaccine is highly recommended for chronically ill children and their household contacts. Care is needed with the use of live attenuated viral vaccines in situations where the child’s illness, or its treatment, may result in impaired immunity. Advice may need to be sought on these patients to clarify the safety of live viral vaccine doses.
(xi) Should children be vaccinated while the child’s mother is pregnant? There is no problem with giving routine vaccinations to a child whose mother is pregnant. MMR vaccine viruses are not transmissible. Administration of varicella vaccine to household contacts of non-immune pregnant women is safe. Transmission of varicella vaccine virus is very rare. There is an almost negligible risk of transmitting varicella vaccine virus from a vaccine-related vesicular rash to contacts. However, vaccine-related rash occurs in 3 to 5% of vaccinees either locally at the injection site or generalised, with a median of only 25 lesions. Furthermore, vaccinating the child of a pregnant mother will reduce the risk of her being infected by her offspring with the more virulent wild virus strain if she is not immune.
(xii) Should children with allergies be vaccinated? What precautions are required for atopic or egg-sensitive children? Asthma, eczema and hay fever are not contraindications to any vaccine on the childhood schedule unless the child is receiving high-dose steroid treatment (see point (vii) above). For other allergies, see Appendix 4, Components of vaccines used in the National Immunisation Program, and the relevant vaccine product information (PI) enclosed in the vaccine package. Unless the child (or person being vaccinated) has an allergy to a specific constituent of a vaccine (or has another contraindication) there is no reason not to vaccinate. An important exception is anaphylactic sensitivity to eggs, characterised by generalised hives, swelling of the mouth or throat, difficulty breathing, wheeze, low blood pressure, and shock. If a person has a history of severe egg allergy, influenza, yellow fever and Q fever vaccines should not be given. Because MMR vaccine viruses are not cultured in eggs and the vaccine does not contain egg protein, MMR can be given safely to those with anaphylactic sensitivity to eggs.4
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Simple dislike of eggs or having diarrhoea or stomach pains after eating eggs are not reasons to avoid MMR and these children require no special precautions. These children can also have all other routine vaccines without special precautions.4 Families with questions about allergies and vaccines are encouraged to discuss this with their immunisation service provider to have any questions promptly answered to avoid unnecessary delays of vaccine doses.
3. Responding to questions and concerns about immunisation Some people express concerns about immunisation. These mostly relate to whether the vaccine is safe and whether vaccines weaken the immune system of the child. Providers should listen to and acknowledge people’s concerns. Providers should discuss the risks and benefits of immunisation with parents/ carers honestly and in a non-defensive manner. Parents/carers and adult vaccine recipients should receive accurate information on the risks from vaccinepreventable diseases and information about vaccine side effects and adverse events (see table inside the front cover Comparison of the effects of diseases and the side effects of vaccines). The following section responds to some concerns raised about the safety of immunisation, and examines the scientific evidence in order to assist providers and parents in making an informed choice about the risks and benefits of vaccination.
a) Vaccine safety (i) How safe are vaccines?
After introduction into vaccination schedules, there is continuing surveillance of efficacy and safety through trials and post-marketing surveillance. In Australia, there are regional and national surveillance systems actively seeking any adverse events following immunisation. This is necessary, as sometimes problems occur after vaccines are registered for use. Regular Australian surveillance reports are published in the journal Communicable Diseases Intelligence.6
(ii) Can too many vaccines overload or suppress the natural immune system? No. The increase in the number of vaccines and vaccine doses given to children has led to concerns about the possible adverse effects of the aggregate vaccine exposure, especially on the developing immune system. In day-to-day life, all children and adults confront enormous numbers of antigens and the immune system responds to each of these in various ways to protect the body. Studies of
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Before vaccines are made available for general use they are tested for safety and efficacy in clinical trials and then in large trials, otherwise known as Phase 2 and 3 trials. All vaccines marketed in Australia are manufactured according to strict safety guidelines and are evaluated by the Therapeutic Goods Administration to ensure they are efficacious and are of adequate quality and safety before marketing approval is granted.
the diversity of antigen receptors indicate that the immune system can respond to an extremely large number of antigens. In addition, the number of antigens received by children during routine childhood vaccination has actually decreased compared with several decades ago. This has occurred in spite of the increase in the total number of vaccines given, and can be accounted for by the removal of 2 vaccines – smallpox vaccine (which contained about 200 different proteins), and whole-cell pertussis vaccine (about 3000 distinct antigenic components) from routine vaccination schedules. In comparison, the acellular pertussis vaccine currently used in Australia has only 3 to 5 pertussis antigens.7
(iii) Do vaccines cause disease? Some studies have suggested a temporal link between vaccinations and certain medical conditions, such as asthma, multiple sclerosis, and diabetes. The allegations of a link are often made for a disease of unknown cause. The appearance of a certain medical condition after vaccination does not necessarily imply that they are causally related. Importantly, however, once an issue is raised it needs prompt research, discussion and then education to avoid propagating a myth. In many cases, subsequent epidemiological studies have indicated that the association is due to chance alone. The following is a list of concerns that have been raised. • Does MMR vaccine cause inflammatory bowel disease or autistic spectrum disorder?8 In 1998, Wakefield et al (Royal Free Hospital, London)9 published a case series study with 12 children suggesting that MMR vaccine caused inflammatory bowel disease (IBD), which then resulted in decreased absorption of essential vitamins and nutrients through the intestinal tract. They proposed that this could result in developmental disorders such as autism. Following the study’s publication, Wakefield suggested that it may be 3 live viruses in the 1 vaccine which was causing the development of the subsequent disorders. He suggested it was preferable to provide MMR vaccination as 3 separate vaccines, a suggestion with no supportive evidence.9 This study had several weaknesses. First, finding out whether or not MMR causes autism is best determined by comparing the incidence of autism in vaccinated versus unvaccinated children. However, the researcher included only vaccinated children. Second, the author claimed that gastrointestinal inflammation contributes to autism. However, in several of the children, their behavioural problems appeared before the onset of bowel disease.10,11 Furthermore, the study was primarily based on parental recall of when the bowel disease and developmental disorders first appeared, and people are more likely to have linked changes in behaviour with memorable events such as vaccination. The Royal Free Hospital study was conducted on a very selective group of patients, all referred to the hospital for gastrointestinal ailments, and such a case series analysis is unable to determine causal links.
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The onset of autism and MMR vaccination may coincide because the average age at which parents report concerns about child development is 18 to 19 months, and more than 90% of children in the UK receive MMR vaccine before their 2nd birthday.12 More rigorous and larger epidemiological studies have found no evidence of an association.13-16 A review by the World Health Organization concluded that current scientific data do not permit a causal link to be drawn between the measles virus and autism or IBD.17An extensive review published in 2004 by the Institute of Medicine, an independent expert body in the United States, concluded that there is no association between the MMR vaccine and the development of autism.18 Reviews by the American Academy of Pediatrics, The British Chief Medical Officer, the UK Medical Research Council, Canadian experts, and numerous other scientific experts have stated that there is no link between autism or IBD and the measles vaccine.14,19-21 See Chapter 3.11, Measles for further information. There is also an MMR vaccine decision aid designed for parents available at http://www.ncirs.usyd.edu.au/decisionaid/index.html. • Do childhood immunisations cause asthma? There is no evidence that vaccination causes or worsens asthma. It is especially important that children with asthma be vaccinated like other children, as catching a disease like whooping cough can make an asthma attack worse. Although influenza vaccine is not routinely recommended for all asthmatics, it is recommended for severe asthmatics, such as those requiring frequent hospitalisation.22 There is no reliable evidence that the hepatitis B vaccine causes multiple sclerosis (MS). With millions of hepatitis B vaccinations administered worldwide, it is likely that surveillance systems in some countries will receive some reports of MS, which seem to be related in time to vaccinations. As with all such reports, however, they suggest only the possibility of an association. Subsequent studies have found no increase in incidence of MS, or even relapse of MS, after hepatitis B vaccination.23-27 In response to a single study by Hernán et al,28 the World Health Organization Global Advisory Committee on Vaccine Safety released the following statement: “multiple studies and review panels have concluded that there is no link between MS and hepatitis B vaccination”.29 In addition, a review by the Institute of Medicine Immunization Safety Review Committee in 2003 found no link between hepatitis B vaccine and certain neurological disorders such as MS.30 A systematic review from the Cochrane Vaccines Field in 2003 also found no evidence of an association between hepatitis B vaccine and MS.31 Recent statements by the World Health Organization and the US Centers for Disease Control and Prevention support this position.29,32,33
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• Does hepatitis B vaccine cause multiple sclerosis?
• Do some vaccines cause ‘Mad Cow Disease’? Variant Creutzfeldt-Jakob disease (vCJD) is considered to be the human equivalent of bovine spongiform encephalopathy (BSE, also known as ‘mad cow disease’). There is no evidence that any case of vCJD has resulted from the administration of any vaccine product, despite millions of doses of vaccine being administered worldwide. Concerns about the risk of transmission of this disease arose because the production of some vaccines requires bovine derivatives such as fetal bovine serum. In Australia, the Therapeutic Goods Administration has confirmed that the vaccines available in this country contain bovine materials preferentially sourced from BSE-free areas, and that they undergo appropriate purification treatment. Therefore, although some vaccines carry a theoretical risk of transmissible spongiform encephalopathies, this risk is infinitesimally small (estimated at less than 1 in a billion).34 The benefits of vaccination are considered to far outweigh any theoretical risk of BSE transmission.35 • Is there a link between vaccination and Sudden Infant Death Syndrome (SIDS)? Despite extensive studies, there is no evidence that vaccination causes SIDS (cot death). Deaths do occasionally occur shortly after vaccination but the relationship is a chance association, since SIDS tends to happen in babies of 2–6 months of age, whether they are vaccinated or not.36 Many studies have conclusively shown that SIDS is not caused by immunisation. In addition, some studies have found a lower rate of SIDS in immunised children.37-39 • Does immunisation cause diabetes? In 1997, a study from Finland suggested a link between Hib vaccination and type 1 diabetes.40 However, subsequent reanalysis of the data did not support such a link.41,42 The conclusion that there is no causal link between any of the childhood vaccines and diabetes has also been supported by a subsequent review of the literature, and the conclusions of 2 workshops held in the USA in 1998.8,41-43 • Does influenza vaccine cause flu? No. It is not possible for influenza vaccine to cause ‘flu’ as it is not a live viral vaccine. As some people experience side effects such as a mild fever after the vaccine, it is understandable that they may confuse these symptoms with actually having the flu. In addition, the influenza vaccine is recommended to be given at the commencement of the flu season. Hence, it is possible that a person who has contracted, and is incubating, influenza during vaccination will mistakenly believe the vaccine to be causal. In addition, influenza vaccine is given at the very time of year when there are a lot of upper respiratory tract infections (URTIs) around. It is not uncommon for someone to attribute an URTI within a week of an influenza vaccine to the vaccine dose. Importantly, URTI symptoms occurring after influenza vaccine should not put people off having the vaccine the following year.
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b) Vaccine content44 (See also Appendix 4 for a list of vaccines used in the NIP which contain these compounds and refer to the relevant vaccine product information (PI) enclosed in the vaccine package.) • Preservatives Preservatives are used to prevent fungal and or bacterial contamination of the vaccine. They include thiomersal, phenoxyethanol, and phenol.
(i) Thiomersal Thiomersal (or thimerosal) is a compound which is partly composed of mercury, ethylmercury. It has been used in very small amounts in vaccines for about 60 years, to prevent bacterial and fungal contamination of vaccines. In the past, the small amount of thiomersal in vaccines was one of several potential sources of mercury. Diet (such as some seafood) and other environmental sources are also possible sources of mercury. Vaccines used in the past, such as DTP, contained only 25 µg of thiomersal per dose.
Currently, all vaccines on the NIP for children <5 years of age are now either free of thiomersal, or contain a reduced (trace) amount of thiomersal. There are certain vaccines that are still most effectively manufactured using a trace amount of thiomersal as the preservative, eg. influenza vaccine. Infants from 6 months of age can be given influenza vaccine safely.
(ii) Phenoxyethanol 2-Phenoxyethanol is an aromatic ether alcohol used as a preservative in many vaccines. It is also used as a preservative in cosmetics. 2-Phenoxyethanol is used in vaccines as an alternative preservative to thiomersal.
Appendix 5 355
Appendices
Mercury causes a toxic effect after it reaches a certain level in the body. Whether or not it reaches a toxic level depends on the amount of mercury consumed and the person’s body weight; individuals with very low body weight are usually more susceptible to toxic effects from a certain intake of mercury. Thus, the possibility existed that vaccination of newborn babies, particularly those of very low birth weight, with repeated doses of thiomersal-containing vaccines, might have resulted in levels of mercury above the recommended guidelines. Thiomersal was removed from vaccines in response to the above theoretical concern and to reduce total exposure to mercury in babies and young children in a world where other environmental sources may be more difficult to eliminate.45-47
(iii) Phenol Phenol is an aromatic alcohol used as a preservative in a few vaccines. • Adjuvants Adjuvants are compounds used to enhance the immune response to vaccination and include various aluminium salts such as aluminium hydroxide, aluminium phosphate and potassium aluminium sulphate (alum). A recent review of all available studies of aluminium-containing diphtheria, tetanus and pertussis vaccines (either alone or in combination) found no evidence that aluminium salts in vaccines cause any serious or long-term adverse events.48
Aluminium A small amount of aluminium salts has been added to some vaccines for about 60 years. Aluminium acts as an adjuvant, which improves the protective response to vaccination by keeping antigens near the injection site so they can be readily accessed by cells responsible for inducing an immune response. The use of aluminium in vaccines means that, for a given immune response, less antigen is needed per dose of vaccine, and a lower number of total doses are required. Although aluminium-containing vaccines have been associated with local reactions and, less often, with the development of subcutaneous nodules at the injection site, other studies have reported fewer reactions with aluminiumadsorbed vaccines than with unadsorbed vaccines. Concerns about the longerterm effects of aluminium in vaccines arose after some studies suggested a link between aluminium in the water supply and Alzheimer’s disease, but this link has never been substantiated. The amount of aluminium in vaccines is very small and the intake from vaccines is far less than that received from diet or medications such as some antacids.49,50 • Additives Additives are used to stabilise vaccines in adverse conditions (temperature extremes of heat and freeze drying) and to prevent the vaccine components adhering to the side of the vial. Examples of additives include: • lactose and sucrose (both sugars); • glycine and monosodium glutamate or MSG (both are amino acids or salts of amino acids); • gelatin, which is partially hydrolysed collagen usually of bovine or porcine origin. Some members of the Islamic and Jewish faiths may object to vaccination, arguing that vaccines can contain pork products. Scholars of the Islamic Organization for Medical Sciences have determined that the transformation of pork products into gelatin will sufficiently alter them thus making it permissible for observant Muslims to receive vaccines, even if the vaccines contain porcine gelatin. Likewise, leaders of the Jewish faith
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have also indicated that pork-derived additives to medicines are permitted. Further information may be obtained from the following websites http://vaccinesafety.edu/Porcine-vaccineapproval.htm and http://www.immunize.org/concerns/porcine.pdf; • human serum albumin (protein). • Manufacturing residuals Manufacturing residuals are residual quantities of reagents used in the manufacturing process of individual vaccines. They include antibiotics (such as neomycin or polymyxin), inactivating agents (eg. formaldehyde) as well as cellular residuals (egg and yeast proteins), traces of which may be present in the final vaccine. Antibiotics are used during the manufacturing process to ensure that bacterial contamination does not occur; traces of these antibiotics may remain in the final vaccine. Inactivating agents are used to ensure that the bacterial toxin or viral components of the vaccine are not harmful, but will result in an immune response. Cellular residuals are minimised by extensive filtering. However, trace amounts may be present in the final product. The most commonly found residual is formaldehyde.
Formaldehyde
• Other Vaccines also may be made up in sterile water or sterile saline (salt-water).
(c) The need for immunisation (i) Isn’t natural immunity better than immunity from vaccination? While vaccine-induced immunity may diminish with time without boosters (vaccine or contact with wild-type infection), ‘natural’ immunity, acquired by catching the disease, is usually life-long, with the exception of pertussis. The problem is that the wild or ‘natural’ disease has a higher risk of serious illness and occasionally death. Children or adults can be revaccinated (with some but not all vaccines) if their immunity from the vaccines falls to a low level or if previous research has shown that a booster vaccination is required for long-term protection. It is important to remember that vaccines are many times safer than the diseases they prevent.
Appendix 5 357
Appendices
Formaldehyde is used during the manufacture of many vaccines. For example, with tetanus vaccines, formaldehyde is used to detoxify the tetanus toxin protein produced. The non-toxic protein which becomes the active ingredient of the vaccine is further purified to remove contaminants and any excess (unreacted or unbound) formaldehyde. The current standard applicable to vaccines for human use in Australia is less than 0.02% w/v of free formaldehyde. The maximum amount of free formaldehyde detected by the Therapeutic Goods Administration during testing of vaccines registered in Australia has been 0.004% w/v, which is well below the standard limit.
(ii) Diseases like measles, polio, whooping cough and diphtheria have already disappeared from most parts of Australia. Why do we need to keep vaccinating children against these diseases? Although these diseases are much less common now, they still exist. The potential problem of disease escalation is kept in check by routine vaccination programs. In countries where vaccination rates have declined, vaccinepreventable diseases have sometimes reappeared. For example, Holland has one of the highest rates of fully vaccinated people in the world. However, in the early 1990s, there was a large outbreak of polio among a group of Dutch people who belonged to a religious group that objected to vaccination. While many of these people suffered severe complications like paralysis, polio did not spread into the rest of the Dutch community. This was due to the high rate of vaccination against polio, which protected the rest of the Dutch community. There have been recent outbreaks of whooping cough, measles and rubella in Australia, and a number of children have died. Cases of tetanus and diphtheria, although rare, still occur. Thus, even though these diseases are much less common now than in the past, it is necessary to continue to protect Australian children, so that the diseases cannot re-emerge to cause large epidemics and deaths. Also, many of the diseases which we vaccinate our children against are still common in other areas of the world. For example, measles still occurs in many Asian countries and many people take holidays or travel for business to these areas. Therefore, it is possible for non-immune individuals to acquire measles overseas, and with the speed of air travel, arrive home and be able to pass measles onto those around them if they are unprotected. Measles is highly infectious and can infect others for several hours after an infected person has left a room. Vaccination, while not 100% effective, can minimise a person’s chance of catching a disease. The more people who are vaccinated the less chance of a disease, such as measles, spreading widely in the community. This is referred to as herd immunity.
(iii) Why do some children get the disease despite being vaccinated? This is possible, since no vaccine is 100% effective. A small proportion of those who are vaccinated will remain susceptible to the disease. However, in the cases in which illness does occur in vaccinated individuals, the illness is usually much less severe than in those who were not vaccinated. The protection provided by the same vaccine to different individuals can differ. For example, if 100 children are vaccinated with MMR, 5 to 10 of the fully vaccinated children might still catch measles, mumps or rubella (although the disease will often be less severe in vaccinated children). If 100 children are vaccinated with a full schedule of pertussis-containing vaccines, 20 of the children might still get whooping cough but, once again, the disease is often less severe in these vaccinated children. To put it another way, if you do not vaccinate 100 children with MMR vaccine, and the children are exposed to measles, all of them will catch the disease with a
358 The Australian Immunisation Handbook 9th Edition
risk of high rates of complications like pneumonia or encephalitis. The reason why fewer children become infected than these figures suggest is due to the high vaccine coverage rates in the community. If there are high coverage rates, there is less chance of contact with the infection and, although children may be susceptible, they have a low chance of contact with the infection.
(iv) What about homeopathic ‘immunisation’? Homeopathic ‘immunisation’ has not been proved to give protection against infectious diseases; only conventional vaccination produces a measurable immune response. The Council of the Faculty of Homeopathy, London, issued a statement in 1993, which reads: “The Faculty of Homeopathy, London, strongly supports the conventional vaccination program and has stated that vaccination should be carried out in the normal way, using the conventional tested and proved vaccines, in the absence of medical contraindications”.51
4. Where can I get more information about vaccination? More information about vaccination can be found in the following publications produced by the Australian Government Department of Health and Ageing: • Understanding childhood immunisation • Immunisation myths and realities – responding to arguments against immunisation: a guide for providers The following two websites include further publications, fact sheets, etc. and are recommended for both immunisation service providers and the general public: • Immunise Australia website http://www.immunise.health.gov.au
Also, check with your local State or Territory public health unit or local council, maternal child health nurse, or public health vaccination clinic for more information (see Appendix 1, Contact details for Australian, State and Territory Government health authorities and communicable disease control).
References Full reference list available on the electronic Handbook or website http://immunise.health.gov.au.
Appendix 5 359
Appendices
• The National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS) website www.ncirs.usyd.edu.au
Appendix 6: Definitions of adverse events following immunisation Notify any events that the reporter considers serious and which may be related to the vaccine or vaccines administered. See Section 1.5.2, Adverse events following immunisation. Abscess Occurrence of a fluctuant or draining fluid-filled lesion at the site of injection, with or without fever. • Bacterial: purulent collection. • Sterile abscess: no evidence of bacterial infection. Acute flaccid paralysis [diagnosis must be made by a physician] Acute onset of flaccid paralysis of one or more limbs following any vaccine. Allergic reaction (generalised) A non-anaphylactic, generalised reaction characterised by 1 or more symptoms or signs of skin and/or gastrointestinal tract involvement WITHOUT respiratory or cardiovascular involvement. (NB. See also ‘Anaphylaxis’). Anaphylaxis A rapidly evolving generalised multi-system allergic reaction characterised by 1 or more symptoms or signs of respiratory and/or cardiovascular involvement AND involvement of other systems such as the skin or gastrointestinal tract. • Respiratory: difficulty/noisy breathing, swelling of the tongue, swelling/ tightness in the throat, difficulty talking/hoarse voice, wheeze or persistent cough. • Cardiac: loss of consciousness, collapse, pale and floppy (babies), hypotension. Arthralgia Joint pain without redness or swelling. Arthritis Joint pain with redness and/or swelling. Brachial neuritis Pain in arm causing persisting weakness of limb on side of vaccination. Death Any death of a vaccine recipient temporally linked to vaccination, where no other clear cause of death can be established.
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Disseminated BCG Disseminated infection occurring after BCG vaccination and confirmed by isolation of Mycobacterium bovis BCG strain. Encephalopathy [diagnosis must be made by a physician] Encephalopathy is an acute onset of major neurological illness temporally linked with vaccination and characterised by any 2 or more of the following 3 conditions: • seizures, • severe alteration in level of consciousness or mental status (behaviour and/or personality) lasting for 1 day or more, and/or • focal neurological signs which persist for 1 day or more. Encephalitis [diagnosis must be made by a physician] Encephalitis is characterised by the above-mentioned symptoms and signs of cerebral inflammation and, in many cases, CSF pleocytosis and/or virus isolation. Extensive limb swelling Swelling of the limb, with or without redness, which: • extends from the joint above to the joint below the injection site, or beyond a joint (above or below the injection site), or • results in the circumference of the limb being twice the normal size. Faint See ‘Vasovagal episode’.
Guillain-Barré Syndrome (GBS) [diagnosis must be made by a physician] Acute onset of rapidly progressive, ascending, symmetrical flaccid paralysis, without fever at onset of paralysis and with or without sensory loss. Cases are diagnosed by cerebrospinal fluid (CSF) investigation showing dissociation between cellular count and protein content. Hypotonic–hyporesponsive episode (shock, collapse) The sudden onset of pallor or cyanosis, limpness (muscle hypotonia), and reduced responsiveness or unresponsiveness occurring after vaccination, where no other cause is evident such as a vasovagal episode or anaphylaxis. The episode usually occurs 1 to 48 hours after vaccination and resolves spontaneously.
Appendix 6 361
Appendices
Fever Only very high fever should be reported, eg. >40.5°C.
Injection site reaction (severe) Reaction (redness and/or swelling) at site of injection which: • persists for more than 3 days AND is associated with ongoing symptoms such as pain or an inability to use the limb (see ‘Brachial neuritis’ above), and • does not fulfil the case definition for extensive limb swelling (see ‘Extensive limb swelling’ above), or • requires hospitalisation. Intussusception [diagnosis must be made by a hospital physician] The invagination of a proximal segment of bowel into the distal bowel lumen. Lymphadenitis (includes suppurative lymphadenitis) Occurrence of either: • at least 1 lymph node, 1.5 cm in diameter or larger, or • a draining sinus over a lymph node. Meningitis [diagnosis must be made by a physician] Acute onset of major illness with fever and often neck stiffness/positive meningeal signs (Kernig, Brudzinski) and with CSF pleocytosis. Nodule A discrete or well demarcated soft tissue mass or lump that is firm and is at the injection site in the absence of abscess formation, warmth and erythema. Orchitis Swelling with pain and/or tenderness of testes. Osteitis Inflammation of the bone due to BCG vaccination. Osteomyelitis Proven bacterial infection of bone. Parotitis Swelling and/or tenderness of parotid gland or glands. Rash Severe or unusual rash. Screaming (persistent) The presence of crying which is continuous and unaltered for longer than 3 hours. Seizure Witnessed sudden loss of consciousness and generalised, tonic, clonic, tonicclonic, or atonic motor manifestations. • febrile seizures: with fever ≥38.5°C, • afebrile seizures: without fever, • syncopal seizures: syncope/vasovagal episode followed by seizure(s). 362 The Australian Immunisation Handbook 9th Edition
Sepsis Acute onset of severe, generalised illness due to bacterial infection and confirmed by positive blood culture. Subacute sclerosing panencephalitis [diagnosis must be made by a physician] Degenerative central nervous system (CNS) condition with laboratory confirmation of abnormal serum and CSF measles antibodies. Syncope See ‘Vasovagal episode’. Thrombocytopenia Platelet count <50 x 109/L. Toxic shock syndrome [diagnosis must be made by a physician] Abrupt onset of fever, vomiting, watery diarrhoea and shock within a few hours of vaccination as can be associated with other conditions listed here. Vaccine-associated paralytic poliomyelitis See ‘Acute flaccid paralysis’. Vasovagal episode (syncope, faint) Episode of pallor and unresponsiveness or reduced responsiveness or feeling light headed AND • occurring while vaccine being administered or shortly after (usually within 5 minutes), AND • bradycardia, AND
(See Table 1.5.1 to distinguish from anaphylaxis). Other severe or unusual events Any unusual event that does not fit into any of the categories listed above, but is of medical or epidemiological interest, should be reported with a detailed description of the clinical features. Report by telephone to State or Territory Health Department or notify by the blue card to ADRAC (see Section 1.5.2, Adverse events following immunisation). Note: The Brighton Collaboration is an international group considering definitions of adverse events following immunisation. Its website is: http://www.brightoncollaboration.org.
Appendix 6 363
Appendices
• resolution of symptoms with change in position (supine position or head between knees or limbs elevated).
Appendix 7: Glossary of technical terms Adjuvant a preparation which may be added to a vaccine to improve the immune response to that vaccine. ADT adult diphtheria and tetanus vaccine (also referred to as dT). Trade name used for diphtheria-tetanus vaccine previously made by CSL for use in adults. Adverse event following immunisation (AEFI) an unwanted reaction following administration of a vaccine, which may or may not be caused by the vaccine; adverse events may be at the site of injection, or may be a general illness or a general allergic reaction. Anaphylaxis a sudden and severe allergic reaction, which results in a serious fall in blood pressure and/or respiratory obstruction and may cause unconsciousness and death if not treated immediately. Attenuation the process of modifying a virus or bacteria to reduce its virulence (diseaseinducing ability) while retaining its ability to induce a strong immune response (immunogenicity). Bacteria microorganisms that are smaller than a blood cell but bigger than a virus; examples of bacterial infections are diphtheria, tetanus, pertussis, Hib and tuberculosis. BCG Bacillus of Calmette-Guérin, a vaccine that protects against tuberculosis. Carrier a person who has an infection which, although not necessarily causing symptoms, may still be active and may spread to others; the carrier state may last for years; examples of infections that can result in the carrier state are hepatitis B and typhoid. Conjugate some bacterial vaccines (eg. Hib and pneumococcal conjugate vaccines) are made from the chemical linking (conjugation) of a tiny amount of the ‘sugar’ (correctly known as the polysaccharide) that makes up the cell coat of the bacteria with a protein molecule, in order to improve the immune response to the vaccine. Contraindication a reason why a vaccine or drug must not be given. Corticosteroid a drug used to reduce inflammation and other immune responses.
364 The Australian Immunisation Handbook 9th Edition
dT diphtheria-tetanus vaccine for use in adults (ADT). DTP/DTPa a vaccine that protects against diphtheria, tetanus and pertussis (whooping cough). The DTP used in Australia and many other industrialised countries is DTPa, which contains an acellular pertussis component made of refined pertussis extracts instead of inactivated whole pertussis bacteria. The acronym DTPa, using capital letters, signifies child formulations of diphtheria, tetanus and acellular pertussis-containing vaccines, and denotes the substantially larger amounts of diphtheria toxoid and pertussis antigens in these formulations than in the adolescent/adult formulations. dTpa adolescent/adult formulation diphtheria-tetanus-acellular pertussis vaccine. dTpa contains substantially lower concentrations of diphtheria toxoid and pertussis antigens than the child formulations (which are signified by using all capital letters (DTPa)). Effectiveness the extent to which a vaccine produces a benefit in a defined population in uncontrolled or routine circumstances. Efficacy the extent to which a vaccine produces a benefit in a defined population in controlled or ideal circumstances.
Encephalopathy a general term to describe a variety of illnesses that affect the brain, including encephalitis. Endemic endemic infections are present all the time in a community. Epidemic epidemic infections are those that spread rapidly in a community; measles and influenza viruses are common causes of epidemics in Australia; small epidemics are often called outbreaks. Febrile related to a fever, as in febrile illness and febrile convulsions. HAV abbreviation for hepatitis A virus, the cause of hepatitis A, a common food-borne infection in travellers to developing countries.
Appendix 7 365
Appendices
Encephalitis inflammation of the brain.
HBsAg hepatitis B surface antigen; a marker in the blood that indicates that the person is a carrier of active hepatitis B virus infection. HBV abbreviation for hepatitis B virus, a virus that is spread in body fluids in various ways including blood-to-blood contact through sharing injection equipment, and through sexual intercourse. Hepatitis an inflammation of the liver; can be caused by viral infections. Hib Haemophilus influenzae type b; a bacterium that causes meningitis and other serious infections in young children. HIV human immunodeficiency virus, or the AIDS virus; people with HIV infection may have weakened immunity and need special vaccinations to protect them against other infections. Human papillomavirus a group of viruses, some of which have been associated with some forms of cervical cancer; some can also cause genital warts. Hypotonic-hyporesponsive episode (HHE) a rare adverse event which may follow some hours after DTPa vaccination; the child becomes pale, limp and unresponsive; the condition may last from a few minutes to hours but causes no long-term serious problems. Immunisation the process of inducing immunity to an infectious agent by administering a vaccine. Immunity the ability of the body to fight off certain infections; immunity can result from natural (‘wild’) infections or from vaccination. Immunogenicity the ability (or the degree) to which a particular substance, in this context a vaccine, may provoke an immune response. Immunoglobulin a protein extract from blood, sometimes called ‘antibody’, which fights off infection; injection of immunoglobulins provides temporary immunity against certain infections.
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Incubation period after a person is infected with bacteria or viruses, it often takes days or weeks for the infection to cause an obvious illness; the time between exposure to the infectious agent and development of the disease is called the incubation period. Infection an infection occurs when bacteria or viruses invade the body; if the body cannot fight the infection, it may cause an illness. Intradermal injection an injection into the surface layers of the skin; this is used for the administration of BCG, the tuberculosis vaccine. Intramuscular (IM) injection an injection into the muscle; vaccines are usually injected into a muscle of the upper outer thigh, or a muscle in the upper arm. IPV inactivated poliomyelitis vaccine; an injectable vaccine formerly known as Salk vaccine. Invasive disease this term is often used when talking about pneumococcal or meningococcal disease. This term means that the bacteria (or germs) have been found in the blood, spinal fluid or another part of the body which would normally be sterile (or germ free). Appendices
Jaundice yellow skin colour that may result from severe hepatitis. JE Japanese encephalitis; a viral encephalitis. MMR measles-mumps-rubella vaccine. MMRV measles-mumps-rubella-varicella vaccine. OPV oral poliomyelitis vaccine; also known as Sabin vaccine. This vaccine is no longer routinely used in Australia. Pandemic influenza a global epidemic that results when a new strain of influenza virus appears in the human population. It causes more severe disease in the population because there is little immunity to this new strain.
Appendix 7 367
Paracetamol a medicine that helps reduce fever; it may be given to minimise fevers following vaccination. Pertussis whooping cough, an illness caused by a bacterium, Bordetella pertussis. Polysaccharide a group of complex carbohydrates (sugars) which make up the cell coating present in some bacteria. Polyvalent vaccine a combination vaccine which protects against more than one disease; examples are DTPa and MMR. PRP-OMP a type of Hib vaccine. PRP-T a type of Hib vaccine. Rotavirus a virus that is a common cause of diarrhoea (and often vomiting as well) in young children. The diarrhoea can be severe in very young children, such that they may need intravenous fluids (ie. through a vein in the arm) in hospital. Rubella a viral illness, sometimes also known as German measles. Subcutaneous (SC) injection an injection into the tissue between the skin and the underlying muscle. Vaccination the administration of a vaccine; if vaccination is successful, it results in immunity. Vaccine a product often made from extracts of killed viruses or bacteria, or from live weakened strains of viruses or bacteria; the vaccine is capable of stimulating an immune response that protects against natural (‘wild’) infection. Varicella chickenpox, an infection caused by the varicella-zoster virus. Virus a tiny living organism, smaller than a bacterium, that can cause infections; measles, rubella, mumps, polio, influenza and hepatitis B are examples of viruses. Zoster an abbreviation for herpes zoster infection (also known as shingles); a painful rash and illness caused by the varicella-zoster (chickenpox) virus.
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Appendix 8: List of commonly used abbreviations ABL
Australian bat lyssavirus
ACIP
Advisory Committee on Immunization Practices
ACIR
Australian Childhood Immunisation Register
ADRAC
Adverse Drug Reactions Advisory Committee
AEFI
adverse event following immunisation
AFP
acute flaccid paralysis
AIDS
acquired immunodeficiency syndrome
anti-HBs
hepatitis B surface antibody
ATAGI
Australian Technical Advisory Group on Immunisation
BCG
Bacillus of Calmette-Guérin
BSE
bovine spongiform encephalopathy
CCM
cold chain monitor
CDT
diphtheria-tetanus vaccine for children (no longer in use)
cm
centimetre
CSF
cerebrospinal fluid
dT
diphtheria-tetanus vaccine for use in adults
DTPa child formulation diphtheria-tetanus-acellular pertussis vaccine
ELISA/EIA
enzyme-linked immunosorbent assay
GVHD
graft versus host disease
HAV
hepatitis A virus
HBIG
hepatitis B immunoglobulin
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCW
Healthcare worker
HepA
hepatitis A
HepB
hepatitis B
HHE
hypotonic-hyporesponsive episode
Hib
Haemophilus influenzae type b
HIV
human immunodeficiency virus
HPV
human papillomavirus
Appendix 8 369
Appendices
dTpa adolescent/adult formulation diptheria-tetanus-acellular pertussis vaccine
HRIG
human rabies immunoglobulin
HSCT
haematopoietic stem cell transplant
HZ
herpes zoster
IM
intramuscular
IMD
invasive meningococcal disease
IPD
invasive pneumococcal disease
IPV
inactivated poliomyelitis vaccine
ITP
idiopathic thrombocytopenia purpura
IU
international units
IV
intravenous
JE
Japanese encephalitis
kg
kilogram
ng
nanogram
μg
microgram
mg
milligram
mL
millilitre
mm
millimetre
4vMenPV
meningococcal polysaccharide vaccine (tetravalent)
MenCCV
meningococcal C conjugate vaccine
MMR
measles-mumps-rubella
MMRV
measles-mumps-rubella-varicella
MS
multiple sclerosis
NHIG
normal human immunoglobulin
NHMRC
National Health and Medical Research Council
NIP
National Immunisation Program
OMP
outer membrane protein
OPV
oral poliomyelitis vaccine (no longer in use)
PHN
post-herpetic neuralgia
PI
product information
7vPCV
7-valent pneumococcal conjugate vaccine
PPD
purified protein derivative
23vPPV
23-valent pneumococcal polysaccharide vaccine
PRP
polyribosylribitol phosphate
SC
subcutaneous
370 The Australian Immunisation Handbook 9th Edition
SIDS
sudden infant death syndrome
SOT
solid organ transplant
TB
tuberculosis
TGA
Therapeutic Goods Administration
TIG
tetanus immunoglobulin
VAPP
vaccine-associated paralytic poliomyelitis
vCJD
variant Creutzfeldt-Jakob disease
VV
varicella vaccine
VZV
varicella-zoster virus
WHO
World Health Organization
ZIG
zoster immunoglobulin
Appendices
Appendix 8 371
Appendix 9: Dates when vaccines became available in Australia Public sector Australia
Vaccine
Exceptions
1945-46
Tetanus toxoid
1953
DTPw (diphtheria/tetanus/pertussis whole cell)
1956 May
Poliomyelitis (SALK)
1966 Sep
Poliomyelitis (OPV) (oral Sabin)
1969
Measles
1971 Feb
Rubella (adolescent girls)
1975
CDT (child diphtheria/tetanus)
1981 Jul
Mumps
1982
ADT (adult diphtheria/tetanus)
1983
Measles/Mumps
1986
CDT-DTP 4th dose introduced (1st pertussis booster)
1987 Nov
NT 1988 Jan SA 1996
Hepatitis B (for at-risk infants)
1989
SA 1996
MMR (infant dose)
1992 May
Hib (for children 18 months to 5 years of age)
1993 Apr
Hib (all infants born from Feb 1993)
1993 Jul
Hepatitis A (Havrix) (unfunded)
1994
MMR (males and females in Grade 6)
1995
CDT-DTP 5th dose introduced (2nd pertussis booster)
1997 Oct
Tas 1997 Oct Qld 1997 Dec
Influenza (program for over 65s)
1997 1998 Jan
DTP acellular (Infanrix) boosters for infants aged 18 months and 4–5 years to replace DTP 4th and 5th doses
Qld 1998 Mar Tas 1998 Mar NT 1998 Apr NSW 1999 SA 1999
Hepatitis B (adolescent dose)
1998
MMR (Primary School program)
1998
MMR/OPV 4-year-old booster (DTP, MMR, OPV) program before commencing school
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Public sector Australia
Pneumococcal polysaccharide 23-valent vaccine (over 65s) (unfunded)
1998 1999 Feb
Vaccine
Exceptions
NT 1997 Aug SA 1997 Aug Qld 1999 Apr
DTPa (Infanrix) for infants aged 2, 4 and 6 months
1999
MMR (18–30-year-old program)
2000
COMVAX (Hep B/Hib) available
2000
Adult diphtheria/tetanus 10-yearly boosters ceased
2000 May
NT 1990 Aug
Hepatitis B (universal infant dose) Hepatitis B booster doses no longer recommended
2001
Pneumococcal conjugate 7-valent vaccine (for Aboriginal and Torres Strait Islander children and all children in Central Australia only)
2001 Dec
Meningococcal C conjugate vaccine (Meningitec) (unfunded)
2001
Varicella (chickenpox) (unfunded)
2001
HibTITER vaccine ceased
2002 Aug
Meningococcal C conjugate vaccine (NeisVac-C) (unfunded)
2002 Oct
Meningococcal C conjugate vaccine (Menjugate) (unfunded)
2003 Sep
DTPa 4th dose at 18 months of age ceased
2003 Jan
Meningococcal C conjugate vaccine (at 12 months of age and catch-up until May 2007 for 1–19-year-olds)
2003 Sep
Pneumococcal conjugate 7-valent vaccine (for children with medical risks <5 years of age)
2004 Jan
dTpa (Boostrix) for 15–17 years (Year 10 school program) replaced ADT
2004 Sep
Combination vaccines with 4, 5 and 6 antigens available
2005 Jan
Pneumococcal conjugate 7-valent vaccine (for infants aged 2, 4 and 6 months and medical at-risk children plus catch-up in 2005 for children born between 1 January 2003 and 31 December 2004)
2005 Jan
Pneumococcal polysaccharide 23-valent vaccine (funded for adults aged >65 years)
2005 Nov
Inactivated polio (IPV) vaccine (given in combination with DTPa scheduled at 2, 4 and 6 months and 4 years in place of OPV)
Appendix 9 373
Appendices
2000
Public sector Australia
Vaccine
Exceptions
2005 Nov
Hepatitis A vaccine (for all Indigenous children aged ≤5 years living in Queensland, the Northern Territory, Western Australia and South Australia)
2005 Nov
Varicella vaccine scheduled at 18 months and 13 years of age
2007 Apr
Human papillomavirus vaccine (for girls aged 12–13 years plus a 2-year catch-up period to end of June 2009 for girls aged 14–26 years)
2007 May
NT 2006 Oct
Rotavirus vaccine (for all children born from 1 May 2007)
374 The Australian Immunisation Handbook 9th Edition
Appendix 10: Summary table – procedures for a vaccination encounter This table summarises the information provided in Chapters 1.3–1.5 and provides an overview of the requirements before, during and after a vaccination encounter. This table can also be photocopied and used as an audit tool, if required. Pre-vaccination procedures (Chapter 1.3)
• Prepare anaphylaxis response kit: check availability of the protocols, equipment and drugs necessary for the management of anaphylaxis, before each vaccination session. (1.3.1) • Only vaccine that has been transported and stored at the correct cold chain temperature of between +2°C to +8°C should be administered. Follow the National Vaccine Storage Guidelines: Strive for 5. (1.3.2) • Perform pre-vaccination screening to determine the person’s medical fitness for vaccination, and possible need for additional vaccines. Any concern about the person’s eligibility for vaccination must be discussed with a medical practitioner, paediatrician or public health physician with expertise in vaccination (see Appendix 1 for phone numbers for State/ Territory health authorities.) If a person’s health status or suitability for vaccination cannot be determined, defer vaccination and seek advice. (1.3.4)
• Obtain valid consent from the person to be vaccinated, or that person’s parent/carer: this includes providing the appropriate information about the risks and benefits of vaccination and the risks of vaccine-preventable diseases. (Written vaccination information can be provided to parents as early as the last trimester of pregnancy or at the well-baby check.) Advise the person to be vaccinated, or the parent/carer of a child, of the incidence of common adverse events that may occur following vaccination. This advice and the parent’s consent should be documented. It is important that the parent be given a contact phone number in case a significant adverse event occurs within 24 to 48 hours of the vaccination. (1.3.3)
Appendix 10 375
Appendices
• Review the individual’s vaccination history and, based on documented evidence, decide on the appropriate vaccine(s) to be administered. If the recommended vaccination schedule for age has not been completed, plan and document a ‘catch-up’ schedule and discuss this with the person or parent/carer. (1.3.5)
Administration of vaccines (Chapter 1.4)
• Follow standard occupational health and safety guidelines to minimise the risk of needle-stick injury. (1.4.1) • Depending on the vaccine(s) that are to be administered, and the age and size of the person to be vaccinated, decide on the appropriate injection site and route, and the injection equipment required (ie. syringe size, needle length and gauge) as recommended in the current NHMRC immunisation guidelines. Use a new, sterile, disposable syringe and needle for each injection. (1.4.2–1.4.6) • Prepare the vaccine (check whether the vaccine is injectable or oral): • Check each individual dose (ie. ampoule, pre-filled syringe or vial) to see that the expiry date has not lapsed, and that there is no particulate matter or colour change in the vaccine. • Reconstitute the vaccine as needed immediately before administration, preferably using a separate needle to draw up the diluent or as recommended by the manufacturer. Use only the diluent supplied with the vaccine. Mix fully, and draw up the vaccine. • Locate the injection site by fully uncovering the appropriate limb(s) and visualising the correct anatomical markers. Position the limb for vaccination so that the muscles are relaxed (usually a flexed position). Keep the limb as immobile as possible without using excessive restraint. Ensure that the skin is visibly clean. (1.4.7–1.4.8) • Administer the vaccine(s) using the recommended technique (IM, SC or Oral). For injectable vaccines, follow the recommendations for administering more than 1 vaccine into a limb during the encounter. Do not inject oral vaccines. Remove the needle briskly after IM injection. (1.4.5, 1.4.9)
376 The Australian Immunisation Handbook 9th Edition
Post-vaccination procedures (Chapter 1.5)
• Immediate after-care • Dispose of used needles, syringes and vaccine vials/ampoules in accordance with standard infection control guidelines. • Cover the puncture wound quickly with a dry cotton wool ball and hypoallergenic tape as needed. Apply gentle pressure for 1–2 minutes but do not massage. • Remove the cotton wool and tape after a few minutes. • Continue using comfort and distraction techniques to alleviate any distress and pain. Note: paracetamol is not used routinely at the time of vaccination but may be recommended as required for fever or pain. (1.5.1) • Managing adverse reactions, documentation and follow-up • Remind the vaccinated person, or the parent/carer of a child, about the possible common adverse events following immunisation and how to manage them. It is preferable to provide this as written information (see inside back cover of this Handbook). • Before departure, inform the person or the parent/carer, preferably in writing, of the date of the next scheduled vaccination.
• Take the opportunity to check the vaccination status of other family members (as appropriate) and provide (or refer) for catch-up vaccination. • Document the details of vaccination:
(i) on a record to be retained by the person, or the parent/carer of a child,
(ii) on the relevant clinical record (electronic or hard-copy), and
(iii) on an ACIR (or equivalent) encounter form, for children <7 years of age.
• Remind the vaccinated person, or the parent/carer of a child, to promptly report any significant adverse event following immunisation to the vaccinator, so that it can be reported to either the Adverse Drug Reactions Advisory Committee (TAS) or to the relevant State/Territory health authorities (ACT, NSW, NT, QLD, SA, VIC and WA). (1.5.2–1.5.4)
Appendix 10 377
Appendices
• The vaccinated person and/or parent/carer should be advised to remain in a nearby area for a minimum of 15 minutes after the vaccination. The area should be close enough to the vaccinator, so that the child/person can be observed and medical treatment can be readily obtained if needed.
Index A
abattoir workers, 107, 258, 260 abbreviations list, 369–71 ABL see Australian bat lyssavirus (ABL) infection Aboriginal and Torres Strait Islander people, 70–4 children and infants, BCG vaccine, 70–1, 300 catch-up, 32, 34–5 Haemophilus influenzae type b, 71, 132, 135 hepatitis A, 72, 144 pneumococcal disease, 34–5, 72, 240–1, 243, 247 hepatitis A, 142 influenza, 190 Japanese encephalitis (JE), 73 pneumococcal disease, 73, 240–1, 246 service delivery to, 73–4 tuberculosis, 297 ACIR, 67 see also Australian Childhood Immunisation Register Adacel, 42, 126, 230, 290 see also dTpa Adacel Polio, 42, 126, 230, 254, 290 see also dTpa-IPV additives in vaccines, 341, 356–7 adjuvants, 341, 356 administration see dosage and administration adoption of children overseas, 159 adrenaline, 64 ADT Booster, 42, 126, 290 see also dT; diphtheria; tetanus Adverse Drug Reactions Advisory Committee (ADRAC), 65 adverse events following immunisation (AEFI), 58–66 cholera vaccine, 123 definition(s) of, 360–3, 364 diphtheria-containing vaccine, 128 Haemophilus influenzae type b vaccine, 137 hepatitis A vaccine, 146
hepatitis B vaccine, 162–3 how to report, 64–5 human papillomavirus (HPV) vaccine, 173–4 immunoglobulins, 177–81 in children and infants, 84 influenza vaccine, 193–4 Japanese encephalitis (JE) vaccine, 199–200 management of, 61–4 measles-containing vaccine, 208–9 meningococcal vaccine, 220 mumps-containing vaccine, 225 pertussis-containing vaccine, 234–5 pneumococcal vaccine, 247, 249 poliomyelitis vaccine, 255 Q fever vaccine, 262–3 rabies vaccine, 118 reporting, 64–5 rotavirus vaccine, 269, 272–3 rubella vaccine, 280–1 smallpox vaccine, 285–6 tetanus-containing vaccine, 295 tuberculosis vaccine, 301 typhoid vaccine, 307 varicella vaccine, 317–8 yellow fever vaccine, 327 Afghanistan, 77 Africa avian influenza, 184 cholera, 120 hepatitis B, 77, 150 measles, 202 meningococcal disease, 79, 214 poliomyelitis, 251 rabies, 110, 115 rubella, 278 yellow fever, 75, 79, 322, 324, 326 aged see older people agricultural college staff and students, 107, 258, 260 allergy, 205, 279, 316, 350–1 see also egg protein allergy aluminium in vaccines, 341, 356 ambulance personnel, 105, 159, 192 Americas cholera, 120 poliomyelitis, 251
378 The Australian Immunisation Handbook 9th Edition
rabies, 110, 115, 119 rubella, 278 tuberculosis, 297 typhoid, 304 aspirin therapy, 191, 207, 318 asplenia (functional or anatomical), 16, 19, 36, 87, 93, 100–1, 136, 138, 213, 218, 244, 246–7 asthma, 61, 191, 350, 353 Australian bat lyssavirus (ABL) infection, 107, 110–9 see also rabies post-exposure prophylaxis, vaccine, 42, 114–6 rabies immunoglobulin (HRIG), 116–7 pre-exposure prophylaxis, 112–4 Australian Childhood Immunisation Register (ACIR), 22–3, 67–9, 202, 332 Australian Red Cross Blood Service (ARCBS), 176, 319 Australian Standard Vaccination Schedule (ASVS), 3 Australian Technical Advisory Group on Immunisation (ATAGI), 334 autism, 61, 209, 352 autistic spectrum disorder, 209, 352 autoimmune diseases, 101–2 see also impaired immunity, individuals with Avaxim, 42, 140 see also hepatitis A (HAV) avian influenza, 184, 186–7 azithromycin, 235–6, 238, 239
B
babies (neonates) see also preterm babies bronchopulmonary dysplasia (BPD), 182 hepatitis B, 156–7, 162, 163 influenza, 185 measles, 211 pertussis, 236, 237, 238 respiratory syncytial virus (RSV), 182 tetanus, 288, 289 tuberculosis, 300 varicella, 309 bacteraemia, 240 Bali Japanese encephalitis (JE) virus in, 198
Index 379
Index
rabies, 110, 115 rubella, 278 yellow fever, 75, 322, 323, 324 anaesthesia, 104 anaphylactoid see anaphylaxis; contraindications anaphylaxis, 61–4 see also contraindications adrenaline use, 64 differentiation from vasovagal episode, 62 management of, 63–4 pre-vaccination screening, 17 signs of, 62 anaphylaxis response kit, 8, 375 animals human rabies from, 110–1 occupational risks and, 107 Q fever from, 258, 260 anthrax, 3 antibiotics diphtheria, 128 false contraindications and, 21, 348 haematopoietic stem cell transplantation and, 97 Haemophilus influenzae type b, 137–8 manufacturing residuals, 341, 357 meningococcal disease, 220 pertussis, 235–9 smallpox, 285 splenic dysfunction and, 101 tetanus, 294 typhoid vaccine, oral and, 83, 305, 307 antibody deficiency disorders, 180 anti-HAV IgG, 139, 142 anti-HAV IgM, 139, 142, 146 anti-HBs, 31, 90, 149, 153, 157, 158, 160–1 armed forces personnel, 106, 159, 297, 306 see also travellers Asia avian influenza, 184 cholera, 120 hepatitis B, 77, 150 Japanese encephalitis (JE), 75, 78, 82, 195, 197–8, 199 measles, 358 meningococcal disease, 214
rabies in, 119 bats see Australian bat lyssavirus (ABL) infection BCG vaccine, 298 see also tuberculosis bleeding disorders, 104, 159, 178, 207–8 blood and organ donors, 150, 159, 175 blood products/transfusions, 102–3, 159, 206, 271, 280, 317 live vaccines and, interval between, 102–3 body-piercers, 107, 159 bone marrow transplantation see haematopoietic stem cell transplantation (HSCT) boosters and revaccination diphtheria, 127, 128, 129 Haemophilus influenzae type b, 134, 136, 138 hepatitis A, 142, 145 hepatitis B, 156, 161–3 human papillomavirus (HPV), 170 Japanese encephalitis (JE), 198, 200 meningococcal disease, 218 pertussis, 228, 231–3, 238, 346–7 pneumococcal disease, 243, 246, 247 poliomyelitis, 255 Q fever, 262 rabies, 113 tetanus, 292–4 typhoid, 145, 306 Boostrix, 42, 126, 230, 291 see also dTpa Boostrix-IPV, 42, 126, 230, 254, 291 see also dTpa-IPV Bordetella pertussis see pertussis botulism antitoxin, 181 Botulism Immune Globulin (BIG), 181 bovine spongiform encephalopathy (BSE), 354 see also mad cow disease brachial neuritis, 61 see also adverse events following immunisation (AEFI) breakthrough varicella, 310–1, 312–3 breastfeeding and lactation, 21, 89, 174 see also pregnancy and vaccination cholera vaccine and, 123 human papillomavirus (HPV) vaccine and, 174 meningococcal vaccine and, 222 Q fever vaccine and, 263
rotavirus vaccine, 268 rubella vaccine and, 280 smallpox vaccine and, 285 bronchopulmonary dysplasia (BPD), 182 BSE see bovine spongiform encephalopathy
C
cancer chemotherapy, 92–4 cardiac disease, 190, 246, 247 cardiovascular disease, 122 carers, 106 carriers hepatitis B, 149–50, 151, 156, 157, 158 meningococcal disease, 213, 220–1 typhoid, 308 catch-up, 21–38 children aged <8, guidelines, 31–2 Haemophilus influenzae type b, 33 minimum age, 30 minimum interval, 29 number of doses required, 28 pneumococcal vaccination, 34–6 worksheet, 27 children aged ≥8, adolescents and adults, 37–8 immigrants, 108 ceftriaxone, 137, 221 CERVARIX, 42, 169 see also human papillomavirus (HPV) cervical cancer, 164, 167–8 chemoprophylaxis see antibiotics chemotherapy, 92–4 chickenpox see varicella childcare facilities Haemophilus influenzae type b, 138 hepatitis A, 147 hepatitis B, 160 measles, 178 pertussis, 232, 236, 237, 238 rubella, 279 childcare workers, 87, 104, 105, 144, 147, 160, 232, 313, 346 children and infants asplenia, 100–1 bleeding disorders, 104 catch-up for, 22–3, 25–30, 33–8
380 The Australian Immunisation Handbook 9th Edition
hepatitis B-containing, 152 measles, mumps and rubella, 203, 224, 277 pertussis-containing, 229–30 poliomyelitis-containing, 253–4 tetanus-containing, 289–91 typhoid-containing, 304 communicability period see infectious period communicable disease control, telephone contact details for, 333 compatibility see interchangeability of vaccines compulsory vaccination, 347 COMVAX, 31, 42, 71, 133 see also Haemophilus influenzae type b concurrent vaccination see simultaneous administration congenital rubella syndrome (CRS), 274–5, 278 congenital varicella syndrome, 309 conjugate vaccines see Haemophilus influenzae type b; meningococcal disease; pneumococcal disease consent, 12–4, 375 contacts (disease) diphtheria, 128–9 Haemophilus influenzae type b, 137–8 hepatitis A, 146–7 hepatitis B, 158 measles, 209–10, 211 meningococcal disease, 213, 218, 219, 220–1 pertussis, 232, 237–8 rotavirus, 271 varicella, 314, 318 contraindications, 14, 20, 60, 347–51 anaphylaxis and, 20, 347–8 BCG vaccine, 300 cancer patients, 92–4 cholera vaccine, 123 corticosteroids, 92, 118, 205, 207, 348–9 diphtheria-containing vaccine, 128 false, 21 Haemophilus influenzae type b vaccine, 137 hepatitis A vaccine, 146
Index 381
Index
consent, 12–3 deceased, notification to ACIR of, 68 HIV-infected, 99 injection sites, 45–6, 345 living overseas, 68 multiple injections, 24, 56–7, 345 positioning for vaccination, 47–51 vaccination after AEFI, 84 with intercurrent illnesses, 348 cholera, 42, 78, 120–3 adverse events, 123 contraindications, 123 dosage and administration, 122 precautions, 123 pregnancy, 87, 123 recommendations, 122 chronic conditions and vaccination, 350 chronic graft-versus-host disease (cGVHD), 97 chronic inflammatory demyelinating polyneuropathy, 180 hepatitis A, 144 hepatitis B, 150, 158 liver disease, 144, 145, 159 neurological conditions see neurological disease renal disease, 90, 191, 246, 247 respiratory conditions, 190–1, 246, 247 cidofovir, 286–7 ciprofloxacin, 231 clarithromycin, 235–6, 239 Clostridium tetani see tetanus CMV Immunoglobulin-VF (human), 182 see also cytomegalovirus; immunoglobulins coadministration see simultaneous administration cold chain, 8–12 combination vaccines diphtheria-containing, 125–6 dT, 126, 290 DTPa-containing, 125–6, 152, 134, 253, 229–30, 289–91 dTpa-containing, 126, 254, 290–1, Haemophilus influenzae type b-containing, 134 hepatitis A-containing, 141
hepatitis B vaccine, 162 HIV-infected individuals, 20, 99, 349 human papillomavirus (HPV) vaccine, 173 immunoglobulins, 178, 180 individuals with impaired immunity, 91, 349 influenza vaccine, 193 Japanese encephalitis (JE) vaccine, 199 live attenuated vaccines and, 20–1, 91 measles-containing vaccine, 205–6 meningococcal vaccine, 219 mumps-containing vaccine, 205–6 pertussis-containing vaccine, 233, 348 pneumococcal vaccine, 248–9 poliomyelitis vaccine, 255 pregnancy, 85, 86, 206 pre-vaccination screening for, 17–20 Q fever vaccine, 262 rabies vaccine, 117 rotavirus vaccine, 270 RSV immunoglobulin, 182 rubella vaccine, 279–80 smallpox vaccine, 285 solid organ transplant (SOT) recipients, 94–6 tetanus-containing vaccine, 295 typhoid vaccine, 307–8 varicella vaccine, 316–7 yellow fever vaccine, 325–6 correctional facility inmates, 108, 159 correctional facility staff, 106, 159, 192 corticosteroids, 16, 20, 92, 118, 205, 207, 246, 279, 300, 317, 348–9 Corynebacterium diphtheriae see diphtheria coughing illness see pertussis Creutzfeldt-Jakob disease (vCJD), 354 see also mad cow disease; bovine spongiform encephalopathy (BSE) cystic fibrosis, 190, 246 cytomegalovirus see also immunoglobulins CMV immunoglobulin, 181–2
D
day-care see childcare facilities deltoid area, 54–5 see also injection site dentists and dental students, 105, 145, 159 Department of Health and Ageing, 334, 359 diabetes, 122, 191, 246, 247, 354 diarrhoea, 60, 62, 63, 78, 122, 123, 270, 273, 307, 308 diphtheria, 124–30, 358 see also DT; dT; dTpa; DTPa adverse events, 128 contraindications, 128 diphtheria antitoxin, 129 dosage and administration, 127 public health management, 128–9 pregnancy, 87, 129 recommendations, 127–8 variations from product information, 129–30 diplomats see travellers distraction techniques, 43 doctors see healthcare workers (HCW) dosage and administration, 39–57, 375–7 adrenaline, 64 BCG vaccine, 298–9 cholera vaccine, 122 diphtheria-containing vaccine, 127 documentation, 66, 377 Haemophilus influenzae type b, 135, 137–8 hepatitis A vaccine, 142–3 hepatitis B vaccine, 153–62 hepatitis B vaccine accelerated schedule, 156 human papillomavirus (HPV) vaccine, 171 immunoglobulins, 146, 163, 176, 178, 179, 182, 183, 210–2, 282, 294–5, 319 influenza vaccine, 189–90 injection sites, 45–6, 51–2 Japanese encephalitis (JE) vaccine, 197 measles-containing vaccine, 203, 210–2 meningococcal vaccine, 217–8 multiple injections, 56–7
382 The Australian Immunisation Handbook 9th Edition
mumps-containing vaccine, 224 pertussis-containing vaccine, 231 pneumococcal vaccine, 243 poliomyelitis vaccine, 254 Q fever vaccine, 260 rabies immunoglobulin (HRIG), 112, 116 rabies vaccine, 112, 115–7 rotavirus vaccine, 268 rubella vaccine, 278 smallpox vaccine, 284 tetanus-containing vaccine, 291 travellers, 76, 80–1, 82–3 typhoid vaccine, 305–6 varicella vaccine, 312, 320 yellow fever vaccine, 324 drug users see injecting drug users Dryvax, 283 see also smallpox dT, 38, 81, 126–7, 292–4 DT (CDT vaccine), 127, 291, 339 dTpa, 38, 81, 96, 98, 125, 126–7, 229, 290 DTPa-containing vaccines, 96, 98,125, 126–7, 229, 290 catch-up, 31 DTPa-hepB-IPV, 125, 152, 229, 253, 290 DTPa-hepB-IPV-Hib, 125, 134, 152, 230, 253, 289 DTPa-IPV, 125–6, 229, 253 290 dTpa-IPV, 126, 230, 254, 290 Dukoral, 42, 121, 122 see also cholera
E
F
fainting see vasovagal episodes farmers, 107, 260 Far North Queensland and Torres Strait Islands, 106, 195, 196, 198 febrile convulsion, 208, 234, 249 febrile illness, acute, 17, 123, 300, 348 febrile seizure see febrile convulsion fetus see pregnancy and vaccination fever, 59–60, 85, 199, 207–8, 220, 223, 234, 249 flu see influenza Fluad, 42, 187, 189 see also influenza Fluarix, 42, 187, 189, 194 see also influenza Fluvax, 42, 187, 189 see also influenza Fluvirin, 42, 187, 189, 194 see also influenza food-handlers, 120, 147, 303, 308 formaldehyde, 341, 357 frequently asked questions (FAQ), 344–59 funeral industry workers see embalmers
Index 383
Index
egg protein allergy, 117, 193, 194, 207–8, 262, 325, 327, 341, 348, 350–1 elderly people see older people embalmers, 107, 159, 300 emergency workers, 106, 159, 192 encephalitis, 75, 201, 225, 286–7, 318, 327, 365 see also Japanese encephalitis (JE) endemic diseases see also epidemic diseases cholera, 120, 122 hepatitis A, 78, 144, 147 hepatitis B, 156, 159 Japanese encephalitis (JE), 195, 198 measles, 201, 205 poliomyelitis, 252, 255 rabies, 78, 110, 111, 113, 115, 117
typhoid, 78, 303–4, 305, 306 yellow fever, 79, 322–3, 324–5, 326 Engerix-B, 42, 151, 156, 340, 343 see also hepatitis B (HBV) epidemic diseases see also endemic diseases influenza, 184–6 Japanese encephalitis (JE), 195 meningococcal disease, 214, 219 pertussis, 227–8 rubella, 274 yellow fever, 323–4 epilepsy see neurological disease equipment for vaccination, 39–41 erythromycin, 235–6, 237, 238 essential service providers, 106, 159, 192 Europe avian influenza, 184 diphtheria, 128 poliomyelitis, 251 rabies, 110 tuberculosis, 297
G
GARDASIL, 42, 169 see also human papillomavirus (HPV) gastroenteritis, 265–6, 270 see also rotavirus gelatin, 341, 356 General Practice Immunisation Incentive (GPII) scheme, 69, 332 genital warts, 164, 168, 171 global epidemiology polio eradication, 252 smallpox eradication, 283 tuberculosis, 297 glossary of technical terms, 364–8 graft-versus-host disease (GVHD), 97, 98 Guillain-Barré Syndrome (GBS), 16, 18, 162, 180, 193–4, 361
H
haematological malignancy, 93, 240, 246, 247 haematopoietic stem cell transplantation (HSCT), 97–8, 137, 138 haemodialysis patients, 158 haemoglobinopathy, 191, 246 Haemophilus influenzae type b, 131–8 Aboriginal and Torres Strait Islander children, 71, 132, 135 adverse events, 137 asplenia (functional or anatomical), 101, 136 catch-up, 31, 33 contraindications, 137 dosage and administration, 135 haematopoietic stem cell transplantation, 97, 137 pregnancy, 87, 138 preterm babies, 31, 90, 136 public health management, 137–8 recommendations, 135–7 variation from product information, 138 Hajj, 79, 219 HAV see hepatitis A (HAV) Havrix, 42, 140, 146 see also hepatitis A (HAV) Havrix Junior, 42, 140 see also hepatitis A (HAV)
hay fever, 350 HBcAg, 149 HBeAg, 149 HbOC, 133, 135 see also Haemophilus influenzae type b HBsAg, 149, 150, 157, 162 HBV see hepatitis B (HBV) H-B-VAX II, 42, 151 see also hepatitis B (HBV) healthcare workers (HCW), 105, 144, 145, 159, 160, 161, 162, 163, 204, 221, 232, 237–8, 255, 279, 281, 300, 313, 315–6, 321, 346 hepatitis A (HAV), 72, 78, 105, 106, 107, 139–48 adverse events, 146 contraindications, 146 dosage and administration, 142–3 immunoglobulin, 146, 177 pregnancy, 88, 148 public health management, 146–7 recommendations, 143–5 hepatitis B (HBV), 77, 135, 144, 149–63, 353 adverse events, 162–3 catch-up, 31, 38 contraindications, 162 dosage and administration, 153–6 immunoglobulin, 151, 157, 163 non-responders, 160–1 post-vaccination serology testing, 160 pregnancy, 88, 163 preterm babies, 31, 90 variation from product information, 163 hepatitis B immunoglobulin (HBIG), 151, 157, 163, 176 see also hepatitis B (HBV) Hepatitis B Immunoglobulin-VF, 163 see also hepatitis B (HBV) herpes zoster (HZ) see zoster Hib see Haemophilus influenzae type b Hiberix, 42, 31, 133, 134 see also Haemophilus influenzae type b Hib (HbOC), 133, 135 see also Haemophilus influenzae type b Hib (PRP-D), 133 see also Haemophilus influenzae type b
384 The Australian Immunisation Handbook 9th Edition
Hib (PRP-OMP)-hepB, 133 see also Haemophilus influenzae type b Hib (PRP-T), 133, 134 see also Haemophilus influenzae type b Hirschsprung’s disease, 270 HIV-infected individuals, 99–100, 122, 146, 158, 191, 199, 205, 206, 349–50 Hodgkin’s disease, 92, 93, 205, 247, 279, 302, 317 see also lymphoma homeless people, 192 homeopathic immunisation, 359 homosexual men see sexual contact HPV infection see human papillomavirus (HPV) human diploid cell vaccine (HDCV), 42, 111, 117, 118, 119 see also rabies human immunoglobulin see immunoglobulins human papillomavirus (HPV), 59, 164–74 adverse events, 173–4 contraindications, 173 dosage and administration, 171 males, 173 precautions, 173 pregnancy, 88, 174 recommendations, 171–3 human rabies immunoglobulin (HRIG), 112, 114–7, 176 see also rabies hyperimmune globulin, 88, 102 hypotonic-hyporesponsive episode (HHE), 233, 235 HZ see zoster
I
Index 385
Index
immigrants, 22, 75, 108 hepatitis B, 150 rubella, 278 immune thrombocytopenia, 180 see also bleeding disorders Immunisation History Statements, 22, 68 immunocompromised see impaired immunity, individuals with immunodeficient see impaired immunity, individuals with immunoglobulins, 102–3, 175–83 see also normal human immunoglobulin (NHIG) adverse events,
intramuscular NHIG, 178–9 intravenous NHIG, 180 availability, 176 botulism antitoxin, 181 cytomegalovirus immunoglobulin, 181–2 dosage and administration, 177, 179 normal human immunoglobulin (NHIG), 175, 176–7, 179 prophylaxis, 177–8 recommendations, intramuscular NHIG, 177–8 intravenous NHIG, 180 respiratory syncytial virus immunoglobulin, 182–3 specific diseases and, 175, 181 hepatitis A, 146, 177 hepatitis B, 151, 157, 163, 177 measles, 177, 210 rabies (HRIG), 112, 114–7, 176 rubella, 280 smallpox, 286–7 tetanus, 294–5 varicella, 178, 317 zoster immunoglobulin (ZIG), 178, 309, 319–20 immunosuppressed see impaired immunity, individuals with immunosuppressive agents, 118, 205, 279, 300, 317 Imogam Rabies, 112 see also rabies impaired immunity, individuals with, 90–2, 349 cholera, 122, 123 contacts of, 20, 91, 192, 209, 271, 285, 308, 313, 314–5, 320, 321 Haemophilus influenzae type b, 132 hepatitis B, 158, 160, 161 human papillomavirus (HPV), 173 immunoglobulins, 178, 180 influenza, 90, 91, 92, 191 Japanese encephalitis (JE), 199 measles, 91, 205, 211 mumps, 91 pneumococcal disease, 90–1, 240, 247 rotavirus, 266, 271 rubella, 91, 279–80 smallpox, 91
tuberculosis, 91, 298 typhoid, 91 varicella, 91, 309, 316–7 yellow fever, 91, 326 zoster (herpes zoster) (HZ), 329 inactivated poliomyelitis vaccine (IPV), 42, 77, 253–4 see also poliomyelitis inactivated vaccines, 87–8 cholera, 121 diphtheria-containing, 125–6 dT, 126, 290 DTPa-containing, 125–6, 152, 134, 253, 229–30, 289–91 dTpa-containing, 126, 254, 290–1, Haemophilus influenzae type b-containing, 134 hepatitis A-containing, 141 human papillomavirus (HPV), 169 influenza, 187–8 Japanese encephalitis (JE), 196 meningococcal, 215, 216 pertussis-containing, 229–30 pneumococcal, 241, 242 poliomyelitis-containing, 253–4 rabies, 111 typhoid, polysaccharide vaccine, 304 incomplete dose see interruption to a vaccination; regurgitation of vaccine India poliomyelitis, 251, 252 typhoid, 304 Indigenous people see Aboriginal and Torres Strait Islander people Indonesia JE virus, 198 poliomyelitis, 252 rabies, 119 Infanrix hexa, 42, 125, 134, 152, 230, 253, 289 see also DTPa-hepB-IPV-Hib Infanrix-IPV, 42, 125, 230, 254, 290 see also DTPa-IPV Infanrix Penta, 42, 125, 152, 229, 253, 290 see also DTPa-hepB-IPV infants see children and infants infectious period hepatitis A, 146 measles, 201 pertussis, 235–6
varicella, 309 inflammatory bowel disease, 61, 122, 209, 352–3 influenza, 72–3, 77, 184–94, 354 adverse events, 193–4 contraindications, 193 dosage and administration, 189–90 precautions, 193 pregnancy, 88, 192, 194 preterm babies, 90 recommendations, 190–3 variation from product information, 194 Influvac, 42, 187 see also influenza injecting drug users, 109, 139, 144, 145, 158, 293 injection site nodules, 60, 356 see also adverse events following immunisation (AEFI) injection site, 45–6, 51–5 see also dosage and administration; intradermal injections; intramuscular injections; subcutaneous injections injection technique, 42, 44–5 see also dosage and administration; intradermal injections; intramuscular injections; subcutaneous injections intellectually disabled people, 144, 145, 159 interchangeability of vaccines Haemophilus influenzae type b, 31, 136 hepatitis A, 141–2 hepatitis B, 161 poliomyelitis, oral and inactivated, 255 rotavirus, 273 interferon-gamma release assays, 302 interruption to a vaccination, 25 see also regurgitation of vaccine intradermal injections, 113–4 Intragam P, 179, 180 see also immunoglobulins intramuscular injections, 42, 44–55 intussusception (IS), 272, 362 invasive pneumococcal disease (IPD), 72, 240–1, 246, 247 IPOL, 42, 253 see also poliomyelitis
386 The Australian Immunisation Handbook 9th Edition
J
Japanese encephalitis (JE), 73, 78, 195–200 adverse events, 199–200 contraindications, 199 dosage and administration, 197 precautions, 199 pregnancy, 88, 200 recommendations, 197–8 variation from product information, 200 jaundice, false contraindication, 21 JE-VAX, 42, 196 see also Japanese encephalitis (JE)
K
Kawasaki disease, 103, 179, 180
L
M
mad cow disease, 354 see also bovine spongiform encephalopathy (BSE) Mantoux technique see tuberculin skin test (TST) manufacturing residuals, 340–3, 357 maternity hospital staff, 105, 237–8 Maternity Immunisation Allowance, 67, 68, 347 measles, 77, 105, 201–12 see also MMR adverse events, 208–9 catch-up, 32, 38 contraindications, 205–6 dosage and administration, 203 immunoglobulin, 177–8, 210–2 precautions, 206–8 pregnancy, 86, 212 public health management, 209–12 recommendations, 203–5 transmissibility, 209 variation from product information, 212 measles-mumps-rubella vaccine see MMR measles-mumps-rubella-varicella vaccine see MMRV meat industry, 106, 258, 260 medical students, 105, 145, 279 Medicare, 67, 332 men who have sex with men see sexual contact Mencevax ACWY, 42, 216, 222 see also meningococcal disease Meningitec, 42, 215, 222 see also meningococcal disease meningococcal disease, 79, 101, 213–22 asplenia (anatomical or functional) and, 101, 218, 219 early clinical management and, 220 meningococcal C conjugate vaccine (MenCCV), 215 adverse events, 220
Index 387
Index
laboratory personnel, 106, 113, 198, 218, 219, 255, 260, 284, 306, 324 lactation see breastfeeding and lactation latent TB infection (LTBI), 301 Latin America see Americas leprosy, 298, 300 leukaemia, 16, 93, 94, 178, 205, 279, 285, 317, 349 limb swelling, 59, 234 Liquid PedvaxHIB, 42, 31, 71, 133, 134 see also Haemophilus influenzae type b live attenuated vaccines, 20–1, 85, 91 BCG, 298 contraindications and, 20, 85, 86, 91 immunoglobulins/blood products and, 16, 18, 102–3, 175–6, 271 interval between, 17, 206, 225, 280, 301 MMR, 201, 223, 274 rotavirus, 267 smallpox, 284 surgery and, 104 typhoid (oral), 304 varicella, 309 yellow fever, 323 liver transplant recipients, 94, 144, 159 livestock industry, 107, 258, 260
local anaesthetic, vaccinations and see topical anaesthetics lockjaw, 288 see also tetanus lymphoma, 93, 205, 247, 279, 285, 302, 317 see also Hodgkin’s disease
catch-up, 32 contraindications, 219 dosage and administration, 217 recommendations, 218 meningococcal polysaccharide vaccine (4vMenPV), 215 adverse events, 220 contraindications, 219 dosage and administration, 217 recommendations, 219 pregnancy, 87, 221–2 public health management, 220–1 variation from product information, 222 Menjugate Syringe, 42, 215, 222 see also meningococcal disease Menomune, 42, 216, 222 see also meningococcal disease mercury, 355 see also thiomersal-free vaccines; thiomersal in vaccines Mérieux Inactivated Rabies Vaccine, 42, 111 see also Australian bat lyssavirus (ABL) infection; rabies Meruvax II, 42, 277 see also rubella Middle East see also Hajj cholera, 120 meningococcal disease, 219 military personnel see armed forces minimum ages for vaccination, 30 minimum dose intervals for National Immunisation Program (NIP) vaccines, 29 MMR (measles-mumps-rubella), 77, 352–3, 358–9 catch-up, 32 for measles, 202 for mumps, 224 for rubella, 275 immunoglobulin/blood products interval, 94, 102–3, 147, 175–6, 210–2 MMRV (measles-mumps-rubellavaricella), 202–4, 206, 224, 310, 312 multiple injections, 24, 56–7, 345 multiple sclerosis (MS), 61, 101–2, 163, 191, 352, 353, 370 mumps, 202, 223–6 see also MMR adverse events, 225
catch-up, 32, 38 contraindications, 205–6, 225 dosage and administration, 224 immunoglobulin, 225 precautions, 225 pregnancy, 86, 225 recommendations, 224–5 variation from product information, 212, 226 Mycobacterium tuberculosis see tuberculosis
N
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS), iii, iv, 13, 353, 359 National Immunisation Program (NIP), 127, 215, 228 components of vaccines used in, 340–3 National Measles Control Campaign, 202, 274 National Meningococcal C Vaccination Program, 215 needles, 44 see also dosage and administration Neisseria meningitidis see meningococcal disease NeisVac-C, 42, 215, 222 see also meningococcal disease neurological disease, 21, 90, 191, 195, 199–200, 233, 348 newborn nurseries, 237–8, 271 normal human immunoglobulin (NHIG), 146–7, 175, 177, 176, 179 see also immunoglobulins Normal Immunoglobulin-VF (human) (NHIG), 177 see also immunoglobulins nurses see healthcare workers (HCW) nursing home residents, 188, 192 nursing home staff, 106, 192 nursing students, 105, 145, 279
O
occupational risks, 104–7 hepatitis A, 144, 145, 147 hepatitis B, 159–60, 161, 162, 163
388 The Australian Immunisation Handbook 9th Edition
P
Pacific Islands see Oceania palivizumab (Synagis), 176, 182–3 see also immunoglobulins
Papua New Guinea, 75, 78, 82, 198, 304 paracetamol, 58, 60, 207, 209, 318, 348 pertussis, 31, 87, 96, 98–9, 105–7, 125, 127, 134, 227–39, 346–7, 358 see also DTPacontaining vaccines adverse events, 234–5 contraindications, 233 dosage and administration, 231 minimum interval between dTpa and dT, 233 precautions, 233–4 pregnancy, 87, 238 public health management, 235–8 recommendations, 231–2 special considerations, 233 variation from product information, 238–9 Pharmaceutical Benefits Advisory Committee (PBAC), 334 phenol, 342, 356 phenoxyethanol, 342, 355 plague, 3 pneumococcal disease, 72, 240–50 asplenia (functional or anatomical), 100–1 invasive pneumococcal disease (IPD), 72, 240–1, 246, 247 pneumococcal conjugate vaccine (7vPCV), 135, 241–2, 243–6 Aboriginal and Torres Strait Islander children, 34–5, 72, 240–1, 243, 245, 247 adverse events, 249 catch-up, 32, 34–6 contraindications, 248 dosage and administration, 243 impaired immunity, individuals with, 90–1, 92 Infanrix hexa and, 134 recommendations, 243–6 pneumococcal polysaccharide vaccine, (23vPPV) 241, 242, 246–8 Aboriginal and Torres Strait Islander children, 72, 245, 247 Aboriginal and Torres Strait Islander people, 73, 241, 246, 248 adverse events, 249 contraindications, 248
Index 389
Index
influenza, 192–3 Japanese encephalitis (JE), 198 measles, 204 meningococcal disease, 218–9, 221 pertussis, 232, 237, 346 poliomyelitis, 255 Q fever, 258, 260 rabies, 113 rubella, 279, 281 smallpox, 284 typhoid, 306, 308 varicella, 313, 315–6, 321 yellow fever, 324 occupation health and safety, 39 see also standard precautions Oceania (includes Pacific Islands) cholera, 120 hepatitis B, 77, 150 poliomyelitis, 251 rabies, 110 rubella, 278 tuberculosis, 297 typhoid, 78, 304 yellow fever, 322 Octagam, 179 see also immunoglobulins older people influenza, 77, 188, 190, 193, 346 pertussis, 19, 232, 346 pneumococcal disease, 77, 101, 246, 248 tetanus, 288 varicella 330 yellow fever, 326 zoster (herpes zoster) (HZ), 329, 330 oncology patients, 92–4 see also impaired immunity, individuals with oral poliomyelitis vaccine (OPV), 60–1, 252, 254, 255, 302, 305 oral vaccines, 42 organ donors see blood and organ donors outbreak control see public health management overseas travel see travellers
dosage and administration, 243 impaired immunity, individuals with, 91 recommendations, 246–8 revaccination with, 247–8 pregnancy, 87, 249 preterm babies, 89, 246 travel and, 77 variation from product information, 250 pneumonia, 72–3, 190, 240, 242 Pneumovax 23, 42, 242 see also pneumococcal disease police, 106, 159, 192 poliomyelitis, 251–6 see also DTPa-hepBIPV-Hib; dTpa-hepB-IPV, inactivated poliomyelitis vaccine (IPV); oral poliomyelitis vaccine (OPV); vaccinederived poliovirus (VDPV) adverse events, 255 catch-up, 32 contraindications, 255 dosage and administration, 254 pregnancy, 88, 255 recommendations, 254–5 variation from product information, 256 polysaccharide vaccines see meningococcal disease; pneumococcal disease; typhoid positioning for vaccination, 47–51 post-exposure treatment Australian bat lyssavirus (ABL) infection, 114–7 hepatitis A, 146–7 hepatitis B, 161–2 immunoglobulins, 177–8 measles, 209–12 meningococcal disease, 220–1 mumps, 225 pertussis, 237–8 rabies, 112, 114–7 varicella, 314, 315–6 post-vaccination procedures, 58–69, 377 see also serology poultry industry, 107, 192 precautions, 14, 40, 348, 350–1 cholera, 123
human papillomavirus (HPV), 173 immunoglobulins, 178, 180 influenza, 193 Japanese encephalitis (JE), 199 measles, 206–8 mumps, 225 pertussis, 233–4 Q fever, 263 rotavirus, 270–2 rubella, 280 smallpox, 285 tetanus, 295 tuberculosis, 301 typhoid, 307 varicella, 317–8 yellow fever, 326 prednisolone, 92, 205, 207, 246, 317, 349 pre-exposure prophylaxis Australian bat lyssavirus (ABL) infection, 112–4 immunoglobulins, 177 rabies, 78, 81, 82, 112–4, 119 pregnancy and vaccination, 16, 18–20, 84–90, 350 BCG vaccine, 86, 300–1 cholera vaccine, 87, 123 contacts, vaccination in, 18, 86, 89, 350 diphtheria-containing vaccine, 87 Haemophilus influenzae type b vaccine, 87 hepatitis A vaccine, 88 hepatitis B vaccine, 88 human papillomavirus (HPV) vaccine, 88, 174 immunoglobulins, 88 influenza vaccine, 88, 192, 194 Japanese encephalitis (JE) vaccine, 88, 200 measles-containing vaccine, 86, 206, 212 meningococcal vaccine, 87, 221–2 mumps-containing vaccine, 86, 225 pertussis-containing vaccine, 87, 232, 346 pneumococcal vaccine, 87, 249 poliomyelitis, 88 Q fever vaccine, 87, 263
390 The Australian Immunisation Handbook 9th Edition
pertussis-containing vaccine, 238–9 pneumococcal vaccine, 250 poliomyelitis vaccine, 256 Q fever vaccine, 264 rabies vaccine, 119 rotavirus vaccine, 273 rubella vaccine, 282 tetanus-containing vaccine, 296 typhoid vaccine, 308 varicella vaccine, 321 yellow fever vaccine, 328 products previously available, 339 products registered but not currently available, 339 public health management diphtheria, 128–9 Haemophilus influenzae type b, 137–8 hepatitis A, 146–7 measles, 209–12 meningococcal disease, 220–1 pertussis, 235–8 rubella, 281 typhoid, 308 varicella, 319–20 purified chick embryo cell vaccine (PCECV), 42, 111, 117, 118 see also rabies Purified Protein Derivative (PPD), 301–2 see also tuberculosis
Q
Q fever, 106, 107, 257–64 adverse events, 263 contraindications, 262 dosage and administration, 260 precautions, 263 pregnancy, 87, 263 pre-vaccination testing, 259, 260–2 recommendations, 260–2 serology, 260–2 skin testing, 261–2 variation from product information, 264 Q fever fatigue syndrome (QFS), 257 Q Fever Management Program, 258 Q-VAX, 42, 259 see also Q fever Q-VAX Skin Test, 259 see also Q fever
Index 391
Index
rabies vaccine, 88, 118 rotavirus vaccine, 86 rubella vaccine, 86, 278, 280, 281, 282 smallpox vaccine, 86, 285, 286 tetanus-containing vaccine, 87 typhoid vaccine, 86, 87, 307, 308 varicella vaccine, 86, 313, 316, 320, 321 yellow fever vaccine, 86, 326, 327, 328 preschool see childcare facilities preservatives in vaccines, 340–3, 355–6 preterm babies, 18, 45, 89 see also babies (neonates) catch-up and, 31 Haemophilus influenzae type b vaccine, 90, 136 hepatitis B vaccine, 90, 157 influenza vaccine, 90 pneumococcal vaccine, 89, 246 poliomyelitis vaccine, 255 rotavirus vaccine, 270 vaccination and, 345–6 pre-vaccination procedures, 14–38, 375 pre-vaccination screening, 8–21, 60, 375 see also serology checklist, 16, 375 Q fever, 260–2, 263 tuberculosis, 299, 301–2 Prevenar, 42, 241 see also pneumococcal disease Priorix, 42, 203 see also MMR; measles, mumps; rubella prisoners and staff see correction facility inmates; correction facility staff product information, variations from BCG vaccine, 302 diphtheria-containing vaccine, 129–30 Haemophilus influenzae type b vaccine, 138 hepatitis B vaccine, 163 influenza vaccine, 194 Japanese encephalitis (JE) vaccine, 200 measles-containing vaccine, 212 meningococcal vaccine, 222 mumps-containing vaccine, 212
R
rabies, 78, 106, 107, 110–9 adverse events, 118 contraindications, 117 dosage and administration, 112 endemic, 110, 111, 113, 115, 117 in Indonesia, 119 post-exposure prophylaxis, vaccine, 114–7 rabies immunoglobulin (HRIG), 103, 116–7 pre-exposure prophylaxis, 78, 81, 82, 112–4 pregnancy, 88, 118 variation from product information, 119 Rabipur Inactivated Rabies Vaccine, 42, 111 see also Australian bat lyssavirus (ABL) infection; rabies refrigerators, 9–12 refugees see immigrants regurgitation of vaccine, 25, 272 see also interruption to a vaccination renal disease see chronic conditions respiratory disease see chronic conditions respiratory syncytial virus (RSV), 176 RSV immunoglobulin (RSVIG), 182–3 respiratory syncytial virus immunoglobulin (RSVIG) see respiratory syncytial virus (RSV) Reye syndrome, 191, 207, 310, 318, 321 rheumatoid arthritis (RA), 101–2 rifampicin, 137–8, 221 Rotarix, 42, 266, 267, 268 see also rotavirus RotaShield, 272 RotaTeq, 42, 266, 267, 268 see also rotavirus rotavirus, 265–73 adverse events, 272–3 catch-up, 32 dosage and administration, 268 pregnancy, 86, 272 recommendations, 268–70 regurgitation of vaccine, 25, 272 variation from product information, 273 route of administration, 41–2
rubella, 105, 274–82, 358 see also MMR adverse events, 280–1 blood products and MMR, 102–3, 206 contraindications, 279–80 dosage and administration, 278 immunoglobulins, 281–2 males, 279 precautions, 280 pregnancy, 86, 281 public health management, 281 recommendations, 278–9 serological testing for, 276–7 variation from product information, 282
S
salicylates see aspirin therapy Salmonella Typhi see typhoid Sandoglobulin NF liquid, 179 see also immunoglobulins Saudi Arabia, 79, 219 screening see pre-vaccination screening; serology seizures or convulsions, history of, 191, 207, 249, 348 see also febrile convulsion serology post-vaccination, 113, 116, 142, 160, 276, 278, 314 pre-vaccination, 84, 97, 108, 143, 260–1, 276–7, 314, 315 sexual contact hepatitis A, 146 hepatitis B, 150–1, 158, 160, 162 HPV infection, 165 men who have sex with men, 108, 139, 144, 145, 158 shearers, 107, 258, 260 shingles see zoster simultaneous administration of vaccines, 56–7 see also multiple injections BCG vaccine, 301 cholera vaccine, 122 Haemophilus influenzae type b, 135 hepatitis A vaccine, 144 hepatitis A/hepatitis B vaccine, 145 hepatitis A/typhoid vaccine, 145 human papillomavirus (HPV) vaccine, 171
392 The Australian Immunisation Handbook 9th Edition
systemic lupus erythematosus (SLE), 101–2
T
tattooists, 107, 159 technical terms, glossary of, 364–8 tetanus, 77, 288–96, 358 see also DT; dT; DTPa; dTpa adverse events, 295–6 contraindications, 295 dosage and administration, 291 precautions, 295 pregnancy, 87, 88, 296 recommendations, 292–3 tetanus-prone wounds, treatment of, 292, 293–5 variation from product information, 296 Tetanus Immunoglobulin-VF (for intravenous use), 295 see also tetanus Tetanus Immunoglobulin-VF (TIG), 294–5 see also tetanus tetravalent meningococcal polysaccharide vaccines see meningococcal disease Therapeutic Goods Administration, 284, 354 thimerosal see thiomersal-free vaccines; thiomersal in vaccines thiomersal-free vaccines, 153, 156, 157, 355 thiomersal in vaccines, 153, 188, 343, 355 thrombocytopenia, 207–8 tick-borne encephalitis, 79 topical anaesthetics, 41, 43, 116 Torres Strait Islanders see Aboriginal and Torres Strait Islander people Torres Strait Islands and Far North Queensland see Far North Queensland and Torres Strait Islands transmission, live vaccines and, 85–9, 91 measles, 209, 212, 349, 350 mumps, 225, 349, 350 rotavirus, 270, 271 rubella, 280, 349, 350 typhoid (oral), 307 varicella, 314–5, 318, 349, 350
Index 393
Index
immunoglobulins/blood products and, 103 inactivated vaccines and immunoglobulins, 176 influenza vaccine, 190 meningococcal vaccine, 217, 222 MMR vaccine, 203, 224, 225, 278, 280 oral cholera and oral typhoid vaccines, 122 pneumococcal vaccine, 243, 246 Rh (D) immunoglobulin (anti-D) and, 176, 206, 279 rotavirus vaccine, 268 rubella vaccine, 278 typhoid, 305 varicella vaccine, 312, 317 yellow fever vaccine, 326 skin cleaning, 43 smallpox, 85, 91, 106, 283–7 adverse events, 286 contraindications, 285 dosage and administration, 284 immunoglobulin, 286 precautions, 285 pregnancy, 86, 286 recommendations, 284 smokers pneumococcal disease, 247, 248 pregnancy and, 84, 87 solid organ transplant (SOT) recipients, 94–6, 145 splenectomy, 16, 19, 36, 93, 100–1, 136, 247 see also asplenia (functional or anatomical) Stamaril, 42, 323 see also yellow fever standard precautions, 39, 105, 159, 270 stem cell transplants see haematopoietic stem cell transplantation (HSCT) steroids see corticosteroids stockyard workers, 107, 258, 260 Streptococcus pneumoniae see pneumococcal disease subcutaneous injections, 42, 55 sudden infant death syndrome (SIDS), 61, 235, 354 surgery, 21, 104 Synagis (palivizumab), 176, 182–3 see also respiratory syncytial virus (RSV)
transplants see haematopoietic stem cell transplantation (HSCT); solid organ transplant (SOT) recipients transport, storage and handling of vaccines see also cold chain BCG vaccine, 298 cholera vaccine, 121 diphtheria-containing vaccine, 127 Haemophilus influenzae type b vaccine, 135 hepatitis A vaccine, 142 hepatitis B vaccine, 153 human papillomavirus (HPV) vaccine, 171 immunoglobulins, 176 influenza vaccine, 189 Japanese encephalitis (JE) vaccine, 197 measles-containing vaccine, 203 meningococcal vaccine, 217 mumps-containing vaccine, 224 pertussis-containing vaccine, 231 pneumococcal vaccine, 242–3 poliomyelitis vaccine, 254 Q fever vaccine, 259 rabies vaccine, 112 rotavirus vaccine, 267 rubella vaccine, 277 smallpox vaccine, 284 tetanus vaccine, 291 typhoid vaccine, 305 varicella vaccine, 311–2 yellow fever vaccine, 323 travellers, 75–83, 91, 100 see also Africa; Americas; armed forces, Asia; Europe; Hajj; Middle East; Oceania cholera, 78, 120, 122 diphtheria, 128 hepatitis A, 78, 88, 144 hepatitis A/typhoid, 145 hepatitis B, 77, 159 infections acquired by, 75–6 influenza, 77, 193 Japanese encephalitis (JE), 78, 197–8 measles, 77, 204–5, 358 meningococcal disease, 79, 219 MMR, 204–5 pneumococcal disease, 77
poliomyelitis, 77, 88, 252, 255 rabies, 78, 88, 111, 113, 115, 117 tetanus, 77, 293 tick-borne encephalitis, 79 tuberculosis, 79, 300 typhoid, 78, 86, 91, 303, 305, 306 varicella, 77 yellow fever, 79, 86, 91, 323, 324–5, 326, 327, 328 tuberculin skin test (TST), 207, 299, 300, 301–2 live vaccines and, 302 tuberculosis (TB), 70–1, 79, 207, 297–302 adverse events, 301 contraindications, 300 dosage and administration, 298–9 precautions, 301 pregnancy, 86, 301 recommendations, 300 tuberculin skin test, 301–2 variation from product information, 302 Tubersol, 301–2 see also tuberculin skin test (TST) Twinrix, 141 see also hepatitis A (HAV); hepatitis B (HBV) Twinrix Junior, 141 see also hepatitis A (HAV); hepatitis B (HBV) Typherix, 42, 304 see also typhoid Typhim Vi, 42, 304 see also typhoid typhoid, 78, 123, 303–8 adverse events, 307 contraindications, 307 dosage and administration, 305–6 hepatitis A/typhoid, 143, 145, 304 precautions, 307 pregnancy, 86, 87, 308 public health management, 308 recommendations, 306 variation from product information, 308
V
Vaccination, commonly asked questions, 344–59 vaccine-associated paralytic poliomyelitis (VAPP), 60–1, 252
394 The Australian Immunisation Handbook 9th Edition
ventrogluteal area, 45, 46, 48, 51, 53–4, 56, 57, 345 see also injection site; injection technique veterinarians, students and staff, 107, 113, 260 Vibrio cholerae see cholera Vivaxim, 42, 141, 304 see also hepatitis A (HAV); typhoid Vivotif Oral, 42, 304 see also typhoid
W
whooping cough see pertussis women see also breastfeeding and lactation; pregnancy and vaccination of child-bearing age and rubella vaccination, 275–7, 278, 279 World Health Organization (WHO), 22, 78, 79, 83, 108, 163, 202, 219, 251, 252, 297, 353
Y
yellow fever, 75, 79, 106, 322–8 adverse events, 327 contraindications, 91, 100, 325–6 dosage and administration, 324 endemic countries, 324 International Certificate of Vaccination against Yellow Fever, 323, 325 precautions, 326 pregnancy, 86, 327 recommendations, 324–5 variation from product information, 328 yellow fever vaccination centres, 325
Z
zoster (herpes zoster) (HZ), 309, 319, 329–31 vaccine, 330–1, 339 zoster immunoglobulin (ZIG), 178, 309, 315, 319–20 see also varicella Zoster Immunoglobulin-VF (human), 319–20 see also varicella
Index 395
Index
vaccine-associated viscerotropic adverse events, 327 vaccine-derived poliovirus (VDPV), 252 vaccines components used in NIP, 340–3 dates when available in Australia, 372–4 failures, 136, 259, 310–1, 312–3 vaccinia immune globulin (VIG), 286–7 see also smallpox vaccinia virus (smallpox), 85, 106, 283 see also smallpox VAQTA, 42, 141 see also hepatitis A (HAV) VAQTA Paediatric/Adolescent formulation, 42, 141, 146 see also hepatitis A (HAV) varicella, 77, 98, 99, 104, 105, 207, 309–21 adverse events, 60, 318 breakthrough varicella, 310–1, 312–3 catch-up, 32 contraindications, 91, 92, 96, 316–7 dosage and administration, 44, 312 immunoglobulin/blood product interval, 94, 102–3, 147, 175–6, 320–1 precautions, 92, 94, 317–8 pregnancy, 86, 320 public health management, 178, 319–20 recommendations, 312–6 serological testing for, 314 variation from product information, 321 varicella-zoster virus (VZV), 309, 329, 330 see also zoster Varilrix, 42, 311 see also varicella Varivax Refrigerated, 42, 311–2, 330 see also varicella vasovagal episodes, 61–2 vastus lateralis, 45, 46, 47, 51–2, 345 see also injection site; injection technique Vaxigrip, 42, 187 see also influenza Vaxigrip Junior, 42, 188, 189 see also influenza
396 The Australian Immunisation Handbook 9th Edition
