Smallpox - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

SMALLPOX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P ...

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SMALLPOX A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Smallpox: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83607-8 1. Smallpox-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on smallpox. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON SMALLPOX................................................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Smallpox ....................................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 61 CHAPTER 2. NUTRITION AND SMALLPOX ..................................................................................... 181 Overview.................................................................................................................................... 181 Finding Nutrition Studies on Smallpox .................................................................................... 181 Federal Resources on Nutrition ................................................................................................. 182 Additional Web Resources ......................................................................................................... 182 CHAPTER 3. ALTERNATIVE MEDICINE AND SMALLPOX .............................................................. 185 Overview.................................................................................................................................... 185 National Center for Complementary and Alternative Medicine................................................ 185 Additional Web Resources ......................................................................................................... 189 General References ..................................................................................................................... 190 CHAPTER 4. DISSERTATIONS ON SMALLPOX ................................................................................ 191 Overview.................................................................................................................................... 191 Dissertations on Smallpox ......................................................................................................... 191 Keeping Current ........................................................................................................................ 192 CHAPTER 5. CLINICAL TRIALS AND SMALLPOX ........................................................................... 193 Overview.................................................................................................................................... 193 Recent Trials on Smallpox ......................................................................................................... 193 Keeping Current on Clinical Trials ........................................................................................... 200 CHAPTER 6. PATENTS ON SMALLPOX ........................................................................................... 203 Overview.................................................................................................................................... 203 Patents on Smallpox .................................................................................................................. 203 Patent Applications on Smallpox............................................................................................... 205 Keeping Current ........................................................................................................................ 207 CHAPTER 7. BOOKS ON SMALLPOX ............................................................................................... 209 Overview.................................................................................................................................... 209 Book Summaries: Federal Agencies............................................................................................ 209 Book Summaries: Online Booksellers......................................................................................... 210 The National Library of Medicine Book Index ........................................................................... 214 Chapters on Smallpox ................................................................................................................ 215 CHAPTER 8. MULTIMEDIA ON SMALLPOX .................................................................................... 217 Overview.................................................................................................................................... 217 Bibliography: Multimedia on Smallpox ..................................................................................... 217 CHAPTER 9. PERIODICALS AND NEWS ON SMALLPOX ................................................................. 221 Overview.................................................................................................................................... 221 News Services and Press Releases.............................................................................................. 221 Academic Periodicals covering Smallpox................................................................................... 226 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 227 Overview.................................................................................................................................... 227 U.S. Pharmacopeia..................................................................................................................... 227 Commercial Databases ............................................................................................................... 228 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 233 Overview.................................................................................................................................... 233 NIH Guidelines.......................................................................................................................... 233 NIH Databases........................................................................................................................... 235 Other Commercial Databases..................................................................................................... 238

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APPENDIX B. PATIENT RESOURCES ............................................................................................... 239 Overview.................................................................................................................................... 239 Patient Guideline Sources.......................................................................................................... 239 Finding Associations.................................................................................................................. 248 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 251 Overview.................................................................................................................................... 251 Preparation................................................................................................................................. 251 Finding a Local Medical Library................................................................................................ 251 Medical Libraries in the U.S. and Canada ................................................................................. 251 ONLINE GLOSSARIES................................................................................................................ 257 Online Dictionary Directories ................................................................................................... 258 SMALLPOX DICTIONARY......................................................................................................... 259 INDEX .............................................................................................................................................. 307

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with smallpox is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about smallpox, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to smallpox, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on smallpox. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to smallpox, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on smallpox. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON SMALLPOX Overview In this chapter, we will show you how to locate peer-reviewed references and studies on smallpox.

Federally Funded Research on Smallpox The U.S. Government supports a variety of research studies relating to smallpox. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to smallpox. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore smallpox. The following is typical of the type of information found when searching the CRISP database for smallpox: •

Project Title: A SAFER AND MORE EFFICACIOUS SMALLPOX VACCINE Principal Investigator & Institution: Yilma, Tilahun D. Professor and Director; Interntl Lab Molecular Biology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, CA 95616 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2006

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

4

Smallpox

Summary: (provided by applicant): In the aftermath of the attacks of September 11 and the anthrax scare, we have a heightened awareness of US vulnerability to bioterrorism. One of the most feared infectious agents is variola virus, the causative agent of smallpox. Various strains of vaccinia virus (VV) are highly effective in preventing this disease, but have definite rates of complications. Severe illness or death is rare in people with normal immune responses, but considerably more common in individuals with cell-mediated immune defects. The number of individuals that are at risk from this normally innocuous vaccine has greatly increased with the spread of the human immunodeficiency virus (HIV), and it now becomes important to improve the efficacy and safety of this vaccine. We have worked extensively with VV as a recombinant vaccine for a number of diseases; our rinderpest vaccine was described as one of two outstanding rVVs in a leading journal (G. Ada, Nature 349:369, 1991). We have also developed strategies for attenuating VV while enhancing efficacy, with one of the most effective being the incorporation of the interferon-gamma (IFN-gamma) gene. We have shown that expression of IFN-gamma leads to a TH1 immune response essential against viral infection with no deleterious effects. We have also studied the effects of inactivating VV immunomodulating genes such as B8R, B13R, and B22R that are virulence factors in VV. Based on our past experience, we propose developing a safer and more efficacious vaccine for smallpox based on the New York City Board of Health (Wyeth) strain of VV that is currently used in the US. We will delete the B8R gene and insertionally inactivate the TK virulence gene with the human IFN-gamma gene to increase attenuation of the virus and the protective cell-mediated immune responses. This recombinant VV will be compared to the parental vaccine in both normal and simian immunodeficiency virus-infected macaques (used as a model for HIV-infected humans) to assess efficacy and safety for normal and immunodeficient individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A THERAPY FOR SMALLPOX Principal Investigator & Institution: Rich, Alexander; Biology; Massachusetts Institute of Technology Cambridge, MA 02139 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This work is directed toward developing a therapy that can be used to prevent the pathogenic effects of variola, the agent of smallpox. The possibility of developing this therapy has arisen from research on vaccinia, a close relative of variola. When vaccinia is given to mice, they die in 4-8 days, depending on viral dosage. A small protein produced by vaccinia, E3L, is essential for lethality in mice. When E3L is partially or wholly deleted, the virus can grow in cell culture, but it is no longer pathogenic. Recent research has demonstrated that the N terminal domain of the vaccinia E3L is a Z-DNA binding protein. This work stems from crystal structures of other related proteins that were co-crystallized with Z-DNA. E3L has the same group of amino acid residues that are essential for Z-DNA recognition as are found in these related proteins. Mutations in E3L that prevent its binding to Z-DNA render the virus harmless in the mouse model. In this work, an attempt will be made to find a small molecule that binds to the Z-DNA binding pocket of the E3L molecule. It is anticipated that binding to that pocket will prevent the E3L molecule from binding to Z-DNA and hence it will lose its pathogenicity. Variola, the agent of smallpox, has a virtually identical E3L molecule, and it is likely that it is also essential for its pathogenicity. A small molecule capable of binding with high affinity to the Z-DNA binding pocket may provide a therapy for preventing smallpox. In the present application, libraries of small molecules will be screened in an effort to obtain one that blocks the action of E3L. This

Studies

5

will be tested initially to prevent the pathogenicity of vaccinia in the mouse model. This should ultimately lead to the prevention of pathogenicity of Variola, which can be tested by others in an available primate model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-ORTHOPOXVIRUS DRUG DISCOVERY AND DEVELOPMENT Principal Investigator & Institution: Schneller, Stewart W. Professor; Chemistry; Auburn University at Auburn Auburn University, AL 36849 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 30-JUN-2004 Summary: (adapted from applicant's abstract): The possibility of biological terrorism has moved from the realm of speculation into reality. This threat can take several forms. One of the most likely pathogens in such a scenario is smallpox. The same characteristics that made smallpox a dreaded human pathogen, including aerosol infectivity and stability outside a human host, make it a potentially devastating biological weapon. Dissemination of smallpox in a major population center could result in the sudden, simultaneous occurrence of thousands of cases of severe illness. The primary reason for this is that so few people are now protected from infection by prior vaccination as a consequence of the declaration in 1980 of the complete eradication of smallpox. Furthermore, vaccination would be of little benefit to persons already infected by terrorist release of the virus and immediate vaccination of the exposed population might not reduce the infectivity of primary cases to prevent secondary transmission. Vaccine availability and quality would also prevent a massive vaccination effort. Because of these limitations, development of chemotherapeutic agents to combat smallpox infection must be undertaken. No such agents currently exist. To address this need, this proposal presents plans for developing drugs that act by inhibiting the enzymes encoded by the smallpox virus upon infection. Focus will be on nucleosides and nucleotides that effect, primarily, nucleic acid metabolism. A consortium of three chemists and two virologists as project leaders, and a virologist consultant, has been put into place for this purpose. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ANTI-SMALLPOX MICOORGANISMS

THERAPEUTICS

FROM

MARINE

Principal Investigator & Institution: Castor, Trevor P. President & Chief Executive Officer; Aphios Corporation 3-E Gill St Woburn, MA 01801 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-AUG-2004 Summary: (provided by investigator): The terrorist events of September 11th and the recent criminal anthrax exposures have increased awareness of the use of smallpox as a biological weapon. A shortage of the vaccine and the incidence of vaccine-related deaths will preclude protection of everyone especially immunocompromised patients. Currently, there are no FDA approved drugs for the treatment of smallpox. Recent literature has suggested that rifampicin, cidofovir, and virazole (ribavirin) are effective against smallpox; all, however, have logistical and medical complications that preclude their effective use. Thus, more effective and safer drugs will be required to combat smallpox in those exposed. Due to diverse microenvironments, oceans and seas contain a wealth of microorganisms that are genetically different from their terrestrial counterparts and represent a new avenue for isolating unique anti-viral therapeutics. The overall goal of this Phase I application is to identify and purify compounds from marine microorganisms that are bioactive against Vaccinia virus (VV). In Phase II, we

6

Smallpox

will conduct in vitro studies with the purified compound, including a detailed evaluation of mechanisms of action. The goal for Phase II is to have a unique compound effective against VV ready for filing with an IND with the FDA, conducting the necessary in vivo clinical trials and initiating the stockpiling of anti-smallpox therapeutics as a preemptive anti-bioterrorism measure in a Phase III commercialization effort. Keywords: Smallpox, Bioterrorism, Therapeutics, Vaccinia, Antiviral Drugs, Marine Microorganisms. Potential Commercial application: The development of unique and cost-effective anti-smallpox drugs from a readily fermentable marine microorganism resource will be of tremendous benefit to the biosecurity of the United States. Such drugs may also become commercially important against other natural and emerging viral threats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASSESSMENT OF SMALLPOX SPECIFIC IMMUNE RESPONSES Principal Investigator & Institution: Denny, Thomas N. Assistant Professor of Pathology,; Pediatrics; Univ of Med/Dent Nj Newark Newark, NJ 07103 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: This proposal, in response to RFA-AI-02-002, seeks funding to study longlasting immunity (e.g. immunological memory or recall) to smallpox (variola) in individuals who were previously vaccinated in the United States commercially approved smallpox vaccine (preparation of live Vaccinia virus). In the aftermath of September 11, 2001, it is now critical to better define mechanisms of smallpox protective immunity or disease resistance in the general population and in those who may be classified immune compromised and therefore, considered at a higher risk of infection. Though smallpox was considered a disease of historical interest only, since its earlier eradication, it as been known to be a significant pathogen for potential bioterrorist activities. Investigation of long-lasting immunity using current state-of-the-art techniques or methodologies may help determine which individuals are better prepared to serve as "first-line" responders. In addition, this information may help determine a better strategy for use of limited, non-universally administrable vaccine material available today. Specific Aim 1: To assess smallpox-specific long-lasting immunologic responses and correlate to donor age and time since last vaccination in healthy individuals that have previously received a smallpox vaccination. Hypothesis: Initial childhood vaccine administration will be associated with differing levels of smallpoxspecific host immune responses that will vary with number of immunizations given and the time since last vaccination. Specific Aim 2: To assess smallpox-specific long-lasting immunologic responses in HIV- and HIV+ individuals through collaboration with the NIAID DAIDS ACTG and correlate to age and infection status in individuals previously having smallpox vaccination. Hypothesis: HIV infection, CD4 or viral load status, time since last vaccination and host age will each be associated differing levels of smallpoxspecific host immune responses. Specific Aim 3: To viral epitope map and evaluate the CD4/CD8 immune subset critical memory component of virus-specific cell-mediated responses in healthy and immune comprised study participants. Herd immunity or natural boosting is absent from this model, it represents a unique opportunity to extensively study pathogen specific immunological memory. Hypothesis: Response level and/or frequency of CD4 or CD8 cells to various immunodominant viral epitopes will change with age, time since last vaccination or presence of disease (e.g, HIV). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

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Project Title: AUGMENTING INNATE AND VACCINE IMMUNE RESPONSE WITH DER-G Principal Investigator & Institution: Zimmerman, Daniel H.; Cel-Sci Corporation 8229 Boone Blvd, Ste 802 Vienna, VA 22182 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Concerns regarding the United States' vulnerability to a terrorist attack with smallpox have stimulated development of new vaccines, prophylactics and therapeutics. However, a new and successful smallpox vaccine intervention program, or one to treat exposed individual requires not only an effective vaccine, but also agents to treat the complications arising from a widespread vaccination program. Recently, we found that derG, an N terminal deamidated analogue of the human MHC II beta-chain (aa135-149) showed significant protective activity in infectious disease models of malaria and HSV and adjuvant activity for vaccines. The primary goals of this application are to determine the protective activity of derG for vaccinia infections, identify its mechanism of action to support its' development as an immunotherapeutic and/or prophylactic for vaccinia and smallpox infections as a single agent and as an adjuvant for vaccinia vaccines. The ultimate goal of these Phase I studies is to develop sufficient data to justify studies in a primate model of efficacy and animal safety and toxicology studies to support human clinical trials. In addition to the concern that smallpox may be used as a weapon of mass destruction, recombinant vaccinia viruses (VV) are also used as vaccines or as vectors for immunotherapy resulting in the recommendation that individuals working with VV vectors be vaccinated. However, the present vaccines, when available, are associated with serious complications in approximately 1:10,000 primary vaccinees, and mortality in about 1:10 6 primary vaccinations. Our strategy is to use derG as prophylaxsis and as an adjuvant for a replication incompetent vaccine prime to limit the toxicity by live vaccinia virus and to target mucosal activity. Thus, these studies will deliver derG and the vaccine by intranasal administration and will monitor both systemic and mucosal (pulmonary) immunity. We propose to use derG, together with an infectious, but replication incompetent VV (irradiated) vaccine to examine the hypothesis that immune augmentation with derG will prolong survival and also provide adjuvant activity for a replication incompetent vaccine, thereby providing an additional reduction in viral burden and prolongation of survival for vaccinia-infected mice as a model of smallpox infection. This hypothesis will be tested with the following Specific Aims: 1: Determine the immunoregulatory and adjuvant properties of derG during VV vaccination of mice. 2: Determine the immune augmenting and adjuvant activity of derG in mice sub-lethally infected with vaccinia as a model of smallpox. 3: Determine the therapeutic potential of immune intervention in the treatment of lethal vaccinia virus infections and identify surrogates of therapeutic activity. In these studies we will follow survival and ovarian viral titers after intranasal challenge with VV. The studies will also analyze the mechanism of action to identify immune surrogates for use in clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BACTERIAL DEVELOPMENT

ANTIGENS

AND

ANTHRAX

VACCINE

Principal Investigator & Institution: Hewlette, Erik; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008

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Smallpox

Summary: The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE), whose theme is "Defense against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens, tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of F. tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection, as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; diagnostics for detection of these pathogens in water, food, and environmental specimens); 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and 4 Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION

BACTERIAL

PATHOGEN

AMPLIFICATION

&

REAL-TIME

Principal Investigator & Institution: U'ren, Jack R. Director of Research; Saigene Corporation 7126 180Th Ave Ne, Ste C-104 Redmond, WA 98052 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-NOV-2003 Summary: (provided by applicant): As we all know, bio-terrorism in America is a reality. However in addition to the Category A agents like anthrax, Yersinia pestis and smallpox, which are difficult to safely grow and disseminate, exist the Category B agents that could be used to infect our food or water supply. These organisms include bacterial pathogens, protozoa, and viruses. In addition to these natural pathogenic organisms they could also be genetically engineered to increase their virulence or to resist standard antibiotic treatments. Therefore new methods for rapid sensitive food and waterborne pathogen detection are greatly needed, especially if they can also be used to identify drug sensitivity within these organisms. Bio-terrorism using a food pathogen is not just a hypothetical threat to America. A religious cult in Dalles Oregon sickened at least 751 people by contaminating food in grocery stores and restaurants in the fall of 1984. The group simply grew cultures of the food pathogen Salmonella typhimurium that they obtained from their local scientific supply house and sprinkled

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9

the cultures on produce in the grocery stores and the restaurant salad bars. If the group had used a more deadly pathogen like Salmonella typhi that causes typhoid fever many people would certainly have died. The overall goal of this program is to develop an integrated isothermal DNA amplification and a probe array detection slide capable of rapidly identifying a variety of food and waterborne pathogens. All of the NIAID Biodefense Category B food and waterborne bacterial pathogens E. coli, Vibrio cholera, Shigella dysentery, Salmonella species, Listeria monocytogenes, Camphylobacter jejuni, and Yersinia enterocolitica will be detected in this program. A single integrated slide capable of isothermal amplifying and detecting all of these organisms in real-time in a closed sealed device is proposed. The program can also distinguish live organisms from dead organisms killed by the food or water sanitation process. Also, the test can be used to identify the antibiotic sensitivity of the pathogen to identify genetically altered organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM AND CYTOTOXIC T LYMPHOCYTES Principal Investigator & Institution: Zweifach, Adam; Assistant Professor; Physiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term goal of this proposal is to understand the role of intracellular calcium signals in the function of cytotoxic T lymphocytes (CTLs). These critical effectors of the immune system kill virus-infected cells and cancer cells and play a major role in the immune response to transplanted tissues; inappropriate killing can cause autoimmune diseases such as Lupus, certain forms of diabetes, and arthritis. Understanding CTL function is therefore important for preventing and treating naturally occurring viral diseases such as AIDS and influenza, and viral diseases such as smallpox used as biological weapons. It is also important for understanding and treating cancers and autoimmune diseases. Finally, the ability to suppress CTL function is vital for successful organ transplantation. One of the main mechanisms CTLs use to kill is the perforin pathway, which involves the exocytotic release of pore-forming peptides and hydrolytic enzymes contained in specialized lytic granules into an area of close apposition formed with the target. Granule exocytosis is known absolutely to require increased intracellular calcium caused by influx across the plasma membrane. However, the specific role(s) of calcium in granule exocytosis are unknown, the number of calcium-dependent steps is unclear, and molecules that confer calcium-dependence have not been identified. The specific aims of this proposal will use a battery of techniques, including novel fluorescence imaging methodologies we have developed, to: 1) determine whether bulk cytosolic calcium increases are sufficient to support granule exocytosis, or whether higher-than-cytosolic calcium increases in microdomains are required. 2) Investigate the calcium dependence of granule reorientation and of reorientation-independent exocytosis. 3) Determine whether immunological synapse formation is calcium dependent, and acts as a slow step in granule reorientation. 4) Investigate the role of the calcium-dependent phosphatase calcineurin in granule exocytosis. These studies will significantly further our understanding of the role of calcium influx in lytic granule exocytosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

10 Smallpox

•

Project Title: CARBOCYCLIC NUCLEOSIDES FOR EMERGING VIRAL DISEASES Principal Investigator & Institution: Chu, Chung K.; Auburn University at Auburn Auburn University, AL 36849 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The need for safe and effective therapeutic agents for highly pathogenic agents is a key to the national biodefense. On the top of these pathogenic agents is Orthopoxvirus, including smallpox, monkeypox, cowpox and vaccinia virus. As smallpox virus is highly contagious by aerosol and the fatality is high, using these viruses for bioterrorism is highly probable. Particularly, the young generation is vulnerable as the virus has been officially eradicated in 1977 and no vaccination has been performed since then. Thus, in this application the major focus will be directed toward the discovery of antivirai agents for Orthopoxvirus based on our preliminary findings. In this regard, we recently discovered interesting carbocyclic nucleosides with potent anti-Orthopox virus activity in collaboration with investigators at the US Army Medical Research Institute for Infectious Diseases. Although these carbocyclic nucleosides are not the clinical candidates, they can serve as lead compounds for future chemical synthesis and biological evaluation. Additionally, Filoviruses, Category A agents (Ebola and Warburg virus) are highly contagious and create serious health crisis around the wodd, and therefore, their therapeutic intervention is part of the national biodefense plans. As the same carbocyclic nucleosides demonstrated interesting antiviral activity against Ebola virus, we will submit our proposed compounds to screen in our core laboratory (US Army Medical Research). Additionally, West Nile virus appears to have spread rapidly throughout the nation since it arrived in the US in 1999 and is has begun creating serious health problems in the US, and we definitely need safe and effective therapeutic agents. Again, series of carbocyclic nucleosides demonstrated interesting antiviral activity against West Nile virus, and therefore, we will continue to synthesize carbocyclic nucleosides for biological evaluation in collaboration with Dr. Robert Sidwell of Utah State University. We will also send the proposed compounds for antiviral evaluation against Hanta virus and other emerging virus if the screening systems become available in our collaborator's laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INFECTION

CD47 HOMOLOGUES

IN

PATHOGENESIS

OF

POXVIRUS

Principal Investigator & Institution: Brown, Eric J. Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This application focuses on the pathogenesis of smallpox, in response to RFA AI-02-002. Smallpox is a major bioterrorism threat because it is infectious by the aerosol route; once infection is established it spreads rapidly from human to human; it has a high case fatality rate among unvaccinated individuals; and there is no effective treatment. Since research on the pathogenesis of smallpox effectively ended more than 30 years ago, the knowledge base for designing new methods for prevention or treatment in light of the new threat of this disease is woefully out of date. All sequenced poxvirus genomes contain an open reading frame (orf) homologous to the ubiquitously expressed vertebrate plasma membrane protein CD47. Poxviruses express a number of proteins homologous to vertebrate proteins, including cytokine- and cytokine receptor-like genes, chemokine- and chemokine receptor-like genes, complement control proteins, and TNF receptor homologues. These

Studies 11

viral proteins have been collectively called immuno-evasins because of their purpose to undermine normal host immune responses. In addition poxviruses express crmA and other proteins whose main purpose is to inhibit the death of infected cells. Both families of poxvirus proteins are important for viral survival, replication, and transmission. CD47 has several known functions that make it an ideal candidate for viral subversion, since it has a role in regulation of phagocytosis, phagocyte activation and migration, immune response to particulate antigens, and apoptosis of lymphocytes. The hypothesis of this application is that the highly conserved open reading frame in poxvirus genomes homologous to CD47 exists to subvert one or more of these CD47 functions to the advantage of the virus. Understanding the functions of this poxvirus CD47 homologue could lead to new approaches to prevention or therapy of smallpox. To understand the functions of this poxvirus orf, we propose to identify host cell ligands for the Variola and Vaccinia orfs homologous to CD47 and determine how the Variola CD47 homologue subverts normal CD47 functions. This increased understanding of this poxvirus homologue of mammalian CD47 will shed light on transmission and pathogenesis of smallpox and will aid in the development of new strategies for prevention and treatment of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL-MEDIATED IMMUNE RESPONSES TO VACCINIA VIRUSES Principal Investigator & Institution: Crowe, James E. Associate Professor of Pediatrics; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Detailed analysis of T cell responses from individuals enrolled in vaccinia virus vaccine trials may dramatically improve our understanding of the effects of dilution on vaccine immunogenicity and on the relationship of cell-mediated immunity to protection from adverse events following immunization. Our experiments will begin to address the level of cell-mediated immunity elicited in naive adults following vaccination with the Aventis Pasteur smallpox vaccine. Furthermore, these studies will establish a paradigm in which researchers can begin to incorporate improved measures of cell-mediated immunity in clinical environments, generating data that will provide useful surrogate biomarkers of immune responses related to adverse events or protection. Specifically, we will test the hypothesis that the lack of a vigorous response of host T cells to immunodominant cytolytic T cell epitopes following primary immunization is associated with adverse events that are related to failure to clear virus shedding rapidly. Previous work examining cell-mediated immunity to vaccinia virus during clinical vaccine trials is very limited. Small studies have examined the effects of smallpox vaccination and identified that human CTL memory responses to vaccinia virus do occur. Much of the work performed to date examining CM1 responses in humans to specific antigens/viruses have been performed using bulk culture proliferation techniques and standard cytotoxicity assays. While these assay provide a measure of T cell responsiveness to specific antigens, they fail to delineate which of the subsets of T cells are involved in protective memory responses or are associated with adverse events. We will examine many of these questions by taking advantage of new technology that allows for examination of T cell responses at the single cell level, and in an immunodominant epitope specific manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

12 Smallpox

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Project Title: CELLULAR IMMUNITY TO CATEGORY A-C VIRUSES IN HUMANS Principal Investigator & Institution: Ennis, Francis A. Professor; None; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The proposed UMASS Center for Translational Research on Human Immunology and Biodefense is a comprehensive, interdepartmental collaboration to address, as its overall scientific theme, the role of human T lymphocyte responses in the immunopathogenesis of and protection from category A-C viral pathogens. The Center encompasses senior and junior investigators with significant prior expertise in human immunology and research on biodefense pathogens, including translation to clinical studies, and is organized around the following components: Project 1 (Poxviruses) will define immunodominant human T cell epitopes of vaccinia virus as markers of vaccine efficacy and advance knowledge toward the development of improved smallpox vaccines. Project 2 (Hantaviruses) will define human immune responses associated with immunopathogenesis of hemorrhagic fever with renal syndrome. Project 3 (Flaviviruses) will define protective and immunopathological cross-reactive human T cell responses to sequential virus infections. The Technical Development Component (TDC) will develop novel solidphase array and proteomics technologies for application in T cell epitope identification, detection and enumeration of virus-specific T cells, and identification of biomarkers of protective or pathological T cell responses. Core facilities will provide flow cytometry, MHC class I production, MHC class II production, and program administration services for use by the research projects and TDC. A Pilot Projects component will support pilot funding of promising novel research concepts proposed by UMMS faculty. An Education component will support short-term training of non-Center investigators. The proposed Center will address important NIAID research priorities related to these biodefense pathogens as well as career development for young investigators. The Center will facilitate synergistic interactions between the various investigators, to be assessed by periodic internal and external review that will greatly enhance the overall research productivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: VACCINES

CHEMOKINE

ADJUVANTS

FOR

BIOTHREAT

PATHOGEN

Principal Investigator & Institution: Howard, Maureen C.; Chemocentryx, Inc. 1539 Industrial Rd San Carlos, CA 94070 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2008 Summary: (provided by applicant): There is an extreme need to develop safer and more efficacious modes of prophylactic and therapeutic vaccination. This need is particularly acute in the area of non-conventional pathogens, such as anthrax and smallpox, due to the ease of weaponizing these agents, and the inadequacy of current prevention and treatment regimens. The goal of this multi-project program proposal is to develop novel, first-in-class immune activating agents to be used as enhanced adjuvants for nonconventional pathogens. Specifically, we aim to exploit the unique power of the chemokine system (a primary regulator of the trafficking patterns of the body's immune cells) to target both the innate immune response and acquired immunity. This will be done by exploiting chemokine-based modalities recently characterized in our organization. Specifically, the following approaches will be employed: (i) The use of a newly discovered chemokine-derived peptide, designated SHAAGtide (or PDX-S),

Studies 13

identified here as a high affinity ligand for the formyl peptide receptor-related molecule FPRL-1, to actively engage innate immune responses; (ii) Using a virally derived chemokine vMCK-2 (or PDX-K), a highly potent attractant of APC and DC in vivo, to enhance acquired immune responses; (iii) The creation of novel medicinal chemical ligands ('chemomimetics') for FPRL-1 and the PDX-K receptor to provide new adjuvant modalities with an expanded range of administration routes; (iv) The creation of in vivo targeting and vaccine delivery vehicles, and finally, (v) Comparative assessment of all such modalities in mouse and non-human primate models to determine which agent (PDX-S, PDX-K, chemomimetic, etc) and form (soluble protein, DNA, medicinal chemical, or viral) shall be advanced through preclinical and into clinical development. Thus we aim to create powerful 'superadjuvants' - with markedly enhanced qualities over currently used adjuvants -for use in protection against Category A-C pathogens. PROJECT 1: Chemokine Adjuvants: The Link to FPR-Like Receptors (Premack, B.) PROJECT 1 (provided by applicant): Chemokines are widely recognized as potent regulators of APC migration and function. As such, there is great unrealized potential in developing vaccine adjuvants and small molecule therapeutics based on the ability of chemokines to promote APC-antigen interactions during the vaccination process. In our comprehensive search for chemokines with APC-modulatory properties for use as chemoadjuvant candidates we have identified a chemokine variant, termed Ckbeta81(25-116), which is a functional ligand for a wide variety of antigen presenting cells bearing either CCR1 or an orphan GPCR termed FPRL1 (formyl peptide receptor-like 1). The protein motif encoded by an alternatively spliced exon, termed "SHAAGtide", contributes entirely to activity on FPRL1. Both Ckbeta8-1(25-116) and the isolated synthetic SHAAGtide peptide bind to and are fully functional chemotactic ligands for FPRLI. FPRL1 agonists such as SHAAGtide have potent immunomodulatory and adjuvant-like properties in vivo. Thus, FPRL1 appears to function as a novel pattern recognition receptor, transducing a variety of pathogenic or 'danger' signals to innate immune system cells such as monocytes, macrophages and dendritic cells. The functional roles of FPRL1 suggest important consequences for the regulation and skewing of innate and adaptive immunity to pathogens. In this set of aims we will develop discrete, deliverable peptide immune adjuvants, as well as drug-like superadjuvants based on stimulating APCs bearing FPRL1. Specific Aim #1 will examine the role of FPRL1 in innate and adaptive immunity. We will initially determine the expression of FPRL1 on human myeloid cells involved in innate immunity then produce monoclonal antibodies for evaluating FPRL1 expression in tissues and for use as tools in evaluating FPRL1 function in innate immunity. We will compare the potency of natural and synthetic viral, bacterial, or chemokine-based ligands for FPRL1 and determination of efficacy of FPLR1 ligands as adjuvant candidates using in vitro models. In Specific Aim #2 we will produce, develop, and evaluate small molecule and peptide agonists of FPRL1 with potential as adjuvant therapies. Our strategy will be to identify agonist hits by robot-assisted migration (RAM) screening of ChemoCentryx drug-like small molecule collection then advance agonist 'hits' to lead compound status. We will then perform full lead optimization of agonists and selection of clinical development candidates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMBINATORIAL APPROACHES TO ANTI-SMALLPOX AGENTS Principal Investigator & Institution: Pirrung, Micheal C. Chemistry; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004

14 Smallpox

Summary: (adapted from the application): The long-term goal of this research is to develop novel anti-biological threat agents using combinatorial methods. The specific objectives of this program are the development of novel anti-smallpox agents. The main projects involve: preparation of libraries of drug-like molecules by high-throughput, parallel synthesis methods, and combinatorial biosynthesis for testing in highthroughput screens. The targets include vaccinia topoisomerase and H1-phosphatase. This project will utilize the following methods: (1) organic synthesis, both in solution and on the solid phase, and combinatorial chemistry; (2) microbial molecular genetics, combinatorial biosynthesis and natural product fermentation; and (3) viral molecular genetics, heterologous protein expression, in vitro enzyme assays, and antiviral assays in tissue culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF T CELL RESPONSE DURING RESPIRATORY INFECTION Principal Investigator & Institution: Alexander-Miller, Martha A. Assistant Professor; Microbiology and Immunology; Wake Forest University Health Sciences WinstonSalem, NC 27157 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): There is an emerging threat of the use of respiratory pathogens as weapons of bioterrorism. Thus it is imperative that we understand the interaction of viral pathogens with the immune response in the specialized microenvironment of the lung. Although a number of pathogens pose a threat, of particular concern is variola virus. Infection with variola virus results not only in significant morbidity, but in significant fatality. As a result of the eradication of smallpox, the vaccine was discontinued in 1973, leaving those under the age of 30 unprotected. In addition there is significant concern regarding the length of time protection is sustained following immunization, such that older individuals are also likely to be susceptible to infection and disease. Surprisingly in spite of the development of an effective vaccine for variola virus, many questions remain in our basic understanding of the interaction of this virus with the host immune response. We have developed a model for respiratory infection with vaccinia virus, the closely related virus used in the vaccine against smallpox. An advantage of the studies in this application is that they focus on the immune response following intranasal infection, the natural route by which variola virus is obtained and a likely route of inoculation for agents of bioterrorism. The studies in this application build on our published novel observation that the CD8+T cell response following intranasal infection of mice with a high dose of vaccinia virus is severely decreased compared to mice receiving 100-fold less virus. The goal of the studies proposed herein is the identification of the mechanism(s) responsible for the decreased T cell response. In aim 1 we will determine whether the reduced response following high dose infection is the result of the inefficient activation/expansion of cells or whether anergy and/or apoptosis is induced in responding CD8+ T cells. In aim two the contribution of antigen presenting cells to the reduced CD8+T cell response observed following high dose infection will be evaluated. The results from these studies will provide new and important information on the negative regulation of the immune response following respiratory infection and may lead to the development of novel therapeutics that can be used to boost the immune response following respiratory infection with viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 15

•

Project Title: CORE--INFORMATICS Principal Investigator & Institution: Gerstein, Mark; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): This Biomedical Informatics Core (BIC) will provide informatics services to support the basic science, preclinical and clinical research programs in each of the NBC research themes (Bacterial Pathogenesis and Therapeutics, Viral Pathogenesis and Therapeutics, B-Cell Related Prophylaxis and Therapeutics, Vaccine Platforms, Diagnostics, and Clinical Paradigms and Immunology: Smallpox). BIC will simultaneously pursue research projects in genomics, proteomics, structural biology, preclinical and clinical informatics designed to 1) rapidly characterize and identify virulent factors of pathogen genomes, 2) delineate the relationship of the pathogen genome to other known genomes, and 3) to provide rapid large scale functional annotation to assist in the immobilization of the pathogen. The resulting set of disparate data will be integrated with BIC services in a Pathogen Platform software environment that can be readily accessed by the appropriate NBC researchers. Thus, the two missions of the BIC will enrich one another. Additionally, the BIC will provide services addressing 1) the storage (a Digital Pathogen Facility/Bank for annotated genome and pre-clinical data), 2) transfer (education on secure file transfer using the SFTP protocol, or the PGP-based encryption of e-mails) and 3) manipulation of sensitive pathogen data in a secure digital laboratory environment (Digital Pathogen Facility of the Pathogen Platform software environment). To understand pathogen biology, pathogen-host interactions, and pursue rational approaches to vaccines and therapeutics, investigators will need to integrate an increasingly large and complex wealth of clinical, genomic, and proteomic data. Research problems will emerge through efforts to address service needs. The ability of the BIC to anticipate and respond to challenges will be enhanced by research programs pursued by members of the BIC. In periods of emergency, the BIC will rapidly realign it activities in coordination with the NBC to assist response efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DECIPHERING TOXIN NEUTRALIZATION BY OLIGOCLONAL ANTIBODY Principal Investigator & Institution: Marks, James D. Professor; Anesthesia and Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): BoNTs are classified as one of the six highest-risk threat agents for bioterrorism (the 'Class A agents'). BoNTs have been produced and weaponized by rogue nations and deployed by terrorist groups. As a result, specific pharmaceuticals are needed for prevention and treatment of intoxication. The goal of this application is to generate a novel Ab that can be used to prevent and treat disease caused by BoNT/A. This application builds on work showing that BoNT/A can be potently neutralized in vivo by combining three mAbs, which recognize the toxin domain (Hc), which binds cellular receptors (oligoclonal Ab). Toxin neutralization by oligoclonal Ab results from a large increase in the affinity of Ab for toxin as well as progressive blockade of the toxin surface interacting with cellular receptors. The precise contribution of these two mechanisms to toxin neutralization is unknown, as is the requirement for mAbs to the toxin-binding domain vs. mAbs to other parts of the toxin.

16 Smallpox

Two important questions remain prior to producing a BoNT/A Ab therapeutic: I) Can the potency of oligoclonal Ab be reproduced in a single mAb (or mAb pair) by significantly increasing the affinity of the mAbs?; and 2) can a similar potency be achieved using mAbs to non-binding domains of the toxin? Reducing the number of mAbs would greatly simplify the complexity and cost of Ab manufacturing. Using nonbinding domain mAbs would demonstrate that potent toxin neutralization does not require mAb binding toxin epitopes that interact with cellular receptors. This would simplify identification of neutralizing Abs. In addition, such mAbs would allow neutralization of second generation BoNTs, where the binding domain has been replaced with a receptor ligand. To determine the impact of affinity on BoNT/A neutralization, the affinity of two mAbs, which bind BoNT/A and neutralize toxin in vitro, will be increased at least 100 fold using in vitro mutagenesis and selection. The impact of affinity on in vitro and in vivo toxin neutralization will be determined for the single mAbs, a combination of the mAb pairs, and oligoclonal Abs. To determine the ability of non-binding domain BoNT/A Abs to neutralize toxin, phage Abs recognizing non-binding domain portions of BoNT/A will be generated and characterized with respect to affinity, epitope, and ability to neutralize toxin in vitro and in vivo. In vitro and in vivo characterization will be performed on individual mAbs, as well as combinations of binding domain and non-binding domain mAbs. Answering the above questions will generate a pharmaceutical for prevention and treatment of BoNT/A disease and also provide a route to similar pharmaceuticals for other BoNT serotypes. In addition, this approach would be applicable to four of the other Class A agents (anthrax, smallpox, plague, and hemorrhagic fever viruses). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEFENSE AGAINST BIOWARFARE AND EMERGING INFECTION AGENTS Principal Investigator & Institution: Levine, Myron M. Director, Ctr for Vaccine Development; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) whose theme is "Defense Against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; and development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg viruses); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of Francisella tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; and attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; and diagnostics for detection of these pathogens in water, food, and

Studies 17

environmental specimens); and 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; and innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and four Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A SAFER SMALLPOX VACCINE Principal Investigator & Institution: Cho, Michael W. Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Smallpox, which is caused by variola virus, is a highly contagious disease with a high fatality rate. A successful, worldwide vaccination campaign during the 1950s-l970s, using live vaccinia virus, resulted in eradication of smallpox. However, there remains a remote, but distinct possibility that large stockpiles of the virus may have been produced and stored as a part of bioweapons program in some countries or by terrorist organizations that are presently hostile to the United States. Smallpox poses a grave danger as an agent of biological weapon because of its highly contagious nature. Since vaccination against the disease stopped during early 1970s in the U.S., a large number of the young generation is unvaccinated and vulnerable to possible bioterrorist attacks. Although existing smallpox vaccine is relatively safe, it is not without serious medical complications including eczema vaccinatum, vaccinia necrosum, and encephalitis. Given the high frequency of AIDS patients who are immunodeficient, use of the current vaccine could result in a serious public health disaster. Therefore, it is imperative to consider developing a secondgeneration smallpox vaccine that is safer, yet as effective as the existing vaccine. Presently, variola virus is not available to perform additional research and the immune correlate of protection against either variola or vaccinia virus is largely unknown. Given these circumstances, a study is proposed with a long-term goal of developing a safer smallpox vaccine, with the following specific aims: (1) to characterize humoral and cellular immune responses against vaccinia virus in macaques previously immunized with the virus; (2) to evaluate immunogenicity and degree of attenuation of three recombinant vaccinia viruses derived from two different vaccinia strains (Western Reserve and Wyeth) in mice; and (3) to compare immunogenicity and safety of the newly generated vaccinia virus(es) with those of currently licensed smallpox vaccine strain in macaques previously infected with chimeric SlV/HIV -1 (SHIV). A successful completion of the proposed projects would allow better understanding of immune correlates of protection against vaccinia virus and could facilitate development of a safer smallpox vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

18 Smallpox

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Project Title: DEVELOPMENT OF A VIRUS VECTOR VACCINE AGAINST ANTHRAX Principal Investigator & Institution: Krajcsi, Peter; Virrx, Inc. 1609 Adgers Wharf Dr St. Louis, MO 63017 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2003 Summary: (provided by applicant): The events on and following September 11, 2001 have revealed our nation's vulnerability to terrorist attacks. Although much talked about during the past decade, the threat of a bioterrorist attack against the United States was not realized until the intentional distribution of weapons grade Bacillus anthracis via the U.S. postal service. These attacks combined with questions concerning the safety of the current vaccine against B. anthracis warrant the rapid development of a new B. anthracis vaccine that is both safe and effective. Using the most recent technological advances in vaccine research, a novel vaccine will be developed that relies upon simultaneous expression of mutant forms of B. anthracis Protective Antigen (PA) and Lethal Factor (LF) in each of two different types of viral vectors. The first vector will be based on vaccinia virus, the virus that was used to eradicate smallpox. The MVA strain of vaccinia virus will be used to construct the vector inasmuch as this strain is attenuated and has been proven to be safe in humans. The second vector will be based on a replication-competent adenovirus vector, allowing high-level expression of the target antigens. A number of vaccine and cancer gene therapy vectors have been developed using replication-competent adenoviruses, emphasizing their safety in humans. The vaccinia- and adenovirus-based vectors will be evaluated individually and in combination for their ability to induce humoral and cell-mediated immune responses in a mouse model. It is anticipated that a prime and boost protocol in which the mice are first immunized with one vector and then immunity is boosted using the second vector will be most effective at generating a robust immune response to the PA and LF antigens. It is anticipated that in a Phase II application, the ability of these two vectors to protect from B. anthracis challenge will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT

DEVELOPMENT

OF

AN

ORAL

DRUG

FOR

SMALLPOX

Principal Investigator & Institution: Painter, George R.; Chimerix, Inc. 4401 Eastgate Mall, Ste 1058 San Diego, CA 92121 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): An orally active antiviral drug for the treatment of smallpox infection resulting from biowarfare or bioterrorism is needed as an alternative therapy for the estimated 40 million Americans who cannot be safely vaccinated. Although Cidofovir (CDV, Vistide(r)) inhibits poxvirus replication in cell culture and in mouse models, it must be administered by intravenous infusion and has shown a high level of nephrotoxicity. Novel, lipid ether conjugates of CDV have recently been described that inhibit smallpox replication in cell culture, and prevent mortality in mouse models of poxvirus infection after oral dosing. In addition, tissue distribution experiments indicate that the lipid-CDV conjugates are not deposited in the kidney, suggesting the possibility of diminished nephrotoxicity. This proposal includes the work necessary to choose a development candidate for the treatment of smallpox from two lead lipid-CDV conjugates (HDP-CDV and ODE-CDV), and to file an IND and conduct a Phase I clinical trial to assess the safety, tolerability and pharmacokinetics of this candidate. Specific aims and milestones that represent critical activities and key

Studies 19

decisions in this proposal are: 1. Synthesize and characterize adequate drug substance to complete Aims 2 through 4. Characterization will include preformulation studies. Alternative routes of synthesis will also be examined. 2. Compare the pharmacokinetics and organ distribution of HDP-CDV and ODE-CDV in mice after oral dosing. 3. Compare the toxicological profiles of oral HDP-CDV and ODE-CDV in a 14-day dose range finding study in mice. 4. Compare the oral efficacy of HDP-CDV and ODE-CDV in mice infected with vaccinia, cowpox and ectromelia virus. The data generated in aims 1 through 4 will be used to choose which candidate to carry into full development (first milestone). At this point a pre-IND meeting will be requested with the FDA to discuss the proposed development plans. 5. Complete absorption, distribution, metabolism and elimination studies necessary to file an IND. 6. Produce cGMP drug substance for use in toxicology studies and Phase I clinical trials. 7. Conduct GLP safety pharmacology and toxicology studies necessary to file an IND. 8. Evaluate the efficacy of the lead compound in the cynomolgus monkey model of smallpox infection in collaboration with USAMRIID. Under the animal efficacy rule (Federal Register 67:37988-98, 2002), this study could provide the efficacy data necessary for FDA approval. 9. Manufacture prototype formulations, and produce cGMP clinical trials material. A Phase I protocol will be finalized in collaboration with the NIAID, and an IND will be filed with the FDA (second milestone). Upon FDA approval, a Phase I trial will be initiated to evaluate the safety, tolerability and pharmacokinetics of a single, escalating dose in human volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF POXVIRUS PROTEINASE INHIBITORS Principal Investigator & Institution: Hruby, Dennis E. Chief Scientific Officer; Microbiology; Oregon State University Corvallis, OR 973391086 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2003 Summary: Smallpox virus and/or genetically-engineered orthopoxvimses are considered one of the most significant threats for malevolent use as potential agents of bioterrorism. Because smallpox was eliminated from the U.S. population in the 1960's, prophylactic immunization was discontinued. The subsequent 40 years have produced a population that is immunologically naive and highly susceptible to orthopoxvirus infection. Due to the small but significant risk of serious complications from vaccination, mass immunization of the populace is contra-indicated. 'Therefore, the focus of the experiments outlined in this proposal is to develop an effective anti-poxvirus drug for use in treating or preventing human disease caused by pathogenic poxviruses. The target of our antiviral drug development efforts will be the poxvirus proteinase responsible for core protein maturation, a step which is absolutely essential for the production and spread of infectious virions. This project will be carried out as a partnership between an academic group at Oregon State University with a long history of research in various aspects of poxvirus proteolysis, and a biopharmaceutical company, SIGA Research Laboratories, which is actively engaged in the development of proteinase inhibitors as anti- infectives. Together, these groups will identify' the viral gene product responsible for catalyzing core protein maturation and use genetic approaches to validate it as an antiviral target. Expression vector technology will be used to express and purify the large quantities of the core protein proteinase. The purified proteinase will serve as the starting material for a two-pronged approach to the identification of potential inhibitors: l) Structure-function analysis coupled with rational drug design; and 2) Development of an in vitro cleavage assay appropriate for use in high-throughput screening against limited libraries of potential proteinase inhibitors.

20 Smallpox

Lead compounds identified by either approach will be tested for the ability to inhibit the replication of various orthopoxviruses in tissue culture cells. If necessary, lead compounds will be subjected to iterative chemistry to improve bioavailability, specificity and potency. The most promising optimized lead compound(s) will then be selected and advanced into preclinical and toxicology studies in preparation for in vivo testing in a murine and1or primate challenge in collaboration with NIAID and USAMRIID investigators. It is anticipated that the results of these experiments will identify one or more antiviral drugs as development candidates to provide a rapidresponse defense against the deliberate introduction of a pathogenic poxvirus into the environment. An event which we all hope never transpires, but for which preparation is vital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF THERAPEUTIC ANTIBODIES FOR VACCINIA VIRUS Principal Investigator & Institution: Cohen, Gary H. Professor and Chair; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): In response to the possible release of smallpox (variola) by bioterrorists, vaccinia virus (VV) vaccination of an at-risk population is the only available prophylactic intervention. However, the vaccine has known complications, especially in immunocompromised hosts, pregnant women and infants. In past vaccination efforts, such complications were treated in the U.S. with vaccinia human immune globulin (VIG) obtained from VV immunized people. Although this material had efficacy, little is known about which components of the immune globulin were effective and there could be batch-to-batch variation in efficacy. Moreover, since routine vaccination has been discontinued for many years, there is only a limited supply of VIG available, and there are concerns about its safety. Our long-term goal is to develop a cocktail of defined and high affinity antibodies to VV proteins that will replace the use of traditional VIG in the event that mass VV vaccination is needed. Our strategy is to develop monoclonal antibodies to various VV envelope proteins that are known to provoke a neutralizing and/or protective response in a mouse model. A cocktail of such antibodies, which we will call VIG-R (replacement) will provide a uniform and secure source of a VV immune therapeutic reagent. In this application, we propose experiments in four specific aims. These are: 1) to express and characterize VV envelope proteins LIR, A33R and B5R in a baculovirus expression system and to prepare mouse and rabbit antibodies to those proteins; 2) to develop and characterize human monoclonal antibodies to LIR, A33R and BSR produced using phage display; and 3) to test the ability of immune reagents against VV proteins to protect mice from challenge with VV. Fulfillment of the aims of this grant should provide new information about each of the VV proteins and antibodies, as well as a source of reagents that can comprise a VIG-R. If our approach appears promising, we will expand this study to include other VV proteins. The reagents developed in this grant application will also be valuable for basic studies concerning the role of these proteins in the VV life cycle and could themselves be considered as vaccine candidates in future investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DEVELOPMENTAL RESEARCH Principal Investigator & Institution: Baseman, Joel B. Professor & Chair; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225

Studies 21

Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: The Developmental Research plan provides for the critical selection, nurturing, development, oversight and management of nascent research programs that is needed to implement a highly relevant and productive program. It will function as an integral component of the Region VI RCE's mission by opening up new lines of research and relevant product development. The plan takes advantage of the region's wealth of relevant scientific expertise to allow for maximal utilization of Developmental Research as a tool to explore promising research leads. The scientific leadership for research projects will be provided both by investigators who are already established in biodefense research, as well as others willing to apply their expertise to a novel aspect of product-oriented biodefense research. In this way, the Developmental Research program will complement the Career Development program in increasing the numbers of dedicated biodefense investigators. An essential feature of this plan is a systematic and rigorous management approach that will allow for the selection of the most relevant and scientifically sound research projects and that will allow for an effective monitoring and evaluation process. The Program will be managed by an Associate Director of the RCE and will draw upon the expertise of the RCE Scientific Advisory Board to reach decisions concerning continued support of productive developmental research versus early discontinuation of unproductive projects, and selection of new projects for funding under this program, thereby contributing to the establishment of a product development pipeline within the RCE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISCOVERY OF ANTIVIRALS AGAINST VACCINIA AND SMALLPOX Principal Investigator & Institution: Ricciardi, Robert P. Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): There is a mounting concern that terrorist groups may possess or can obtain their own stocks of variola virus, the etiological agent of smallpox infection. To respond to this specific threat, the United States must have at its disposal supplies of both vaccinia virus vaccine and antiviral compounds directed against smallpox infection. The antiviral compounds are needed in situations in which the vaccine is contraindicated, such as immunosuppression. In addition, the antiviral compounds are needed to blunt adverse complications that are known to be associated with vaccine administration. An ideal antiviral should also be able to directly prevent smallpox infection in situations where vaccine delivery is delayed. Toward this end, antivirals directed against the vaccinia virus DNA polymerase (V AC-POL) and processivity factor (V AC-PF) have great potential. In general, PFs act as clamps that slide along the DNA and bind to their respective POLs. Through this POL/PF interaction, DNA synthesis will be processive, generating new DNA strands that are thousands of nucleotides long. Viruses that have mutated PFs are defective in replication since POL alone can synthesize only short DNA products (as few as three nucleotides). A strongly favorable feature of PFs is that they function with their own POLs, so that an antiviral that targets a viral PF should be very specific and not interfere with cellular replication. V AC-POL and V AC-PF interaction has been recently characterized and both proteins can be purified and combined to function in processive DNA synthesis. The goal of this project is to discover antivirals that will specifically block processive DNA synthesis by V AC-POL and V AC-PF. A newly developed mechanistic rapid plate assay will be used to screen thousands of potentially inhibitory

22 Smallpox

compounds. This high throughput screening will be followed by procedures to evaluate the inhibitory compounds and to ultimately test their ability to block vaccinia virus infection. A drug that prevents vaccinia processive DNA synthesis will be useful in curtailing vaccinia vaccine complications. The same drug may also directly block variola infection since the POLs and PFs, respectively, of vaccinia and variola have 97% direct homology. The approach may help deliver the 'just-in-time' need for reagents to combat a smallpox bioterrorism threat. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISCOVERY OF SUBUNIT VACCINES FOR SMALLPOX Principal Investigator & Institution: Sykes, Kathryn F.; Macrogenics, Inc. 1500 E Gude Dr, Ste B Rockville, MD 20850 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: Eradication of smallpox as a natural pathogen happened 20 years ago. Eradication of smallpox as a biothreat is now our objective. New stockpiles of safe and efficacious smallpox vaccine are needed to protect both the civilian and military populations against deliberate release of the smallpox virus. Currently there is no commercially available vaccine, and the previously approved one is a live vaccinia inoculum associated with more adverse events than any other approved vaccine. Recent work has focused on improving the manufacturing process of the original vaccinia vaccine strain and testing other live attenuated viruses. We propose to discover new vaccine candidates from viral components. A subunit design would be safer and more easily controlled during manufacture. Since we anticipate obtaining multiple protective subunits, these can be mixed and matched to effectively defend against wild type, natural variants, and bioengineered smallpox isolates. To identify antigens of smallpox that carry vaccine potential, the goal of our proposed project is to screen all the genes of the closely related cowpox virus for their ability to protect against disease in its natural murine host. This genome-level approach is feasible because the viral genome databases are available and we have developed the platform technologies that make a comprehensive screen fast and efficient. We will establish the electronic and molecular protocols to synthetically generate a thousand codon-optimized gene sequences. It will be used to produce a library of high quality cowpox subgenes. An advanced library screening method employing multiplex arrays will enable us to screen all the subgenes for protection in one experiment. Vaccine candidates will be confirmed and immune characterized. Both the cowpox candidates and their variola homologs will be formatted three ways and evaluated in immune and cowpox protection assays. This project will uncover new subunit vaccine candidates against variola and prepare them for final validation in a primate challenge experiment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DNAVACCINE DENGUE/VACCINIA

DELIVERY

FOR

BIODEFENSE

WITH

Principal Investigator & Institution: King, Alan D. Chief Scientific Officer; Cyto Pulse Sciences, Inc. 7513 Connelley Dr, Ste C Hanover, MD 21076 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term project objective is the commercialization of a safe, effective, easy to use, and painless polynucleotide vaccine delivery system that can be used in polynucleotide vaccines for biodefense against NIAID Category A, B and C Pathogens. Polynucleotide vaccines are on the forefront of

Studies 23

vaccine development. They are important because of the fast development times possible and because cell mediated immune responses can be induced. The delivery system proposed here will be effective for most polynucleotide vaccines. This delivery system specifically addresses the requirement as presented in the NIAID Strategic Plan for Biodefense Research, February 2002, page 8. In addition to Biodefense, this system will provide effective polynucleotide vaccine delivery for less lethal viruses, some cancers and some third world diseases. The defense and commercial applications are extensive. The polynucleotide vaccine delivery system described here uses a microneedle array with the polynucleotide coated right on the needle in the array. There are hundreds of needles each about 0.15 mm long. This array in inserted into the skin with the needle penetrating to about the basal lamina. After insertion the polynucleotide leaves the needle surface and an electric field is used to permeabilize dendritic and epithelial cell membranes to permit the polynucleotide to enter the cell. The system will be tested with the WRAIR/Cyto Pulse dengue DNA vaccine which will be used as a model for hemorrhagic fever viruses and the USAMRIID vaccinia DNA plasmid which is the primary vaccine for small pox. The specific aims of this project are to design and develop to FDA QSR Standards the vaccine delivery system prototype and to test the prototype in a human trial. This is a fast-track application. In Phase I, a system design will be completed including the hand-piece, microneedle array and miniature waveform generator. The coating chemistry and specific waveforms will be optimized in mice. In Phase II, a prototype of the final design will be completed. Safety and efficacy will be demonstrated in mice and safety will be demonstrated in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOMINANCE VACCINATION

IN

T

CELL

RESPONSES

TO

SMALLPOX

Principal Investigator & Institution: Sette, Alessandro B. Head and Member; La Jolla Institute for Allergy/Immunolgy Allergy and Immunology San Diego, CA 921211118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Vaccination against variola virus (the causative agent of smallpox) is currently accomplished by vaccinia virus. Little is known about 1) the antigens and epitopes targeted by the cellular responses in humans immunized with vaccinia virus, and 2) which responses are crossreactive with variola virus and hence would be expected to contribute to the protection engendered by the vaccine. In the first part of the studies proposed herein, we will 1) determine immunodominant antigens recognized by Class I and Class II restricted responses in humans immunized with vaccinia virus, 2) map the epitopes recognized within each antigen, and 3) determine their degree of crossreactivity with homologous variola virus-derived sequences. We anticipate that these studies will lead to the definition of a broad range of epitopes, facilitate a rigorous definition of correlates of protection against smallpox infection in humans, and also enable the evaluation of the performance of different vaccine candidates. Vaccinia virus is also actively investigated as a potential vaccine delivery vehicle, either alone or in prime/boost regimens, for disease indications such as HIV, malaria and cancer. Thus, it should be noted that identification and characterization of the determinants recognized by humans infected/vaccinated by vaccinia virus would also enable the characterization and optimization of experimental vaccines utilizing vaccinia virus-derived vectors as a delivery system. The vaccinia-based vaccines currently available, while effective, are associated with significant and serious, albeit rare, side effects. Because of these side effects, and because of the worldwide eradication of variola virus, vaccination of the general population was deemed as no longer

24 Smallpox

desirable. Recent renewed concerns have been raised over bioterrorist use of the virus. In the context of the studies proposed herein, a concern could be raised that if the vaccinia-induced protection is mediated by relatively few immunodominant and crossreactive antigens, a modified smallpox virus could be engineered that lacks those crossreactive epitopes. Under this terrifying scenario, the protection elicited by the vaccinia would be ineffective against the biological weapon. In the second part of the grant, we propose to counter this risk through the identification of variola virus-specific determinants derived from immunodominant antigens in the context of the vaccinia virus responses, but not crossreactive with the homologous variola virus sequences. These variola virus-derived epitopes would be incorporated in an optimized multideterminant vaccine construct, inserted in the currently available vaccinia vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL CONSEQUENCES OF VACCINATION IN AD TG MICE Principal Investigator & Institution: Morgan, David G. Pharmacology and Therapeutics; University of South Florida 4202 E Fowler Ave Tampa, FL 33620 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 30-JUN-2005 Summary: (Adapted from the Investigator's Abstract): Vaccination is the only prophylactic or therapeutic intervention that has ever eliminated a disease (e.g. smallpox). It also has well established utility in disease therapy (e.g. rabies). Transgenic mouse models of Alzheimer's disease (AD) develop high density A-beta deposits in cerebral cortex and hippocampus, neuritic changes and, ultimately, inflammatory reactions to these deposits. Recently, vaccination of the PDAPP transgenic mouse with A-beta peptide was found to prevent A-beta deposition in the brain. Unfortunately, the functional consequences of this treatment could not be effectively assessed in these mice, owing to severe learning and memory deficiencies observed early in the lifespan. The investigators propose to assess the functional consequences of vaccination in their doubly transgenic mAPP/mPS1 -mouse model of AD. These mice develop learning and memory deficits which correlate with the accumulation of A-beta, deposits. They will test whether vaccines that prevents/reduces A-beta accumulation can either attenuate or aggravate the behavioral deficits found in these mice. They predict different outcomes depending on the age of vaccination. They will verify histopathologically and biochemically that the vaccines reduce A-beta loads in the CNS, while carefully documenting the degree of inflammation found in these mice. In addition to testing the vaccination hypothesis, these data will address the question of A-beta amyloid's role in cognitive dysfunction. Anticipating that prophylactic vaccination at early ages will ameliorate some of the behavioral deficits normally occurring in these mice, they'll investigate alternatives to the A-beta1-42 peptide as vaccines, and test their effectiveness in old as well as young mice. One less expensive alterative to peptides are DNA vaccines, a novel inoculation technique which elicits both humoral and cellular immunity. This technology is already in human clinical trials. Passive immunization with polyclonal and monoclonal antibody preparations is an alterative to vaccines that will be tested for efficacy in this animal model. Advantages of passive immunization are safety and potentially greater effectiveness in older individuals with poor immunization responses to vaccines. Together, these later studies will determine the relative contributions of humoral and cellular immune reactions in mediating the effects of vaccines in transgenic mouse models of AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 25

•

Project Title: POXVIRUSES

GENERATION

OF

PROTECTION

AGAINST

'STEALTH'

Principal Investigator & Institution: Ramsay, Alistair J. Professor; Medicine; Louisiana State Univ Hsc New Orleans New Orleans, LA 70112 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Smallpox virus is a major threat for bio-terrorist attacks since the majority of the population is now susceptible following its eradication from the wild. Vaccinia virus (VV) vaccine stocks are now very limited and serious concerns have been raised about the safety and long-term usefulness of VV immunization prompting urgent calls for improved vaccination strategies. Cause for further alarm is that poxviruses, among a variety of pathogens, may relatively easily be engineered to increase their virulence, often rendering host immune responses ineffective. Such 'stealth' viruses may even overcome immunity in previously vaccinated individuals. The primary focus of this application is to evaluate novel strategies against highly virulent poxviruses and against stealth viruses with a capacity to suppress host antiviral immunity. Recently we developed a consecutive DNA/poxvirus "prime-boost" protocol that induces unprecedented levels of antiviral immunity of high avidity for the immunizing antigen. T cell responses are characterized by high levels of IFNg production and are sustained for months, being rapidly activated upon re-exposure to antigen. Here, we will determine whether these special qualities render prime-boost vaccinees protection against virulent poxvirus infection. Our vaccines comprise (i) novel DNA plasmids encoding immunogenic poxvirus proteins, bearing highly adjuvant backbones, and (ii) attenuated poxviruses (VV and fowlpox). Initially, combinations of DNA/poxvirus and poxvirus/poxvirus will be tested and T and B cell responses characterized and correlated with protective efficacy after challenge with viruses of high (ectromelia, mousepox) or relatively low (VV) virulence. Next, the most immunogenic of these strategies will be tested against infection with immunosuppressive stealth viruses. To facilitate these studies, we developed a mouse model of infection with ectromelia encoding IL-4 (EV-IL-4). This virus displays remarkably increased pathogenicity through inhibition of antiviral T cell responses and, strikingly, has a high mortality rate, even in EV- and VV - immune animals. Finally, we will use this model to test whether direct neutralization of a viral virulence factor (i.e. encoded IL-4) represents an effective therapeutic strategy. This application addresses important objectives of the RFA of direct relevance to development of safer and more effective vaccination strategies against virulent poxviruses and has implications for prophylaxis of other pathogens posing grave threats as potential bio-weapons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HETEROPOLYMER COMPLICATIONS

SYSTEM

TO

TREAT

VACCINIA

Principal Investigator & Institution: Pincus, Steven E.; Elusys Therapeutics 10 Bloomfield Ave Pine Brook, NJ 07058 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Smallpox is a particularly dangerous biological weapon because it can be manufactured in large quantities, stored for an extended period of time, and delivered as an infectious aerosol. It is highly infectious and has a death rate as high as 25%. The only approved smallpox vaccine (live vaccinia virus) is available in very limited quantities (15.4 million doses) and is decades old. Current efforts are underway to produce enough vaccine to vaccinate the entire US population.

26 Smallpox

A problem with this vaccination strategy is that a large segment of the population is susceptible to severe adverse reactions associated with the vaccine, including bloodborne dissemination of the vaccinia virus and even death. This threat is even greater now than when smallpox vaccinations were routine (prior to 1974) due to the growing population of immunosuppressed individuals. The broad long-term objective of the project is to develop bispecific antibodies (Heteropolymers, HPs) for treatment of complications associated with the administration of smallpox vaccine. In the present work, we hypothesize that vaccinia virus, the active component of smallpox vaccine, can be bound to erythrocytes (Es) via HPs, cleared to acceptor macrophages, and destroyed without killing the target cells. The HPs will consist of one monoclonal antibody (MAb) against a vaccinia protein expressed on the surface of extracellular (EEV) or intracellular (IMV) virus, cross-linked to a second MAb specific for E Complement Receptor Type I (CR1). The goal of the present work is to identify at least one anti-vaccinia HP that will be a candidate for use in future primate studies to establish efficacy against vaccinia complications following administration to immunocompromised animals. To achieve that goal, we will screen the anti-vaccinia MAb panel to identify the high affinity antibodies that bind EEV or IMV forms in solution phase and, preferably, neutralize the virus. The selected MAbs will be used to prepare HPs by cross-Iinking to a MAb specific for human E CR1. The ability of these HPs to bind EEV or IMV forms of vaccinia and transfer it to acceptor macrophages will be tested. We will also determine whether HP bound vaccinia is infectious. We will determine whether these HPs can prevent vaccinia virus spread and pathology in immunocompromised transgenic mice (expressing human CR1). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH TITER VIG FOR THE TREATMENT OF SMALLPOX Principal Investigator & Institution: Nur, Israel; Omrix Biopharmaceuticals Science Park Bldg 14 Nes-Ziona, Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Long-term objectives Based on preliminary studies on Israeli volunteers, it was concluded that only 60% of the population revaccinated against Smallpox reacted to the vaccine, of whom only 10% did so at very high titers. The aim of this R&D project is to develop and produce a high-titer, small volume Vaccinia Immune Globulin (HT-VIG) as an effective countermeasure to Smallpox and the side effects of the Vaccinia vaccine, which can be administered by intra-muscular or intra-venous mutes, including self-injection. The resulting product will be at least ten times more concentrated than existing VIG preparations that are based on immunoglobulin preparations from non-selected, pooled plasma, and it will have greater efficacy. Importantly, it will be a safe and effective prophylactic treatment against Smallpox for people excluded from the Vaccinia vaccination due to immunodeficiency or other risk factors. Given the heightened risk of a Smallpox outbreak due to bio-terrorism, the project's importance and health relevance cannot be underestimated. Specific Aims Omrix' existing ELISA test will be validated, establishing the correlation between it and the standard Vaccinia neutralization assay. The validated ELISA test will be used to determine the level of anti-Vaccinia immunoglobulins in human plasma samples. Following that, the ELISA will be used to screen USA plasma derived from re-vaccinated donors and select high titer anti Vaccinia plasma samples. These samples will be used to produce a limited number of batches of High-Titer VIG, which will then be characterized by use of the ELISA test and the standard Vaccinia Neutralization Bioassay. Development of a concentrated HT-VIG formulation for either

Studies 27

small volume IV or IM administration. Research Design & Methods As well as employing standard operating procedures for plasma collection and fractionation, innovative methodology will be employed in two areas of the program: 1) a new validated ELISA screening test will enable selection of very high titer plasma samples resulting in a high potency, small volume HT-VIG product; 2) the development of the HT-VIG product will include the new viral removal steps developed by Omrix, such as nano-filtration and solvent detergent treatment, which exhibit high margins of viral inactivation of all known viruses, including Parvo-viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST PROTEINS IN VACCINIA VIRAL MEMBRANE BIOGENESIS Principal Investigator & Institution: Hsu, Victor W. Assistant Profesor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Much interest exists in understanding the replication of vaccinia virus, as it represents the model system to understand poxviruses that include variola virus, the causative agent of smallpox. A key phase of viral replication involves the acquisition of membranes, as this event transforms noninfectious assembling viral cores into infectious virions. Accumulated evidence suggests that the virus acquires two set of membranes from organellar compartments of the host. The inner set of membranes is derived from the Endoplasmic Reticulum Golgi Intermediate Compartment (ERGIC) to form an intracellular mature virus (IMV), while the outer set of membranes is subsequently acquired from the trans-Golgi network to form an intracellular envelope virus. Viral proteins that participate in membrane wrapping are beginning to be identified, but host proteins that would also be predicted to play a key role during this process, as the membranes are derived from host organelles, have remained unknown. In preliminary studies, we have found that vaccinia virus specifically concentrates a host protein, a subunit of the COPI coat complex, on its inner set of membranes. Thus, we propose to elucidate how the COPI coat complex might play a role in viral biogenesis. First, we will determine the stage of viral biogenesis when COPI is first detected on viral membranes. Second, we will determine which viral stage might be arrested when COPI function is abrogated. Third, we will determine whether the virus usurps any of the known host regulatory proteins to recruit COPI onto viral membranes. Fourth, we will test whether any of the current known viral proteins that regulate viral morphogenesis affects COPI recruitment onto viral membranes. These sequential approaches also suggest a systematic way of identifying potential other host proteins that would be predicted to affect IMV formation, as it is the first stage that the virus becomes infectious. Thus, we will screen the currently known transport regulators that function at the ERGIC compartment to test whether any is similarly enriched on viral membranes. Subsequently, the function of candidate host proteins will be abrogated to determine whether viral biogenesis is affected. These efforts will likely not only provide a better understanding of how the virus interacts with its host during replication, but also suggest novel biochemical targets in the future rational design of therapeutic intervention against poxviruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HOST RESPONSES TO SMALLPOX AND MONKEYPOX Principal Investigator & Institution: Relman, David A. Assistant Professor; Microbiology and Immunology; Stanford University Stanford, CA 94305

28 Smallpox

Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): Despite the almost unparalleled impact of small pox on human history, our knowledge and understanding of the molecular and cellular biology and the pathophysiology of Variola infection are severely limited, as a paradoxical result of the eradication of naturally-occurring smallpox in 1977 and the ensuing restrictions on work with the Variola virus. Today, as we face the suddenly renewed threat of smallpox outbreaks, there is an urgent need to develop, as quickly as possible, a systematic understanding of the molecular, cellular and organismal biology of Variola infection. A detailed understanding of the molecular and cellular events in smallpox infection will provide a crucial foundation for rational development of strategies for treating the disease and managing its spread. The recent emergence of significant Monkeypox outbreaks in the human population in Africa highlights the broader importance of orthopoxviruses as potential threats to public health. Parallel studies of Monkeypox and Vaccinia will therefore be important elements of a comprehensive strategy to map the common molecular features of poxvirus infection and to define the unique mechanisms that Variola and Monkeypox employ to thwart or subvert the host's defense mechanisms. The long-term objectives of this proposal are to elucidate the replication and virulence mechanisms of Variola virus and related poxviruses in their primate hosts, and provide insights and tools that can lead to diagnostic, therapeutic, and preventative strategies for smallpox and other poxvirus diseases. The short-term objectives are to construct a systematic, detailed map of the viral and host gene expression programs in Variola and Monkeypox infections, to relate specific features of the gene expression programs to cellular molecular and physiological features of the host-virus interactions, and to characterize the molecular mechanism of a viral strategy for thwarting a critical host defense mechanism. The specific aims of this proposal are 1) to characterize Variola virus and Monkeypox virus infection of primate cells, with emphasis on cytokine and receptor expression, gIobal host and viral gene expression profiles, and host cell response as a function of cell type; 2) to characterize the responses of cynomolgus macaques to infection by Variola and Monkeypox viruses, with emphasis on host defense molecules, pathology, cell tropism; and correlations with gene expression patterns; and 3) to define the molecular mechanisms used by Variola and Monkeypox viruses to alter host interferon responses in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN IMMUNITY TO VACCINIA VIRUS Principal Investigator & Institution: Kazura, James W. Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Current policy to protect Americans against smallpox mandates immunization of naive and previously vaccinated adults with live vaccinla virus (VV). Knowledge of adaptive immunity to VV is limited to descriptions of neutralizing antibodies, cytotoxic T lymphocyte (CTL) activity, and lymphocyte proliferation responses, largely because widespread vaccination ceased before the current era of molecular immunology. Research in this project will examine the evolution of VVspecific memory T cells in newly vaccinated and re-vaccinated (boosted) adults. The relationship of VV-specific adaptive immunity to viral load and innate immunity will be determined in conjunction with projects by Storch and Stanley. The specific aims are to: 1. Identify immunodominant VV epitopes that induce CD8+ T cell memory. Artificial neural networks and computational algorithms will initially be used to select peptide

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epitopes, followed by evaluation of peptide binding to HLA class I alleles and assessment of the ability of peptides to stimulate IFN-gamma and IL-2 responses by HLA-matched and HLA-mismatched primary vaccinees and adults given booster doses of VV. 2. Determine the functional phenotype of CD8+ cells during the inductive and memory phases of adaptive immunity to VV. HLA class I tetramer-peptide complexes will be used to identify and quantify CD8+ cells bearing TCR specific for VV epitopes before vaccination and 9 days, 6, 12, and 24 months post-vaccination. Lymphocytes producing putative mediators of immunity (IFN-gamma, perforin, MIP-1alpha) and bearing memory markers (CD45RO, CD45RA, CCR7) will be evaluated prospectively in primary vaccinees and boosted adults. 3. Evaluate the clonotypic repertoire of VVspecific CD8+ cells following primary vaccination and boosting of previously vaccinated adults. TCR Vbeta usage and CDR3 length and sequence polymorphism will be evaluated prospectively in selected HLA-A2+ and HLA-A11+ individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN MONOCLONAL ANTIBODIES TO REPLACE VIG FOR THERAPY Principal Investigator & Institution: Cavacini, Lisa A.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Prior to Edward Jenner's demonstration in 1796 that immunization with cowpox protected against smallpox infection, virtually everyone contracted smallpox with mortality as high or higher than 30%. A global campaign using vaccinia immunization for protection from smallpox infection resulted in the eradication of smallpox in 1977. Subsequently the WHO recommended that all countries cease vaccination and laboratory stocks be destroyed or transferred to one of two repositories at the CDC in the United States or the Institute of Virus Preparations in Moscow, Russia. Routine vaccination in the United States has not occurred for more than thirty years. Therefore, the vast majority of the population is at risk of smallpox infection. Just as smallpox was used as a bioweapon prior to the development of vaccination, it currently represents a potential biological weapon with the majority of the world population at risk. Vaccination within the first few days after exposure is effective at preventing infection in some with a significant decrease in mortality. However, there are rare and serious complications in some vaccinated individuals. The vaccination is contraindicated in a number of groups of people. Vaccinia immune globulin (VIG) has been used as prophylaxis for treating individuals for which contra indications exist for smallpox vaccine and for treatment of those with complications of vaccinations. With the threat of smallpox being used as an agent of bioterrorism, it is prudent to develop alternatives for the use of VIG for prophylaxis and treatment. Supplies of VIG are scarce given that individuals have not been systematically vaccinated for more than 30 years. Furthermore, the validation and safety of VIG remains an issue. Therefore, we propose to generate human monoclonal antibodies as a replacement for VIG. Monoclonal antibodies can be produced with exquisite specificity and can be modified to enhance functional activity. The use of fully human monoclonal antibodies eliminates problems associated with xenogeneic, chimeric or humanized antibodies which include immunogenicity, biological half-life, and inefficient effector function. The development of a cocktail of human monoclonal antibodies that neutralize virus and/or mediate antibody-dependent cellular cytotoxicity can serve as a safe, effective replacement for VIG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE EVASION MECHANISMS OF ECTROMELIA VIRUS Principal Investigator & Institution: Fremont, Daved H. Assistant Professor of Pathology; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Poxviruses are a family of large DNA viruses that encode up to 200 distinct open reading frames. The large size of the poxvirus genome is an important feature that has allowed them to acquire multiple immunomodulatory genes and thereby evolve unique strategies for evasion from host anti-viral responses. Ectromelia virus (EV) is a member of the orthopoxvirus family and is a highly virulent rodent pathogen that causes the disease mousepox. EV is similar to variola virus, the causative agent of human smallpox. Our primary hypothesis is that secreted and cell membrane associated proteins encoded by EV likely serve important roles in viral evasion of host mediated innate and adaptive immune responses. Using a bioinformatics approach coupled to the established literature, we have selected 28 target proteins from the EV Moscow strain genome that will be investigated by a combination of biochemical, functional, and crystallographic tools in a high-throughput, structural genomics style approach. Our primary targets of investigation include the seven known cytokine and chemokine decoy receptors encoded by the virus that are specific for TNF, CD30L, IL-18, IFN-alpha, IFN-gamma, IL-1beta, and CC-chemokines. We are also targeting three proteins with sequence similarity to natural killer receptors of the C-type lectin family. We have the following specific aims for the exploration of these potential agents of immune subterfuge: (1) Establish baculovirus and bacterial oxidative refolding expression systems for targeted EV encoded proteins to be used in functional and structural studies; (2) Identify and characterize the interactions between EV proteins and their host ligands and receptors; (3) Determine the structural basis of EV protein function by x-ray crystallography and structure-based mutagenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNODOMINANT EPITOPES OF A SMALLPOX VACCINE IN HUMANS Principal Investigator & Institution: Buller, Mark R. Professor; Molecular Microbiol and Immun; St. Louis University St. Louis, MO 63110 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The zenith of the disease smallpox and its eradication in 1977 from human populations occurred prior to the modern era of immunology and molecular biology. Consequently there is little knowledge concerning the immune correlates for recovery from smallpox or the cross-reactive proteins expressed by baccinia virus that were responsible for its success as the smallpox vaccine. The only vaccination indicator that correlated with protection from severe smallpox was the scar. In response to the threat of bioterrorism, the U.S. government has redoubled its efforts to provide strategies that will protect the American public from an outbreak of smallpox or human monkeypox. As part of a comprehensive, multifaceted plan, the U.S. government has contracted with Acambis Inc. and Baxter Healthcare Corp. to produce approximately 209 million doses of a new tissue culture smallpox vaccine. In addition, proposals are being considered for the next generation of smallpox vaccine that will have an enhanced safety profile, causing fewer vaccinerelated complications, especially in immunosuppressed individuals. Evaluating the efficacy of the new Acambis and Baxter vaccine or other second-generation vaccines with enhanced safety profiles will be problematic without detailed knowledge of the

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immunogenicity of vaccines proven to be efficacious in the smallpox eradication program. Detailed studies on human B and T cell immune responses to proteins encoded by vaccinia virus should help fill this gap in knowledge, and may also identify targets of neutralizing, complement-fixation or ADCC (antibody-dependent cell cytotoxity) antibodies, which may facilitate the development of an efficacious replacement for VIG. We propose to characterize the vaccinia virus-encoded proteins recognized by B and T cell responses during the vaccination of volunteers with the DryVax vaccine. The Specific Aims are to: 1. Characterize the antibody responses to immunodominant vaccinia virus proteins and 2. Identify the epitope specificity of representative vaccinia virus-specific T cell clones. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOGENETICS OF SMALLPOX VACCINATION Principal Investigator & Institution: Stanley, Samuel L. Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The goal of this project is to identify genes that are involved in susceptibility and resistance to human vaccinia infection, and, consequently, in some of the adverse effects seen with smallpox vaccination. We (R.B.B.) recently led a multi-center prospective study on the clinical response to vaccinia immunization in 680 naive individuals. Among the 665 individuals responding to the vaccine, 84 (13%) developed fever, muscle aches and lymphadenopathy giving rise to what we have called Acute Vaccinia Syndrome (AVS) in approximately 30% of vaccines. The timing of the onset of these symptoms matched the timing of the highest levels of viral shedding, indicating that fever, and the other components of AVS appear to be secondary to the virus. We hypothesize that individuals developing AVS (and especially fever) have diseasepredisposing alleles that are associated with abnormal innate immune or delayed adaptive immune responses to vaccinia. These individuals may be more susceptible to poxviruses in general, and could constitute a group at increased risk for mortality if exposed to smallpox. We propose to identify genes that are expressed in response to vaccinia infection at the site of inoculation and systemically using a transcriptional analysis. We will compare responses between individuals that develop AVS, and those individuals who develop no adverse reactions to immunization. These studies will provide us with a transcriptional profile of the host response to vaccinia infection, identify key molecules in the host response, and, establish parameters for protective immune responses that could be used to test the efficacy of new vaccines. We will also identify alleles associated with adverse effects to vaccinia immunization and abnormal innate immune responses to the virus through the analysis of haplotypes based on single nucleotide polymorphisms in candidate genes. The identify of these alleles may provide clues to the critical elements of the host response to poxvirus, and could provide a method to identify individuals at increased risk for adverse effects to the vaccine, or more severe disease with poxvirus infection. The design of the study, with the inclusion of transcriptional profiling of individuals receiving vaccinia immunization coupled with a detailed virologic and immunologic profile, ensures that we will obtain valuable information on the host response to vaccinia immunization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVING HEALTHCARE RESPONSES TO BIOTERRORIST EVENTS Principal Investigator & Institution: Miller, George J.; Altarum Institute Box 134001, 3520 Green Ct, Ste 300 Ann Arbor, MI 481051579 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2006 Summary: The Altarum Institute and its partners are pleased to submit this response to the Grant Opportunity provided by the Agency for Healthcare Research and Quality (AHRQ) by focusing the proposed Partnership for Quality on application of Modeling and Simulation Informatics to enhance both Rural and Urban Health Systems Homeland Security and Readiness. The United States faces a shortfall in our ability to quantitatively assess the robustness of the U.S. medical infrastructure in responding to various terrorist threats or combinations of these threats. Simulation modeling provides a tool for considering these complex scenarios, which literally cannot be solved through actual experimentation due to cost, logistical or other considerations. Under this grant application, Altarum and its partners, the Michigan Center for Biological Information, the University of Michigan Department of Emergency Medicine, and the Texas Community Emergency Health Care Initiative (CEHI) propose testing a simulation model called the Healthcare Complex Model (HCM) for its utility and validity to support bioterrorism readiness planning. We propose that during Phase I, we test and validate the HCM's ability to support planning for a rural healthcare network and identify further enhancements needed in the model for urban settings. In first year of Phase II, we propose that modeling capabilities be enhanced by applying the HCM in an actual urban scenario with our partners in Michigan. In Phase II years 2 and 3, we propose further testing with increasingly larger and more complex networks under different bioterrorism attack scenarios. One of the significant benefits from this Grant will be objectively documented outcomes and outputs which are derived from the application of HCM (under our study rural vs. urban setting) in terms of delivery system, staffing, supplies, patient flow, etc. Such information will prove useful to develop a consistent and coherent framework for biodefense preparedness training by forming the basis of the useful "case studies" for the full range of training modalities employed and reviewed in the AHRQ Evidence Report # 51 and could mitigate the effect of inconsistent objectives and methods from the heterogeneous training by building more consistent training curricula as well as content. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERACTIVE OUTBREAK RESPONSE INFORMATION TRIAGE SYSTEM Principal Investigator & Institution: Powell, Tracey T.; Home Access Health Corporation 2401 W Hassell Rd, Ste 1510 Hoffman Estates, IL 60195 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Health organizations often have difficulty managing daily demands for services. A major disease outbreak or bioterrorism attack will gridlock the system. Accessa, with technical assistance from Ingham County Public Health Service (ICPHS), will develop and validate an outbreak response system intended to assist public health departments handle high call volumes and allay public fear. This rules-based Internet and interactive voice response system will disseminate information, automatically triage high volumes of citizen information requests, and assess the probability of exposure and transfer high-risk individuals for appropriate intervention. It will provide coded number, quality controlled and medically directed

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Internet and/or telephone two-way communication for test scheduling, results reporting to facilitate case management. In Phase I, Accessa will utilize interviews, questionnaires and Nominal Group Process sessions to conduct a needs assessment, complete system design and produce a prototype module on smallpox. The prototype module will be validated by separate focus groups made up of health officials and lay public. in Phase II, Accessa will construct a scalable system and conduct a statistically valid evaluation comparing ASR to current ICPHS response services, in a virtual event simulation. A framework for additional disease modules will also be constructed. A panel of recognized experts will review activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KAPOSIN AND LANA-1 OF HHV8 AS VACCINE TARGETS Principal Investigator & Institution: Srinivasan, Alagarsamy; Professor; Microbiology and Immunology; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Given the oncogenic capabilities of HHV-8, it has been suggested that an understanding of the viral genes with the potential to induce transformation of cells may contribute towards the elucidation of KS pathogenesis. In addition, such genes may also serve as ideal targets for both therapeutic and vaccine interventions. For this purpose, we have considered HHV-8 genes which are expressed during latency, as tumor 'spindle" cells of KS and B-cells are latently infected with HHV8. Of the genes encoded by HHV-8 with transformation potential [K1, glycoprotein; k9, interferon regulatory factor; K12, kaposin; orf73, latency-associated antigen (LANA-1); and orf74, a vlL-8 receptor homolog ], kaposin and LANA-1 are transcribed in latently infected cells along with v-cyclin and v-FLIP. Both v-cyclin and v-FLIP are viral homologs of cellular genes and thus may not be suitable as targets for vaccine strategies due to autoimmunity. This has prompted us to initiate work on Kaposin and LANA-1 as the likely viral target proteins for vaccine approaches to induce immunity against HHV8. The recent demonstration of CTL epitopes in Kaposin further lends supports to this concept. Vaccines have been successfully used against viral infections (smallpox, polio, varicella) in the past and the correlates of protective immunity may include both the humoral and cellular responses. Based on this, we hypothesize that the expression of Kaposin and LANA-1, in the absence of other HHV-8 proteins, may lead to an induction of potent and durable humoral and cellular immune responses which may be of value in eliminating cells infected with HHV-8 and interfering with the development of KS. Towards this, we propose the following aims: i) to generate DNA vaccine vectors encoding native and modified forms of Kaposin and LANA-1. ii) Characterize the cellular and humoral immune responses against Kaposin and LANA-1 using mice as the animal model, iii) Strategies to enhance the immune responses against Kaposin, and iv) to assess the level of protection induced by latent genes using tumor cells expressing viral proteins as the challenge model. The results from these studies are likely to provide baseline information for further exploration in the development of vaccines against HHV-8. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANSIM OF DEXH/D PROTEINS Principal Investigator & Institution: Jankowsky, Eckhard; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106

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Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): DExH/D proteins are involved in virtually all aspects of RNA metabolism in the cell and in many viruses. Numerous proteins from this family have been shown to play direct roles in disease states such as in tumorigenesis and in the replication of the hepatitis C and the smallpox virus. DExH/D proteins unwind RNA structures (RNA helicase) and/or re-arrange RNA-protein complexes (RNPase) in an ATP-dependent fashion. Despite the biological importance of DExH/D proteins, their mechanism of action is not understood, mainly due to the highly complex nature of the reactions. We propose to gain essential insight into these questions by employing single molecule fluorescence in conjunction with biochemical approaches to investigate the prototypical DExH/D protein NPH-II from vaccinia virus. First, we will develop a mechanistic framework for RNA helicase activity at the single molecule level to address the fundamental question the how DExH/D proteins use ATP to effect conformational changes in RNA. Using single molecule fluorescence energy transfer (FRET) we will determine how ATP binding and hydrolysis is coupled to conformational changes in the RNA, to the oligomeric state of NPH-II, and to the translocation of NPH-II during duplex unwinding. Second, we will probe translocation of NPH-II along single stranded RNA. It has been hypothesized that an ability to translocate along single stranded RNA could give rise to the multiple activities of DExH/D proteins such as duplex unwinding and remodeling of RNA protein complexes. Yet, translocation along single stranded RNA has never been tested. We will directly test whether NPH-II translocates along single stranded RNA using single molecule FRET. Third, we will investigate the physical basis of RNPase activity. Employing a biochemical approach, we will test whether DExH/D proteins displace other proteins from RNA through direct physical contact, or through induction of torsional strain in the RNA to flip other proteins off the RNA. In addition we will investigate how NPH-II couples ATP binding and hydrolysis to the remodeling of RNAprotein complexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMBRANE-STABILIZED LYMPHOTOXIN AS A VACCINE ADJUVANT Principal Investigator & Institution: Cantwell, Mark J.; Tragen Pharmaceutics 10150 Sorrento Valley Rd, Ste100 San Diego, CA 92121 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-NOV-2003 Summary: (provided by applicant): Recent events have re-emphasized the need for the development of methods to potentiate or expand the stocks of currently available vaccines. This is especially true for those vaccines that protect against biological agents that have the greatest potential to inflict widespread morbidity and mortality, such as smallpox and anthrax. Available vaccines that target these biologic agents were developed decades ago and the anti-microbial protection these vaccines afford are rather limited. Furthermore, production of these vaccines was curtailed years ago and the availability of the remaining vaccine stocks is limited. Thus, there is an urgent need to identify adjuvant methods that either shorten the time required to achieve protective immunization or allow for immunization with either less vaccine or fewer injections per person, thereby effectively expanding the number of doses available with current vaccine stocks. To address this issue, Tragen Pharmaceuticals is developing novel adjuvants from members of the tumor necrosis factor family. One such adjuvant we have developed is a membrane-stabilized form of lymphotoxin. Through membranestabilization, Tragen Pharmaceuticals aims to increase the therapeutic activity of

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lymphotoxin while eliminating the systemic toxicity of the native form of this molecule that has prevented its use as a therapeutic product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTIPLEX PCR DETECTION OF CDC 'A' BIOTERRORISM AGENTS Principal Investigator & Institution: Henrickson, Kelly J. Associate Professor; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Anthrax and other agents of biological warfare have recently received intense publicity. These weapons are an increasingly fearsome danger to our civilization. Agents identified by the CDC (category "A") to pose the greatest threat include Variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum toxin (botulism), Francisella tularensis (tularemia), and a group of RNA viruses that cause hemorrhagic fevers (VHFs, e.g., Ebola). Accurate and efficient techniques to identify and diagnose these agents are severely limited. This lack of good diagnostic tests hampers the majority of goals set forth by the NIAID and CDC to prepare the U.S. to counter future bioterrorism attacks. Available older techniques have proven unreliable. Modern molecular tests like individual PCR assays have been developed for some agents. These offer increased speed and sensitivity but because there are so many bioterrorism agents it is prohibitive to run dozens of "singleplex" arrays on each specimen. Similarly, recently reported microchip (MAGI Chip) arrays and other microarrays suffer from either needing PCR amplification first, or from the high cost to make the arrays, and the need for sophisticated equipment. A single assay (or two) that could detect a large number of bioterrorism agents rapidly, sensitively, specifically, and cheaply would greatly enhance antiterrorism planning and biodefense. Our laboratory has pioneered a method of multiplex PCR that can accomplish this goal. This proprietary method (two U.S. patents) has been used commercially in the Hexaplex(r) Assay, which can detect seven common respiratory viruses in a single test. The Specific Aims of this project are: 1) To determine if a multiplex PCR-enzyme hybridization assay (EHA) can be made using our unique technology that will identify all of the CDC Category "A" Bioterrorism agents that are DNA based; 2) RNA based; and finally 3) a single combined multiplex (RNA/DNA) PCR assay with an analytical sensitivity equal to "singleplex" real time assays as developed by the CDC. Specific Aim 4: To determine if this multiplex assay is equivalent to these "singleplex" assays in a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUTRALIZING ANTIBODIES AGAINST ORTHOPOX VIRUSES Principal Investigator & Institution: Burton, Dennis R. Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-MAY-2005 Summary: There is concern that variola virus, the causative agent of smallpox which was eradicated as a human pathogen more than two decades ago, forms a threat to humans once again, this time as an agent of bioterrorism. The use of variola virus in a bioterrorist attack would be met by the use of the licensed live vaccinia virus vaccine. This vaccine may cause serious side effects which can be successfully treated with vaccinia immune globulin (VIG) derived from hyperimmune individuals. VIG however is in short supply and future availability is uncertain, and in addition suffers from the

36 Smallpox

general concerns of using human blood products for therapeutic applications. This proposal aims to prepare and characterize human monoclonal antibodies against vaccinia virus which, likely formulated as an antibody cocktail, will constitute a replacement for VIG. We will isolate neutralizing antibodies against both infectious forms of vaccinia virus, i.e. intracellular mature virus (IMV) and extracellular enveloped virus (EEV). We will place particular emphasis on isolating antibodies against EEV, as EEV mediates dissemination of infection and is the viral form against which protective immune responses are directed. Inactivation of vaccinia virus will be studied in vitro and in vivo, and will be aimed at designing an antibody cocktail that provides protection against vaccinia virus infection in pre-exposure and post- exposure immunopropylaxis. The antibody cocktail designed may provide a treatment for smallpox itself. To examine the impact of passive immunization in immunoprophylaxis and immunotherapy of a smallpox-like disease in a non-human primate model, we will use an experimental model of monkeypox virus infection Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NORTHEAST BIODEFENSE CENTER Principal Investigator & Institution: Lipkin, W Ian. Professor; Wadsworth Center Empire State Plaza Albany, NY 12237 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The northeastern United States is highly vulnerable to emerging infectious diseases and terrorism. With the outbreak of West Nile virus, the World Trade Center tragedy, and subsequent anthrax attacks, Region II has the experience and resolve to mobilize its rich resources in biomedical research to advance the nation's biodefense agenda. Region II institutions will establish a Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Disease Research. This consortium, the Northeast Biodefense Center (NBC), will comprise investigators at more than 25 academic and research institutions in New York, New Jersey, Connecticut, Massachusetts and Puerto Rico. The NBC will have strong links to state, federal and local government agencies and laboratories, as well as biotech and pharmaceutical companies. Major basic and translational research programs will be pursued in six thematic areas: 1) B-Cell Related Prophylaxis and Therapeutics; 2) Bacterial Pathogenesis and Therapeutics; 3) Vaccine Platforms; 4) Viral Pathogenesis and Therapeutics; 5) Smallpox Vaccine: Clinical, Immune, and Viral Outcomes; 6) Pathogen Detection and Diagnostics. These programs will intersect with cores that provide support in Informatics, Proteomics, Protein Expression, Monoclonal Antibodies, Animal Models, as well as Administration. Each research program will integrate and intensify the work of several accomplished investigators and will focus on select agents and toxins including Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, Staphylococcus enterotoxin B, pox viruses, and viruses that cause hemorrhagic fever or encephalitis. Zoonotic diseases will be emphasized due to significance in this region, expertise of NBC members, and access to unique resources such as Plum Island Animal Disease Center and networks of investigators and clinicians in comparative medicine. Streamlined technology transfer procedures will be established to facilitate delivery to industry of vaccines, therapeutics, and diagnostics. The translational arm of the NBC has begun with a study of smallpox vaccination and will develop the region's infrastructure for human vaccine trials. Training programs will be established to promote biodefense research objectives by supporting new investigators, senior investigators, and support personnel. An emergency response plan has been developed

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to rapidly realign the NBC's activities and provide facilities, including cores and scientific support, to first line responders in the event of a biodefense emergency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL ADJUVANTS/DELIVERY SYSTEMS FOR BIODEFENSE VACCINES Principal Investigator & Institution: Valiante, Nicholas M. Director; Chiron Corporation 4560 Horton St Emeryville, CA 94608 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 28-FEB-2006 Summary: (provided by applicant): The quest for safer and more effective vaccines has taken on a sudden urgency with the very real threat of bioterrorism. Only a handful of vaccines covering a small proportion of potential biowarfare agents are available (e.g. anthrax and smallpox) and even these suffer from extremely poor safety profiles. Therefore, next generation vaccines for these and many other category A-C pathogens with improved safety and the capacity to induce more rapid, more potent and broader protection are needed. As part of our ongoing efforts to develop improved vaccines for a variety of bacterial and viral pathogens, we are developing novel and powerful vaccine delivery and adjuvant platforms that efficiently target the innate immune response. These platforms are ideally suited to meet many of the new challenges of biodefense vaccines. Specifically, we propose to use a powerful drug discovery engine aimed at identifying small molecule immune potentiators (SMIPs) and then optimizing their therapeutic indices through a reiterative hit-to-lead process. Lead compounds will be tested as adjuvants for subunit vaccines against category A-C pathogens in combination with microparticle delivery systems developed at Chiron. Our initial focus will be on enhancing the immunogenicity of recombinant protective antigen (rPA) from B. anthracis due to the fact that this is a well characterized antigen for a category A pathogen with an established record in challenge models. This will be done by first formulating rPA with our existing delivery systems and synthetic MPL derivatives to evaluate the general performance of these novel formulations in immunogenicity/ protection studies (Aim 1). Then in combination with our SMIP discovery efforts (Aim 2), optimized adjuvant-delivery formulations of rPA will be evaluated in animal models (Aim 3). Due to the flexibility of our platforms, other more experimental vaccine candidates such as capsular antigen for anthrax and candidate antigens for other potential bioterrorism agents (e.g.Y. pestis) will also be evaluated after proof of concept is achieved with the optimal adjuvant-delivery system combination for rPA. These efforts meet the near term needs for more effective and safer biodefense vaccines and set the foundation for improved innate immune-based therapies of the future through our SMIP design and discovery program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL TARGETS FOR TREATMENT OF SMALLPOX Principal Investigator & Institution: Shuman, Stewart H. Professor; Sloan-Kettering Institute for Cancer Res New York, NY 10021 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The goal of this project is to identify novel targets and drugs for the treatment and prophylaxis of smallpox. Anti-poxvirus drug targets are a pressing issue, given the concern that smallpox may be used as a bioterrorism weapon against an unvaccinated population. We propose to discover new inhibitors of poxvirus replication targeted to essential virus-encoded enzymes that are required for

38 Smallpox

viral gene expression and DNA metabolism. The poxvirus mRNA capping apparatus, consisting of RNA triphosphatase. RNA guanylyltransferase, and RNA (guanine-7)methyltransferase enzymes, is a promising drug target because the organization of the three catalytic sites is distinct from that of human host cell capping system. The poxvirus type 18 DNA topoisomerase is an attractive target in light of its unique DNA recognition specificity, compact structure, and distinctive pharmacological sensitivities compared to human topoisomerase I. The specific aims of this application are: (1) To identify small molecules that bind to the target viral enzymes by in vitro screening of an encoded split-synthesis combinatorial library immobilized on a solid bead support (one compound per bead). (2) To test the individual compounds identified in the primary screen for their ability to inhibit the catalytic activities of the target triphosphatase, guanylyltransferase, methyltransferase, and topoisomerase enzymes. (3) To dissect the mechanisms of inhibition of catalytic activity by the compounds identified in the secondary screen, via kinetic analysis of the component steps of the capping and topoisomerase reactions. (4) To assay the enzyme inhibitors for their effects on vaccinia virus replication in cell culture, using plaque reduction and one-step growth assay methods. (5) To evaluate the mechanism of antiviral action by assessing the effects of the lead drug compounds on the major landmarks of the poxvirus replication cycle: viral mRNA and protein synthesis, DNA replication, telomere resolution, and virion morphogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL VACCINES FOR SMALLPOX Principal Investigator & Institution: Weiner, David B. Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The current bioterrorism threat has refocused our nation on the issue of our population's susceptibility to a smallpox attack. As a precaution, deployment of dilution of the current stock of vaccine and deployment of a tissue culture version of the VACV vaccine have been requisitioned. This vaccine and likely the new stocks carried a risk of Significant Adverse Events of 1 per 10,000 vaccinated individuals. However, that vaccine was last used in a very different environment. The high-risk groups for AE's include the elderly, the very young, immunocompromised individuals and others. The percentage and absolute numbers of the US population that falls within these categories has risen dramatically in the past 30 years. The greater than 750,000 persons living in the US that are HIV-positive is one clear example. This suggests that the AE risk of the VACV may be unacceptable and can only be deployed as a last resort. However, the option of abandoning this approach and developing new approaches leaves us at risk for a possibly unknown period of time. The hypothesis to be tested in this application is that there is a third option, to develop a strategy that uses the current vaccine yet limits its pathogenesis while improving its potency. It is our hypothesis that priming with enhanced expressing plasmid vaccines that induce nonneutralizing cellular immune responses will prime for successful and even enhanced boosting with the current vaccine, yet limit its associated pathogenesis. This application will use quantitative T cell assays including Elispot and ICC and tetramer analysis, and novel human HLA+DR positive transgenic mice that we have developed to pursue the three specific aims. Novel cellular reagents including MHC class I tetramers will be developed that will have significant value in following VACV challenge in humans as they may be useful as cellular surrogates for the current site

Studies 39

reaction take. Together these studies will establish if this simple and novel approach can bridge the current situation and produce a safer more effective smallpox vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUCLEOSIDE THERAPEUTICS AGAINST POX AND FILO VIRUSES Principal Investigator & Institution: Nair, Vasu; Head; Auburn University at Auburn Auburn University, AL 36849 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The genus, Orthopoxvirus, of the Poxviridae family of viruses includes variola, cowpox, vaccinia and monkeypox viruses, all of which can cause very serious human infections. The etiologic agent of smallpox is the variola virus. Of the potential weapons of bioterrorism, smallpox poses one of the greatest threats. The family, Filoviridae, appears to have a single genus, Filovirus, and has two known species, Ebola and Marburg. They cause severe hemorrhagic fever with accompanying high rates of mortality. The potential use of these viruses in warfare or bioterrorism is also of very serious concern. There are no drugs available that provide significant protection against both the orthopoxviruses and the filoviruses. This project is concerned with the discovery of compounds of therapeutic significance against pox and filo viruses. Synthetic approaches to five classes of novel ribonucleosides bearing specifically modified surrogate nucleobases or surrogate carbohydrate moieties are planned. These target compounds have been molecularly designed to be potent potential inhibitors of viral replication through inhibition of inosine monophosphate dehydrogenase (IMPDH), or inhibition of viral RNA polymerases, or inhibition of viral mRNA capping or through a combination of these effects. Antiviral studies of the target compounds and selected monophosphates and their isosteres against orthopox, filo, and other viruses will be carried out through collaboration with a large team of virologists with expertise in the area of these viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORTHOPOX IMMUNIZATION IN NORMALS& PATIENTS WITH CANCER Principal Investigator & Institution: Reinherz, Ellis L. Chief; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): While worldwide eradication of smallpox represents a major accomplishment of medicine in the 20th century, use of this virus as a bioterrorism agent against our largely disease-susceptible civilian population could result in unprecedented mortality. Individuals at risk for live-virus vaccine complications, including those with cancer and eczema, comprise a large percentage of the US population, mandating against massive large-scale vaccination. Recent developments in immunology, both with regard to mechanistic understanding of adaptive and innate immune responses now allow for evaluation of the cellular and humoral bases of protective immunity against orthopox and other classes of viruses. These advances include details of immune recognition at a structural level, antigen presentation, cell migration and T cell memory. Here, four groups of investigators will utilize their considerable talents in vaccinology, virology, immunology, cutaneous biology, structure and bioinformatics to identify critical orthopox epitopes affording protective human immunity. Project 1 will examine protective immunity to vaccinia virus in normal and high-risk patients elicited during virus vaccination trials based on

40 Smallpox

parameters identified in Project 2. Project 2 will identify T cell epitopes shared by vaccinia, MVA and smallpox by genome-wide comparison using bioinformatics and position-specific scoring matrices, and confirmed by T cell functional assays and mass spectrometry. Antigen-specific T memory cells elicited through vaccination will be assessed by pMHC tetramers, conventional and new biomarkers of T cell memory and molecularly detailed T cell memory repertoires as examined by single cell PCR at different times post-vaccination. Likewise, targets and biophysical parameters of human neutralizing antibodies to vaccinia and variola, the latter in conjunction with CDC, will be identified using recombinant orthopox proteins, BIAcore, ELISA and neutralization studies. In Project 3, investigators from the Harvard Skin Disease Research Center will examine human skin elements of orthopox vaccinated normals or atopic dermatitis patients for productive viral infection, and compare and contrast the nature of central memory and skin homing effector T cells therein. Murine models using biologic response modifiers and transgenic mice will be exploited to examine how manipulation of the cutaneous environment alters vaccination efficacy. Project 4 will use contemporary molecular genetics to mutate vaccinia virus-Wyeth strain to lower virulence by deleting immune escape functions but maintaining host range, replication and immunogenicity. Pathogenicity and immunogenicity assessment will be in C57BL/6, transgenic or mutant mice using systematic, mucosal and dermal scarification infectious routes. An Educational Component, Pilot Project Component and Research Resource Technical Development Component are proposed for rapid dissemination of methods and reagents resulting from this Center's effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS ENTOMOPOXVIRUS

AND

GENE

REGULATION

OF

Principal Investigator & Institution: Moyer, Richard W. Professor; Molecular Genetics & Microbiol; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Entomopoxviruses (EPV's) are the most distant relatives of vertebrate orthopoxviruses (OPV's) such as vaccinia (VV) and variola (smallpox). Vertebrate poxviruses, are particularly masterful in deflecting the immune and other defense responses of the infected host. We have completed the genomic sequence of the EPV from Amsacta moorei (AmEPV), one of the few EPV's which can be easily grown in cell culture and readily manipulated. AmEPV, causes a lethal, disseminated infection of insects but is devoid of the immune modifier genes known to act as virulence factors of vertebrate poxviruses. We plan to focus on the major aspects of AmEPV infection of Lymantria dispar (LD) larvae as a model for the pathogenesis of poxviruses in lower eukaryotes. We have three Specific Aims. The first Specific Aim is to quantify and completely characterize the pathobiology of larvae infected with AmEPV by either direct injection or by feeding (per os). These studies will include a full time course of infection, evaluation of spread, yields and cellular involvement. In our second Specific Aim, we will determine why AmEPV, unlike any other known poxvirus encodes a third or "extra" subunit of the viral encoded poly (A) polymerase, an enzyme essential for viral mRNA synthesis. This unusual feature of the virus promises insight into some of the basic biology of gene expression governing all poxviruses. In our third Specific Aim, we will examine the role of specific genes on the pathobiology of AmEPV infections. We will initially concentrate on a "Kunitz-type" protease inhibitor and a 1365 amino acid ABC transporter gene neither of which have been reported in any other virus. We will begin by generating "knockouts" using a procedure which by design will

Studies 41

also tell us whether the gene is essential for growth. Virus deleted for the selected gene will be evaluated for effects on pathogenesis. We also plan to extend these studies and examine virus encoded superoxide dismutase (SOD) and inhibitor of apoptosis protein (IAP) as examples of other genes likely to play significant roles in the infectious process. Each gene will be evaluated for biochemical function. Collectively, the proposed experiments will elucidate added diversity by which viruses counter the defenses of host organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POX VIRUS IMMUNOLOGY AND VACCINE DEVELOPMENT Principal Investigator & Institution: Ahmed, Rafi; Director; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-DEC-2007 Summary: (provided by applicant): There is a serious need for a smallpox vaccine alternative because of the significant incidence of adverse events to the current vaccine (Dryvax). Large groups in the American population are not qualified to receive the current smallpox vaccine due to immunodeficiency (from genetic causes, HIV, or immunosuppressive drugs), old age, skin disorders, young age (< 1 yr), or pregnancy. These groups are major populations and must be accounted for in any reasonable national smallpox vaccination strategy. Therefore, assessment of the immunogenicity of alternative smallpox vaccines such as modified vaccinia Ankara (MVA) must be done accurately and expeditiously. Our access to samples from ongoing clinical trials of Dryvax and MVA, our expertise in quantitating both cellular and humoral immunity, and our immunologic proteomics approach places our research group in a unique position to address this important issue. Long term protective immunity to smallpox is likely provided by three arms of the immune system: circulating neutralizing antibodies, memory B cells, and memory T cells. Virtually none of the vaccinia protein targets responsible for these T cell, B cell, and neutralizing antibody responses have been identified. The experiments in this proposal are designed to determine the dominant anti-smallpox immune responses and to compare the magnitude and breadth of the T and B cell responses induced by Dryvax versus MVA. This valuable information will not only allow an accurate assessment of the quality of the immune responses elicited by the alternative smallpox vaccine MVA but can also then be immediately parlayed into additional areas of proposed research such as: 1) diagnostic tools for measuring long term smallpox immunity in vaccinees; 2) development of simple, rapid, and sensitive immunological tools for assessing recent smallpox (variola major) exposure/infection; and 3) development of therapeutic anti-smallpox neutralizing monoclonal human antibodies. Finally, the knowledge acquired from the detailed studies described herein regarding the immunodominant protein targets of human vaccinia-specific T and B cells will lay the foundation for developing a safe and effective smallpox subunit vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POXVIRUS AND MHC CLASS II ANTIGEN PRESENTATION Principal Investigator & Institution: Blum, Janice S. Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Poxviruses have evolved multiple mechanisms to modulate and evade host immunological responses. The orthopoxvirus, vaccinia is currently being employed as a vaccine to induce protective immunity and prevent transmission of the class A

42 Smallpox

bioterrorism agent, smallpox (variola). Immunization with vaccinia can induce both cellular and humoral immunity in humans, yet concerns have been raised with respect to vacccine efficiency, longevity and safety particularly with regards to immunocompromised individuals. Elucidating novel mechanisms of poxviral immune evasion, is therefore an important priority with regards to developing improved, safer vaccines. This proposal will test the hypothesis that vaccinia virus disrupts MHC class II-restricted antigen presentation, thus compromising the activation of host cellular immune responses during infection. Studies in humans indicate that months to years after immunization with vaccinia, virus-specific CD8+ and CD4+ T cells can be detected. Yet, an early, transient decrease in T cell responsiveness has been reported and linked to potential defects in antigen presentation. Pilot studies here demonstrated that vaccinia infection of professional antigen presenting cells disrupts MHC class II-restricted antigen presentation to T cells. Aim 1 of this proposal, will test whether viral inhibition of class II presentation is linked to the structure, abundance, or compartmentalization of an antigen. Aim 2 will determine whether vaccinia-derived proteins directly block the interaction of MHC class II molecules with T cell receptors, as well as investigating viral mechanisms to thwart antigen processing. Aim 3 will examine vaccinia viral infection in vivo, specifically monitoring early effects of the virus on class II presentation pathways within distinct antigen presenting cells. The overall goal of this work is to elucidate novel mechanisms by which vaccinia and other orthopoxviruses subvert MHC class II antigen processing and presentation. The results obtained should prove useful in the design of new interventions and improved vaccines to overcome the immunomodulatory properties of poxviruses and thus, enhance protective immunity. Class II presentation is an essential function of professional antigen presenting cells. Investigations here in project 4 are therefore, integral to the program's goal to define and understand mechanisms by which poxviruses subvert antigen presenting cell function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POXVIRUS IMMUNITY AND DNA/MVA HIV VACCINES Principal Investigator & Institution: Amara, Rama R. None; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-OCT-2007 Summary: (provided by applicant): We recently demonstrated the ability of an AIDS vaccine consisting of DNA priming and recombinant modified vaccinia Ankara (MVA) booster immunizations (DNA/MVA SHIV vaccine) to control a pathogenic SHIV 89.6P challenge that was administered seven months after the final immunization in macaques (Amara et. al., Science 292, 69-74, 2001). The prototype HIV-1 clade B version of our DNA/MVA vaccine (DNA/MVA HIV vaccine) is entering phase I safety trials in humans in January of 2003. Due to the recent bioterrorism threat the US government is prepared to vaccinate at least a subset of people with the current smallpox vaccine (Dryvax/New York Board of Health strain of vaccinia). The anti-vaccinia virus immunity generated by Dryvax may limit the boosting ability of MVA, hence the efficacy of DNA/MVA HIV vaccines. This is a very important question that needs to be addressed as DNA/MVA vaccines go forward in human trials. There is a serious need for a smallpox vaccine alternative because of the high incidence of adverse events to the current vaccine. Also, many people are not qualified to receive the current smallpox vaccine due to immunodeficiency, skin disorders, old age, young age (< 1 yr), or pregnancy. These groups are major populations and must be accounted for in any reasonable national smallpox vaccination strategy. MVA was developed towards the end of smallpox eradication for use in immunocompromised individuals and was used

Studies 43

to vaccinate about 120,000 individuals. However, because smallpox had been controlled in first world countries by the time that MVA was developed, individuals who were vaccinated with MVA were not exposed to variola, and the efficacy of MVA as a smallpox vaccine was not determined. In this proposal we wish to address 1) the effect of preexisting immunity to smallpox on the ability of DNA/MVA vaccine to control pathogenic SHIV challenge, 2) the ability of vaccinia-specific immune responses raised by DNA/MVA vaccine to protect from a lethal monkeypox challenge and 3) the ability of a candidate DNA/MVA vaccine to control both SHIV and monkeypox challenges that are administered sequentially in the presence and absence of preexisting immunity to smallpox. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POXVIRUS MODULATION OF DENDRITIC CELL-MEDIATED IMMUNITY Principal Investigator & Institution: Chang, Cheong H. Assistant Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: One of the strategies utilized by VV to evade the host immune surveillance is inhibition of dendritic cell (DC) maturation. DC maturation is defined functionally as the acquisition of potent xmmunogenic capacity. This includes up-regulation of surface MHC class I and class II molecules, as well as CD40, CD80, and CD86, which mediate efficient antigen presentation and stimulation of naive T cells. Mature dendritic cells (mDCs) also produce cytokines and chemokines and are responsible for directing T cells to a defined differentiation pathway, which in turn evokes a specific immune response. Although the significance of dendritic ceils (DCs) for a proper immune response is clear, very little is known regarding how W infection affects DC functions and host immune responses. We hypothesize that VV infection induces irreversible events in ammature DCs, which paralyze VV-infected DCs to respond to a maturation signal, resulting in the loss of VV-specific immunity, in a host. Therefore, the goal of this project is to test this hypothesis by investigating the underlying mechanisms of how VV modulates DCmediated immune responses. VV has been used as a vaccine for smallpox, and widely used as a vehicle to introduce a foreign gene to cells. If VV inhibits DC maturation, however, the usage of VV as a vaccine needs to be re-evaluated. A better understanding of DC maturation at a molecular level in the context of VV infection is crucial and required to design better strategies to prevent the loss of life and complications associated with viruses such as smallpox, which is the ultimate goal of the Program Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POXVIRUS PRESENTATION

PHOSPHATASE

INHIBITION

OF

ANTIGEN

Principal Investigator & Institution: Kaplan, Mark H. Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Smallpox results from infection with the poxvirus Variola. While the WHO has eradicated smallpox worldwide through vaccination programs, clandestine stores of Variola Virus still pose a potential threat from terrorist initiated biowarfare. Vaccination for smallpox is achieved through inoculation with Vaccinia virus, a highly related

44 Smallpox

poxvirus. While Variola infection is pathogenic and fatal in 30-40% of infected individuals, Vaccinia is immunizing and usually not associated with disease. There is no effective treatment for Variola infected patients. Identifying and working with potential targets for treatment of smallpox is thus important. However, work with Variola virus is not possible for both public safety and ethical concerns. The Vaccinia virus phosphatase, VH1, is critical for viral replication and may also play an important role in evasion of host defense during infection, possibly by interfering with the innate immune response stimulated by interferons. This phosphatase is conserved in most poxviral genomes, including Variola. Our goal in this project is to characterize the Vaccinia VH1, and by using site-directed mutagenesis to generate the smallpox phosphatase, compare the function of the Variola virus counterpart for their role in evading host defense. Our hypothesis is that the Variola phosphatase will function more efficiently than the Vaccinia counterpart and may contribute to the pathogenicity of Variola infection. Variola phosphatase may also offer an attractive target for pharmaceutical intervention of smallpox infection. The goals of this project will be achieved by examining the effects of Vaccinia and Variola phosphatase function on signaling and transcription factor activation, cytokine induced gene transcription and biological functions including cytokine production and antigen presentation. These studies will complement other projects in the Program that also examine aspects of poxvirus subversion of antigen presentation during infection. Our project examines one poxviral protein for its effects while other projects focus on whole virus. Thus, for a subset of viral responses, our studies may provide mechanism for poxviral-mediated alterations in antigen presentation. Overall, these studies will increase our understanding of poxvirus biology and poxvirus mediated immune evasion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POXVIRUS SCR-CONTAINING PROTEINS AS THERAPEUTIC TARGETS Principal Investigator & Institution: Isaacs, Stuart N. Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: The ability to vaccinate an at-risk civilian population with vaccinia virus is central to preparing for the potential threat of smallpox bioterrorism. However, a critical limitation of this strategy is the recognized complications of vaccinia vaccination, particularly in immunocompromised hosts, pregnant women, and infants. Therapeutic interventions currently available to counter such complications are inadequate and novel strategies are needed. We propose to develop such new therapies that target related, yet functionally distinct, vaccinia proteins. The vaccinia complement-control protein (VCP) and the extracellular enveloped virus (EEV)-specific B5R protein both contain short consensus repeat (SCR) units present in complement regulatory proteins. We have shown that VCP and the B5R proteins are critical for pathogenesis in vivo. VCP inhibits complement activation and helps the virus evade the host complement mediated attack. The B5R protein is essential for efficient viral dissemination. Our hypothesis is that these viral SCR-containing proteins have critical functions in pathogenesis that make them uniquely suited to serve as novel targets for therapeutic strategies directed at complications occurring during vaccinia immunization. Individuals with life-threatening vaccinia virus vaccine complications usually have defective cell-mediated or humoral immunity, but typically have intact innate immune function. A therapeutic inhibitor of VCP's complement control activity would therefore be a novel approach to managing vaccinia vaccine complications because such an

Studies 45

inhibitor would allow the host's innate immune system to regain control of the infection. In Specific Aim number 1, we will utilize phage library display to identify specific inhibitors of VCP that prevent its inhibition of the complement cascade. The B5R protein is one of several EEV-specific proteins. B5R also contains SCRs and, while complement regulatory activity has not been identified, we and others have demonstrated that B5R is critical for EEV formation and viral spread in vivo. In addition, recent reports have shown that B5R is one of the principal targets for EEV neutralizing antibodies. Thus, therapeutic targeting of B5R offers an additional way of controlling vaccinia virus replication and dissemination. In Specific Aim number 2 we will develop monoclonal antibodies (mAbs) to the B5R protein and identify mAbs that neutralize EEV. We believe that identification of such mAbs (along with a cocktail of humanized mAbs to other EEV-specific proteins) can form the basis for a passive immune neutralization strategy to control vaccinia virus vaccine complications. We anticipate that these proteins will provide novel targets for immunomodulation of vaccinia virus. In addition, because both VCP and BSR are present in variola virus, these new therapies may be effective against smallpox infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POXVIRUS VACCINE RESEARCH Principal Investigator & Institution: Isaacson, Stuart H.; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Bioterrorism with variola virus is of immense concern because (a) virtually the entire world population is susceptible since routine vaccination was discontinued; (b) there are no treatments; (c) the virus in aerosol form is stable; (d) the virus is transmissible person-to-person; and (e) infection results in high morbidity and mortality. Vaccination with vaccinia virus (VV) was a key factor in eradicating smallpox. The necessity to vaccinate an at-risk population with W is central to preparing for the potential threat of smallpox bioterrorism. However recognized complications of vaccinia vaccination, especially in immunocompromised hosts, pregnant women, and infants impose serious limitations of this strategy. In past vaccination efforts, such complications were treated in the U.S. with human vaccinia immune globulin (VIG) obtained from W immunized people. Current stocks of VIG are low, and while new stocks are being generated, there are still serious drawbacks to relying on a blood product. Consequently, there is a critical need to develop therapeutic interventions to counter complications from the current vaccine and to develop a safer vaccine. As part of the mid-Atlantic Regional Center of Excellence in Biodefense & Emerging Infectious Diseases, our poxvirus research project's hypothesis is that vaccine candidates and new therapies can be developed by understanding and targeting poxvirus proteins recognized by the humoral and innate immune system. To do this we will: 1. Develop a subunit vaccine against smallpox (variola) virus (Cohen/Eisenberg/Friedman, U. Penn) 2. Identify new targets of neutralizing antibody (Isaacs, U. Penn) 3. Identify the targets of VIG using a proteomics approach (Lambris, U. Penn) 4. Develop an ectromelia virus challenge system in the mouse as a model of smallpox pathogenesis and prevention (Braciale, U. Virginia) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

46 Smallpox

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Project Title: POXVIRUS/HOST INTERACTIONS OF THE D4R VIRULENCE FACTOR Principal Investigator & Institution: Gray, Todd A.; Wadsworth Center Empire State Plaza Albany, NY 12237 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2004 Summary: (provided by applicant): The objective of this project is to identify cellular targets of the smallpox D4R virulence factor, with the ultimate goal of identifying pharmacological inhibitors specific for the viral protein while minimizing deleterious effects on the homologous cellular proteins. We have identified and characterized the two primary cellular genes of the makorin (MKRN) gene family that encode proteins of unknown function containing multiple zinc-finger motifs. We also provide evidence that the poxvirulence factor, D4R, is derived from a transduced ancestral MKRN cDNA. D4R orthologs are frequently mutated in attenuated vaccinia viruses, and deletion of the mousepox orthologous p28 gene renders the virus non-lethal. Published and anecdotal evidence support a model in which D4R intervenes in a makorin pathway to prevent normal antiviral apoptotic culling. The molecular mechanism is likely to involve the conserved RING zinc-finger in the cellular and viral derivatives to function as an E3 ubiquitin ligase, targeting specific apoptotic regulators for degradation. It is anticipated that the cellular and viral proteins will have shared activity and specificity profiles. In this grant proposal, we would like to directly address these issues using a combination of mouse models and protein analyses. Our specific aims are: (1) to evaluate apoptotic roles for makorin-1, makorin-2, and D4R proteins in mouse models; (2) to determine molecular targets of makorin and D4R proteins; and (3) to assess whether the interacting targets are ubiquitinated by makorin and D4R proteins. Mouse models created in this proposal will be used for future in vivo studies of ectromelia virulence, and the identification of molecular targets of D4R/makorin proteins will provide insight into this important poxvirus/host cell interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF AIRBORNE SMALLPOX TRANSMISSION Principal Investigator & Institution: Milton, Donald K. Lecturer; Environmental Sci & Engineering; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Vaccine development alone may not be sufficient to protect the U.S. against bioterrorist attack with smallpox, especially against an engineered virus containing an IL4 gene. Major vulnerabilities remain, even with a wellorganized vaccination program in place, including mass disruption caused by fear of an epidemic and the morbidity and mortality of a nationwide smallpox vaccination program. Therefore, in response to the RRGP-BTRR request for "new prevention strategies for those at risk of exposure," we propose to investigate the effectiveness of ultraviolet (254 nm) germicidal irradiation (UVGI) as a strategy for preventing dissemination of variola major virus in hospitals and other public buildings. As a prevention strategy air sanitation has several important attributes: it can be deployed safely before an outbreak; it can build public confidence; it can limit the growth of an outbreak during the critical period prior to identification of the outbreak and the start of a vaccination campaign; and it can have public health benefits even if an attack with smallpox never occurs by reducing spread of other airborne infections. In this project, we will use a low virulence vaccinia virus strain, provided by Acambis Corp., as a

Studies 47

simulant for variola major. Initial experiments will be performed in a small aerosol chamber to validate sampling and analysis methods and to determine the UVGI induced exponential decay constants for vaccinia as a function of droplet nuclei size and relative humidity. Then, we will simulate "real world" conditions in a hospital room size chamber (4.5 m x 3 m x 2.9 m) to determine the utility of upper room UVGI for elimination of poxvirus aerosols. Aerosolized virus will be collected in a liquid swirling sampler and a cascade impactor and cultured to determine infectivity. Upper-room UVGI can potentially lower the concentration of infective organisms in the lower part of the room and thereby control the spread of airborne infections among room occupants, without exposing occupants to a significant amount of UV. This work will provide a sound scientific basis for decisions on whether to recommend wide spread implementation of upper room UVGI in hospitals and public buildings as a first line of defense against smallpox and other bioengineered airborne communicable infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PUBLIC HEALTH RESPONSE Principal Investigator & Institution: Burke, Donald S. Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: This "Public Health Response Research" project is submitted as one of six research projects in the application for a multi-institutional Middle Atlantic Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Diseases Research. The objective of this project is to immediately accelerate the clinical evaluation and deployment of new biomedical technologies that may be crucial for an effective public health 0response to a bioterrorism or emerging infectious disease event. The project encompasses three sub-projects, all of which involve immediate evaluation of novel biotechnologies in human subjects. Sub-project 1 is designed to rapidly transition novel needle-free technologies for vaccine administration into routine use. The specific aims of this sub-project are to evaluate cutaneously administered immunostimulatory patches to boost responses to anthrax vaccines and botulinum toxoid, to evaluate intranasal administration of recombinant anthrax protective antigen, and to evaluate jet injector administration of recombinant anthrax protective antigen. Sub-project 2 is designed to use measurements of peripheral blood lymphocyte gene expression profiles from vaccinated persons to improve the diagnosis, prognosis, and prevention of smallpox vaccine adverse events. The specific aims of this sub-project are to define the natural history of vaccinia-induced immune dysregulation, to correlate favorable and unfavorable outcomes with specific gene transcript profiles, and to use the technology to identify individuals at increased risk of vaccine adverse reactions. Sub-project 3 is designed to evaluate rapid innovative genomics- and proteomics-based diagnostic technologies in real emergency room settings. The specific aims of this project are to evaluate novel universal bacterial and viral diagnostics, to evaluate blood lymphocyte gene expression profiles in common febrile illnesses, like influenza, that could be mistaken for bioterror threats, and to use mass spectrometry-based proteomics on respired air from patients to diagnose acute pulmonary infections. As additional new genomics- and proteomics-based technologies are generated from the Middle Atlantic RCE and elsewhere, they will be rapidly evaluated for their utility in the public heath biodefense response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

48 Smallpox

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Project Title: RAPID TURN-AROUND TESTING FOR BIOTERRORISM AGENTS Principal Investigator & Institution: Prudent, James R. Chief Scientific Officer; Eragen Biosciences, Inc. 918 Deming Way, Ste 201 Madison, WI 53717 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 14-JAN-2003 Summary: (provided by applicant): The goal of this project, over Phase I and Phase II, is to develop and validate a new diagnostic platform for biowarfare detection that provides ultrafast design and implementation. Today, both the scientific and security communities believe that advances in biotechnology have increased the concern for misuse in biological weapon programs. As reports of anthrax attacks across the United States multiplied late last year, an increasing concern grew that new strains with altered genomes may appear. Therefore, new diagnostic technologies that provide quick turnaround assays to previously unknown biowarfare strains are needed. To this end, we developed a novel platform, GENE-CODE 2.0, that provides an ultraquick turnaround to real-time PCR genetic testing. GENE-CODE 2.0 employs an expanded genetic information system (AEGIS) that allows for site-specific enzymatic incorporation of reporter molecules during PCR. The platform has already been demonstrated to the commercial market for ultrasensitive quantitative anthrax detection. In Phase I we will design and demonstrate the platform on CDC Category A biological terror agents. In Phase II we will develop multiplexed systems to analyze multiple genetic sites within a given biowarfare agent with internal assay capabilities that will allow the manufacturer to change sequence specificity in an ultrafast manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGION VI CENTER FOR BIODEFENCE AND EMERGING INFECTIONS Principal Investigator & Institution: Walker, David H. Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): In response to NIAID's call for the creation of strong infrastructure and multifaceted research and development activities applying the best basic, translational, and clinical science to the generation of new diagnostic, therapeutic and vaccine countermeasures for Category A, B, and C pathogens posing threats as agents of bioterrorism, 22 institutions in Texas, New Mexico, Oklahoma, Arkansas, and Louisiana have combined their energy, creativity, and resources to propose creation of the Region Vl Center of Excellence for Biodefense and Emerging Infectious Diseases (Region Vl RCE). Nine scientific cores will provide access to state-of-the-art proteomics, genomics, standardized small animal and non-human primate models of infectious diseases, BSL-4 laboratory facilities, and GLP scale-up production, as well as crosscutting functions in computational biology and a streamlined process for translational development of vaccines and drugs leading to FDA approval. A wealth of scientific expertise on biothreat agents and contemporary biomedical technology will be applied to establishing the scientific basis and translating it through 11 major research projects, 3 developmental research projects, and 4 career development projects to the development of vaccines against Rift Valley fever, tularemia, smallpox, Venezuelan, eastern, and western equine encephalitis, brucellosis, and typhus; new therapeutic agents against Bacillus anthracis (including the spore), arenaviruses, filoviruses, alphaviruses, flaviviruses, and poxviruses, as well as novel approaches to synthesis of chemical libraries that will promote future drug discovery; and advanced diagnostic methods for Q fever and typhus as well as computational analysis of all host response

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biosignatures observed within the RCE for the construction of diagnostic and prognostic algorithms and analysis of host responses to infection and immunization. A consistently strong spirit of cooperation among traditionally competing institutions has established an interlocking network of projects, cores, and administration that will strengthen and flourish as the Center is implemented. The guidance of this network of interactive research projects and core resource facilities will be executed under a comprehensive administrative plan to contribute substantially to the nation's biodefense mission by fulfilling a carefully crafted scientific strategy on a common theme; Collaborations for host-pathogen biology based development of novel vaccines, diagnostics, and therapeutics against biothreat agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF THE E3L GENE IN POXVIRUS PATHOGENESIS Principal Investigator & Institution: Jacobs, Bertram L. Professor; Microbiology; Arizona State University P.O. Box 873503 Tempe, AZ 852873503 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The Aim of this proposal is to understand the function of one of the major vaccinia virus (VV) interferon (IFN)-resistance and neurovirulence genes, E3L. Since VV is the vaccine for smallpox, a potential biowarfare/bioterrorism agent, analysis of this virulence factor may lead to development of safer, more effective vaccines for defense against bioterrorism attacks. In addition, these safer, more effective strains of VV may be valuable for use of VV as a general vaccine vector. Since the E3L gene is highly conserved between VV and all strains of variola virus, the causative agent of smallpox, this work may lead to development of anti-smallpox drugs. The work described in this proposal will continue investigations into defining the roles that the biochemical characteristics of the E3Lencoded proteins play in evasion of the host defenses by VV. Mutants that separately affect each of the known biochemical characteristics associated with E3L-encoded proteins will be prepared and characterized. These well-characterized mutants will then be used to determine the role of each of the biochemical characteristics of E3L in each of the known biological functions of E3L, including pathogenesis in the mouse model. Finally, suppressor mutations will be obtained and analyzed for specific mutations in E3L. The E3L system is unique in allowing analysis of the function of this important virulence gene from the molecular level to the level of pathogenesis in a whole animal. Thus, this work will lead to translation of basic molecular knowledge of E3L function into clinically relevant applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SCANNING THE VACCINIA PROTEOME FOR ANTISMALLPOX ANTIGENS Principal Investigator & Institution: Roth, David A. Assistant Professor of Medicine; Gene Therapy Systems, Inc. 10190 Telesis Ct San Diego, CA 921212719 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2003 Summary: (provided by applicant): A technology developed by Gene Therapy Systems Inc. under a previously funded Phase I SBIR grant will be applied to producing the complete proteome from vaccinia virus and the proteome will be applied to the general problem of identifying potent vaccine antigens affective against smallpox. The technology called Transciptionally Active PCR (TAP) is a method for generating functional PCR fragments that can be used directly in in vitro transfection assays, and in

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vivo. TAP fragments can also be used as templates in cell free in vitro transcription/translation reactions generating >20 micrograms of protein/50 microliter reaction volume, and the TAP system has been placed onto a robotics workstation enabling 384 different purified proteins to be produced and purified in 1 day.This system will be used to amplify and purify all 266 proteins encoded by vaccinia virus and the proteins will be used to scan humoral and cellular immune responses in vaccinia virus vaccinated mice. In this way humoral and cellular "vaccine antigen potency indexes" will be generated for each antigen. These potency indexes will be used together with other immunological and bioinformatics criteria to identify likely candidate antigens for a DNA vaccine. Plasmids encoding the antigens identified in this way, will be injected into mice and the mice will be challenged with an infectious dose of virus to determine DNA vaccine efficacy of the different antigens. The outcome of these challenge studies will be used to validate and refine this approach for identifying effective vaccine antigen candidates.The assays developed in mice will be adapted to human tissue samples, and the humoral aid cellular vaccine antigen potency indexes will be determined in a small group of vaccinia virus vaccinated human volunteers. Since vaccinia virus is substantially homologous to variola virus and since the vaccinia virus vaccine is known to be effective against variola virus infection, the responsive antigens identified from this assay will be candidates for use in a DNA or subunit subunit vaccine against smallpox. This vaccine will have no risk of producing vaccinia virus disease or Eczema vaccinatum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SMALL REPLICATION

MOLECULE

INHIBITORS

OF

SMALLPOX

VIRUS

Principal Investigator & Institution: Jordan, Robert; Viropharma, Inc. 405 Eagleview Blvd Exton, PA 19341 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2004 Summary: (provided by investigator): Smallpox virus (variola) is a potential biological weapons agent due to its ease of dissemination, person to- person transmissibility and potential to cause widespread illness and death. Smallpox virus is classified as a Category A bioweapons agent by the Centers for Disease Control and Prevention (CDC). Currently, there are no FDA-approved antiviral drugs to prevent or treat smallpox infection. The overall goal of our Smallpox Virus Biodefense Program is to discover and develop small molecule drugs for prevention and treatment of smallpox virus infection. The specific aims of this Phase 1 application are to: 1. Establish a validated virus-specific high throughput-screening assay using a cowpox virus (BSL-2) surrogate for authentic variola virus. 2. Identify specific inhibitors that target wild type and drug resistant variants of cowpox virus from VIROPHARMA's proprietary chemically diverse library of over 400,000 small molecule compounds. 3. Characterize inhibitor compounds ("hits") for chemical tractability, antiviral potency and spectrum and selectivity in order to identify promising "quality hits". 4. Confirm antiviral specificity and selectivity of quality hits against the authentic variola virus in cell culture (performed through collaborating laboratories); 5. Investigate the mechanism of antiviral action of "confirmed quality hits"; and 6. Conduct initial drug metabolism, genotoxicity & pharmacokinetic evaluations on confirmed quality hits. The end result of Phase 1 work will be identification of quality hits specific for variola virus. Advancement of these compounds in Phase 2 will involve: (1) hit-to-lead medicinal chemistry to identify leads with good potential for chemical structure-biological activity relationships (SAR); (2) lead compound optimization for antiviral potency, selectivity

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and spectrum of antiviral activity and drug metabolic and pharmacokinetics properties; (3) mechanism of action and drug resistance characterizations; and (4) efficacy evaluations in suitable animal models. At the end of Phase 2, we anticipate to have identified at least one pre-clinical candidate compound that is suitable for advancement into formal IND toxicological and model animal efficacy evaluations for the prevention and treatment of smallpox virus infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SMALLPOX TREATMENT BY RNA INTERFERENCE Principal Investigator & Institution: Herweijer, Hans; Director of Preclinical Research; Mirus Corporation 505 S Rosa Rd, #104 Madison, WI 53711 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 29-FEB-2004 Summary: (provided by applicant): While eradicated as an endemic disease, smallpox remains a threat to human health because it may be used by bioterrorists. The potential spread of variola virus or recombinant forms of variola or other poxviruses requires the development of novel therapeutic approaches. We propose to develop and utilize RNA interference (RNAi) technology to treat smallpox. RNAi is accomplished by the introduction of double-stranded RNA into the cell, resulting in sequence specific degradation of the target mRNA. Application of short (21-25 bp) double stranded RNA (siRNA) also induces effective RNAi and limits non-specific effects. We have recently demonstrated that siRNA can be efficiently introduced into mammalian cells in vivo, and can be used to modulate gene expression. In this SBIR Phase I grant proposal, we will determine if poxvirus gene expression can be inhibited by siRNA. For these experiments, we will use vaccinia virus as a highly relevant model for variola virus. Several genes from different viral pathways (transcription, replication, virion formation, virulence) will be targeted in vitro. Effects upon target gene expression and viral replication will be measured. These experiments should demonstrate the feasibility of using siRNA for smallpox therapy or prophylaxis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SMALLPOX VACCINE CLINICAL RESEARCH CENTER Principal Investigator & Institution: Belshe, Robert B. Professor of Medicine & Microbiology; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: With the imminent institution of smallpox vaccination for healthcare workers and first responders, there is an urgent need to better understand the biology of vaccinia infection in humans. In response, we are creating a new Core Facility, the Smallpox Vaccine Clinical Research Center, to coordinate and facilitate clinical/translational research on smallpox for the MRCE. The Smallpox Vaccine Clinical Research Center will serve two allied missions. First, it will be the clinical/translational research arm of the MRCE, facilitating the research designed to answer critical questions about viral shedding, protective immunity, and susceptibility to poxvirus infections (see the Strategic Projects of Storch, Kazura, and Belshe, section C). In this mode it will directly support and execute translational research protocols on projects of special interest to the MRCE mission. The initial protocols will test the efficacy and mechanism of action of vaccinia immune globulin; an additional project is to fully characterize the immunologic responses of a non-responder to vaccinia immunization. Standard research protocols for characterizing individuals with severe adverse effects to smallpox vaccination will also be supported. The Smallpox Vaccine Clinical Research Center will serve its second

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mission by becoming the regional center for the diagnosis and care of individuals with serious adverse effects after smallpox vaccination. In addition to providing state of the art diagnostics and care, for these individuals, when appropriate, the Smallpox Vaccine Clinical Research Center will offer to enroll them into clinical/translational protocols on the adverse effects of smallpox vaccination. If possible, these individuals will undergo many of the detailed virologic, immunologic, and genetic studies outlined in the projects of Drs. Storch, Kazura, and Belshe. Some of these individuals may have immunodeficiencies (e.g. those with generalized vaccinia or progressive vaccinia) and these will be fully characterized. In this capacity the Smallpox Vaccine Clinical Research Center will also become a database for adverse effects to smallpox vaccine in this area, and facilitate any national efforts in this area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SMALLPOX VIRULENCE AND COMPLEMENT REGULATORY PROTEINS Principal Investigator & Institution: Atkinson, John P. Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Public health concems have emerged regarding use of smallpox as a bioterrorist weapon since most Americans are no longer immune. Poxviruses subvert the complement system via the expression of regulatory proteins. In variola, vaccinia and ectromelia, the proteins are called SPICE (for smallpox inhibitor of complement enzymes), VCP (vaccinia virus complement control protein) and EMICE (an uncharactedzed analog in ectromelia that we have labeled "ectromelia inhibitor of complement enzymes"). These secreted virulence factors down-regulate complement activation by mimicking the functional repertoire of a family of host proteins called the Regulators of Complement Activation (RCA). The viral proteins are also structurally related to their host counterparts. Specific Aims: 1. To characterize the complement inhibitory profile of SPICE compared to its human counterparts. We will identify the principal complement-evading activity of SPICE and this will become a target for neutralization. These assessments will take place with the native soluble protein as well as after it attaches to cells via either its heparin-binding site(s) or by addition of an anchor. 2. To determine the complement regulatory sites of SPICE. These experiments will take advantage of the functional profiles (defined in Aim 1) and the sequences of active sites of RCA proteins that are homologous to corresponding regions of SPICE, VCP, and EMICE. These two sets of data provide a logical strategy for a mutational analysis to locate the active sites. 3. To characterize the complement regulatory activity of EMICE. This mousepox protein has not been evaluated for its complement inhibitory (virulence) activity. It is about 90% identical to SPICE and VCP. We will first characterize its regulatory activity for human and mouse complement. Second, we will assess its role in vivo as a virulence factor by infecting sensitive and resistant mouse strains with the ectromelia virus deleted of its complement regulator. The proposed experiments should provide novel information relative to the pathogenesis of poxvirus infections of man and mouse. Additionally, these results will serve as a guide to produce a less toxic small pox vaccine and to identify a viral target for mAb treatment of variola infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRAINING IN EMERGING INFECTIOUS DISEASES Principal Investigator & Institution: Doms, Robert W. Professor and Chair; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): In response to increased concern about emerging and re-emerging infectious diseases, particularly Class A-C agents that could be used as weapons of bioterrorism, the microbiology community at the University of Pennsylvania proposes to establish a Training Program in Emerging Infectious Diseases. The Training Program would initially support two Ph.D. and two M.D./Ph.D. or V.M.D./Ph.D. predoctoral fellows as well as three postdoctoral fellows, enabling them to work in any one of 14 laboratories directed by Principal Investigators who study important viral or parasitic pathogens that are classified as either emerging or reemerging threats to human health. The trainers associated with this T32 proposal have been selected because their research programs in these areas are well-established and are being supported by NIH grants and/or have published papers on this topic. The trainers study a number of important viral and parasitic pathogens. Six of the trainers on this grant study smallpox proteins or are developing anti-vaccinia agents, and currently hold one R01, two R21s and one U01 grants to support work in this area (Isaacs, Rosengard, Cohen, Eisenberg, Friedman, Ricciardi). Four trainers on this grant study Ebola virus, holding one R01 and two R21 grants and having published several papers in the last two years (Bates, DoTs, Shen, Harty). Collaborations with colleagues at USAMRIID make it possible to perform experiments with live Ebola virus. Other important emerging viral diseases that are subjects of significant research efforts by the trainers include West Nile virus and Dengue (DoTs, Bates). Emerging and re-emerging parasitic diseases are the focus of research efforts by the trainers and include Malaria, a major focus of the Roos laboratory which plays a major role in managing the Plasmodium genome project. Outbreaks of leishmaniasis (Scott) in Afghan refugee camps in Pakistan and other regions, have demonstrated increased incidence of old infections from a confluence of wars, population shifts, and development into little populated regions. Due to climactic changes and large-scale water resources development projects, there have been notable new outbreaks of schistosomiasis in previously unaffected areas (Pearce, Shen). Increased infections due to toxoplasma gondii have also been reported (Roos, Hunter). With time, we anticipate that other Penn investigators will join this training program as they shift their research focus to include emerging infectious diseases. The research opportunities provided by the trainers coupled with strong institutional commitment and an extensive and well-organized training program will provide excellent training in emerging infectious diseases to students and postdoctoral fellows. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VACCINIA DNA REPLICATION Principal Investigator & Institution: Traktman-Duncan, Paula; Professor & Chairman; Microbiol & Molecular Genetics; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2001; Project Start 01-DEC-1984; Project End 30-NOV-2003 Summary: (from the abstract): The coordinated execution of faithful DNA replication is among the most basic and crucial of all biological processes. Comparative analysis of the cis- and trans-acting components of the replication machinery in diverse organisms has been invaluable in gaining an understanding of how DNA replication initiates and

54 Smallpox

proceeds. Our laboratory has been engaged in a molecular genetic and biochemical analysis of vaccinia virus DNA replication. The vaccinia genome is a linear duplex of 192 kb with covalently closed hairpin termini. We have recently developed a minichromosome assay which has enabled us to demonstrate that linear plasmid sequences capped with viral telomeres of >150 bp replicated efficiently within infected cells. We have also shown that infected cells and virions contain proteins which can form specific protein/DNA complexes with the viral telomeres. In the first aim of this grant, we propose extensive analyses designed to reveal the precise features of the sequence and structure of the telomeres that are required for directing template replication. We also propose to purify the telomere-binding proteins and more fully characterize their interaction with the viral DNA. Identification of the genes encoding these proteins will allow us to determine the role(s) that these protein play in the viral life cycle. Vaccinia virus displays an unusual degree of physical and genetic autonomy from the host cell. It replicates solely within the cytoplasm, and is thought to encode most of the functions necessary for transcription, DNA replication, morphogenesis of the viral particle, and numerous interactions with the host's immune/ inflammatory system. Among the virus 200 genes are many with known or proposed roles in DNA replication. In the second aim of this grant, we will utilize genetic and biochemical approaches to more fully define the function of the B1 protein kinase, the D4 uracil DNA glycosylase, the I3 single stranded binding protein, the D5 DNA-independent NTPase, the A20 processivity factor, and the E9 DNA polymerase. We will also initiate studies to characterize protein:protein interactions between these replication proteins and other, as yet unknown, components of the replication apparatus. Finally, we will refine our in vitro replication system with goal of reconstructing many of the steps involved in vaccinia replication. Although smallpox has been eradicated, poxviruses remain of significant biomedical importance. Molluscum contagiosum is found as an opportunistic infection in 20 percent of AIDS patients, and vaccinia now plays an important role as a recombinant vaccine for many pathogens. Thus, gaining an understanding of poxvirus replication is of significant practical importance and well as intellectual interest. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINIA IMMUNE GLOBULIN FROM CLONED TRANSGENIC CATTLE Principal Investigator & Institution: Robl, James M. Professor of Veterinary and Animal Scien; Hematech, Llc 33 Riverside Ave Westport, CT 06881 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-MAR-2003 Summary: (provided by applicant): The SBIR proposal addresses a critical national need for therapies to treat complications from smallpox vaccination. Vaccination against smallpox is accompanied with numerous adverse reactions, some of which have high fatality rates. Ironically, it was the eradication of smallpox, which the WHO declared complete worldwide in 1979, and the cessation of routine immunizations against smallpox that has left the majority of Americans alive today susceptible to the disease and hence vulnerable to a bioterrorist smallpox attack. The only known treatment for complications from smallpox vaccination is subsequent inoculation with antibody against vaccinia virus, the immunogen in the vaccine (VIG). National stores of this reagent, which is isolated from the blood of vacinees, is in short supply, and in the absence of a smallpox immunization program, is difficult to replenish. This proposal is to develop a large animal system for producing human polyclonal antibody against vaccinia virus, It has been shown that trangenic mice carrying an artificial human chromosome (HAC) produce human polycolonal antibody of all classes and with a

Studies 55

broad repertoire when challenged with antigen. In the current work, a similar strategy would be applied to cattle, where the yield of antibody would be far greater than with mice. We have already shown that we can create cattle clones that have a HAC containing the human Ig genes, and that the chromosome is stable and is expressed throughout fetal development into neonatal life. Further work is proposed to characterize the immune response to vaccinia virus in normal and in cloned calves. This novel and practical solution to the limited supply of human VIG has several advantages. First, it would enable the production of large quantities of human antibody at a reasonable cost. Second, it would provide greater flexibility in designing immunization strategies for producing high titer, high specificity antibody beyond what is possible with human volunteers. Third, it would provide a new enabling technology for producing clinically important human antibody reagents against other bacterial and viral pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINIA VIRUS BIOCHEMICAL GENETICS Principal Investigator & Institution: Condit, Richard C. Professor; Molecular Genetics & Microbiol; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2003; Project Start 01-JUL-1990; Project End 30-APR-2008 Summary: (provided by applicant): The goal of this project is to understand the regulation of vaccinia virus post-replicative mRNA 3' end formation. In recent years it has become increasingly clear that post-initiation events in transcription, including transcription elongation, termination and RNA cleavage, comprise important control points for regulation of gene expression. Recent experiments demonstrate that postreplicative mRNA 3' end formation is regulated during vaccinia virus infection. The working hypothesis for this project is that several vaccinia viral gene products, including positive elongation factors (G2R, J3R), a transcript release factor (A18R), a site specific RNA cleavage factor, the RNA polymerase itself, additional associated factors (H5R, unidentified host factor), and at least one additional unidentified IBT resistance factor, work together, perhaps as part of a transcription elongation complex, to regulate formation of the 3' ends of intermediate and late vaccinia viral mRNAs. The aims of the project are designed to test, refine, and extend this hypothesis. Specifically, 1) an in vitro transcription assay will be refined and used to define the biochemical activities of several putative transcription elongation and/or termination factors, 2) new IBT resistant virus mutants will be mapped and characterized to identify novel transcription elongation factors and 3) a virus induced mRNA 3' end cleavage factor will be purified, and the protein and its encoding gene will be characterized. A study of regulation of post-initiation events in transcription is important for understanding regulation of vaccinia virus gene expression in particular, and the system may prove to be an important model for study of regulation of transcription elongation in eukaryotes in general. Importantly, the value this type of research in basic poxvirology to public health has been significantly increased recently given the potential for use of smallpox as a bioterrorist weapon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VACCINIA VIRUS INHIBITION ON IMMUNE RESPONSES Principal Investigator & Institution: Brutkiewicz, Randy R. Assistant Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167

56 Smallpox

Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Vaccinia virus (VV) is a member of the poxviridae family with approximately 95% homology to the human pathogen variola virus, the causative agent of smallpox, declared eradicated in 1980. VV has been used for the protective immunization of individuals against smallpox for well over 100 years until its routine use was suspended in the 1970s. However, recent events have resulted in a rethinking of the immunization of healthcare workers as well as the general population, as the threat of the intentional release of variola virus as a bioterrorism weapon has become a potential reality. Interestingly, although VV has been used as a vaccine, the immune response to the virus, considering the state of the art of immunology at the time it was routinely used in the general population, has really been poorly characterized. For example, although it is known that VV induces a cytotoxic T lymphocyte (CTL) response that peaks within one week post-infection, the immunodominant (or subdominant) major histocompatibility complex (MHC) class I-presented peptides are completely unknown. Furthermore, the effects of a VV infection on various aspects of the innate immune response (e.g., NK and NKT cells), have not been extensively studied. Our hypothesis is that VV is capable of inhibiting components of both the innate and adaptive immune responses that could ultimately compromise the optimum level of protection afforded by a VV-based vaccine. To test this hypothesis, the following specific aims are proposed: 1. Determine the mechanism(s) by which CD1d1-mediated antigen presentation to NKT cells is altered following a VV infection, 2. Identify immunodominant and subdominant MHC class I VV epitopes presented to VV-specific CTL, and 3. Analyze the mechanism(s) responsible for the VV-induced reduction in MHC class 1-mediated antigen presentation to CTL. These studies will identify specific targets in the innate and adaptive antiviral immune response that VV and other poxviruses use to evade host immunity. This project is an integral part of the highly interactive and complementary Program Project entitled, "Poxvirus Modulation of Immune Responses". Its role in understanding the inhibitory effects of a poxvirus infection on the innate and adaptive immune responses will be critical information needed in the design of new generation and highly effective VVbased vaccines that would also be protective in the event of an intentional exposure of a population to variola virus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VACCINIA VIRUS LATE TRANSCRIPTION FACTOR Principal Investigator & Institution: Wright, Cynthia F. Associate Professor; Pathology and Lab Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The poxviruses are DNA-containing viruses that replicate in the cytoplasm of eukaryotic cells and are pathogenic to many animal species. The poxviruses known to cause human disease include variola, the causative agent of smallpox, molluscum contagiosum, an opportunistic pathogen often infecting AIDS patients, and monkeypox. Gene expression in vaccinia virus, the prototypic member of the poxvirus family, is temporally regulated and can be divided into early, intermediate, and late phases. All three phases of gene expression rely on multiple virally-encoded factors and a multisubunit RNA polymerase with homology to eukaryotic RNA polymerase II. One factor needed for late transcription in vitro has been partially purified from infected cells and designated VLTF-X. Recently, transcription complementation assays were used to demonstrate that VLTF-X activity is present in the cytoplasm and nucleus of uninfected HeLa cells. VLTF-X activity from uninfected cells is indistinguishable from that

Studies 57

recovered from infected cells by a variety of biochemical criteria, leading to the hypothesis that VLTF-X is a factor provided by the host cell. Also, a late promoter DNAbinding activity co-purifies with VLTF-X, suggesting that the biochemical role of this factor may be in late promoter recognition. The experiments of this proposal were designed to identify this factor, define its biochemical role in vaccinia virus late transcription, and to define how the protein functions through a comprehensive mutagenesis analysis. These objective will be accomplished by: (1) cloning the gene encoding VLTF-X either by extensive purification of the factor followed by identification of the purified proteins or by using late promoter-containing oligonucleotides to screen an expression library (2) mapping contacts between VLTF-X and DNA through a variety of chemical and enzymatic techniques (3) defining all of the proteins participating in the late transcription system and defining protein-protein contacts and (4) studying the function of VLTF-X through mutagenesis of the protein. These studies have the potential to uncover a previously unidentified role for the host cell in poxvirus infections. Also, it is expected that knowledge of the transcriptional processes of the virus will increase its application as a vector for gene expression and vaccine use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIROLOGY AND SMALLPOX VACCINATIONS Principal Investigator & Institution: Storch, Gregory; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The broad objective of this project is to use conventional and molecular techniques to define the virologic events following smallpox vaccination in vaccinianaive and vaccinia-experienced individuals. The specific alms are to: 1) Define the virologic events associated with smallpox vaccination. 2) Determine whether multiple viral variants are present within the Dryvax vaccine, and if so, to investigate their role in the virology of smallpox vaccination and in adverse reactions. 3) Define the virologic events associated with adverse reactions to smallpox vaccination. 4) Examine the virologic response to treatment with vaccinia immune globulin (VIG) and/or cidofovir in vaccinees who require these therapies to control adverse reactions. A quantitative real-time PCR assay will be developed and used to measure the level of vaccinia DNA at regular intervals after vaccination. Specimens will also be cultured for vaccinia virus. These studies will be useful for defining the possible contagiousness of individuals having smallpox vacciniation and for helping determine the need for donor deferral for voluntary blood donations. The data will also provide a basis for studies of the immunology and immunogentics of vaccinia. Studies will be performed of Dryvax vaccine to define variants within the vaccine virus. In collaboration with the Genome Sequencing Center, the complete nucleotide sequence of 5 variant strains will be determined. Specific assays will be developed and used to define the contribution of variants to immunogenicity and reactogenicity of the vaccine. Smallpox adverse reaction clinics will be established at each participating medical center to evaluate individuals with possible adverse reactions. Individuals seen in these clinics will be recruited to participate in detailed studies of the virology, immunology, and immunogenetics of smallpox vaccination. These studies will investigate the virology of adverse reactions, the relationship between viral and immunologic events, and the genetic basis for both. For individuals having severe adverse reactions, virologic studies will be used to help evaluate and guide therapy with VIG and cidofovir. The studies described will form a basis for evaluating Dryvax as well as future smallpox vaccines. The assays to be developed and the clinics to be established will provide an

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infrastructure that will be available to respond to a bioterrorist attack on the United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VULNERABILITY TO SMALLPOX DUE TO DECLINING CTL IMMUNITY Principal Investigator & Institution: Mbawuike, Innocent N. Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Discontinuation of smallpox vaccination since 1971 has led to waning of acquired immunity in the U.S. general population, thus, raising the risk of major epidemics from intentional release of smallpox by terrorists or unfriendly governments. The CDC has shown that vaccinia immunization, which led to the eradication of smallpox worldwide, caused excess rates of severe complications and death among older persons. Since higher morbidity and mortality rates from many other viral infections in older persons have been attributed to a deficiency in virus-specific HLA-restricted CTL response, the elderly will be expected to possess reduced vacciniaspecific CTL activity and therefore be more susceptible to smallpox disease as well as complications from vaccinia immunization. The goals of this study are to: 1) profile the sero-prevalence and memory CD8+ CTL activity status against vaccinia in representative young adult and elderly U.S. populations, 2) identify easily detectable and quantifiable surrogates of CTL competence against smallpox infection and 3) explore immunological basis for complications from vaccinia vaccination. Levels of vaccinia-specific memory CD8 CTL activity will be determined in peripheral blood lymphocytes of U.S. born healthy adults (35-49 and 50-64 years old) and elderly adults (~65 years old) who have previously been vaccinated with vaccinia and compared with young adults (18-32 years old) who are recent (<1 year) vaccinia recipients or vaccinia naive. Virus serum neutralization antibody and virus specific IgG antibody titers will be determined and correlated with CTL activity. The frequency of CD8+ T cells expressing interferon (IFN)-gamma (a CTL surrogate) and interleukin (IL)-4 (a CTL antagonist) will be measured using ELISPOT and flow cytometry. The functions of IFN-gamma and IL-4 will be assessed using antisense oligonucleotides and/or antibodies. Selected proinflammatory cytokines and chemokines (IL-1a, TNF-a, IL-6, IL-8 and lL-13) will be analyzed. It is postulated that among previously vaccinated persons: a) the elderly will have significantly reduced CD8+ CTL memory in comparison to younger persons, b) levels of vaccinia-specific antibody and memory CD8+ CTL activity will decline with time, c) IFN-gamma production will be a good surrogate of CTL activity and d) increases in specific pro-inflammatory cytokines or chemokines will be associated with the intensity of vaccinia vaccination lesions. The results should provide guidance in decisions to revaccinate the public, particularly the elderly and other immunodeficient persons, in the event of a biological attack with smallpox and offer needed insight into the mechanism of vaccinia complications in the elderly. Data from recent vaccinees might also serve as reference values for new smallpox vaccines that might be developed since specific correlates of immunity against smallpox (other than a vaccine "take") are currently not available. By correlating these responses with vaccinia lesion sizes in new vaccinees, markers of severe complications from vaccinia vaccination may be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: XIV INTERNATIONAL POXVIRUS/IRIDOVIRUS WORKSHOP Principal Investigator & Institution: Niles, Edward G. Professor; Microbiology; State University of New York at Buffalo 402 Crofts Hall Buffalo, NY 14260 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): The upcoming Workshop is the fourteenth in a series initiated in 1978. This biennial meeting alternates between a site in Europe and North America. Since its inception the Workshop has been dedicated to the discussion of aspects of the life cycle of large double stranded DNA containing viruses of eukaryotic organisms. Poxviruses are the focus of the majority of the presentations but studies of African Swine Fever Virus, Chlorella Viruses and a variety of iridoviruses are also significant contributions to the meeting. Principal topics include virus genomics, gene expression, genome replication and recombination, virus assembly, host/virus interactions, vector design, vaccine development and pathogenesis. The importance of poxviruses in biomedical history is illustrated by the successful use of vaccinia virus in the eradication of smallpox. Today, poxviruses continue to be the focus of intensive research due to their unique life cycle, their informative host interactions and their use as effective vectors engineered for protein production. For example, poxvirus vectors are employed not only for protein purification but importantly they serve as essential reagents in a host of immunological studies, in investigations of negative strand RNA virus gene expression and replication, and in the recent use of poxvirus recombinants to stimulate DNA based vaccines. Furthermore, new insights into the molecular details of host responses to virus infections are continually being gleaned through studies of the many poxvirus-encoded factors designed to counteract the host antiviral systems. Continued investigations of the mechanisms of viral gene expression, mRNA processing, DNA replication and recombination provide new views not only of the viral life cycle but also yield new insights into mechanisms employed by their hosts. This meeting is the premier forum for the discussion of the life cycles of large eukaryotic DNA viruses. We anticipate having approximately 100 oral and 100 poster presentations with a total attendance of 200 scientists. We expect thr-lt the 2002 Workshop will prove to be as stimulating and as informative as its predecessors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “smallpox” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for smallpox in the PubMed Central database:

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Attitudes of healthcare workers in U.S. hospitals regarding smallpox vaccination. by Yih WK, Lieu TA, Rego VH, O'Brien MA, Shay DK, Yokoe DS, Platt R. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165598

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Canada stocks up on smallpox vaccine, pushes bioterrorism training. by Kondro W. 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81639

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Cardiac cases trigger advisory about smallpox vaccination. by Sullivan P. 2003 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153694

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Detection of Smallpox Virus DNA by LightCycler PCR. by Espy MJ, Cockerill III FR, Meyer RF, Bowen MD, Poland GA, Hadfield TL, Smith TF. 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=130682

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Does smallpox still pose a threat? by Weir E. 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81649

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Emergency response to a smallpox attack: The case for mass vaccination. by Kaplan EH, Craft DL, Wein LM. 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125076

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Risks of serious complications and death from smallpox vaccination: A systematic review of the United States experience, 1963 --1968. by Aragon TJ, Ulrich S, Fernyak S, Rutherford GW. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194634

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Smallpox still poses a threat. by Devlin HR. 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100866

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Smallpox still poses a threat. by Weir E. 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100867

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Smallpox vaccination advice. by Hoey J. 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=134298

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The spectre of smallpox. by Godard TS. 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161617

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US hospitals balking at smallpox vaccination. by Sibbald B. 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152707

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US, UK and Canada begin preparations for possible smallpox bioterror attacks. by Kerr C. 2003 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140450

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Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement. by Rosengard AM, Liu Y, Nie Z, Jimenez R. 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124380

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WHO marks 25th anniversary of last naturally acquired smallpox case. by [No authors listed]; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=134150

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with smallpox, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “smallpox” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for smallpox (hyperlinks lead to article summaries): •

A call for the destruction of smallpox virus stores. Author(s): Donohoe MT. Source: American Journal of Public Health. 1996 February; 86(2): 268. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8633752&dopt=Abstract

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A case of asthma after vaccination against smallpox. Author(s): Ekbom K. Source: Acta Med Scand Suppl. 1966; 464: 170-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229012&dopt=Abstract

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A century and a half of the history of the life sciences in Alabama, smallpox epidemic in Jefferson County. Author(s): Holley HL. Source: Ala J Med Sci. 1979 April; 16(2): 140-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=382901&dopt=Abstract

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A clinical and laboratory study of smallpox in Brazil. Accuracy of the laboratory diagnosis of smallpox in patients with Brazilian variola minor infection. Author(s): Noble J Jr, Long GW, Kirchner E, Sesso J. Source: Am J Trop Med Hyg. 1970 November; 19(6): 1020-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5533180&dopt=Abstract

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A comparative study of smallpox vaccination techniques under field conditions. Author(s): Banerji SC, Sharma KL, Srivastava BC, Gupta RD. Source: The Indian Journal of Medical Research. 1972 May; 60(5): 772-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4663247&dopt=Abstract

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A comparative study of the rotary lancet and bifurcate needle techniques of smallpox vaccination. Author(s): Nath LM, Rao YS, Rao TM. Source: The Indian Journal of Medical Research. 1970 March; 58(3): 388-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5524452&dopt=Abstract

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A comparison between two techniques of smallpox vaccination. Author(s): Petersen ES, Norby G. Source: Dan Med Bull. 1966 October; 13(6): 168-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5927702&dopt=Abstract

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A comparison of a threat of smallpox in the United States and Pakistan from a student perspective. Author(s): Loughran R, Lambert K. Source: Ky Nurse. 2003 January-March; 51(1): 11. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655810&dopt=Abstract

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A comparison of the protective effect of methisazone and a hyperimmune antivaccinial gamma-globulin in primary smallpox vaccination carried out in the presence of contraindications. Author(s): Jaroszynska-Weinberger B, Meszaros J. Source: Lancet. 1966 April 30; 1(7444): 948-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4160646&dopt=Abstract

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A comparison of two methods of vaccination against smallpox in Nigeria. Author(s): Snell PH. Source: West Afr Med J. 1965 December; 14(6): 233-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5864822&dopt=Abstract

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A critical examination of the Indian smallpox eradication program. Author(s): Gelfand HM. Source: Am J Public Health Nations Health. 1966 October; 56(10): 1634-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5951483&dopt=Abstract

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A death from inoculated smallpox in the English royal family. Author(s): Baxby D. Source: Medical History. 1984 July; 28(3): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6390027&dopt=Abstract

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A different view of smallpox and vaccination. Author(s): Mack T. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 460-3. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496354&dopt=Abstract

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A discussion on technologies for rural health. Smallpox eradication. Author(s): Henderson DA. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 1977 October 19; 199(1134): 83-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=21417&dopt=Abstract

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A hole in the homeland defense. Fixated on smallpox, U.S. is unprepared for a more likely terror threat. Author(s): Kellerman A. Source: Modern Healthcare. 2003 April 21; 33(16): 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747115&dopt=Abstract

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A mass smallpox vaccination campaign: reasonable or irresponsible? Author(s): Modlin JF. Source: Effective Clinical Practice : Ecp. 2002 March-April; 5(2): 98-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990219&dopt=Abstract

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A model for a smallpox-vaccination policy. Author(s): Bozzette SA, Boer R, Bhatnagar V, Brower JL, Keeler EB, Morton SC, Stoto MA. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 416-25. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496353&dopt=Abstract

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A new look at an old disease: smallpox and biotechnology. Author(s): McClain CS. Source: Perspectives in Biology and Medicine. 1995 Summer; 38(4): 624-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7659492&dopt=Abstract

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A note on the development of the bifurcated needle for smallpox vaccination. Author(s): Rubin BA. Source: Who Chron. 1980 May; 34(5): 180-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7376638&dopt=Abstract

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A philatelist's history of smallpox variolation. Author(s): Tierney J. Source: Medicine and Health, Rhode Island. 1998 March; 81(3): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9560566&dopt=Abstract

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A possible relation between human pathogenicity of smallpox vaccines and virus growth at elevated temperatures. Author(s): Baxby D. Source: J Hyg (Lond). 1974 August; 73(1): 35-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4371600&dopt=Abstract

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A postevent smallpox mass vaccination clinic exercise. Author(s): Andress K. Source: Disaster Management & Response : Dmr : an Official Publication of the Emergency Nurses Association. 2003 April-June; 1(2): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704322&dopt=Abstract

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A preliminary study for the evaluation of the primary smallpox vaccination in Alexandria. Author(s): Guindi SW, Wahdan MH, Mourad AS. Source: J Egypt Public Health Assoc. 1976; 51(5): 276-88. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1025254&dopt=Abstract

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A prospective study of serum antibody and protection against smallpox. Author(s): Mack TM, Noble J Jr, Thomas DB. Source: Am J Trop Med Hyg. 1972 March; 21(2): 214-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5061278&dopt=Abstract

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A reality in our time--certification of the global eradication of smallpox. Author(s): Wehrle PF. Source: The Journal of Infectious Diseases. 1980 October; 142(4): 636-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7003037&dopt=Abstract

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A report on the assessment of national smallpox eradication programme in East Nimar district (M.P.). Author(s): Mittal MC, Dwivedi MC. Source: Indian J Public Health. 1968 July; 12(3): 149-58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5732715&dopt=Abstract

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A search for the causes of severity in smallpox. Author(s): Sarkar JK, Mitra AC. Source: J Indian Med Assoc. 1968 September 16; 51(6): 272-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4303279&dopt=Abstract

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A severe complication of smallpox vaccination. Author(s): Larsen AA. Source: Can Med Assoc J. 1966 June 18; 94(25): 1316-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5947200&dopt=Abstract

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A simple and fast method of smallpox vaccination. Author(s): Martin Du Pan R. Source: Public Health. 1966 July; 80(5): 217-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5946220&dopt=Abstract

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A simple smallpox vaccination technique. Author(s): Grounds M. Source: The Medical Journal of Australia. 1972 March 18; 1(12): 608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5024448&dopt=Abstract

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A smallpox false alarm. Author(s): Hanrahan JA, Jakubowycz M, Davis BR. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 467-8; Discussion 467-8. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496349&dopt=Abstract

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A smallpox shot? The vaccine works but carries real risks. How to tell if you should take it. Author(s): Gupta S. Source: Time. 2002 December 23; 160(26): 78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510488&dopt=Abstract

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A smallpox vaccination survey in New South Wales. Author(s): Freedman ML. Source: The Medical Journal of Australia. 1968 January 20; 1(3): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5639835&dopt=Abstract

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A spotlight on smallpox. Author(s): Kawalek A, Rudikoff D. Source: Clinics in Dermatology. 2002 July-August; 20(4): 376-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208625&dopt=Abstract

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A study of immunity to smallpox in persons who have experienced a previous attack. Author(s): Vichniakov VE. Source: Bulletin of the World Health Organization. 1968; 39(3): 433-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5303909&dopt=Abstract

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A study of inapparent infection in smallpox. Author(s): Heiner GG, Fatima N, Daniel RW, Cole JL, Anthony RL, McCrumb FR Jr. Source: American Journal of Epidemiology. 1971 September; 94(3): 252-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4999240&dopt=Abstract

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A study of intrafamilial transmission of smallpox. Author(s): Heiner GG, Fatima N, McCrumb FR Jr. Source: American Journal of Epidemiology. 1971 October; 94(4): 316-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5110548&dopt=Abstract

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A study of New and Old World monkeys to determine the likelihood of a simian reservoir of smallpox. Author(s): Noble J Jr. Source: Bulletin of the World Health Organization. 1970; 42(4): 509-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4317468&dopt=Abstract

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A study of the effect of simultaneous vaccination with BCG and smallpox vaccine in newborn infants. Author(s): Lin HT. Source: Bulletin of the World Health Organization. 1965; 33(3): 321-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5294917&dopt=Abstract

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A successful eradication campaign. Global eradication of smallpox. Author(s): Fenner F. Source: Reviews of Infectious Diseases. 1982 September-October; 4(5): 916-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6293036&dopt=Abstract

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A survey of complications to smallpox vaccination. Author(s): Hallett P. Source: The Medical Journal of Australia. 1969 May 3; 1(18): 898-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4182378&dopt=Abstract

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A trial with a mixed BCG-smallpox vaccine given intradermally. Author(s): Vaughan JP, Menu JP, Lindqvist KJ, Vennema A. Source: J Trop Med Hyg. 1973 October; 76(10): 262-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4752166&dopt=Abstract

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ABO blood groups and smallpox in a rural population of West Bengal and Bihar (India). Author(s): Vogel F, Chakravartti MR. Source: Humangenetik. 1966; 3(2): 166-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5984976&dopt=Abstract

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ABO blood groups in active cases of smallpox. Author(s): Sukumaran PK, Master HR, Undevia JV, Balakrishnan V, Sanghvi LD. Source: Indian Journal of Medical Sciences. 1966 February; 20(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5909504&dopt=Abstract

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Accuracy of smallpox diagnosis by immunfluorescence with a purified conjugate. Author(s): Noble J Jr, Loggins MS. Source: Appl Microbiol. 1970 May; 19(5): 855-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4192888&dopt=Abstract

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ACIP issues guidelines on the use of smallpox vaccine in a pre-event vaccination program. Author(s): Schroeder BM; Advisory Committee on Immunization Practices; National Vaccine Advisory Committee; Healthcare Infection Control Practices Advisory Committee. Source: American Family Physician. 2003 August 1; 68(3): 554, 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924838&dopt=Abstract

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Active search operations for smallpox--an Ethiopian experience. Author(s): De Quadros CA, Weithaler KL, Siemon J. Source: International Journal of Epidemiology. 1973 Autumn; 2(3): 237-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4776011&dopt=Abstract

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Acute disseminated encephalo-myelitis complicating smallpox. Author(s): Sood SC, Singh H. Source: Indian Pediatrics. 1967 September; 4(9): 361-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5589489&dopt=Abstract

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Addressing the unthinkable: preparing to face smallpox. Author(s): Lovinger S. Source: Jama : the Journal of the American Medical Association. 2002 November 27; 288(20): 2530. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444846&dopt=Abstract

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Adverse reactions after smallpox vaccination. Author(s): Feery BJ. Source: The Medical Journal of Australia. 1977 August 6; 2(6): 180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=20557&dopt=Abstract

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Adverse reactions to smallpox vaccine: the Israel Defense Force experience, 1991 to 1996. A comparison with previous surveys. Author(s): Haim M, Gdalevich M, Mimouni D, Ashkenazi I, Shemer J. Source: Military Medicine. 2000 April; 165(4): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10803002&dopt=Abstract

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After smallpox eradication: yaws? Author(s): Hopkins DR. Source: Am J Trop Med Hyg. 1976 November; 25(6): 860-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1034444&dopt=Abstract

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Aftermath of a hypothetical smallpox disaster. Author(s): Bardi J. Source: Emerging Infectious Diseases. 1999 July-August; 5(4): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458963&dopt=Abstract

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Age distribution of patients in endemic smallpox. II. Author(s): Roberts CJ. Source: Cent Afr J Med. 1967 March; 13(3): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5337661&dopt=Abstract

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Air sampling of smallpox virus. Author(s): Thomas G. Source: J Hyg (Lond). 1974 August; 73(1): 1-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4371586&dopt=Abstract

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Air-transport, a main cause of smallpox epidemics today. Author(s): Hagelsten JO, Jessen K. Source: Aerosp Med. 1973 July; 44(7): 772-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4715093&dopt=Abstract

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Alastrim smallpox variola minor virus genome DNA sequences. Author(s): Shchelkunov SN, Totmenin AV, Loparev VN, Safronov PF, Gutorov VV, Chizhikov VE, Knight JC, Parsons JM, Massung RF, Esposito JJ. Source: Virology. 2000 January 20; 266(2): 361-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639322&dopt=Abstract

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Algorithms in the diagnosis and management of exotic diseases. XIX. Major tropical viral infections: smallpox, yellow fever, and Lassa fever. Author(s): Robbins FC, Mahmoud AA, Warren KS. Source: The Journal of Infectious Diseases. 1977 February; 135(2): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=839094&dopt=Abstract

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An advisory committee statement (ACS). National Advisory Committee on Immunization (NACI). Statement on smallpox vaccination. Author(s): National Advisory Committee on Immunization. Source: Can Commun Dis Rep. 2002 January 15; 28(Pt 1): 1-12. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728646&dopt=Abstract

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An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Author(s): Wehrle PF, Posch J, Richter KH, Henderson DA. Source: Bulletin of the World Health Organization. 1970; 43(5): 669-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5313258&dopt=Abstract

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An analysis of the proposed national strategy for smallpox vaccination of health care workers. Author(s): Alswede M. Source: Air Medical Journal. 2003 January-February; 22(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522359&dopt=Abstract

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An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine. Author(s): Damaso CR, Esposito JJ, Condit RC, Moussatche N. Source: Virology. 2000 November 25; 277(2): 439-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11080491&dopt=Abstract

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An epidemiologic investigation of suspected smallpox. Author(s): Grant M. Source: Gp. 1965 December; 32(6): 106-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5838431&dopt=Abstract

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An epidemiological analysis of the 1971 smallpox outbreak in Aralsk, Kazakhstan. Author(s): Zelicoff AP. Source: Critical Reviews in Microbiology. 2003; 29(2): 97-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901677&dopt=Abstract

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An estimation of the impact of smallpox eradication on the expectation of life in selected less developed countries. Author(s): Namfua P, Kim YJ, Mosley WH. Source: World Health Stat Q. 1978; 31(2): 110-9. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=726504&dopt=Abstract

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An evaluation of measles and smallpox vaccines simultaneously administered. Author(s): Budd MA, Scholtens RG, McGehee RF Jr, Gardner P. Source: Am J Public Health Nations Health. 1967 January; 57(1): 80-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6066713&dopt=Abstract

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An hypothesis for the periodicity of smallpox epidemics as revealed by time series analysis. Author(s): Duncan SR, Scott S, Duncan CJ. Source: Journal of Theoretical Biology. 1993 January 21; 160(2): 231-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8474252&dopt=Abstract

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An increased frequency of chromosomal changes and SCE's in cultured blood lymphocytes of 12 subjects vaccinated against smallpox. Author(s): Knuutila S, Maki-Paakkanen J, Kahkonen M, Hokkanen E. Source: Human Genetics. 1978 February 23; 41(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=631863&dopt=Abstract

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An outbreak of smallpox in an urban area. Author(s): Heydenreich JS. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1965 June 12; 39(21): 463-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5825727&dopt=Abstract

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An overview on the use of a viral pathogen as a bioterrorism agent: why smallpox? Author(s): Mahy BW. Source: Antiviral Research. 2003 January; 57(1-2): 1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615297&dopt=Abstract

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An update on smallpox. Author(s): Meadows M. Source: Fda Consumer. 2003 March-April; 37(2): 28-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715767&dopt=Abstract

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Analysis of the complete genome of smallpox variola major virus strain Bangladesh1975. Author(s): Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR, Parsons JM, Venter JC, Esposito JJ. Source: Virology. 1994 June; 201(2): 215-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8184534&dopt=Abstract

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Anaphylactoid purpura associated with smallpox vaccination. Author(s): Wong KY. Source: Hawaii Med J. 1971 September-October; 30(5): 388-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5160225&dopt=Abstract

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Ankyloblepharon following smallpox. Author(s): Saxena RC, Garg KC, Ramchand S. Source: American Journal of Ophthalmology. 1966 January; 61(1): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5904373&dopt=Abstract

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Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room. Author(s): Cunha BA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 August; 8(8): 489-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197871&dopt=Abstract

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Antibody response in haemorrhagic smallpox. Author(s): Sarkar JK, Chatterjee SN, Mitra AC, Mondal A. Source: The Indian Journal of Medical Research. 1967 November; 55(11): 1143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5582780&dopt=Abstract

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Antibody response in non-haemorrhagic smallpox patients. Author(s): Downie AW, Saint Vincent L, Goldstein L, Rao AR, Kempe CH. Source: J Hyg (Lond). 1969 December; 67(4): 609-18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4982558&dopt=Abstract

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Anticipating smallpox as a bioterrorist weapon. Author(s): Mortimer PP. Source: Clinical Medicine (London, England). 2003 May-June; 3(3): 255-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848261&dopt=Abstract

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Apparatus for mass vaccination against smallpox. Author(s): Peterson N. Source: Acta Med Scand Suppl. 1966; 464: 43-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5228764&dopt=Abstract

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Appropriate technology in the development of freeze-dried smallpox vaccine. Author(s): Collier LH. Source: Who Chron. 1980 May; 34(5): 178-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7376637&dopt=Abstract

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Are we prepared for a smallpox attack? Author(s): Munoz E. Source: N J Med. 2002 April; 99(4): 32-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977778&dopt=Abstract

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Assay of neutralizing antibody against variola virus by the degree of focus reduction on HeLa cell cultures and its application to revaccination with smallpox vaccines of various potencies. Author(s): Kitamura T, Shinjo N. Source: Bulletin of the World Health Organization. 1972; 46(1): 15-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4337628&dopt=Abstract

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Assessment of immunity status of primary school children against smallpox in a rural population of Bundelkhand. Author(s): Kumar A, Vekma BL, Srivstava RN. Source: Indian J Pediatr. 1978 August; 45(367): 255-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=730288&dopt=Abstract

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Assessment of Ladakh smallpox eradication programme activities. Author(s): Jezek Z, Kanth MH. Source: Indian J Public Health. 1978 January-March; 22(1): 63-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669766&dopt=Abstract

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Assessment of smallpox eradication status in Abhujmar Bestar District, Madhya Pradesh State, India. Author(s): Nair CP. Source: Indian J Public Health. 1978 January-March; 22(1): 75-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669767&dopt=Abstract

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Assessment of smallpox immunity status in Haryana state by scar survey 1970. Author(s): Chopra RL, Mehta JN. Source: Indian J Public Health. 1972 July; 16(3): 123-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4662225&dopt=Abstract

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Assessment of vaccination coverage, vaccination scar rates, and smallpox scarring in five areas of West Africa. Author(s): Henderson RH, Davis H, Eddins DL, Foege WH. Source: Bulletin of the World Health Organization. 1973; 48(2): 183-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4541684&dopt=Abstract

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At start of second smallpox-free decade, debate continues about keeping virus. Author(s): Sternberg K. Source: Jama : the Journal of the American Medical Association. 1988 October 21; 260(15): 2172. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2845158&dopt=Abstract

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Attenuated smallpox vaccine. Author(s): Krugman S, Katz SL. Source: The New England Journal of Medicine. 1970 February 5; 282(6): 344. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5410834&dopt=Abstract

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Attenuated smallpox vaccine. Author(s): Neff JM. Source: The New England Journal of Medicine. 1970 February 5; 282(6): 343-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5410833&dopt=Abstract

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Attitudes and knowledge about smallpox immunization among mothers. Author(s): Gulati PV, Amar S. Source: Indian J Pediatr. 1973 September; 40(308): 312-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4784729&dopt=Abstract

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Basal cell carcinoma arising in a smallpox vaccination site. Author(s): Rich JD, Shesol BF, Horne DW 3rd. Source: Journal of Clinical Pathology. 1980 February; 33(2): 134-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7364950&dopt=Abstract

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Basal cell epithelioma at site and following smallpox and vaccination. Author(s): Zelickson AS. Source: Archives of Dermatology. 1968 July; 98(1): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5661633&dopt=Abstract

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Basal cell epithelioma in smallpox vaccination scar. Report of a case. Author(s): Riley KA. Source: Archives of Dermatology. 1970 April; 101(4): 416-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5440815&dopt=Abstract

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Basal cell epithelioma in smallpox vaccination scar-fifty years later. Author(s): Kulwin MH. Source: Imj Ill Med J. 1975 December; 148(6): 612-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=317&dopt=Abstract

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Basal-cell epithelioma occurring in a smallpox vaccination scar. Author(s): Castrow FF, Williams TE. Source: J Dermatol Surg. 1976 May; 2(2): 151-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=932293&dopt=Abstract

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Best age for smallpox vaccination. Author(s): Polk LD. Source: Clinical Pediatrics. 1970 March; 9(3): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5414948&dopt=Abstract

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Biological agents as weapons 1: smallpox and botulism. Author(s): Whitby M, Street AC, Ruff TA, Fenner F. Source: The Medical Journal of Australia. 2002 May 6; 176(9): 431-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056996&dopt=Abstract

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Biologically false-positive serologic tests for syphilis due to smallpox vaccination. Author(s): Grossman LJ, Peery TM. Source: American Journal of Clinical Pathology. 1969 March; 51(3): 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5765139&dopt=Abstract

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Bioterrorism watch. APIC: smallpox plan uses outdated infection control. Author(s): Evans G. Source: Ed Manag. 2002 June; 14(6): Suppl 3-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046240&dopt=Abstract

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Bioterrorism. Blocking smallpox: a second defense. Author(s): Cohen J. Source: Science. 2001 October 19; 294(5542): 500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11641477&dopt=Abstract

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Bioterrorism. Go slow with smallpox shots, panel says. Author(s): Enserink M. Source: Science. 2003 January 24; 299(5606): 486-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543939&dopt=Abstract

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Bioterrorism. How devastating would a smallpox attack really be? Author(s): Enserink M. Source: Science. 2002 May 31; 296(5573): 1592-5. Erratum In: Science 2002 July 26; 297(5581): 522. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040157&dopt=Abstract

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Bioterrorism. New look at old data irks smallpox-eradication experts. Author(s): Enserink M. Source: Science. 2003 January 10; 299(5604): 181. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522221&dopt=Abstract

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Bioterrorism. Smallpox vaccinations: how much protection remains? Author(s): Cohen J. Source: Science. 2001 November 2; 294(5544): 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691969&dopt=Abstract

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Biowarfare. Did bioweapons test cause a deadly smallpox outbreak? Author(s): Enserink M. Source: Science. 2002 June 21; 296(5576): 2116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077372&dopt=Abstract

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Black death, smallpox, and continuity in nature: philosophies in generating new knowledge from clinical experiences. Author(s): Blackstone EH. Source: The Thoracic and Cardiovascular Surgeon. 1999 October; 47(5): 279-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599954&dopt=Abstract

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By the way doctor. I was relieved to read that the United States will soon have enough smallpox vaccine for everyone. Should my family and I be vaccinated? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2002 July; 9(11): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138026&dopt=Abstract

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By the way, doctor. I'm 50 years old, and like everybody else my age, I was vaccinated against smallpox before first grade. Do I still have some immunity? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2002 December; 10(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499129&dopt=Abstract

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C.N.S. involvement after smallpox revaccination. Author(s): Thalassinos NC, Contoyannis P. Source: Lancet. 1973 May 19; 1(7812): 1130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4122057&dopt=Abstract

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Camelpox and smallpox. Author(s): Bedson HS. Source: Lancet. 1972 December 9; 2(7789): 1253. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4117743&dopt=Abstract

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Can Culex pipiens fatigans or Aedes aegypti spread smallpox? A preliminary report. Author(s): Sarkar JK, Hati AK, Mitra AC. Source: Bull Calcutta Sch Trop Med. 1971 April; 19(2): 35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4348264&dopt=Abstract

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Can postexposure vaccination against smallpox succeed? Author(s): Mortimer PP. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 March 1; 36(5): 622-9. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594644&dopt=Abstract

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Can smallpox response teams use the experience of disease management programs? Author(s): Kozma CM. Source: Manag Care Interface. 2003 February; 16(2): 45-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647526&dopt=Abstract

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Cardiac cases trigger advisory about smallpox vaccination. Author(s): Sullivan P. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 April 29; 168(9): 1167. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719328&dopt=Abstract

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Cardiac complications after vaccination for smallpox. Author(s): Moschos A, Papaioannou AC, Nicolopoulos D, Anagnostakis D. Source: Helv Paediatr Acta. 1976 October; 31(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=977376&dopt=Abstract

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Cardiac deaths after a mass smallpox vaccination campaign--New York City, 1947. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 October 3; 52(39): 933-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523370&dopt=Abstract

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Case isolation and contact tracing can prevent the spread of smallpox. Author(s): Eichner M. Source: American Journal of Epidemiology. 2003 July 15; 158(2): 118-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851224&dopt=Abstract

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Case report: pulmonary calcification in smallpox handler's lung. Author(s): Foster DR. Source: The British Journal of Radiology. 1994 June; 67(798): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8032817&dopt=Abstract

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Caution in the administration of smallpox vaccine. Author(s): Prozesky OW, Smith LS. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1978 July 1; 54(1): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=694695&dopt=Abstract

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CDC has anthrax, smallpox vaccination guidelines available. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 November 1; 58(21): 2008, 2011. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11715817&dopt=Abstract

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CDC releases guidelines for treating adverse reactions to smallpox vaccination. Author(s): Morantz CA; CDC. Source: American Family Physician. 2003 April 15; 67(8): 1827, 1829-30, 1833-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725463&dopt=Abstract

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Certification of smallpox eradication. Author(s): Brilliant LB, Hodakevic LN. Source: Bulletin of the World Health Organization. 1978; 56(5): 722-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=153803&dopt=Abstract

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Chemoprophylaxis of smallpox and treatment of vaccinia gangrenosa with 1methylisatin 3-thiosemicarbazone. Author(s): Bauer DJ. Source: Antimicrobial Agents Chemother. 1965; 5: 544-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5883471&dopt=Abstract

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Chickenpox confused with smallpox. Case report. Author(s): Kassanoff I, Carpenter RL. Source: J Okla State Med Assoc. 1970 January; 63(1): 8-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5511577&dopt=Abstract

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Chickenpox resembling smallpox. Author(s): Jo KIAN TJAIJ. Source: Paediatr Indones. 1965 January-June; 5(1-2): 400-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5874444&dopt=Abstract

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Chief medical officer confirms key health workers will be vaccinated against smallpox. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2002 October 19; 325(7369): 855. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386031&dopt=Abstract

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Chromosomal aberrations and SCE in lymphocytes of children revaccinated against smallpox. Author(s): Kucerova M, Polivkova Z, Matousek V. Source: Mutation Research. 1980 July; 71(2): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7393242&dopt=Abstract

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Chromosome after smallpox vaccination. Author(s): Matsaniotis N, Maounis F, Kiossoglou KA, Anagnostakis DE. Source: Lancet. 1968 May 4; 1(7549): 978. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4171601&dopt=Abstract

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Claim that smallpox vaccine protects against HIV is premature, say critics. Author(s): Lenzer J. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 699. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512458&dopt=Abstract

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Clinical and immunological study of percutaneous revaccination in children who originally received smallpox vaccine subcutaneously. Author(s): Cherry JD, Rolfe UT, Dudley JP, Garakian AJ, Murphy M. Source: Journal of Clinical Microbiology. 1978 February; 7(2): 158-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=632346&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization. Author(s): Benenson AS, Cherry JD, McIntosh K, Connor JD, Alling DW, Nakano J, Rolfe UT, Schanberger JE, Todd WA, DeCastro F, Horvath FL, Bairan A, Phillips IA, Galasso GJ, Matthels MJ. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=188950&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination. Author(s): Cherry JD, McIntosh K, Connor JD, Benenson AS, Alling DW, Rolfe UT, Todd WA, Schanberger JE, Mattheis. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 145-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=188951&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary subcutaneous vaccination. Author(s): Connor JD, McIntosh K, Cherry JD, Benenson AS, Alling DW, Rolfe UT, Schanberger JE, Mattheis MJ. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=833447&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination. Author(s): McIntosh K, Cherry JD, Benenson AS, Connor JD, Alling DW, Rolfe UT, Todd WA, Schanberger JE, Mattheis MJ. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=188952&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination. Author(s): Cherry JD, Connor JD, McIntosh K, Benenson AS, Alling DW, Rolfe UT, Schanberger JE, Mattheis MJ. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=188953&dopt=Abstract

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Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Summary. Author(s): Galasso GJ, Mattheis MJ, Cherry JD, Connor JD, McIntosh K, Benenson AS, Alling DW. Source: The Journal of Infectious Diseases. 1977 January; 135(1): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=833448&dopt=Abstract

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Clinical assessment of an isothizole thiosemicarbazone against smallpox. Author(s): Sharma R. Source: J Indian Med Assoc. 1968 December 16; 51(12): 610-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5729412&dopt=Abstract

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Clinical investigation of smallpox in 1767. Author(s): Boylston AW. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1326-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973370&dopt=Abstract

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Clinical laboratory experiences with a more attenuated Enders' measles virus vaccine (Moraten) combined with smallpox vaccine. Author(s): Weibel RE, Stokes J Jr, Buynak EB, Leagus MB, Hilleman MR. Source: Pediatrics. 1969 April; 43(4): 567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4304934&dopt=Abstract

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Clinical observations on smallpox: a study of 1233 patients admitted to the Infectious Diseases Hospital, Calcutta, during 1973. Author(s): Mazumder DN, Mitra AC, Mukherjee MK. Source: Bulletin of the World Health Organization. 1975; 52(3): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1084800&dopt=Abstract

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Clinical responses to undiluted and diluted smallpox vaccine. Author(s): Frey SE, Couch RB, Tacket CO, Treanor JJ, Wolff M, Newman FK, Atmar RL, Edelman R, Nolan CM, Belshe RB; National Institute of Allergy and Infectious Diseases Smallpox Vaccine Study Group. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1265-74. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923490&dopt=Abstract

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Clinical-laboratory experiences with combined dried live measles-smallpox vaccine. Author(s): Weibel RE, Stokes J Jr, Buynak EB, Hilleman MR, Grunmeier PW. Source: Pediatrics. 1966 June; 37(6): 913-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5933940&dopt=Abstract

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Combined BCG and smallpox immunization: a preliminary report on a method using the W.H.O. bifurcated needle. Author(s): Vaughan JP, Lindqvist K, Brooke D, Doyle RF. Source: East Afr Med J. 1972 March; 49(3): 207-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5047805&dopt=Abstract

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Combined BCG and smallpox vaccination (A field trial in Rwanda). Author(s): Heyworth B. Source: Journal of Tropical Pediatrics. 1970 March; 16(1): 17-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5309892&dopt=Abstract

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Commentary on implications of the 1971 outbreak in Aralsk, Kazakhstan, for U.S. Smallpox Vaccination Policy (No. 1). Author(s): Atlas RM, Clover R. Source: Critical Reviews in Microbiology. 2003; 29(2): 159-61; Discussion 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901680&dopt=Abstract

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Commentary on the 1971 smallpox epidemic in Aralsk, Kazakhstan, and the Soviet Biological Warfare Program (No. 2). Author(s): Gilsdorf JR. Source: Critical Reviews in Microbiology. 2003; 29(2): 163-7; Discussion 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901681&dopt=Abstract

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Commentary: smallpox eradication in west and central Africa revisited. Author(s): Foege WH. Source: Bulletin of the World Health Organization. 1998; 76(3): 233-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744242&dopt=Abstract

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Comparative analysis of the degree of specific humoral immunity, content of serum immunoglobulins and isolation of vaccinia virus in children with post-vaccinal encephalitis after smallpox vaccination. Author(s): Gurvich EB. Source: J Hyg Epidemiol Microbiol Immunol. 1981; 25(3): 311-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6117594&dopt=Abstract

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Comparative studies of smallpox vaccination by the bifurcated needle and rotary lancet techniques. Author(s): Pattanayak S, Arora DD, Sehgal CL, Raghavan NG, Topa PK, Subrahmanyam YK. Source: Bulletin of the World Health Organization. 1970; 42(2): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5310142&dopt=Abstract

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Comparative study of cutaneous scars and HAI antibodies after smallpox revaccination. Author(s): Topciu VL, Voiculescu D, Giurca A, Plavosin L, Moldovan E. Source: Virologie. 1976 April-June; 27(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=973343&dopt=Abstract

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Comparative study of haemagglutination-inhibiting-antibody and neutralising antibody in sera of cases of smallpox. Author(s): Sarkar JK, Chatterjee SN, Mitra AC, Mandal A. Source: Bull Calcutta Sch Trop Med. 1966 January; 14(1): 4-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5961043&dopt=Abstract

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Complement requirement of the neutralizing antibody appearing after immunization with smallpox vaccine. Author(s): Nishimura C, Nomura M, Kitaoka M, Takeuchi Y, Kimura M. Source: Jpn J Microbiol. 1968 June; 12(2): 256-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5303512&dopt=Abstract

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Complications and management of smallpox vaccination in the child with eczema. Author(s): Willis JT, Riley HD Jr. Source: J Okla State Med Assoc. 1966 July; 59(7): 385-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5940337&dopt=Abstract

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Complications and management of smallpox vaccination in the child with exzema. Author(s): Willis JT, Riley HD Jr. Source: J Okla State Med Assoc. 1966 July; 59(7): 385-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5939063&dopt=Abstract

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Complications of smallpox vaccination in Alabama, 1968. Author(s): Sinclair MC, Lane JM, Donald WJ, Esco LC. Source: Southern Medical Journal. 1972 January; 65(1): 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5058090&dopt=Abstract

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Complications of smallpox vaccination in Kentucky in 1968. Results of a statewide survey. Author(s): Nitzkin JL, Anderson L, Skaggs JW, Hernandez C. Source: J Ky Med Assoc. 1971 March; 69(3): 184-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5545791&dopt=Abstract

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Complications of smallpox vaccination in Washington, 1968. Author(s): Thompson RS, Lane JM, Francis BJ. Source: Northwest Med. 1971 March; 70(3): 180-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5101814&dopt=Abstract

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Complications of smallpox vaccination United States 1963. II. Results obtained by four statewide surveys. Author(s): Neff JM, Levine RH, Lane JM, Ager EA, Moore H, Rosenstein BJ, Millar JD, Henderson DA. Source: Pediatrics. 1967 June; 39(6): 916-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4381735&dopt=Abstract

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Complications of smallpox vaccination, 1968 surveillance in a Comprehensive Care Clinic. Author(s): Neff JM, Drachman RH. Source: Pediatrics. 1972 September; 50(3): 481-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5056427&dopt=Abstract

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Complications of smallpox vaccination, 1968. Author(s): Lane JM, Ruben FL, Neff JM, Millar JD. Source: The New England Journal of Medicine. 1969 November 27; 281(22): 1201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4186802&dopt=Abstract

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Complications of smallpox vaccination, 1968. Results of a statewide survey in Alaska. Author(s): Clark PS, Lane JM. Source: Calif Med. 1971 September; 115(3): 7-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5094595&dopt=Abstract

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Complications of smallpox vaccination, 1968: results of ten statewide surveys. Author(s): Lane JM, Ruben FL, Neff JM, Millar JD. Source: The Journal of Infectious Diseases. 1970 October; 122(4): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4396189&dopt=Abstract

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Complications of smallpox vaccination, Maryland 1968. Author(s): Mellin H, Neff JM, Garber H, Lane JM. Source: Johns Hopkins Med J. 1970 March; 126(3): 160-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5438372&dopt=Abstract

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Complications of smallpox vaccination. Author(s): Kumar LR, Gopal B. Source: Indian Pediatrics. 1969 August; 6(8): 557-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5358615&dopt=Abstract

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Complications of smallpox vaccination. Author(s): McElwain WP. Source: J Ky Med Assoc. 1972 March; 70(3): 165-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4401915&dopt=Abstract

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Complications of smallpox vaccination. Author(s): Brown EH. Source: Postgraduate Medical Journal. 1965 October; 41(480): 634-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4378510&dopt=Abstract

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Complications of smallpox vaccination. I. National survey in the United States, 1963. Author(s): Neff JM, Lane JM, Pert JH, Moore R, Millar JD, Henderson DA. Source: The New England Journal of Medicine. 1967 January 19; 276(3): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4381041&dopt=Abstract

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Complications of smallpox vaccination: surveillance during an island-wide program in Puerto Rico, 1967-1968. Author(s): Ratner LH, Lane JM, Vicens CN. Source: American Journal of Epidemiology. 1970 March; 91(3): 278-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4391875&dopt=Abstract

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Concomitant enterovirus infecton, smallpox vaccination, and exanthem. Author(s): Cherry JD, Jahn CL. Source: The Journal of Pediatrics. 1965 October; 67(4): 679-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5832562&dopt=Abstract

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Concurrent smallpox and chickenpox. Author(s): Sarkar JK, Mitra AC, Mukherjee MK, Dumbell KR, Almeida JD. Source: Bulletin of the World Health Organization. 1976; 54(1): 119-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=188559&dopt=Abstract

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Confronting emerging infections: lessons from the smallpox eradication campaign. Author(s): Foege WH. Source: Emerging Infectious Diseases. 1998 July-September; 4(3): 412-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9716959&dopt=Abstract

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Congenital smallpox. Author(s): Sharma R, Jagdev DK. Source: Scandinavian Journal of Infectious Diseases. 1971; 3(3): 245-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4331837&dopt=Abstract

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Conjunctivitis and subclinical infection in smallpox. Author(s): Kempe CH, Dekking F, Saint Vincent L, Rao AR, Downie AW. Source: J Hyg (Lond). 1969 December; 67(4): 631-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4311574&dopt=Abstract

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Consent and compensation: a social compact for smallpox vaccine policy in the event of an attack. Author(s): Faden RR, Taylor HA, Seiler NK. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1547-51. Epub 2003 Jun 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802754&dopt=Abstract

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Consequences of smallpox vaccination in leprosy patients. Author(s): Saha K, Mittal MM, Ray SN. Source: Infection and Immunity. 1973 September; 8(3): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4199714&dopt=Abstract

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Contact vaccinia--transmission of vaccinia from smallpox vaccination. Author(s): Neff JM, Lane JM, Fulginiti VA, Henderson DA. Source: Jama : the Journal of the American Medical Association. 2002 October 16; 288(15): 1901-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377090&dopt=Abstract

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Containing bioterrorist smallpox. Author(s): Halloran ME, Longini IM Jr, Nizam A, Yang Y. Source: Science. 2002 November 15; 298(5597): 1428-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434061&dopt=Abstract

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Continuing mortality and morbidity from smallpox vaccination. Author(s): Du Mont GC, Beach RC. Source: British Medical Journal. 1979 May 26; 1(6175): 1398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=445099&dopt=Abstract

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Contraindication to smallpox vaccination. Author(s): Steele AS. Source: British Medical Journal. 1973 June 2; 2(5865): 552. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4714495&dopt=Abstract

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Contraindications to smallpox vaccination. Author(s): Greville RW. Source: The Medical Journal of Australia. 1968 July 13; 2(2): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4174893&dopt=Abstract

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Contraindications to smallpox vaccination. Author(s): Vaughan BD. Source: The Medical Journal of Australia. 1968 June 15; 1(24): 1070. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5663704&dopt=Abstract

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Contraindications to smallpox vaccination. Author(s): Christie AB. Source: British Medical Journal. 1973 June 23; 2(5868): 714. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4733256&dopt=Abstract

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Contraindictions to smallpox vaccination. Author(s): Dudgeon JA. Source: British Medical Journal. 1973 August 4; 3(5874): 292. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4723477&dopt=Abstract

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Contribution to the problem of challenge vaccination. Observations on vaccination of cured smallpox cases in India in 1971, 1972 and 1973. Author(s): Zikmund V, Das N, Krishnayengar R, Kameswara Rao B. Source: Indian J Public Health. 1978 January-March; 22(1): 102-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669754&dopt=Abstract

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Control of smallpox and influenza. Author(s): Meiklejohn G. Source: The Journal of Infectious Diseases. 1973 February; 127(2): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4689635&dopt=Abstract

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Control of smallpox. Author(s): Parry WH. Source: Lancet. 1973 May 19; 1(7812): 1114. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4122023&dopt=Abstract

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Control of smallpox. Author(s): Parry WH. Source: Lancet. 1973 May 5; 1(7810): 989-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4121605&dopt=Abstract

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Control of smallpox. Author(s): Hobday TL. Source: Lancet. 1966 July 2; 2(7453): 39-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4161063&dopt=Abstract

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Correlation between cutaneous reaction in vaccinees immunized against smallpox and antibody titer determined by plaque neutralization test and ELISA. Author(s): Lublin-Tennenbaum T, Katzenelson E, el-Ad B, Katz E. Source: Viral Immunology. 1990 Spring; 3(1): 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2297392&dopt=Abstract

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Cost-benefit analysis of the intensified campaign against smallpox in India. Author(s): Ramaiah TJ. Source: Nihae Bull. 1976; 9(3): 169-203. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=829270&dopt=Abstract

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Cost-effectiveness analysis of the intensified campaign against smallpox in India. Author(s): Ramaiah TJ. Source: Nihae Bull. 1976; 9(3): 205-19. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=829271&dopt=Abstract

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Counterimmunoelectrophoresis for the diagnosis of smallpox. Author(s): Kelkar SS, Niphadkar KB. Source: Singapore Med J. 1976 June; 17(2): 104-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=982085&dopt=Abstract

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Countering the posteradication threat of smallpox and polio. Author(s): Henderson DA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 January 1; 34(1): 79-83. Epub 2001 November 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731949&dopt=Abstract

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Coxsackie virus infection simulating smallpox. Author(s): Mukherjee MK, Sarkar JK, Mitra AC, De S, Roy I, Dumbell KR, Almeida JD. Source: Indian J Dermatol. 1976 October; 22(1): 86-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1029722&dopt=Abstract

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Critical evaluation of smallpox vaccination for laboratory workers. Author(s): Isaacs SN. Source: Occupational and Environmental Medicine. 2002 September; 59(9): 573-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205229&dopt=Abstract

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Current concepts of smallpox and rubella immunization. Author(s): Marks MI. Source: J Maine Med Assoc. 1972 January; 63(1): 5-8 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5058614&dopt=Abstract

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Current status of smallpox vaccine. Author(s): LeDuc JW, Becher J. Source: Emerging Infectious Diseases. 1999 July-August; 5(4): 593-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458973&dopt=Abstract

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Cutaneous complications of smallpox vaccination scars. Author(s): Onwukwe MF. Source: International Journal of Dermatology. 1973 September-October; 12(5): 290-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4747621&dopt=Abstract

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Cutaneous complications of smallpox vaccination. Author(s): Coskey RJ, Bryan HG. Source: Mich Med. 1967 August; 66(15): 957-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6073265&dopt=Abstract

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Cutaneous responses to smallpox revaccination with calf lymph and the effect of fluorocarbon purification of the vaccine. Author(s): Polak MF, Huisman J, Bos JM, Hekker AC. Source: Bulletin of the World Health Organization. 1972; 47(2): 185-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4539413&dopt=Abstract

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D.A. Henderson: bringing the lessons of smallpox home. Author(s): Morgan W. Source: Md Med J. 1989 October; 38(10): 805-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2685493&dopt=Abstract

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Deaths attributable to smallpox vaccination, 1959 to 1966, and 1968. Author(s): Lane JM, Ruben FL, Abrutyn E, Millar JD. Source: Jama : the Journal of the American Medical Association. 1970 April 20; 212(3): 441-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4392370&dopt=Abstract

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Defending against viruses in biowarfare. How to respond to smallpox, encephalitides, hemorrhagic fevers. Author(s): Straight TM, Lazarus AA, Decker CF. Source: Postgraduate Medicine. 2002 August; 112(2): 75-6, 79-80, 85-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198755&dopt=Abstract

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Dermatofibroma occurring in a smallpox vaccination scar. Author(s): Hendricks WM. Source: Journal of the American Academy of Dermatology. 1987 January; 16(1 Pt 1): 1467. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3805387&dopt=Abstract

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Dermatofibrosarcoma protuberans occurring in a smallpox vaccination scar. Author(s): Green JJ, Heymann WR. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5 Suppl): S545. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734474&dopt=Abstract

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Destruction of smallpox stocks. Author(s): Griffiths PD. Source: Reviews in Medical Virology. 1999 October-December; 9(4): 217-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10578116&dopt=Abstract

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Detection by radioimmunoassay of antibodies in human smallpox patients and vaccinees. Author(s): Ziegler DW, Hutchinson HD, Koplan JP, Nakano JH. Source: Journal of Clinical Microbiology. 1975 March; 1(3): 311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=170309&dopt=Abstract

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Detection of smallpox virus DNA by LightCycler PCR. Author(s): Espy MJ, Cockerill III FR, Meyer RF, Bowen MD, Poland GA, Hadfield TL, Smith TF. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 1985-8. Erratum In: J Clin Microbiol 2002 November; 40(11): 4405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037052&dopt=Abstract

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Developing new smallpox vaccines. Author(s): Rosenthal SR, Merchlinsky M, Kleppinger C, Goldenthal KL. Source: Emerging Infectious Diseases. 2001 November-December; 7(6): 920-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747717&dopt=Abstract

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Diagnosing smallpox in possible bioterrorist attack. Author(s): Madeley CR. Source: Lancet. 2003 January 11; 361(9352): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531572&dopt=Abstract

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Diagnosis and management of smallpox. Author(s): Breman JG, Henderson DA. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1300-8. Epub 2002 March 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923491&dopt=Abstract

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Diagnosis of smallpox. Author(s): Regan TD, Norton SA. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 690-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200561&dopt=Abstract

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Diagnosis, management, and containment of smallpox infections. Author(s): Veenema TG. Source: Disaster Management & Response : Dmr : an Official Publication of the Emergency Nurses Association. 2003 January-March; 1(1): 8-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688304&dopt=Abstract

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Differentiation of smallpox and camelpox viruses in cultures of human and monkey cells. Author(s): Baxby D. Source: J Hyg (Lond). 1974 April; 72(2): 251-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4362412&dopt=Abstract

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Diffusion of a smallpox epidemic in Launceston, Tasmania in 1903. Author(s): Michalek RJ, McGlashan ND. Source: Geogr Med. 1987; 17: 151-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3322942&dopt=Abstract

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Diplomatic immunity. Smallpox safeguard for healthcare workers plagued by logistical issues. Author(s): Piotrowski J. Source: Modern Healthcare. 2002 July 29; 32(30): 32-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195666&dopt=Abstract

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Direct BCG vaccination--simultaneous BCG and smallpox vaccination. Author(s): Baily GV. Source: Bull Int Union Tuberc. 1968 December; 41: 53-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5710261&dopt=Abstract

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Discoid lupus erythematosus occurring in a smallpox vaccination scar. Author(s): Lupton GP. Source: Journal of the American Academy of Dermatology. 1987 October; 17(4): 688-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3668013&dopt=Abstract

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Discontinuation of routine smallpox vaccination. Author(s): Chin J. Source: Calif Med. 1972 May; 116(5): 68. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4639849&dopt=Abstract

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Discontinuation of routine smallpox vaccination. Author(s): Shaw EB. Source: Calif Med. 1972 March; 116(3): 73-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5014767&dopt=Abstract

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Disease and its impact on politics, diplomacy, and the military: the case of smallpox and the Manchus (1613-1795). Author(s): Chang CF. Source: Journal of the History of Medicine and Allied Sciences. 2002 April; 57(2): 177-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995595&dopt=Abstract

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Disease as device: the role of smallpox in Bleak House. Author(s): Gurney MS. Source: Literature and Medicine. 1990; 9: 79-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2243500&dopt=Abstract

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Distinguishing smallpox from chickenpox. Author(s): Lovell RD. Source: Ed Manag. 2002 January; 14(1): Suppl 1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883056&dopt=Abstract

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Doctor Thomas Dimsdale, and smallpox in Russia. The variolation of the Empress Catherine the Great. Author(s): Griffiths J. Source: Bristol Med Chir J. 1984 January; 99(369): 14-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6367898&dopt=Abstract

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Does smallpox still pose a threat? Author(s): Weir E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 November 13; 165(10): 1380. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760991&dopt=Abstract

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Dose-related effects of smallpox vaccine. Author(s): Frey SE, Newman FK, Cruz J, Shelton WB, Tennant JM, Polach T, Rothman AL, Kennedy JS, Wolff M, Belshe RB, Ennis FA. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1275-80. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923489&dopt=Abstract

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Dr William Woodville (1752-1805) and the St Pancras Smallpox Hospital. Author(s): Cook GC. Source: J Med Biogr. 1996 May; 4(2): 71-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11616267&dopt=Abstract

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Dr. Thomas Dimsdale and smallpox inoculation in Russia. Author(s): Clendenning PH. Source: Journal of the History of Medicine and Allied Sciences. 1973 April; 28(2): 109-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4572621&dopt=Abstract

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Duck and cover: a prudent defense against smallpox. Author(s): Jeffcoat MK. Source: The Journal of the American Dental Association. 2003 April; 134(4): 408, 410. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733765&dopt=Abstract

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Duration of immunity after smallpox vaccination: a study on vaccination policy against smallpox bioterrorism in Japan. Author(s): Arita I. Source: Japanese Journal of Infectious Diseases. 2002 August; 55(4): 112-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403907&dopt=Abstract

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Duration of virus excretion in the throat of asymptomatic household contacts of smallpox patients. Author(s): Sarkar JK, Mitra AC, Mukherjee MK. Source: The Indian Journal of Medical Research. 1974 December; 62(12): 1800-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4377667&dopt=Abstract

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Dutch health service is asked to draw up smallpox contingency plans. Author(s): Sheldon T. Source: Bmj (Clinical Research Ed.). 2003 February 22; 326(7386): 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595361&dopt=Abstract

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Dynamics of anti-vaccinia HAI antibodies during the first month after smallpox revaccination at 20 years. Author(s): Topciu V, Voiculescu D, Moldovan E, Plavosin L, Giurca A. Source: Virologie. 1977 October-December; 28(4): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=602021&dopt=Abstract

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Early detection of smallpox. Author(s): Sitzman K. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2002 September; 50(9): 428. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244582&dopt=Abstract

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ECG-changes without subjective symptoms after smallpox vaccination of military personnel. Author(s): Ahlborg B, Linroth K, Nordgren B. Source: Acta Med Scand Suppl. 1966; 464: 127-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229008&dopt=Abstract

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Eczematous skin disease and recall of past diagnoses: implications for smallpox vaccination. Author(s): Naleway AL, Belongia EA, Greenlee RT, Kieke BA Jr, Chen RT, Shay DK. Source: Annals of Internal Medicine. 2003 July 1; 139(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834312&dopt=Abstract

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Editorial: Operation smallpox. Author(s): Mukerjee AB. Source: J Indian Med Assoc. 1975 April 16; 64(8): 212. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1159303&dopt=Abstract

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Editorial: smallpox prevention and control. Author(s): Best EJ. Source: Dent Dig. 1969 August; 75(8): 326. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5256973&dopt=Abstract

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Editorial: the risk of anthrax and smallpox in Australia. Author(s): Smallwood R. Source: Commun Dis Intell. 2001 November; 25(4): 188-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806654&dopt=Abstract

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Edward Jenner (1749-1823). The history and effects of smallpox, inoculation, and vaccination. Author(s): Bloch H. Source: Am J Dis Child. 1993 July; 147(7): 772-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8322750&dopt=Abstract

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Edward Jenner and the eradication of smallpox. Author(s): Willis NJ. Source: Scott Med J. 1997 August; 42(4): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9507590&dopt=Abstract

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EEG investigations of smallpox vaccination. Author(s): Enge S, Lorenzoni E. Source: Electroencephalography and Clinical Neurophysiology. 1970 March; 28(3): 323. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4190130&dopt=Abstract

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Effect of interval between inoculation of live smallpox and yellow-fever vaccines on antigenicity in man. Author(s): Tauraso NM, Myers MG, Nau EV, O'Brien TC, Spindel SS, Trimmer RW. Source: The Journal of Infectious Diseases. 1972 October; 126(4): 362-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4672744&dopt=Abstract

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Effect of simultaneous BCG and smallpox vaccination in schoolchildren. Report of a WHO-sponsored preliminary study. Author(s): Christensen H, Kjolbye E, Aung Tun U. Source: Bulletin of the World Health Organization. 1966; 35(4): 633-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5297559&dopt=Abstract

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Effect of smallpox vaccination on the product of conception. Author(s): Mihailescu R, Petrovici M. Source: Arch Roum Pathol Exp Microbiol. 1975 January-June; 34(1-2): 67-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1212077&dopt=Abstract

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Effect of smallpox vaccination on the tuberculin test. Author(s): Maniar B, Chinwala S, Seervai M. Source: Indian Pediatrics. 1971 September; 8(9): 431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5167195&dopt=Abstract

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Efficacy of UK smallpox vaccine questioned. Author(s): Hodgson J. Source: Nature Biotechnology. 2002 September; 20(9): 859-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205491&dopt=Abstract

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Efficiency of smallpox revaccination repeated at three-year intervals. II. Comparative study of the international reference strain (Elstree) and the Hungarian vaccine strain (Budapest). Author(s): Nyerges G, Hollos I, Losonczy G. Source: Acta Microbiol Acad Sci Hung. 1968; 15(3): 187-97. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5720872&dopt=Abstract

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Efficiency of smallpox revaccinations repeated at three year intervals. I. Follow-up of the immunological status of the staff of an infectious disease hospital. Author(s): Nyerges G, Hollos I, Losonczy G. Source: Acta Microbiol Acad Sci Hung. 1968; 15(2): 129-39. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5679788&dopt=Abstract

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Efforts of Indian railways in eradication of smallpox. Author(s): Sinha NK. Source: Indian J Public Health. 1978 April-June; 22(2): 210-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=711293&dopt=Abstract

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Electron microscopy in the rapid diagnosis of smallpox. Author(s): Cruickshank JG, Bedson HS, Watson DH. Source: Lancet. 1966 September 3; 2(7462): 527-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4161644&dopt=Abstract

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Emergency physicians' perspectives on smallpox vaccination. Author(s): Kwon N, Raven MC, Chiang WK, Moran GJ, Jui J, Carter RA, Goldfrank L; EMERGEncy ID Net Study Group. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 June; 10(6): 599-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782519&dopt=Abstract

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Emergency response to a smallpox attack: the case for mass vaccination. Author(s): Kaplan EH, Craft DL, Wein LM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 August 6; 99(16): 10935-40. Epub 2002 July 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118122&dopt=Abstract

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Encephalitis complicating smallpox vaccination. Author(s): Miravalle A, Roos KL. Source: Archives of Neurology. 2003 July; 60(7): 925-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873847&dopt=Abstract

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End of routine smallpox vaccination in childhood. Author(s): Foege WH, Lane JM. Source: Annals of Internal Medicine. 1972 February; 76(2): 324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5009600&dopt=Abstract

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Endemic smallpox in rural East Pakistan. I. Methodology, clinical and epidemiologic characteristics of cases, and intervillage transmission. Author(s): Thomas DB, McCormack WM, Arita I, Khan MM, Islam S, Mack TM. Source: American Journal of Epidemiology. 1971 May; 93(5): 361-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5556397&dopt=Abstract

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Endemic smallpox in rural East Pakistan. II. Intervillage transmission and infectiousness. Author(s): Thomas DB, Arita I, McCormack WM, Khan MM, Islam S, Mack TM. Source: American Journal of Epidemiology. 1971 May; 93(5): 373-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4326604&dopt=Abstract

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Epidemic of smallpox among the evacuees from Bangladesh in Salt Lake area near Calcutta. Author(s): Mazumder DN, Chakraborty AK. Source: J Indian Med Assoc. 1973 April 16; 60(8): 275-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4727920&dopt=Abstract

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Epidemiologic investigation of a smallpox outbreak in a town reported to be “100 per cent vaccinated”. Author(s): Morris L, Jose O, Martinez AV. Source: American Journal of Epidemiology. 1970 November; 92(5): 294-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4319713&dopt=Abstract

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Epidemiological and virological studies on the off-season smallpox cases in Calcutta. Author(s): Sarkar JK, Ray S, Manji P. Source: The Indian Journal of Medical Research. 1970 July; 58(7): 829-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5491311&dopt=Abstract

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Epidemiological studies in smallpox. A study of intrafamilial transmission in a series of 254 infected families. Author(s): Rao AR, Jacob ES, Kamalakshi S, Appaswamy S, Bradbury. Source: The Indian Journal of Medical Research. 1968 December; 56(12): 1826-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5732451&dopt=Abstract

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Epidemiology in the global eradication of smallpox. Author(s): Henderson DA. Source: International Journal of Epidemiology. 1972 Spring; 1(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4669176&dopt=Abstract

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Epidemiology of smallpox in Stockholm 1963. Author(s): Zetterberg B, Ringertz O, Svedmyr A, Wallmark G, Alin K. Source: Acta Med Scand Suppl. 1966; 464: 7-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229016&dopt=Abstract

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Epidemiology of smallpox in West Pakistan. 3. Outbreak detection and interlocality transmission. Author(s): Thomas DB, Mack TM, Ali A, Muzaffar Khan M. Source: American Journal of Epidemiology. 1972 February; 95(2): 178-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5060375&dopt=Abstract

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Epidemiology of smallpox in West Pakistan. I. Acquired immunity and the distribution of disease. Author(s): Mack TM, Thomas DB, Ali A, Muzaffar Khan M. Source: American Journal of Epidemiology. 1972 February; 95(2): 157-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5060373&dopt=Abstract

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Epidemiology of smallpox in West Pakistan. II. Determinants of intravillage spread other than acquired immunity. Author(s): Mack TM, Thomas DB, Muzaffar Khan M. Source: American Journal of Epidemiology. 1972 February; 95(2): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5060374&dopt=Abstract

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Epidemiology of smallpox in west Pakistan. III. Outbreak detection and interlocality transmission. 1971. Author(s): Thomas DB, Mack TM, Ali A, Khan MM. Source: American Journal of Epidemiology. 1995 March 15; 141(6): 490-501; Discussion 489. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7900715&dopt=Abstract

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Epidemiology. Controlling smallpox. Author(s): Koopman J. Source: Science. 2002 November 15; 298(5597): 1342-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434038&dopt=Abstract

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Eradicating smallpox. Author(s): Glaser RJ. Source: Pharos Alpha Omega Alpha Honor Med Soc. 1978 July; 41(3): 44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=693574&dopt=Abstract

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Eradication by vaccination: the memorial to smallpox could be surrounded by others. Author(s): Preston NW. Source: Prog Drug Res. 1993; 41: 151-89. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8108558&dopt=Abstract

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Eradication of smallpox and elimination of poliomyelitis: contrasts in strategy. Author(s): Sabin AB. Source: Jpn J Med Sci Biol. 1981 April; 34(2): 109-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7311107&dopt=Abstract

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Eradication of smallpox by the World Health Organization. Author(s): Keswani SG. Source: J Am Med Womens Assoc. 1977 September; 32(9): 334-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=197146&dopt=Abstract

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Eradication of smallpox. Author(s): Lambo TA. Source: The New England Journal of Medicine. 1981 July 23; 305(4): 224. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7242605&dopt=Abstract

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Eradication smallpox: global. Author(s): Bahl MR. Source: Med J Zambia. 1975 December-1976 January; 9(6): 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1235829&dopt=Abstract

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Erythema multiforme complicating smallpox vaccination. Author(s): Scott EG, Pankey GA. Source: J Miss State Med Assoc. 1969 February; 10(2): 41-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5763298&dopt=Abstract

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Evaluation of 21st-century risks of smallpox vaccination and policy options. Author(s): Lane JM, Goldstein J. Source: Annals of Internal Medicine. 2003 March 18; 138(6): 488-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639083&dopt=Abstract

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Evaluation of a measles-smallpox vaccination campaign by a sero-epidemiologic method. Author(s): Breman JG, Coffi E, Bomba-Ire R, Foster SO, Herrmann KL. Source: American Journal of Epidemiology. 1975 December; 102(6): 564-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=173183&dopt=Abstract

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evaluation of egg inoculation and precipitation in gel test for laboratory diagnosis of smallpox. Author(s): Sehgal CL, Pal SC. Source: The Indian Journal of Medical Research. 1974 August; 62(8): 1134-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4374430&dopt=Abstract

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Evaluation of smallpox vaccination policy. Author(s): Arita I, Breman JG. Source: Bulletin of the World Health Organization. 1979; 57(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=218745&dopt=Abstract

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Evaluation of the fluorescent antibody technique for the diagnosis of smallpox. Author(s): el-Ganzoury AL. Source: Journal of Clinical Pathology. 1967 November; 20(6): 879-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4881833&dopt=Abstract

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Evaluation of the precipitation-in-gel reaction in the diagnosis of smallpox. Author(s): Mitra AC, Sarkar JK, Mukherjee MK, Chakravarty MS. Source: Bulletin of the World Health Organization. 1973; 49(6): 555-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4374321&dopt=Abstract

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Evaluation of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. I. Clinical and serologic response to primary vaccination. Author(s): Wesley RB, Speers WC, Neff JM, Ruben FL, Lourie B. Source: Pediatric Research. 1975 August; 9(8): 624-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1098000&dopt=Abstract

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Evaluation of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. II. Clinical and serologic observations of response to revaccination with calf lymph vaccine. Author(s): Speers WC, Wesley RB, Neff JM, Goldstein J, Lourie B. Source: Pediatric Research. 1975 August; 9(8): 628-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1171424&dopt=Abstract

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Evaluation of virological laboratory methods for smallpox diagnosis. Author(s): Nakano JH. Source: Bulletin of the World Health Organization. 1973 May; 48(5): 529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4359680&dopt=Abstract

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Evolution of smallpox eradication programme in India. Author(s): Basu RN. Source: Indian J Public Health. 1976 April-June; 20(2): 51-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1022708&dopt=Abstract

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Exotic infectious diseases: smallpox. Author(s): Nicol W. Source: R Soc Health J. 1980 April; 100(2): 41-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6992193&dopt=Abstract

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Expected adverse events in a mass smallpox vaccination campaign. Author(s): Kemper AR, Davis MM, Freed GL. Source: Effective Clinical Practice : Ecp. 2002 March-April; 5(2): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990216&dopt=Abstract

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Experience with electron microscopy in the differential diagnosis of smallpox. Author(s): Long GW, Nobel J Jr, Murphy FA, Herrmann KL, Lourie B. Source: Appl Microbiol. 1970 September; 20(3): 497-504. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4322005&dopt=Abstract

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Experimental smallpox in chimpanzees. Author(s): Kalter SS, Rodriguez AR, Cummins LB, Heberling RL, Foster SO. Source: Bulletin of the World Health Organization. 1979; 57(4): 637-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=316740&dopt=Abstract

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Experiments on terminal disinfection by formaldehyde vapor in the case of smallpox. Author(s): Grossgebauer K, Spicher G, Peters J, Kuwert E, Pohle HD, Kerner H. Source: Journal of Clinical Microbiology. 1975 December; 2(6): 516-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1206108&dopt=Abstract

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Experts weigh prevention, therapy for ocular vaccinia in smallpox vaccinees. Author(s): Vastag B. Source: Jama : the Journal of the American Medical Association. 2003 May 7; 289(17): 2198-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734118&dopt=Abstract

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Facing up to smallpox. Author(s): Carmichael M. Source: Newsweek. 2002 October 7; 140(15): 73, 75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389313&dopt=Abstract

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Failure of cytosine arabinoside in treating smallpox. A double-blind study. Author(s): Dennis DT, Doberstyn EB, Awoke S, Royer GL Jr, Renis HE. Source: Lancet. 1974 August 17; 2(7877): 377-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4136735&dopt=Abstract

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False positive results in V D R L slide test following smallpox immunization. Author(s): Seet LC, Sng EH, Thomas M. Source: Asian J Infect Dis. 1979 September; 3(3): 137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=554603&dopt=Abstract

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Farewell to smallpox vaccination. Author(s): Arita I. Source: Dev Biol Stand. 1979; 43: 283-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=520675&dopt=Abstract

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Field evaluation of combined more attenuated live measles (Moraten)-smallpox vaccine in Honduras and Costa Rica. Author(s): Villarejos VM, Rodriguez-Aragones A, Gunera N, Arguedas JA, Buynak EB, Hilleman MR. Source: American Journal of Epidemiology. 1971 May; 93(5): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5556398&dopt=Abstract

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Field investigation of an outbreak of smallpox at Bawku, Ghana: May-October, 1967. Author(s): De Sario V. Source: East Afr Med J. 1970 October; 47(10): 524-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5521242&dopt=Abstract

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Field trials of methisazone as a prophylactic agent against smallpox. Author(s): Heiner GG, Fatima N, Russell PK, Haase AT, Ahmad N, Mohammed N, Thomas DB, Mack TM, Khan MM, Knatterud GL, Anthony RL, McCrumb FR Jr. Source: American Journal of Epidemiology. 1971 November; 94(5): 435-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4941154&dopt=Abstract

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Fighting smallpox on the Texas border: an episode from PHS's proud past. Author(s): Michael JM, Bender TR. Source: Public Health Reports (Washington, D.C. : 1974). 1984 November-December; 99(6): 579-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6440202&dopt=Abstract

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First Department of Defense Smallpox Vaccination Program Report. Author(s): Winkenwerder W Jr. Source: Miss Rn. 2003 Spring; 65(1): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710160&dopt=Abstract

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Five years of freedom from smallpox. Author(s): Ladnyi ID, Jezek Z, Gromyko A. Source: J Hyg Epidemiol Microbiol Immunol. 1983; 27(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6854010&dopt=Abstract

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Flocculating antigen in the sera of haemorrhagic smallpox cases. Author(s): Ray S, Mitra AC, Sarkar JK. Source: Bull Calcutta Sch Trop Med. 1967 July; 15(3): 102-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4307212&dopt=Abstract

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Focal and generalized folliculitis following smallpox vaccination among vaccinianaive recipients. Author(s): Talbot TR, Bredenberg HK, Smith M, LaFleur BJ, Boyd A, Edwards KM. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3290-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824211&dopt=Abstract

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Freeze-dried smallpox vaccine; report of a trial in Kuala Lumpur. Author(s): Maitland HB. Source: Med J Malaya. 1965 September; 20(1): 8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4221441&dopt=Abstract

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French reactions to Jenner's discovery of smallpox vaccination: the primary sources. Author(s): Meynell E. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 1995 August; 8(2): 285-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11639810&dopt=Abstract

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From inoculation to vaccination: smallpox in Sweden in the eighteenth and nineteenth centuries. Author(s): Skold P. Source: Population Studies. 1996 July; 50(2): 247-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11613334&dopt=Abstract

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From the Centers for Disease Control and Prevention. Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices. Author(s): Advisory Committee on Immunization Practices. Source: Jama : the Journal of the American Medical Association. 2003 April 23-30; 289(16): 2064. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709453&dopt=Abstract

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Further studies with precipitation in gel test in diagnosis of smallpox. I. Studies on detection of antibodies in sera by pig test. Author(s): Rao AR, Savithri Sukumar M, Kamalakshi S, Paramasivam TV, Ramakrishnan S. Source: The Indian Journal of Medical Research. 1972 September; 60(9): 1254-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4350577&dopt=Abstract

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Gamma-globulin levels in healthy infants after smallpox vaccination. Author(s): Suharjono, Saidi SR, Budjang RF, Pelenkahu TB. Source: Paediatr Indones. 1969 July-August; 9(4): 161-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4187010&dopt=Abstract

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Gearing up for smallpox. Author(s): McConnell J. Source: The Lancet Infectious Diseases. 2002 July; 2(7): 390. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127345&dopt=Abstract

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Germany's smallpox jab plan meets with resistance. Author(s): Habeck M. Source: The Lancet Infectious Diseases. 2003 March; 3(3): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614715&dopt=Abstract

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Global eradication of smallpox: WHO's insurance policy. Author(s): El-Zawarhy MA. Source: Paediatr Indones. 1979 March-April; 19(3-4): 123-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=503544&dopt=Abstract

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Global smallpox eradication. Author(s): Arita I. Source: Indian J Public Health. 1978 January-March; 22(1): 1-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669753&dopt=Abstract

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Granuloma pyogenicum--a hitherto unrecognized complication of smallpox vaccination. Author(s): Zayid I, Farraj S. Source: The British Journal of Dermatology. 1974 March; 90(3): 293-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4823086&dopt=Abstract

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Graves' disease presenting as localized myxoedematous infiltration in a smallpox vaccination scar. Author(s): Pujol RM, Monmany J, Bague S, Alomar A. Source: Clinical and Experimental Dermatology. 2000 March; 25(2): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733638&dopt=Abstract

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Haemagglutination-inhibiting variola antibodies in blood serum of former smallpox patients, their healthy siblings, and unvaccinated controls from other areas. Author(s): Chakravartti MR, Vogel F. Source: Humangenetik. 1971; 11(4): 336-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4323810&dopt=Abstract

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Haemorrhagic smallpox. Author(s): Downie AW, Fedson DS, Saint Vincent L, Rao AR, Kempe CH. Source: J Hyg (Lond). 1969 December; 67(4): 619-29. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4311573&dopt=Abstract

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Haemorrhagic smallpox. Author(s): Upadhaya AK. Source: J Indian Med Assoc. 1969 January 1; 52(1): 36-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5801455&dopt=Abstract

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Haemorrhagic smallpox. 2. Specific bleeding and coagulation studies. Author(s): McKenzie PJ, Githens JH, Harwood ME, Roberts JF, Rao AR, Kempe CH. Source: Bulletin of the World Health Organization. 1965; 33(6): 773-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5295401&dopt=Abstract

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Haemorrhagic smallpox. I. Preliminary haematological studies. Author(s): Roberts JF, Coffee G, Creel SM, Gaal A, Githens JH, Rao AR, Sundara Babu BV, Kempe CH. Source: Bulletin of the World Health Organization. 1965; 33(5): 607-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5295141&dopt=Abstract

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Has smallpox finally been eradicated? Author(s): Michaeli D. Source: Public Health Rev. 1998; 26(3): 305-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10444967&dopt=Abstract

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Hazards of smallpox vaccination. Author(s): Watts GT. Source: British Medical Journal. 1976 October 2; 2(6039): 813. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=974630&dopt=Abstract

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Hazards of smallpox vaccination. Author(s): Kellerman F. Source: British Medical Journal. 1976 September 11; 2(6036): 638. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=963473&dopt=Abstract

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Hazards of smallpox vaccination. Author(s): Lane JM. Source: Jama : the Journal of the American Medical Association. 1982 May 21; 247(19): 2709. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7200533&dopt=Abstract

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Health professionals challenge US smallpox vaccination plan. Author(s): Moynihan R. Source: Bmj (Clinical Research Ed.). 2003 January 25; 326(7382): 179. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543820&dopt=Abstract

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Hemorrhagic smallpox. A study of 22 cases to determine the cause of bleeding. Author(s): Mehta BC, Doctor RG, Purandare NM, Patel JC. Source: Indian Journal of Medical Sciences. 1967 August; 21(8): 518-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5595756&dopt=Abstract

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Herpesvirus hominis infection at a smallpox vaccination site. Author(s): Warren WS, Salvatore MA. Source: Jama : the Journal of the American Medical Association. 1968 September 23; 205(13): 931-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4299836&dopt=Abstract

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HHS proposes smallpox vaccination for medical workers. Author(s): Szabo J. Source: Mlo: Medical Laboratory Observer. 2002 November; 34(11): 41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442726&dopt=Abstract

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HHS tries to boost smallpox programme. Author(s): Quirk M. Source: The Lancet Infectious Diseases. 2003 April; 3(4): 181. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679248&dopt=Abstract

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Historical epidemiology of smallpox in Aland, Finland: 1751-1890. Author(s): Mielke JH, Jorde LB, Trapp PG, Anderton DL, Pitkanen K, Eriksson AW. Source: Demography. 1984 August; 21(3): 271-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6383886&dopt=Abstract

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History and recent developments of smallpox vaccine. Author(s): Singh LM. Source: J Indian Med Assoc. 1977 March 1; 68(5): 105-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=903636&dopt=Abstract

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Hopkins Dean criticizes smallpox research. Author(s): Birmingham K. Source: Nature Medicine. 2002 March; 8(3): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875469&dopt=Abstract

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How technology contributed to the success of global smallpox eradication. Author(s): Arita I. Source: Who Chron. 1980 May; 34(5): 175-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7376636&dopt=Abstract

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Human monkeypox and smallpox viruses: genomic comparison. Author(s): Shchelkunov SN, Totmenin AV, Babkin IV, Safronov PF, Ryazankina OI, Petrov NA, Gutorov VV, Uvarova EA, Mikheev MV, Sisler JR, Esposito JJ, Jahrling PB, Moss B, Sandakhchiev LS. Source: Febs Letters. 2001 November 30; 509(1): 66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734207&dopt=Abstract

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Human poxvirus disease after smallpox eradication. Author(s): Breman JG, Nakano JH, Coffi E, Godfrey H, Gautun JC. Source: Am J Trop Med Hyg. 1977 March; 26(2): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=192091&dopt=Abstract

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Human poxvirus infection after the eradication of smallpox. Author(s): Baxby D. Source: Epidemiology and Infection. 1988 June; 100(3): 321-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837403&dopt=Abstract

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Humoral immunity and cutaneous reactions after smallpox revaccination. Correlations with persistent scars from childhood. Author(s): Topciu V, Voiculescu D, Plavosin L, Giurca A, Moldovan E. Source: Arch Roum Pathol Exp Microbiol. 1976 January-June; 35(1-2): 125-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1008687&dopt=Abstract

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Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines. Author(s): Drexler I, Staib C, Kastenmuller W, Stevanovic S, Schmidt B, Lemonnier FA, Rammensee HG, Busch DH, Bernhard H, Erfle V, Sutter G. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 January 7; 100(1): 217-22. Epub 2002 December 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518065&dopt=Abstract

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II. Disease and social change. Smallpox in Kenya, 1880-1920. Author(s): Dawson MH. Source: Soc Sci Med [med Anthropol]. 1979 December; 13B(4): 245-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=395652&dopt=Abstract

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Images in clinical medicine. Progression of the lesion at the site of inoculation after smallpox vaccination. Author(s): Rubins K, Relman DA. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556544&dopt=Abstract

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Images in clinical medicine. Smallpox--26 years ago. Author(s): Herron C. Source: The New England Journal of Medicine. 1996 May 16; 334(20): 1304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8609948&dopt=Abstract

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Immune responses to measles and smallpox vaccinations in malnourished children. Author(s): Ifekwunigwe AE, Grasset N, Glass R, Foster S. Source: The American Journal of Clinical Nutrition. 1980 March; 33(3): 621-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7355846&dopt=Abstract

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Immunity conferred by smallpox vaccine. How long does immunity last? Author(s): Jacobs A. Source: Bmj (Clinical Research Ed.). 2002 May 11; 324(7346): 1157; Author Reply 1157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003901&dopt=Abstract

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Immunization against smallpox before Jenner. Author(s): Langer WL. Source: Scientific American. 1976 January; 234(1): 112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=766184&dopt=Abstract

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Immunization against smallpox. Author(s): Kaplan C. Source: British Medical Bulletin. 1969 May; 25(2): 131-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4918528&dopt=Abstract

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Immunogenicity of smallpox vaccines prepared from strains of different reactogenicity. Author(s): Nyerges G, Csukas M. Source: Acta Microbiol Acad Sci Hung. 1972; 19(2): 103-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4670218&dopt=Abstract

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Immunoglobulin levels in the blood serum of children developing neurological complications after immunization against smallpox. Author(s): Gurvich EB, Ozeretskovsky NA, Malkina LA. Source: Padiatr Grenzgeb. 1980; 19(2): 119-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6108547&dopt=Abstract

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Immunological studies in smallpox. Author(s): Seal SC, Roy DK. Source: The Indian Journal of Medical Research. 1968 April; 56(4): 467-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5687704&dopt=Abstract

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Incidental subcutaneous administration of high dosage smallpox vaccine in vaccinated adults. Author(s): Toma E, Mihancea N, Paun L, Mihailescu R, Popescu E. Source: Arch Roum Pathol Exp Microbiol. 1981 April-June; 40(2): 137-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7305648&dopt=Abstract

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India's scientists question need for research on smallpox virus. Author(s): Kumar S. Source: Lancet. 2001 April 7; 357(9262): 1106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297978&dopt=Abstract

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India's shame. A war on smallpox but a welcome for cigarettes. Author(s): Nath UR. Source: N Y State J Med. 1983 December; 83(13): 1320-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6582388&dopt=Abstract

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Indications for smallpox vaccination: policies still differ. Author(s): Baxby D. Source: Vaccine. 1993; 11(4): 395-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470422&dopt=Abstract

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Infectious diseases. Smallpox vaccination campaign in the doldrums. Author(s): Enserink M. Source: Science. 2003 May 9; 300(5621): 880-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738820&dopt=Abstract

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Inoculating for smallpox. Author(s): Greene J. Source: Hospitals & Health Networks / Aha. 2003 April; 77(4): 52-4, 56-7, 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735180&dopt=Abstract

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Inoculation against smallpox as the precursor to vaccination. Author(s): van Oss CJ. Source: Immunological Investigations. 2000 November; 29(4): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130785&dopt=Abstract

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Inoculation for smallpox (variolation) as performed in England prior to Jenner's discovery. Author(s): Cone TE Jr. Source: Pediatrics. 1972 December; 50(6): 889. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4564599&dopt=Abstract

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Intact smallpox virus particles in an Italian mummy of sixteenth century. Author(s): Fornaciari G, Marchetti A. Source: Lancet. 1986 September 13; 2(8507): 625. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2875332&dopt=Abstract

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Interim smallpox guidelines for the United Kingdom. Author(s): Harling R, Morgan D, Edmunds WJ, Campbell H. Source: Bmj (Clinical Research Ed.). 2002 December 14; 325(7377): 1371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480827&dopt=Abstract

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Intimidation, coercion and resistance in the final stages of the South Asian Smallpox Eradication Campaign, 1973-1975. Author(s): Greenough P. Source: Social Science & Medicine (1982). 1995 September; 41(5): 633-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7502097&dopt=Abstract

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Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study. Author(s): Pfahlberg A, Kolmel KF, Grange JM, Mastrangelo G, Krone B, Botev IN, Niin M, Seebacher C, Lambert D, Shafir R, Schneider D, Kokoschka EM, Kleeberg UR, Uter W, Gefeller O. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 570-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230497&dopt=Abstract

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Investigation of hospital-associated smallpox--Vitoria, Espirito Santo. Author(s): Morris L, de Lemos AL, da Silva OJ. Source: Am J Public Health Nations Health. 1970 December; 60(12): 2331-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5530418&dopt=Abstract

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Investigation of smallpox suspected cases in the final stage of Indian smallpox eradication programme. Author(s): Jezek Z, Basu RN, Arya ZS. Source: Indian J Public Health. 1978 January-March; 22(1): 107-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669755&dopt=Abstract

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Investigations on allergic and serological reactions following inoculation of inactivated smallpox vaccines by cutaneous scarification. Author(s): Giurca A, Topciu VL, Voiculescu D, Moldovan E, Plavosin L. Source: Virologie. 1976 July-September; 27(3): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1006976&dopt=Abstract

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Is monkeypox a reservoir of smallpox? Author(s): Danilevicius Z. Source: Jama : the Journal of the American Medical Association. 1972 December 25; 222(13): 1645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4629139&dopt=Abstract

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Is smallpox a hazard in church crypts? Author(s): Baxter PJ, Brazier AM, Young SE. Source: Br J Ind Med. 1988 May; 45(5): 359-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3288275&dopt=Abstract

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Isolation of vaccinia virus from the cerebrospinal fluid following anti-smallpox primovaccination in a subject with chronic ethylism. Author(s): Topciu V, Vasilescu I, Plavosin L, Moldovan E. Source: Virologie. 1977 January-March; 28(1): 85-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=851003&dopt=Abstract

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Isolation of vaccinia virus from the pharynx of children vaccinated against smallpox. Author(s): Gurvich EB, Braginskaya VP, Shenkman LS, Sokolova AF, Davydova AV. Source: J Hyg Epidemiol Microbiol Immunol. 1974; 18(1): 69-76. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4473485&dopt=Abstract

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Isolation of vaccinia virus from the sternal puncture of a smallpox revaccinee with latent leukosis. Author(s): Topciu V, Roth V, Vasilescu I, Plavosin L, Moldovan E. Source: Virologie. 1977 April-June; 28(2): 161-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=867808&dopt=Abstract

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Isolation of virus from the urine, conjunctiva and throat of smallpox cases. Author(s): Sarkar JK, Mitra AC, Mukherjee MK, De S, Mazumdar DG. Source: Bull Calcutta Sch Trop Med. 1972 July; 20(3): 37-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4371892&dopt=Abstract

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Italian smallpox of the sixteenth century. Author(s): Fornaciari G, Marchetti A. Source: Lancet. 1986 December 20-27; 2(8521-22): 1469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2878330&dopt=Abstract

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Jadassohn tumour arising at smallpox vaccination site. Author(s): Porter D, Earle J. Source: The British Journal of Dermatology. 1972 February; 86(2): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5017293&dopt=Abstract

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John Jeffries and the struggle against smallpox in Boston (1775-1776) and Nova Scotia (1776-1779). Author(s): Cash P, Pine C. Source: Bulletin of the History of Medicine. 1983 Spring; 57(1): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6344944&dopt=Abstract

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Keratoacanthoma in a smallpox vaccination site. Author(s): Haider S. Source: The British Journal of Dermatology. 1974 June; 90(6): 689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4852612&dopt=Abstract

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Laboratory aids to the control of smallpox in countries where the disease is not endemic. Author(s): Dumbell KR. Source: Prog Med Virol. 1968; 10: 388-97. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4304592&dopt=Abstract

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Laboratory diagnosis of smallpox. Author(s): Macrae AD. Source: Mon Bull Minist Health Public Health Lab Serv. 1967 October; 26: 189-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4964983&dopt=Abstract

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Laboratory diagnosis of smallpox: role of the Virus Reference Laboratory, Colindale, 1947-70. Author(s): Macrae AD. Source: J Hyg (Lond). 1982 December; 89(3): 399-407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6296227&dopt=Abstract

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Lack of correlation between complications after smallpox vaccination and the ABO blood-group system. Author(s): Gurvich EB, Lakotkina EA, Kossova ET, Stepanenkova LP, Pozdnyakova IS, Ozeretskovskij NA. Source: J Hyg Epidemiol Microbiol Immunol. 1980; 24(2): 200-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6106028&dopt=Abstract

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Lady Mary Wortley Montagu and the Reverend Cotton Mather: their campaigns for smallpox inoculation. Author(s): Roberts S. Source: J Med Biogr. 1996 August; 4(3): 129-36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11616303&dopt=Abstract

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Lady Mary Wortley Montague's contribution to the eradication of smallpox. Author(s): Rathbone J. Source: Lancet. 1996 June 1; 347(9014): 1566. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8684145&dopt=Abstract

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Large-scale use of freeze-dried smallpox vaccine prepared in primary cultures of rabbit kidney cells. Author(s): Hekker AC, Bos JM, Rai NK, Keja J, Cuboni G, Emmet B, Djalins J. Source: Bulletin of the World Health Organization. 1976; 54(3): 279-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1088108&dopt=Abstract

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Leicester and smallpox: the Leicester method. Author(s): Fraser SM. Source: Medical History. 1980 July; 24(3): 315-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6997656&dopt=Abstract

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Lessons learnt from the intensified campaign against smallpox in India and their possible applicability to other health programmes, with particular reference to eradication of dracunculiasis. Author(s): Sharma MI. Source: J Commun Dis. 1980 June; 12(2): 59-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6458633&dopt=Abstract

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Letter: “Wild white” viruses and smallpox. Author(s): Dumbell KR. Source: Lancet. 1974 September 7; 2(7880): 585. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4140287&dopt=Abstract

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Letter: Continue smallpox vaccination. Author(s): Tizes R. Source: American Journal of Public Health. 1973 December; 63(12): 1022. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4759865&dopt=Abstract

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Letter: Disinfectants and smallpox. Author(s): Kelsey JC. Source: Lancet. 1975 February 8; 1(7902): 337. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=46481&dopt=Abstract

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Letter: Herpes zoster following primary smallpox vaccination. Author(s): Verbov J. Source: The British Journal of Dermatology. 1974 January; 90(1): 110-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4811832&dopt=Abstract

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Letter: Lack of smallpox protection. Author(s): Szalay GC. Source: Jama : the Journal of the American Medical Association. 1974 November 25; 230(8): 1125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4479447&dopt=Abstract

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Letter: Relaxation of requirements on smallpox vaccination. Author(s): Balla JI. Source: The Medical Journal of Australia. 1975 January 25; 1(4): 122. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1134414&dopt=Abstract

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Letter: Selective smallpox vaccination for special risk groups. Author(s): Tizes R. Source: Jama : the Journal of the American Medical Association. 1974 July 8; 229(2): 142. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4406820&dopt=Abstract

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Letter: Smallpox vaccination and eczema. Author(s): Formby D. Source: The Medical Journal of Australia. 1974 October 26; 2(17): 644. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4444614&dopt=Abstract

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Letter: Smallpox vaccination and eczema. Author(s): Ferry B. Source: The Medical Journal of Australia. 1974 October 19; 2(16): 612. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4437425&dopt=Abstract

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Letter: Smallpox vaccination and eczema. Author(s): Stuart J. Source: The Medical Journal of Australia. 1974 August 17; 2(7): 269. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4420071&dopt=Abstract

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Letter: Smallpox vaccination in infancy. Author(s): Wurapa FK, Pacsa S, Addy PA, Amoah S. Source: Lancet. 1975 February 15; 1(7903): 404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=46559&dopt=Abstract

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Letter: Smallpox vaccination. Author(s): Moghadam H. Source: Can Med Assoc J. 1973 September 15; 109(6): 458 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4742912&dopt=Abstract

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Letter: Smallpox vaccine for herpes zoster. Author(s): Chang SL. Source: Jama : the Journal of the American Medical Association. 1974 April 1; 228(1): 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4406140&dopt=Abstract

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Letter: Vaccination of smallpox contacts. Author(s): Bousfield G, Dick G. Source: British Medical Journal. 1974 May 25; 2(916): 441-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4835307&dopt=Abstract

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Letter: Vaccination of smallpox contacts. Author(s): Emond RT, McKendrick GD. Source: British Medical Journal. 1974 April 20; 2(911): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4132987&dopt=Abstract

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Letter: Vaccination of smallpox contacts. Author(s): Bauer DJ. Source: British Medical Journal. 1974 March 23; 1(907): 576. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4131646&dopt=Abstract

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Letter: Vaccination of smallpox contacts. Author(s): Bousfield G, Dick G. Source: British Medical Journal. 1973 November 17; 4(5889): 423. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4749796&dopt=Abstract

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Limited smallpox vaccination to resume in United States. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 February 1; 60(3): 219-20, 222. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613227&dopt=Abstract

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Malignancy in a smallpox vaccination scar. Report on another case. Author(s): Friedman MM, Miller-Cranko JA. Source: Cent Afr J Med. 1972 July; 18(7): 142. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4666456&dopt=Abstract

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Malignant change in smallpox vaccination scars. Author(s): Goncalves JC. Source: Archives of Dermatology. 1966 February; 93(2): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5904032&dopt=Abstract

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Malignant fibrous histiocytoma arising in a smallpox vaccination scar. Author(s): Slater DN, Parsons MA, Fussey IV. Source: The British Journal of Dermatology. 1981 August; 105(2): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6269571&dopt=Abstract

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Malignant tumors in smallpox vaccination scars: a report of 24 cases. Author(s): Marmelzat WL. Source: Archives of Dermatology. 1968 April; 97(4): 400-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4296119&dopt=Abstract

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Mass campaign against smallpox in Thailand. Author(s): Trishnananda M. Source: International Journal of Dermatology. 1971 January-March; 10(1): 29-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5900079&dopt=Abstract

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Mass vaccination against smallpox and mortality in Yugoslavia in 1972. Author(s): Radovanovic Z, Djordjevic Z. Source: Trans R Soc Trop Med Hyg. 1979; 73(1): 122. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=442173&dopt=Abstract

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Matthieu Maty and the adoption of inoculation for smallpox in Holland. Author(s): Janssens U. Source: Bulletin of the History of Medicine. 1981 Summer; 55(2): 246-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7020808&dopt=Abstract

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Maxwell Finland Lecture. Smallpox: is the end in sight? Author(s): Meiklejohn G. Source: The Journal of Infectious Diseases. 1976 March; 133(3): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1254992&dopt=Abstract

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Measures for smallpox eradication in the Czech countries at the beginning of the 19th century. Author(s): Raska K. Source: International Journal of Epidemiology. 1976 September; 5(3): 227-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=791874&dopt=Abstract

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Methotrexate and smallpox vaccination. Author(s): Allison J. Source: Lancet. 1968 December 7; 2(7580): 1250. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4177233&dopt=Abstract

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Modeling potential responses to smallpox as a bioterrorist weapon. Author(s): Meltzer MI, Damon I, LeDuc JW, Millar JD. Source: Emerging Infectious Diseases. 2001 November-December; 7(6): 959-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747722&dopt=Abstract

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Modelling the different smallpox epidemics in England. Author(s): Duncan SR, Scott S, Duncan CJ. Source: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 1994 December 29; 346(1318): 407-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7746845&dopt=Abstract

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Moments in surgical history: Zabdiel Boylston and smallpox inoculation. Author(s): Rutkow IM. Source: Archives of Surgery (Chicago, Ill. : 1960). 2001 October; 136(10): 1213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585519&dopt=Abstract

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Monkeypox and its relevance to smallpox eradication. Author(s): Henderson DA, Arita I. Source: Who Chron. 1973 April; 27(4): 145-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4351716&dopt=Abstract

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Mummified, frozen smallpox: is it a threat? Author(s): Lewin PK. Source: Jama : the Journal of the American Medical Association. 1985 June 7; 253(21): 3095. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3999295&dopt=Abstract

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Myocarditis after smallpox vaccination: a case report. Author(s): Saurina G, Shirazi S, Lane JM, Daniel B, DiEugenia L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 145-6. Epub 2003 June 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830420&dopt=Abstract

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Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. Author(s): Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, Gray GC, Ostroff S, Eckart RE, Hospenthal DR, Gibson RL, Grabenstein JD, Arness MK, Tornberg DN; Department of Defense Smallpox Vaccination Clinical Evaluation Team. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824210&dopt=Abstract

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Myths in medicine. Surveillance-containment is key to eradication of smallpox. Author(s): Baxby D. Source: Bmj (Clinical Research Ed.). 1995 January 7; 310(6971): 62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7827578&dopt=Abstract

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National preparedness for biological warfare and bioterrorism: smallpox and the ophthalmologist. Author(s): Maki DG. Source: Archives of Ophthalmology. 2003 May; 121(5): 710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742850&dopt=Abstract

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Natural transmission of smallpox from man to performing monkeys. An ecological curiosity. Author(s): Mack TM, Noble J Jr. Source: Lancet. 1970 April 11; 1(7650): 752-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4191250&dopt=Abstract

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Nature, nurture and my experience with smallpox eradication. Author(s): Fenner F. Source: The Medical Journal of Australia. 1999 December 6-20; 171(11-12): 638-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721355&dopt=Abstract

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Need for smallpox vaccination in high-risk groups. Author(s): Burnside WW. Source: The Journal of Pediatrics. 1973 May; 82(5): 892-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4698967&dopt=Abstract

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Neonatal smallpox vaccination--a sound proposition for smallpox endemic areas. Author(s): Ukeje MA. Source: J Trop Med Hyg. 1972 August; 75(8): 149-52. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4668709&dopt=Abstract

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Neonatal vaccination against smallpox by intradermal route: a clinical assessment. Author(s): Ray S, Indra S, Roy A, Roy IB. Source: The Indian Journal of Medical Research. 1970 March; 58(3): 382-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5524451&dopt=Abstract

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Neurological complication after smallpox vaccination. Author(s): Goswamy BM. Source: J Assoc Physicians India. 1969 January; 17(1): 41-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5346496&dopt=Abstract

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Neurological complications after smallpox vaccination. Author(s): Holmgren B, Lindblom U. Source: Acta Med Scand Suppl. 1966; 464: 105-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229006&dopt=Abstract

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Neuromyelitis optica: severe demyelination occurring years after primary smallpox vaccination. Author(s): Adams JM, Brown WJ, Eberle ED, Vorlty A. Source: Rev Roum Neurol. 1973; 10(3): 227-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4726780&dopt=Abstract

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New smallpox case seems lab-caused. Author(s): Wade N. Source: Science. 1978 September 8; 201(4359): 893. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=684414&dopt=Abstract

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No smallpox in Vietnam. Author(s): Lane JM. Source: The New England Journal of Medicine. 1970 December 24; 283(26): 1468. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5481785&dopt=Abstract

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Nodulus cutaneus with hemorrhage in a smallpox vaccination scar. Author(s): Rubin Z, Hyman AB. Source: Archives of Dermatology. 1965 October; 92(4): 406-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5835332&dopt=Abstract

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Nursing smallpox and its consequences. February 1921. Author(s): Foley EL. Source: The American Journal of Nursing. 2002 February; 102(2): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953521&dopt=Abstract

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Occupationally-acquired smallpox in an IgM-deficient health worker. Author(s): Brilliant LB, Nakano JH, Kitamura T, Hodakevic LN, Bharucha PB. Source: Bulletin of the World Health Organization. 1981; 59(1): 99-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7020974&dopt=Abstract

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Ocular complications of smallpox vaccination. Author(s): Pepose JS, Margolis TP, LaRussa P, Pavan-Langston D. Source: American Journal of Ophthalmology. 2003 August; 136(2): 343-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888060&dopt=Abstract

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Old smallpox vaccination may still protect. Author(s): Hopkins Tanne J. Source: Bmj (Clinical Research Ed.). 2002 September 7; 325(7363): 513. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217986&dopt=Abstract

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Ongoing debate over smallpox vaccinations continues. Author(s): Howard-Ruben J. Source: Ons News / Oncology Nursing Society. 2003 June; 18(6): 12, 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817403&dopt=Abstract

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Operation smallpox zero. Author(s): Jezek Z, Basu RN. Source: Indian J Public Health. 1978 January-March; 22(1): 39-43. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669762&dopt=Abstract

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Oral drug and old vaccine renew smallpox bioterror debate. Author(s): Morris K. Source: The Lancet Infectious Diseases. 2002 May; 2(5): 262. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062979&dopt=Abstract

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Oral immunization against smallpox. Author(s): Hochstein-Mintzel V, Stickl H, Huber HC. Source: Dev Biol Stand. 1976; 33: 260-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=182585&dopt=Abstract

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Orally available cidofovir derivative active against smallpox. Author(s): Bradbury J. Source: Lancet. 2002 March 23; 359(9311): 1041. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937193&dopt=Abstract

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Organization of hospital care for smallpox cases at the hospital for infectious diseases in Stockholm. Author(s): Strom J. Source: Acta Med Scand Suppl. 1966; 464: 66-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229015&dopt=Abstract

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Oscillatory dynamics of smallpox and the impact of vaccination. Author(s): Duncan CJ, Duncan SR, Scott S. Source: Journal of Theoretical Biology. 1996 December 21; 183(4): 447-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9015459&dopt=Abstract

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Osteo-articular complications of smallpox vaccination. Author(s): Singhal RK. Source: J Indian Med Assoc. 1970 July 1; 55(1): 20-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5474321&dopt=Abstract

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Osteological evidence for smallpox: a possible case from seventeenth century Ontario. Author(s): Jackes MK. Source: American Journal of Physical Anthropology. 1983 January; 60(1): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6346891&dopt=Abstract

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Outbreak of smallpox in some villages of Jaipur district, Rajasthan, during 1968. Author(s): Pattanayak S, Sehgal PN, Raghavan NG. Source: The Indian Journal of Medical Research. 1970 April; 58(4): 416-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5506665&dopt=Abstract

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Outbreaks of smallpox due to variolation in China, 1962-1965. Author(s): Yutu JA, Jing M, Guang XH. Source: American Journal of Epidemiology. 1988 July; 128(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837897&dopt=Abstract

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Outcry greets US plan to test smallpox vaccine on children. Author(s): Check E. Source: Nature. 2002 November 14; 420(6912): 110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432349&dopt=Abstract

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Palaeontology of smallpox. Author(s): Zuckerman AJ. Source: Lancet. 1984 December 22; 2(8417-18): 1454. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6151058&dopt=Abstract

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Parental knowledge and attitude to smallpox vaccination in a rural community of south India. Author(s): Rao DC. Source: Indian J Pediatr. 1975 February; 42(325): 46-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1150315&dopt=Abstract

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Participation of the public in global smallpox eradication. Author(s): Foster SO. Source: Public Health Reports (Washington, D.C. : 1974). 1978 March-April; 93(2): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=635088&dopt=Abstract

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Partnerships plan for potential smallpox. Author(s): Cole JA. Source: Oreg Nurse. 2003 February; 68(1): 4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641043&dopt=Abstract

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Pathogenesis and potential antiviral therapy of complications of smallpox vaccination. Author(s): Bray M. Source: Antiviral Research. 2003 April; 58(2): 101-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742570&dopt=Abstract

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Pattern of intrafamilial transmission of smallpox in Calcutta, India. Author(s): Mukherjee MK, Sarkar JK, Mitra AC. Source: Bulletin of the World Health Organization. 1974; 51(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4376976&dopt=Abstract

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Penetrating keratoplasty for adherent leukoma of smallpox. Author(s): Law WN. Source: American Journal of Ophthalmology. 1981 December; 92(6): 811-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7032302&dopt=Abstract

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Periostitis following smallpox vaccination. Author(s): Bennett NM, Yung AP, Lehmann NI. Source: The Medical Journal of Australia. 1968 June 15; 1(24): 1052-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5663700&dopt=Abstract

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Peripheral nerve and root disturbances following active immunization against smallpox and tetanus. Author(s): Deliyannakis E. Source: Military Medicine. 1971 May; 136(5): 458-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4343647&dopt=Abstract

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Perspectives on smallpox eradication. Author(s): Marennikova SS. Source: Epidemiology (Cambridge, Mass.). 2003 January; 14(1): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500054&dopt=Abstract

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Pigmented hairy scar following smallpox vaccination. Author(s): Kumar LR, Goyal BG. Source: Indian J Pediatr. 1968 June; 35(245): 283-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5726879&dopt=Abstract

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Plasma 17-OCHS levels after vaccination against smallpox and measles in children. Author(s): Hassan AI, Zeitoun MM, Hussein ZM, Fahmy MS, Ragab M, Hussein M. Source: Acta Paediatr Scand. 1972 September; 61(5): 577-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5053135&dopt=Abstract

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Politics and public health: smallpox in Milwaukee, 1894-1895. Author(s): Leavitt JW. Source: Bulletin of the History of Medicine. 1976 Winter; 50(4): 553-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=797419&dopt=Abstract

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Positive response to US smallpox vaccine policy. Author(s): Nierengarten MB. Source: The Lancet Infectious Diseases. 2003 February; 3(2): 60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560175&dopt=Abstract

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Possible alternatives to routine smallpox vaccination in the United States. Author(s): Benenson AS. Source: American Journal of Epidemiology. 1971 April; 93(4): 248-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5550340&dopt=Abstract

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Possible changes in the frequency of the human ABO blood groups in Iceland due to smallpox epidemics selection. Author(s): Adalsteinsson S. Source: Annals of Human Genetics. 1985 October; 49 ( Pt 4): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3865623&dopt=Abstract

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Potency and stability of freeze-dried smallpox vaccine. Author(s): Huang CT, Tsai CF. Source: Taiwan Yi Xue Hui Za Zhi. 1970 July; 69(7): 362-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5290113&dopt=Abstract

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Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections. Author(s): Baker RO, Bray M, Huggins JW. Source: Antiviral Research. 2003 January; 57(1-2): 13-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615299&dopt=Abstract

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Potential virulence determinants in terminal regions of variola smallpox virus genome. Author(s): Massung RF, Esposito JJ, Liu LI, Qi J, Utterback TR, Knight JC, Aubin L, Yuran TE, Parsons JM, Loparev VN, et al. Source: Nature. 1993 December 23-30; 366(6457): 748-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8264798&dopt=Abstract

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Poxvirus dilemmas--monkeypox, smallpox, and biologic terrorism. Author(s): Breman JG, Henderson DA. Source: The New England Journal of Medicine. 1998 August 20; 339(8): 556-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9709051&dopt=Abstract

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Precipitation in gel test in diagnosis of smallpox. Author(s): Rao AR, Sukumar MS, Kamalakshi S, Paramasivam TV, Shantha M, Parasuraman AR. Source: The Indian Journal of Medical Research. 1970 March; 58(3): 271-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5002992&dopt=Abstract

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Pre-event smallpox vaccination: unresolved issues. Author(s): Gordon SM. Source: Cleve Clin J Med. 2003 February; 70(2): 80-1, 85-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636337&dopt=Abstract

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Preparation for an outbreak of smallpox in Israel. Author(s): Slater PE, Anis E, Leventhal A. Source: Isr Med Assoc J. 2002 July; 4(7): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120461&dopt=Abstract

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Preparing for smallpox: occupational health nursing update. Author(s): Cunha BE, Wachs JE. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 May; 51(5): 227-33; Quiz 234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769169&dopt=Abstract

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Preventing the return of smallpox. Author(s): Breman JG, Arita I, Fenner F. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 463-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556549&dopt=Abstract

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Prevention of smallpox in Alta California during the Franciscan Mission Period (17691833). Author(s): Valle RK. Source: Calif Med. 1973 July; 119(1): 73-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4581417&dopt=Abstract

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Primary induction of human CD8+ cytotoxic T lymphocytes and interferon-gammaproducing T cells after smallpox vaccination. Author(s): Ennis FA, Cruz J, Demkowicz WE Jr, Rothman AL, McClain DJ. Source: The Journal of Infectious Diseases. 2002 June 1; 185(11): 1657-9. Epub 2002 May 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023773&dopt=Abstract

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Primary malignant melanoma in a smallpox vaccination scar: report of a case and review of the literature. Author(s): De Oreo G. Source: International Journal of Dermatology. 1973 July-August; 12(4): 217-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4723522&dopt=Abstract

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Primary vaccination against smallpox in children under the age of five years--a rural field study. Author(s): Guiati PV, Singh KP. Source: Indian J Pediatr. 1976 July; 43(342): 185-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1002224&dopt=Abstract

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Principles and lessons from the smallpox eradication programme. Author(s): Henderson DA. Source: Bulletin of the World Health Organization. 1987; 65(4): 535-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3319270&dopt=Abstract

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Problem of persistence of facial pock marks among smallpox patients. Author(s): Jezek Z, Basu RN, Arya ZS. Source: Indian J Public Health. 1978 January-March; 22(1): 95-101. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669769&dopt=Abstract

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Problems in the wake of smallpox eradication. Author(s): Dagnew MB. Source: World Health Forum. 1988; 9(3): 382. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3252822&dopt=Abstract

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Problems of smallpox immunization. Author(s): Libov AL. Source: Indian J Pediatr. 1967 December; 34(239): 445-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5594850&dopt=Abstract

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Proceedings: Smallpox--point of no return. Author(s): Vella EE, Balaam CP. Source: Trans R Soc Trop Med Hyg. 1975; 69(4): 434. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=175530&dopt=Abstract

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Progress in international smallpox eradication. Author(s): Cockburn WC. Source: Am J Public Health Nations Health. 1966 October; 56(10): 1628-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5951482&dopt=Abstract

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Progress of the global smallpox eradication programme in 1974. Author(s): Tomaszunas S. Source: Bull Inst Marit Trop Med Gdynia. 1975; 26(3-4): 407-14. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1203604&dopt=Abstract

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Prophylaxis of smallpox with methisazone. Author(s): Bauer DJ, St Vincent L, Kempe CH, Young PA, Downie AW. Source: American Journal of Epidemiology. 1969 August; 90(2): 130-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5804361&dopt=Abstract

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Protective plastic film dressing in smallpox vaccination. Author(s): Rylander R. Source: Public Health Reports (Washington, D.C. : 1974). 1968 September; 83(9): 787-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4970979&dopt=Abstract

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Public health. Rough-and-tumble behind Bush's smallpox policy. Author(s): Cohen J, Enserink M. Source: Science. 2002 December 20; 298(5602): 2312-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493889&dopt=Abstract

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Public reactions to immunization in infants against smallpox in Jakarta. Author(s): Widodo Talogo R. Source: Paediatr Indones. 1964 October-December; 4(4): Suppl: 253-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5873102&dopt=Abstract

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Pulmonary calcification following smallpox handler's lung. Author(s): Ross PJ, Seaton A, Foreman HM, Morris Evans WH. Source: Thorax. 1974 November; 29(6): 659-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4375310&dopt=Abstract

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Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses. Author(s): Terajima M, Cruz J, Raines G, Kilpatrick ED, Kennedy JS, Rothman AL, Ennis FA. Source: The Journal of Experimental Medicine. 2003 April 7; 197(7): 927-32. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668642&dopt=Abstract

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Queen Elizabeth I's bout with smallpox. Author(s): Tierney J. Source: Medicine and Health, Rhode Island. 1998 June; 81(6): 223. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9654904&dopt=Abstract

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Questions and answers about autoimmunity and the smallpox vaccine. Author(s): Halsey N, Rose N. Source: Isr Med Assoc J. 2003 January; 5(1): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592957&dopt=Abstract

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Rapid methods of diagnosis in smallpox. Author(s): Bedson HS. Source: Proc R Soc Med. 1969 April; 62(4): 373-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4980489&dopt=Abstract

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Rate of inactivation of smallpox and vaccinia viruses by fixatives used in histological methods. Author(s): Potajallo U, Towianska A, Dabrowski J. Source: Biul Inst Med Morsk Gdansk. 1968; 19(1): 49-57. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4300247&dopt=Abstract

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Reaction to tuberculin, susceptibility to diphtheria and immunity against smallpox among medical students over a decade. Author(s): Whitted HH, Heshmat MY, Prater LB Jr. Source: Journal of the National Medical Association. 1971 July; 63(4): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5142144&dopt=Abstract

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Reaction to tuberculin, susceptibility to diphtheria and immunity against smallpox among medical students over a decade. Author(s): Whitted HH, Heshmat MY, Prater LB Jr. Source: Med Ann Dist Columbia. 1971 June; 40(6): 361-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5282766&dopt=Abstract

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Recalling 1947 smallpox outbreak. Nurse helped vaccinate New Yorkers in massive effort. Author(s): Trossman S. Source: The American Nurse. 2003 March-April; 35(2): 1, 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815822&dopt=Abstract

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Recent events and observations pertaining to smallpox virus destruction in 2002. Author(s): Henderson DA, Fenner F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 October 1; 33(7): 1057-9. Epub 2001 August 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528580&dopt=Abstract

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Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Author(s): Wharton M, Strikas RA, Harpaz R, Rotz LD, Schwartz B, Casey CG, Pearson ML, Anderson LJ; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 April 4; 52(Rr-7): 1-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710832&dopt=Abstract

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Recommendations on smallpox immunization. Author(s): Piszczek EA, Stebbins EL, Adriani J, Lull GF, Niess OK. Source: Imj Ill Med J. 1972 November; 142(5): 526-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4404741&dopt=Abstract

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Recruitment begins for US smallpox vaccine trial. Author(s): McLellan F. Source: Lancet. 2001 November 17; 358(9294): 1708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728564&dopt=Abstract

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Recurrent herpes simplex infection at a smallpox vaccination site. Author(s): Mintz L. Source: Jama : the Journal of the American Medical Association. 1982 May 21; 247(19): 2704-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7200532&dopt=Abstract

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Reinvestigation of smallpox outbreaks. Author(s): Jezek Z, Basu RN, Arya ZS. Source: Indian J Public Health. 1978 January-March; 22(1): 82-94. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669768&dopt=Abstract

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Relation between smallpox and the ABO blood groups in a rural population of West Bengal. Author(s): Chakravartti MR, Verma BK, Hanurav TV, Vogel F. Source: Humangenetik. 1966; 2(1): 78-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5925855&dopt=Abstract

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Relation between smallpox vaccination and outcome of pregnancy. Author(s): Saxen L, Cantell K, Hakama M. Source: Am J Public Health Nations Health. 1968 October; 58(10): 1910-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5693017&dopt=Abstract

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Relation between the neutralizing and haemagglutination-inhibiting antibodies in smallpox. Author(s): Sarkar JK, Chatterjee SN, Mitra AC, Mondal A. Source: The Indian Journal of Medical Research. 1969 January; 57(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5770847&dopt=Abstract

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Relationship of clinical severity, antibody level, and previous vaccination state in smallpox. Author(s): Sarkar JK, Mitra AC, Chakravarty MS. Source: Trans R Soc Trop Med Hyg. 1972; 66(5): 789-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4647651&dopt=Abstract

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Relevance of some poxvirus infections in monkeys to smallpox eradication. Author(s): Gispen R. Source: Trans R Soc Trop Med Hyg. 1975; 69(3): 299-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=52212&dopt=Abstract

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Remission of chronic lymphocytic leukemia after smallpox vaccination. Author(s): Yettra M. Source: Archives of Internal Medicine. 1979 May; 139(5): 603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=443961&dopt=Abstract

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Remission of chronic lymphocytic leukemia after smallpox vaccination. Author(s): Hansen RM, Libnoch JA. Source: Archives of Internal Medicine. 1978 July; 138(7): 1137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=666477&dopt=Abstract

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Report of a conference. Projected studies on immunization against smallpox. Author(s): Galasso GJ. Source: The Journal of Infectious Diseases. 1970 May; 121(5): 575-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5420322&dopt=Abstract

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Report on measures taken to contain and eradicate the smallpox outbreak locale in the city of Aralsk (September/October, 1971). Author(s): Sarynov E, Kulmakhanov B, Makatov Z. Source: Critical Reviews in Microbiology. 2003; 29(2): 109-44; Discussion 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901678&dopt=Abstract

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Report on measures taken to contain and eradicate the smallpox outbreak locale in the city of Aralsk, Part II. Author(s): Sarynov E, Kulmakhanov B. Source: Critical Reviews in Microbiology. 2003; 29(2): 145-8; Discussion 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901679&dopt=Abstract

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Requiem for smallpox. The demise of a disease. Author(s): Stuttgen G, Parish LC. Source: International Journal of Dermatology. 1990 October; 29(8): 596-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2242952&dopt=Abstract

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Response of specific skin hypersensitivity and haemagglutination inhibiting antibody after smallpox vaccination in human newborns and adults. Author(s): Saha K, Chawla SL, Saini L, Gupta S. Source: Scandinavian Journal of Immunology. 1973; 2(3): 261-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4358796&dopt=Abstract

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Response to smallpox vaccine in persons immunized in the distant past. Author(s): Frey SE, Newman FK, Yan L, Lottenbach KR, Belshe RB. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3295-9. Erratum In: Jama. 2003 July 16; 290(3): 334. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824212&dopt=Abstract

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Responses to smallpox vaccine. Author(s): Frelinger JA, Garba ML. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 689-90; Author Reply 689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201305&dopt=Abstract

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Responses to smallpox vaccine. Author(s): Sauri MA. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 689-90; Author Reply 689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200560&dopt=Abstract

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Results of a virological study of smallpox convalescents and contacts: short communication. Author(s): Shelukhina EM, Marennikova SS, Maltseva NN, Matsevich GR, Hasmi AA. Source: J Hyg Epidemiol Microbiol Immunol. 1973 March; 17(3): 266-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4355334&dopt=Abstract

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Revaccination against smallpox. Author(s): Rylander R. Source: Public Health Reports (Washington, D.C. : 1974). 1969 July; 84(7): 635-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4980177&dopt=Abstract

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Revaccination against smallpox. Morphological and serological studies, with special reference to neutralizing antibodies. Author(s): Herrlich A, Adldinger H, Mobest H. Source: Ger Med Mon. 1966 July; 11(7): 266-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5330048&dopt=Abstract

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Revaccination studies in children with graded potency of smallpox vaccines. Author(s): Pattanayak S, Sehgal CL, Choudhury S, Vijayan P. Source: The Indian Journal of Medical Research. 1977 June; 65(6): 756-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=203527&dopt=Abstract

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Rhazes. The original portrayer of smallpox. Author(s): Behbehani AM. Source: Jama : the Journal of the American Medical Association. 1984 December 14; 252(22): 3156-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6389914&dopt=Abstract

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Rider Haggard and smallpox. Author(s): Thomson WA. Source: Journal of the Royal Society of Medicine. 1984 June; 77(6): 506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6376808&dopt=Abstract

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Risk of cutaneous vaccinia from health care workers who receive smallpox vaccine. Author(s): Mermel LA. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 844-5 Author Reply 845. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588263&dopt=Abstract

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Risks and benefits of vaccinia vaccine use in the worldwide smallpox eradication campaign. Author(s): Fenner F. Source: Research in Virology. 1989 September-October; 140(5): 465-6; Discussion 487-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2685955&dopt=Abstract

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Risks of smallpox vaccination complications in the United States. Author(s): Lane JM, Millar JD. Source: American Journal of Epidemiology. 1971 April; 93(4): 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4396307&dopt=Abstract

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Risks of smallpox vaccination. Author(s): Fulginiti VA. Source: Jama : the Journal of the American Medical Association. 2003 September 17; 290(11): 1452; Author Reply 1452. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129976&dopt=Abstract

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Risks to children of health care personnel receiving smallpox vaccination. Author(s): Cherry JD. Source: The Pediatric Infectious Disease Journal. 2003 June; 22(6): 574-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799516&dopt=Abstract

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Role of hospital in smallpox outbreak in Kuwait. Author(s): Arita I, Shafa E, Kader A. Source: Am J Public Health Nations Health. 1970 October; 60(10): 1960-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5528490&dopt=Abstract

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Role of laboratory diagnosis in the smallpox eradication programme in India. Author(s): Jezek Z, Basu PN, Sehgal S, Balasubramaniam S, Arya ZS. Source: Indian J Public Health. 1978 January-March; 22(1): 113-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=208966&dopt=Abstract

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Role of the World Health Organization in the world-wide eradication of smallpox. Author(s): Ladnyi ID, Jezek Z, Gromyko A. Source: Z Gesamte Hyg. 1983 September; 29(9): 490-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6362235&dopt=Abstract

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Role of transfer factor in treating complications of smallpox vaccination. Author(s): Lankford J, Humphrey GB, Grooms AM, Nitschke R. Source: J Okla State Med Assoc. 1973 January; 66(1): 7-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4569110&dopt=Abstract

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Routine childhood vaccination against smallpox reconsidered. Author(s): Lane JM, Millar JD. Source: The New England Journal of Medicine. 1969 November 27; 281(22): 1220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4186804&dopt=Abstract

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Routine smallpox vaccination. Author(s): Dick G. Source: British Medical Journal. 1971 July 17; 3(767): 163-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5557869&dopt=Abstract

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Routine smallpox vaccination--no longer advisable? Author(s): Polk LD. Source: Clinical Pediatrics. 1972 January; 11(1): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5061324&dopt=Abstract

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Royal College of Radiologists Annual Undergraduate Essay Prize. Melanoma: the new smallpox? Can vaccines be used to treat melanoma? Author(s): Forbes G. Source: Clin Oncol (R Coll Radiol). 2002 February; 14(1): 17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898780&dopt=Abstract

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Safeguarding our nation's children: the diagnosis, management, and containment of smallpox in infants and children. Author(s): Veenema TG. Source: Biological Research for Nursing. 2003 April; 4(4): 295-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698922&dopt=Abstract

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Scientists split on US smallpox decision. Author(s): Wadman M. Source: Nature. 1999 April 29; 398(6730): 741. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235249&dopt=Abstract

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Separate worlds set to collide: smallpox, vaccinia virus vaccination, and human immunodeficiency virus and acquired immunodeficiency syndrome. Author(s): Amorosa VK, Isaacs SN. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 426-32. Epub 2003 July 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884168&dopt=Abstract

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Serologic responses of children after primary vaccination and revaccination against smallpox. Author(s): Wulff H, Chin TD, Wenner HA. Source: American Journal of Epidemiology. 1969 October; 90(4): 312-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5823442&dopt=Abstract

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Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Author(s): Belyakov IM, Earl P, Dzutsev A, Kuznetsov VA, Lemon M, Wyatt LS, Snyder JT, Ahlers JD, Franchini G, Moss B, Berzofsky JA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 5; 100(16): 9458-63. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869693&dopt=Abstract

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Should remaining stocks of smallpox virus be destroyed? Author(s): Razzell P. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 1995 August; 8(2): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11639811&dopt=Abstract

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Should smallpox vaccine be tested in children? Author(s): Baltimore RS, Jenson HB. Source: Current Opinion in Infectious Diseases. 2003 June; 16(3): 237-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821814&dopt=Abstract

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Should smallpox virus be destroyed? The relevance of the origins of vaccinia virus. Author(s): Baxby D. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 1996 April; 9(1): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11613268&dopt=Abstract

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Should you volunteer for the smallpox vaccine? Author(s): Lorenzo P. Source: Rn. 2003 April; 66(4): 69-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715459&dopt=Abstract

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Smallpox - a potential biowarfare weapon: destroy the virus or keep the vaccine for ever. Author(s): Datta KK, Singh J. Source: Indian Pediatrics. 2002 March; 39(3): 317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933893&dopt=Abstract

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Smallpox 2002 - Silent Weapon. Author(s): Dixon B. Source: Current Biology : Cb. 2002 March 19; 12(6): R195-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909542&dopt=Abstract

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Smallpox and bioterrorism. Author(s): Huff DM. Source: Cleve Clin J Med. 2002 May; 69(5): 360; Author Reply 360-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022377&dopt=Abstract

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Smallpox and bioterrorism. Author(s): Drazen JM. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1262-3. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923485&dopt=Abstract

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Smallpox and pregnancy: from eradicated disease to bioterrorist threat. Author(s): Suarez VR, Hankins GD. Source: Obstetrics and Gynecology. 2002 July; 100(1): 87-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100808&dopt=Abstract

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Smallpox and public health: a reality check. Author(s): Merkle PB. Source: Science. 2002 October 4; 298(5591): 57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365436&dopt=Abstract

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Smallpox and Queen Anne. Author(s): Keynes M. Source: Journal of the Royal Society of Medicine. 1997 January; 90(1): 60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9059392&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Worthington MG, Ross JJ. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740967&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Fett JD. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740966&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Neff JM, Lane JM, Fulginiti VA. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740965&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Snyder KM. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740964&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Milton DK. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740963&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Letai AG. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1920-5; Author Reply 1920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736287&dopt=Abstract

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Smallpox and smallpox vaccination. Author(s): Lane JM. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 691-2; Author Reply 691-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200562&dopt=Abstract

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Smallpox and smallpox vaccine--just the facts. Author(s): Sawyer PP. Source: Home Healthcare Nurse. 2003 February; 21(2): 130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574685&dopt=Abstract

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Smallpox and the Native American. Author(s): Patterson KB, Runge T. Source: The American Journal of the Medical Sciences. 2002 April; 323(4): 216-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003378&dopt=Abstract

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Smallpox and vaccination. Author(s): Grist NR. Source: Lancet. 2003 April 5; 361(9364): 1228. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686073&dopt=Abstract

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Smallpox as a biological weapon: implications for the critical care clinician. Author(s): Foster D. Source: Dimensions of Critical Care Nursing : Dccn. 2003 January-February; 22(1): 2-7; Quiz 8-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548096&dopt=Abstract

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Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. Author(s): Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J, Osterholm MT, O'Toole T, Parker G, Perl T, Russell PK, Tonat K. Source: Jama : the Journal of the American Medical Association. 1999 June 9; 281(22): 2127-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367824&dopt=Abstract

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Smallpox bioterror response. Author(s): Kaplan EH, Wein LM. Source: Science. 2003 June 6; 300(5625): 1503-4; Author Reply 1503-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791963&dopt=Abstract

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Smallpox compensation legislation passes. Author(s): McKeon E. Source: The American Journal of Nursing. 2003 June; 103(6): 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802150&dopt=Abstract

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Smallpox defense. Author(s): Spake A. Source: U.S. News & World Report. 2002 October 7; 133(13): 64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375482&dopt=Abstract

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Smallpox eradication in Brazil, 1967-69. Author(s): de Carvalho Filho ES, Morris L, de Lemos AL, Ponce de Leon J, Escobar A, da Silva OJ. Source: Bulletin of the World Health Organization. 1970; 43(6): 797-807. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5314627&dopt=Abstract

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Smallpox eradication in Rajasthan, India. Author(s): Singh P, Tomaszunas S, White E. Source: Acta Tropica. 1977 September; 34(3): 257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=21557&dopt=Abstract

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Smallpox eradication in West and Central Africa: surveillance-containment or herd immunity? Author(s): Kaplan EH, Wein LM. Source: Epidemiology (Cambridge, Mass.). 2003 January; 14(1): 90-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500053&dopt=Abstract

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Smallpox eradication: progress and problems. Author(s): Ladnyi ID, Breman JG. Source: Dev Biol Stand. 1978; 41: 281-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=223913&dopt=Abstract

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Smallpox eradication--a cold war victory. Author(s): Henderson D. Source: World Health Forum. 1998; 19(2): 113-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9652207&dopt=Abstract

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Smallpox immunization in the 21st century: the old and the new. Author(s): Wright ME, Fauci AS. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3306-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824215&dopt=Abstract

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Smallpox immunization. Panel urges caution over heart problems. Author(s): Couzin J. Source: Science. 2003 June 27; 300(5628): 2013-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829752&dopt=Abstract

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Smallpox in Glasgow, 1900-1902. Author(s): McVail JC. Source: Reviews in Medical Virology. 2002 September-October; 12(5): 267-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211041&dopt=Abstract

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Smallpox in man and animals. Author(s): Sarkar JK. Source: J Indian Med Assoc. 1969 October 1; 53(7): 352-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5392338&dopt=Abstract

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Smallpox in the ED. Author(s): Coleman EA. Source: The American Journal of Nursing. 2002 September; 102(9): 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394009&dopt=Abstract

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Smallpox in the post-eradication era. Author(s): Huycke MM. Source: J Okla State Med Assoc. 2002 November; 95(11): 725-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471737&dopt=Abstract

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Smallpox in Wandsworth 1967. Author(s): Gordon H, Lewis JT. Source: Public Health. 1969 January; 83(2): 97-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5799308&dopt=Abstract

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Smallpox legislation introduced. Author(s): Donnellan C; ANA. Source: The American Journal of Nursing. 2003 April; 103(4): 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677118&dopt=Abstract

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Smallpox manifestations and survival during the Boston epidemic of 1901 to 1903. Author(s): Albert MR, Ostheimer KG, Liewehr DJ, Steinberg SM, Breman JG. Source: Annals of Internal Medicine. 2002 December 17; 137(12): 993-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484715&dopt=Abstract

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Smallpox redux. We suddenly find ourselves with plenty of vaccine. Should we go ahead and inoculate everyone now? Author(s): Spake A. Source: U.S. News & World Report. 2002 April 8; 132(11): 46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951339&dopt=Abstract

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Smallpox research activities: U.S. interagency collaboration, 2001. Author(s): LeDuc JW, Damon I, Relman DA, Huggins J, Jahrling PB. Source: Emerging Infectious Diseases. 2002 July; 8(7): 743-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095449&dopt=Abstract

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Smallpox shots: make them mandatory. When it comes to epidemic diseases, you don't get to decide. The state decides. Author(s): Krauthammer C. Source: Time. 2002 December 23; 160(26): 84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510489&dopt=Abstract

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Smallpox smarts. Amid an uncertain threat, arm yourself with knowledge. Author(s): Rosen DS. Source: Health News. 2003 March; 9(3): 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703435&dopt=Abstract

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Smallpox still a danger. Author(s): Rhode JG. Source: Tex Med. 2002 November; 98(11): 10-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448948&dopt=Abstract

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Smallpox still poses a threat. Author(s): Devlin HR. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 April 16; 166(8): 1012; Author Reply 1012. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002973&dopt=Abstract

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Smallpox transmission in Southern Dahomey. A study of a village outbreak. Author(s): Henderson RH, Yekpe M. Source: American Journal of Epidemiology. 1969 November; 90(5): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5356949&dopt=Abstract

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Smallpox transmission risks: how bad? Author(s): Kahn LH. Source: Science. 2002 July 5; 297(5578): 50-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102091&dopt=Abstract

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Smallpox update. Author(s): Chang D, Matuszak D. Source: Md Med. 2003 Winter; 4(1): 31-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652861&dopt=Abstract

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Smallpox vaccination after a bioterrorism-based exposure. Author(s): Bicknell WJ, James K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 467. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884184&dopt=Abstract

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Smallpox vaccination and adverse reactions. Guidance for clinicians. Author(s): Cono J, Casey CG, Bell DM; Centers for Disease Control and Prevention. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 February 21; 52(Rr-4): 1-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617510&dopt=Abstract

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Smallpox vaccination and HIV infection. Author(s): Bartlett JG. Source: Hopkins Hiv Rep. 2003 January; 15(1): 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542002&dopt=Abstract

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Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome. Author(s): Bartlett JG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 15; 36(4): 468-71. Epub 2003 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567305&dopt=Abstract

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Smallpox vaccination and risk of allergy and asthma. Author(s): Bager P, Westergaard T, Rostgaard K, Nielsen NM, Melbye M, Aaby P. Source: The Journal of Allergy and Clinical Immunology. 2003 June; 111(6): 1227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789221&dopt=Abstract

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Smallpox vaccination and the HIV-infected patient: a roundtable. Author(s): Bartlett J, del Rio C, DeMaria A Jr, Sepkowitz KA. Source: Aids Clin Care. 2003 July; 15(7): 61-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913953&dopt=Abstract

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Smallpox vaccination and the nurse. Author(s): Clements TI. Source: Kans Nurse. 2003 May; 78(5): 5-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830676&dopt=Abstract

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Smallpox vaccination and the patient with an organ transplant. Author(s): Dropulic LK, Rubin RH, Bartlett JG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 March 15; 36(6): 786-8. Epub 2003 Mar 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627364&dopt=Abstract

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Smallpox vaccination and the patient with HIV/AIDS. Author(s): Bartlett JG. Source: Iapac Mon. 2003 March; 9(3): 61-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744197&dopt=Abstract

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Smallpox vaccination becomes a social, financial. Author(s): Dove A. Source: Nature Medicine. 2002 May; 8(5): 428. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984568&dopt=Abstract

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Smallpox vaccination begins in U.S.--precautions needed. Author(s): James JS. Source: Aids Treat News. 2002 December 20; (386): 2-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569873&dopt=Abstract

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Smallpox vaccination campaign for Rhode Island hospital personnel. Author(s): Schaffner W, Adair R. Source: Public Health Reports (Washington, D.C. : 1974). 1969 May; 84(5): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4976807&dopt=Abstract

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Smallpox vaccination followup: IOM suggests changes, widespread civilian vaccinations to begin. Author(s): James JS. Source: Aids Treat News. 2002 December 27; (387): 4-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635625&dopt=Abstract

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Smallpox vaccination for emergency physicians. Author(s): AAEM/SAEM Smallpox Vaccination Working Group. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 June; 10(6): 681-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782532&dopt=Abstract

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Smallpox vaccination for emergency physicians: joint statement of the AAEM and the SAEM. Author(s): Moran GJ, Everett WW, Karras DJ, Pesik NT, Sztajnkrycer MD; American Academy of Emergency Medicine; Society for Academic Emergency Medicine. Source: The Journal of Emergency Medicine. 2003 April; 24(3): 351-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676316&dopt=Abstract

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Smallpox vaccination in 2003: key information for clinicians. Author(s): Bartlett J, Borio L, Radonovich L, Mair JS, O'Toole T, Mair M, Halsey N, Grow R, Inglesby TV. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 1; 36(7): 883-902. Epub 2003 March 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652390&dopt=Abstract

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Smallpox vaccination in Senta County in the early 19th century. Author(s): Curcic M, Tari L. Source: Med Pregl. 2000 July-August; 53(7-8): 413-22. English, Croatian. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214489&dopt=Abstract

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Smallpox vaccination policy: Part II-Preparedness begins. Author(s): Benjamin GC. Source: Physician Executive. 2003 March-April; 29(2): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685275&dopt=Abstract

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Smallpox vaccination policy--the need for dialogue. Author(s): Fauci AS. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1319-20. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923487&dopt=Abstract

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Smallpox vaccination program implementation raises concerns and questions. Author(s): Rainer SR. Source: N J Nurse. 2003 February; 33(2): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674881&dopt=Abstract

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Smallpox vaccination revisited. Author(s): Sibley CL. Source: The American Journal of Nursing. 2002 September; 102(9): 26-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394015&dopt=Abstract

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Smallpox vaccination techniques; from knives and forks to needles and pins. Author(s): Baxby D. Source: Vaccine. 2002 May 15; 20(16): 2140-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972983&dopt=Abstract

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Smallpox vaccination to combat bioterrorism. Author(s): Arya SC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830424&dopt=Abstract

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Smallpox vaccination. Author(s): Kula S. Source: Archives of Disease in Childhood. 2003 October; 88(10): 841. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500295&dopt=Abstract

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Smallpox vaccination. Author(s): Artenstein AW. Source: The New England Journal of Medicine. 2003 May 8; 348(19): 1925; Author Reply 1925. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736288&dopt=Abstract

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Smallpox vaccination. Author(s): Hushaw JR. Source: Jama : the Journal of the American Medical Association. 1977 October 17; 238(16): 1723. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=578265&dopt=Abstract

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Smallpox vaccination. Author(s): Krugman S, Katz SL. Source: The New England Journal of Medicine. 1969 November 27; 281(22): 1241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5347840&dopt=Abstract

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Smallpox vaccination. Author(s): Shaper AA. Source: Can Med Assoc J. 1969 August 9; 101(3): 174. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5806890&dopt=Abstract

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Smallpox vaccination. What the pediatrician needs to know. Author(s): Waecker NJ Jr, Hale BR. Source: Pediatric Annals. 2003 March; 32(3): 178-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661492&dopt=Abstract

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Smallpox vaccination: a national survey of emergency health care providers. Author(s): Everett WW, Coffin SE, Zaoutis T, Halpern SD, Strom BL. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2003 June; 10(6): 606-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782520&dopt=Abstract

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Smallpox vaccination: a review, part I. Background, vaccination technique, normal vaccination and revaccination, and expected normal reactions. Author(s): Fulginiti VA, Papier A, Lane JM, Neff JM, Henderson DA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 15; 37(2): 241-50. Epub 2003 Jul 10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856217&dopt=Abstract

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Smallpox vaccination: a review, part II. Adverse events. Author(s): Fulginiti VA, Papier A, Lane JM, Neff JM, Henderson DA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 15; 37(2): 251-71. Epub 2003 Jul 10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856218&dopt=Abstract

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Smallpox vaccination: a shot in the dark? Author(s): Freeman PB. Source: Optometry. 2003 March; 74(3): 141-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645847&dopt=Abstract

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Smallpox vaccination: Risk considerations for patients with atopic dermatitis. Author(s): Engler RJ, Kenner J, Leung DY. Source: The Journal of Allergy and Clinical Immunology. 2002 September; 110(3): 35765. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209080&dopt=Abstract

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Smallpox vaccination: the Minnesota story. Author(s): Golden G. Source: Minn Med. 2003 June; 86(6): 20-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834209&dopt=Abstract

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Smallpox vaccination--implications for the occupational health professional. Author(s): DesRoches P. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 June; 51(6): 240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846455&dopt=Abstract

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Smallpox vaccinations: a volunteer program in the volunteer state. Author(s): Pafford-Failor M. Source: Tenn Nurse. 2003 Summer; 66(2): 14-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847871&dopt=Abstract

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Smallpox vaccinations: the risks and the benefits. Author(s): Conti R. Source: Issue Brief (Commonw Fund). 2003 April; (620): 1-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693396&dopt=Abstract

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Smallpox vaccination--the call to arms. Author(s): Schraeder TL, Campion EW. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 381-2. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496350&dopt=Abstract

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Smallpox vaccination--update. 1981. Author(s): Banker DD. Source: Indian Journal of Medical Sciences. 2001 November; 55(11): 621-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512471&dopt=Abstract

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Smallpox vaccine and pregnancy. Author(s): Amstey MS, Gall SA. Source: Obstetrics and Gynecology. 2002 December; 100(6): 1356; Author Reply 1356. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468187&dopt=Abstract

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Smallpox vaccine development quickened. Author(s): Birmingham K, Kenyon G. Source: Nature Medicine. 2001 November; 7(11): 1167. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689864&dopt=Abstract

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Smallpox vaccine encephalomyelitis. (Case report). Author(s): Vega LA. Source: W V Med J. 1969 September; 65(9): 300-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4389849&dopt=Abstract

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Smallpox Vaccine Injury Compensation Program: Smallpox (Vaccinia) Vaccine Injury Table. Interim final rule. Author(s): Health Resources and Services Administration, HHS. Source: Federal Register. 2003 August 27; 68(166): 51492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952013&dopt=Abstract

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Smallpox vaccine policy: the national debate. Author(s): Benjamin GC. Source: Physician Executive. 2002 September-October; 28(5): 64-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416388&dopt=Abstract

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Smallpox vaccine program lagging. Author(s): Piotrowski J. Source: Modern Healthcare. 2003 May 19; 33(20): 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800582&dopt=Abstract

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Smallpox vaccine program launched amid concerns raised by expert panel, unions. Author(s): Stephenson J. Source: Jama : the Journal of the American Medical Association. 2003 February 12; 289(6): 685-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585929&dopt=Abstract

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Smallpox vaccine revisited. Author(s): Capriotti T. Source: Dermatology Nursing / Dermatology Nurses' Association. 2002 December; 14(6): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592794&dopt=Abstract

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Smallpox vaccine revisited. Author(s): Capriotti T. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2002 August; 11(4): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219432&dopt=Abstract

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Smallpox vaccine. Author(s): Committee on Infectious Diseases. American Academy of Pediatrics. Source: Pediatrics. 2002 October; 110(4): 841-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359807&dopt=Abstract

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Smallpox vaccine. Author(s): Joseph PR. Source: Pediatric Annals. 2000 May; 29(5): 263. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826318&dopt=Abstract

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Smallpox vaccine. Author(s): Katz J. Source: Science. 1999 September 24; 285(5436): 2067. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523198&dopt=Abstract

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Smallpox vaccine: don't do it. Author(s): Cohen HW, Eolis SL. Source: The American Journal of Nursing. 2003 March; 103(3): 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626934&dopt=Abstract

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Smallpox vaccine: not worth the risk. Author(s): Annas GJ. Source: The Hastings Center Report. 2003 March-April; 33(2): 6-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760109&dopt=Abstract

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Smallpox vaccine: the reality, the risk. Author(s): Taccetta-Chapnick M. Source: Rn. 2003 July; 66(7): 52-8; Quiz 60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900999&dopt=Abstract

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Smallpox vaccine--do school nurses know how to respond? Author(s): Bobo N. Source: Nasnewsletter. 2002 September; 17(5): 14-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298227&dopt=Abstract

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Smallpox vaccines. Author(s): Peterson C. Source: The American Journal of Nursing. 2003 January; 103(1): 112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544068&dopt=Abstract

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Smallpox vaccines. New cache eases shortage worries. Author(s): Enserink M. Source: Science. 2002 April 5; 296(5565): 25-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934993&dopt=Abstract

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Smallpox visits the White House. Author(s): Aronson SM. Source: Medicine and Health, Rhode Island. 2002 February; 85(2): 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881164&dopt=Abstract

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Smallpox, big decision. Health care workers must decide whether to be vaccinated. Author(s): Ortolon K. Source: Tex Med. 2003 February; 99(2): 42-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647631&dopt=Abstract

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Smallpox, big worries. Preparing medical-response teams is easier said than done, according to healthcare providers across the nation. Author(s): Piotrowski J. Source: Modern Healthcare. 2003 January 6; 33(1): 6-7, 12-3, 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545520&dopt=Abstract

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Smallpox, bioterrorism, and the neurologist. Author(s): Cleri DJ, Villota FJ, Porwancher RB. Source: Archives of Neurology. 2003 April; 60(4): 489-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707060&dopt=Abstract

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Smallpox, October 1945. Author(s): Dworetzky M. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1329. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923486&dopt=Abstract

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Smallpox, polio and now a cancer vaccine? Author(s): Kufe DW. Source: Nature Medicine. 2000 March; 6(3): 252-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10700218&dopt=Abstract

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Smallpox. Author(s): Dacko A, Hardick K, Yoshida T. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 April; 71(4): 319-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729099&dopt=Abstract

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Smallpox. Author(s): Reilly CM, Deason D. Source: The American Journal of Nursing. 2002 February; 102(2): 51-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953520&dopt=Abstract

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Smallpox. Author(s): Larner AJ. Source: The New England Journal of Medicine. 1996 September 19; 335(12): 901; Author Reply 902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8778627&dopt=Abstract

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Smallpox. Author(s): Aly A, Aly S. Source: The New England Journal of Medicine. 1996 September 19; 335(12): 900-1; Author Reply 902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8778626&dopt=Abstract

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Smallpox. Author(s): Maher JP. Source: The New England Journal of Medicine. 1996 September 19; 335(12): 900; Author Reply 901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8778625&dopt=Abstract

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Smallpox. Leaks produce a torrent of denials. Author(s): Cohen J. Source: Science. 2002 November 15; 298(5597): 1313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434025&dopt=Abstract

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Smallpox: a 21st century killer? Author(s): Ratzan SC. Source: Journal of Health Communication. 2003 January-February; 8(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635807&dopt=Abstract

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Smallpox: a disease of the past? Consideration for midwives. Author(s): Constantin CM, Martinelli AM, Foster SO, Bonney EA, Strickland OL. Source: Journal of Midwifery & Women's Health. 2003 July-August; 48(4): 258-67, 302-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867910&dopt=Abstract

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Smallpox: a history of its rise and fall. Author(s): Radetsky M. Source: The Pediatric Infectious Disease Journal. 1999 February; 18(2): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10048677&dopt=Abstract

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Smallpox: a possible public health threat, again. Author(s): Thomas JR. Source: Mo Med. 2000 April; 97(4): 125. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790985&dopt=Abstract

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Smallpox: a potential agent of bioterrorism. Author(s): Whitley RJ. Source: Antiviral Research. 2003 January; 57(1-2): 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615298&dopt=Abstract

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Smallpox: a review of clinical disease and vaccination. Author(s): Lofquist JM, Weimert NA, Hayney MS. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 April 15; 60(8): 749-56; Quiz 757-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749161&dopt=Abstract

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Smallpox: An attack scenario. Author(s): O'Toole T. Source: Emerging Infectious Diseases. 1999 July-August; 5(4): 540-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458962&dopt=Abstract

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Smallpox: an update for nurses. Author(s): Constantin CM, Martinelli AM, Bonney EA, Strickland OL. Source: Biological Research for Nursing. 2003 April; 4(4): 282-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698921&dopt=Abstract

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Smallpox: anything to declare? Author(s): Smith GL, McFadden G. Source: Nature Reviews. Immunology. 2002 July; 2(7): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094226&dopt=Abstract

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Smallpox: clinical and epidemiologic features. Author(s): Henderson DA. Source: Medicine and Health, Rhode Island. 2002 March; 85(3): 107-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917745&dopt=Abstract

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Smallpox: clinical and epidemiologic features. Author(s): Henderson DA. Source: Emerging Infectious Diseases. 1999 July-August; 5(4): 537-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458961&dopt=Abstract

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Smallpox: clinical highlights and considerations for vaccination. Author(s): Mahoney MC, Symons AB, Kimmel SR. Source: Journal of Postgraduate Medicine. 2003 April-June; 49(2): 141-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867690&dopt=Abstract

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Smallpox: gone but not forgotten. Author(s): Ellner PD. Source: Infection. 1998 September-October; 26(5): 263-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9795781&dopt=Abstract

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Smallpox: preparation without inoculation. Author(s): Nelson K. Source: Lancet. 2003 August 23; 362(9384): 626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947947&dopt=Abstract

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Smallpox: the disease and strategies for its control. Author(s): Walsh M. Source: Nurs Times. 2002 December 17-2003 January 6; 98(51): 26-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567874&dopt=Abstract

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Smallpox: the main site of transmission is the oropharynx. Author(s): Baron S. Source: Journal of Dental Research. 2003 April; 82(4): 252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651925&dopt=Abstract

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Smallpox--eradicated, but a growing terror threat. Author(s): Tegnell A, Wahren B, Elgh F. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 August; 8(8): 504-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197872&dopt=Abstract

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Smallpox--no longer is it only a disease of historical interest. Author(s): Hedge DD. Source: S D J Med. 2003 January; 56(1): 11-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647371&dopt=Abstract

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Spotty defense. Big cities are late to vaccinate against smallpox. Author(s): Alpert M. Source: Scientific American. 2003 May; 288(5): 20, 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701323&dopt=Abstract

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Standardization of smallpox vaccines and the eradication programme--a WHO perspective. Author(s): Arita I. Source: Dev Biol Stand. 1999; 100: 31-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616173&dopt=Abstract

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Statement of Barbara Blakeney, MS, APRN, BC, ANP President, American Nurses Association. Regarding National Network for Immunization Information (NNii) smallpox vaccination survey findings--January 22, 2003. Author(s): Blakeney B. Source: Ala Nurse. 2003 March-May; 30(1): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715480&dopt=Abstract

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Status of eradication of smallpox (and control of measles) in West and Central Africa. Author(s): Millar JD, Foege WH. Source: The Journal of Infectious Diseases. 1969 December; 120(6): 725-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5374972&dopt=Abstract

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Status of nation's smallpox vaccine reserve improves. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 May 1; 59(9): 822, 827. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004457&dopt=Abstract

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Strategy in national smallpox eradication programme of Burma. Author(s): Ko UK. Source: Trans R Soc Trop Med Hyg. 1970; 64(3): 444-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4247692&dopt=Abstract

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Strengthening national preparedness for smallpox: an update. Author(s): LeDuc JW, Jahrling PB. Source: Emerging Infectious Diseases. 2001 January-February; 7(1): 155-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266310&dopt=Abstract

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Studies on the off-season smallpox in Calcutta in 1967. Author(s): Sarkar JK, Ray S, Manji P. Source: Bull Calcutta Sch Trop Med. 1970 April; 18(2): 43-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5517776&dopt=Abstract

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Support for smallpox vaccinations. Author(s): Holloway B. Source: The American Journal of Nursing. 2003 July; 103(7): 116; Author Reply 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877139&dopt=Abstract

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Support for smallpox vaccinations. Author(s): Hurley D. Source: The American Journal of Nursing. 2003 July; 103(7): 116; Author Reply 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877138&dopt=Abstract

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Support for smallpox vaccinations. Author(s): Frazier A. Source: The American Journal of Nursing. 2003 July; 103(7): 116; Author Reply 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877137&dopt=Abstract

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Support for smallpox vaccinations. Author(s): Skidmore SL. Source: The American Journal of Nursing. 2003 July; 103(7): 116; Author Reply 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877136&dopt=Abstract

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Support for smallpox vaccinations. Author(s): Keely J. Source: The American Journal of Nursing. 2003 July; 103(7): 116; Author Reply 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877135&dopt=Abstract

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SWOT analysis: strengths, weaknesses, opportunities and threats of the Israeli Smallpox Revaccination Program. Author(s): Huerta M, Balicer RD, Leventhal A. Source: Isr Med Assoc J. 2003 January; 5(1): 42-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592958&dopt=Abstract

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T and B rosetting lymphocytes in the blood of smallpox patients. Author(s): Jackson TM, Zaman SN, Huq F. Source: Am J Trop Med Hyg. 1977 May; 26(3): 517-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=326070&dopt=Abstract

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Take rates by double versus single insertions of smallpox vaccine in revaccinees. Author(s): Lane JM, Mack TM, Millar JD. Source: Public Health Reports (Washington, D.C. : 1974). 1970 October; 85(10): 928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4990250&dopt=Abstract

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Tapping the flow of information in a rural region: the example of the smallpox eradication program in Bihar, India. Author(s): Morinis EA. Source: Hum Organ. 1980 Summer; 39(2): 180-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10247228&dopt=Abstract

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Ten years of freedom from smallpox: lessons and experiences. Dedicated to the tenth anniversary of worldwide freedom from smallpox. Author(s): Jezek Z, Khodakevich LN. Source: J Hyg Epidemiol Microbiol Immunol. 1987; 31(3): 237-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3680936&dopt=Abstract

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Ten years without smallpox. Author(s): Jezek Z. Source: Bull Int Union Tuberc Lung Dis. 1988 June; 63(2): 35-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3224206&dopt=Abstract

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Tennessee prepares for the threat of smallpox. Author(s): McIntyre PS. Source: Tenn Med. 2003 August; 96(8): 377-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971074&dopt=Abstract

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Tennessee prepares for the threat of smallpox. Author(s): McIntyre PS. Source: Tenn Nurse. 2003 Summer; 66(2): 8-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847870&dopt=Abstract

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Tenth anniversary of smallpox eradication. Author(s): Jezek Z. Source: Bull Pan Am Health Organ. 1988; 22(1): 89-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3289658&dopt=Abstract

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Testing the potency of smallpox vaccines, anti-smallpox immune sera and immunoglobulins with the use of own reference vaccine and standard immunoglobulin. Author(s): Hegedus L, Szathmary J, Koller M. Source: Ann Immunol Hung. 1972; 16(0): 157-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4137964&dopt=Abstract

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The 1971 smallpox outbreak in the Soviet city of Aralsk: implications for Variola virus as a bioterrorist threat. Introduction. Author(s): Tucker JB, Zilinskas RA. Source: Critical Reviews in Microbiology. 2003; 29(2): 81-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901676&dopt=Abstract

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The 1972 smallpox outbreak in Khulna Municipality, Bangladesh. I. Methodology and epidemiologic findings. Author(s): Sommer A, Foster SO. Source: American Journal of Epidemiology. 1974 April; 99(4): 291-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4818719&dopt=Abstract

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The 1972 smallpox outbreak in Khulna Municipality, Bangladesh. II. Effectiveness of surveillance and containment in urban epidemic control. Author(s): Sommer A. Source: American Journal of Epidemiology. 1974 April; 99(4): 303-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4818720&dopt=Abstract

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The age-dependent risk of postvaccination complications in vaccinees with smallpox vaccine. Author(s): Gurvich EB. Source: Vaccine. 1992; 10(2): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1347190&dopt=Abstract

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The archaeological recovery of smallpox victims in Hawaii: scientific investigation or public health threat? Author(s): Kennedy J. Source: Perspectives in Biology and Medicine. 1994 Summer; 37(4): 499-509. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8084738&dopt=Abstract

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The big deal about smallpox. Smallpox vaccine program leaves many unanswered questions. Author(s): Jacobs L. Source: Revolution. 2003 January-February; 4(1): 22-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685326&dopt=Abstract

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The case for abolishing routine childhood smallpox vaccination in the United States. Author(s): Neff JM. Source: American Journal of Epidemiology. 1971 April; 93(4): 245-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5550339&dopt=Abstract

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The case for continuing “routine” childhood smallpox vaccination in the United States. Author(s): Katz SL. Source: American Journal of Epidemiology. 1971 April; 93(4): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4396308&dopt=Abstract

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The case for voluntary smallpox vaccination. Author(s): Bicknell WJ. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1323-5. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923492&dopt=Abstract

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The cause of death in smallpox: an examination of the pathology record. Author(s): Martin DB. Source: Military Medicine. 2002 July; 167(7): 546-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125845&dopt=Abstract

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The clinical features of smallpox. 3. Author(s): Roberts CJ. Source: Cent Afr J Med. 1967 April; 13(4): 88-95. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6044924&dopt=Abstract

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The confirmation and maintenance of smallpox eradication. Author(s): Breman JG, Arita I. Source: The New England Journal of Medicine. 1980 November 27; 303(22): 1263-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6252467&dopt=Abstract

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The conquest of smallpox. Author(s): Booth C. Source: The Quarterly Journal of Medicine. 1985 December; 57(224): 811-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3912793&dopt=Abstract

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The conquest of smallpox. Author(s): Feery BJ. Source: Aust Fam Physician. 1976 July; 5(6): 720-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=63281&dopt=Abstract

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The conquest of smallpox. Author(s): Barclay WR. Source: Jama : the Journal of the American Medical Association. 1978 October 27; 240(18): 1991-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=691227&dopt=Abstract

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The cost of disease eradication. Smallpox and bovine tuberculosis. Author(s): Nelson AM. Source: Annals of the New York Academy of Sciences. 1999; 894: 83-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10681974&dopt=Abstract

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The danger of resurgence of smallpox due to deliberate introduction: the need for a national policy. Author(s): Raghunath D. Source: Natl Med J India. 2003 January-February; 16(1): 51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715964&dopt=Abstract

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The destruction of smallpox virus stocks in national repositories: a grave mistake and a bad precedent. Author(s): Roizman B, Joklik W, Fields B, Moss B. Source: Infect Agents Dis. 1994 October; 3(5): 215-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7866654&dopt=Abstract

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The development of the virus concept as reflected in corpora of studies on individual pathogens. 5. Smallpox and the evolution of ideas on acute (viral) infections. Author(s): Wilkinson L. Source: Medical History. 1979 January; 23(1): 1-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=368466&dopt=Abstract

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The dynamics of smallpox epidemics in Britain, 1550-1800. Author(s): Duncan SR, Scott S, Duncan CJ. Source: Demography. 1993 August; 30(3): 405-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8405606&dopt=Abstract

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The edge of utility: slaves and smallpox in the early eighteenth century. Author(s): Stewart L. Source: Medical History. 1985 January; 29(1): 54-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3883084&dopt=Abstract

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The effect of early BCG and smallpox immunization on serum bilirubin levels in the newborn. Author(s): Sinniah D, Nagalingam I, Chua CP, Khoo KP, Dugdale AE. Source: Clinical Pediatrics. 1974 September; 13(9): 765-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4429633&dopt=Abstract

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The effect of measles infection and of vaccination with certain live vaccines upon humoral immunity to smallpox. Author(s): Marennikova SS, Askerov VF. Source: Bulletin of the World Health Organization. 1968; 39(2): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5303411&dopt=Abstract

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The effect of mixed infections induced by adenovirus type 5 and vaccinia or smallpox virus, on the ultrastructure of KB cells II. Observations of changes in the ultrastructure of KB cells during 6--11 days infection with adenovirus type 5 and Vaccinia virus. Author(s): Kubica B. Source: Bull Inst Marit Trop Med Gdynia. 1978; 29(3-4): 249-58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=215254&dopt=Abstract

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The effect of mixed infections induced by adenovirus type 5 and vaccinia or smallpox virus, on the ultrastructure of KB cells. III. Changes in the ultrastructure of KB cells within 6--11 days infection with Adenovirus type 5 and Smallpox virus. Author(s): Kubica B. Source: Bull Inst Marit Trop Med Gdynia. 1978; 29(3-4): 259-66. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=215255&dopt=Abstract

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The effect of revaccination against smallpox on serum antibodies. Author(s): Mannweiler E, Geister R. Source: Ger Med Mon. 1968 December; 13(12): 582-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5735339&dopt=Abstract

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The effect of the number of incisions used in primary vaccination against smallpox on the intensity of antibody formation: a preliminary communication. Author(s): Shneyderman AE, Petranovskaya MR, Marennikova SS. Source: J Hyg Epidemiol Microbiol Immunol. 1973 March; 17(3): 257-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4795563&dopt=Abstract

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The effect of the smallpox eradication measles control programme on measles admissions to the Lagos infectious diseases hospital Yaba Nigeria. Author(s): Smith EA, Foster SO. Source: West Afr Med J Niger Pract. 1970 April; 19(2): 51-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5533347&dopt=Abstract

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The elimination of preventable asthma. Lessons from smallpox. Author(s): Music SI. Source: N C Med J. 1999 July-August; 60(4): 227-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10424121&dopt=Abstract

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The elimination of smallpox from Israel. Author(s): Slater PE, Leventhal A, Anis E. Source: Isr Med Assoc J. 2001 January; 3(1): 71-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344812&dopt=Abstract

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The end of routine smallpox vaccination in the United States. Author(s): Kempe CH. Source: Pediatrics. 1972 April; 49(4): 489-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5013413&dopt=Abstract

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The end of smallpox. Author(s): Meiklejohn G. Source: Adv Intern Med. 1978; 23: 385-404. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=626120&dopt=Abstract

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The epidemiological observations made in the two smallpox outbreaks in the land of Northrhine-Westphalia, 1962 at Simmerath (Eifel region) and 1970 at Meschede. Author(s): Richter MK. Source: Bull Soc Pathol Exot Filiales. 1971 September-October; 64(5): 775-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5172710&dopt=Abstract

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The epidemiology and clinical features of smallpox. Author(s): Ramsay AM. Source: Public Health. 1972 January; 86(2): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5073520&dopt=Abstract

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The epidemiology of smallpox in the Republic of Mali. Author(s): Imperato PJ, Sow O, Fofana B. Source: Trans R Soc Trop Med Hyg. 1972; 66(1): 176-82. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5048071&dopt=Abstract

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The eradication of smallpox in Shanghai, China, October 1950-July 1951. Author(s): Hui X, Yutu J. Source: Bulletin of the World Health Organization. 1981; 59(6): 913-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6978198&dopt=Abstract

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The eradication of smallpox. Author(s): Henderson DA. Source: Scientific American. 1976 October; 235(4): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=788150&dopt=Abstract

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The eradication of smallpox. Author(s): Khodakevich LN, Tekeste Y. Source: Ethiop Med J. 1979 April; 17(2): 49-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=520302&dopt=Abstract

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The eradication of smallpox. Author(s): Fenner F. Source: Prog Med Virol. 1977; 23: 1-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=201963&dopt=Abstract

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The evidence in favour of immunisation--a world without smallpox--a world without polio. Author(s): Thomas AK. Source: The Medical Journal of Australia. 1994 September 5; 161(5): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7830676&dopt=Abstract

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The evidence in favour of immunisation--a world without smallpox--a world without polio. Author(s): Feery BJ, Boughton CR. Source: The Medical Journal of Australia. 1994 April 18; 160(8): 459-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8170416&dopt=Abstract

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The Fielding H. Garrison Lecture: The odyssey of smallpox vaccination. Author(s): Bowers JZ. Source: Bulletin of the History of Medicine. 1981 Spring; 55(1): 17-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7011450&dopt=Abstract

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The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis. Author(s): Fenner F. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 1983 June 22; 218(1212): 259-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6136042&dopt=Abstract

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The front line of smallpox preparedness. Author(s): Petersen JM. Source: Mlo: Medical Laboratory Observer. 2003 February; 35(2): 52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624878&dopt=Abstract

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The geographical transmission of smallpox in the Franco-Prussian War: prisoner of war camps and their impact upon epidemic diffusion processes in the civil settlement system of Prussia, 1870-71. Author(s): Smallman-Raynor M, Cliff AD. Source: Medical History. 2002 April; 46(2): 241-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024810&dopt=Abstract

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The global eradication of smallpox. Author(s): Strassburg MA. Source: American Journal of Infection Control. 1982 May; 10(2): 53-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7044193&dopt=Abstract

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The global eradication of smallpox. Author(s): Fenner F. Source: The Medical Journal of Australia. 1980 May 17; 1(10): 455-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7412674&dopt=Abstract

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The global programme of smallpox eradication. Author(s): Ladnyi ID, Arita I, Jezek Z. Source: J Hyg Epidemiol Microbiol Immunol. 1981; 25(3): 217-32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7299106&dopt=Abstract

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The histopathological changes in the temporal bone resulting from acute smallpox and chickenpox infection. Author(s): Bordley JE, Kapur YP. Source: The Laryngoscope. 1972 August; 82(8): 1477-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5053988&dopt=Abstract

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The history and traditional treatment of smallpox in Ethiopia. Author(s): Pankhurst R. Source: Medical History. 1965 October; 9(4): 343-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5323754&dopt=Abstract

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The history of smallpox: an old story of current significance. Author(s): Ray JW, Polk HC Jr. Source: J Ky Med Assoc. 1980 April; 78(4): 206-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6988535&dopt=Abstract

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The impact of city surveillance teams in Bangladesh during the smallpox eradication campaign. Author(s): Vetter NJ, Mehta H, Tarantola D. Source: International Journal of Epidemiology. 1976 December; 5(4): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1010664&dopt=Abstract

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The impact of smallpox on the native population of the 18th century South. Author(s): Wood PH. Source: N Y State J Med. 1987 January; 87(1): 30-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3550543&dopt=Abstract

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The influence of John Hunter's inoculation practice on Edward Jenner's discovery of vaccination against smallpox. Author(s): Turk JL, Allen E. Source: Journal of the Royal Society of Medicine. 1990 April; 83(4): 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2187990&dopt=Abstract

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The influence of modifications in the potency of smallpox vaccines on the immunological reactivity of the organism. Author(s): Topciu V, Giurca A, Voiculescu D, Moldovan E, Plavosin L. Source: Virologie. 1977 January-March; 28(1): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=851001&dopt=Abstract

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The influence of smallpox revaccination upon the foetus. Author(s): Teodorescu M, Topciu V, Plavosin L, Tudose N, Moldovan E. Source: Virologie. 1975; 26(2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1224533&dopt=Abstract

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The international standard for anti-smallpox serum. Author(s): Anderson SG, Skegg J. Source: Bulletin of the World Health Organization. 1970; 42(4): 515-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4988404&dopt=Abstract

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The introduction of jet injection mass vaccination into the national smallpox eradication program of Brazil. Author(s): Millar JD, Morris L, Macedo Filho A, Mack TM, Dyal W, Medeiros AA. Source: Trop Geogr Med. 1971 March; 23(1): 89-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5573585&dopt=Abstract

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The IOM committee on smallpox vaccination. Author(s): Dili Z; IOM committee. Source: The American Journal of Nursing. 2003 April; 103(4): 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705272&dopt=Abstract

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The Jenner bicentenary: the introduction and early distribution of smallpox vaccine. Author(s): Baxby D. Source: Fems Immunology and Medical Microbiology. 1996 November; 16(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8954347&dopt=Abstract

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The Jenner bicentenary; still uses for smallpox vaccine. Author(s): Baxby D. Source: Epidemiology and Infection. 1996 June; 116(3): 231-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666065&dopt=Abstract

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The key to success: the role of local government in the organization of smallpox vaccination in Sweden. Author(s): Skold P. Source: Medical History. 2000 April; 44(2): 201-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829424&dopt=Abstract

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The last known outbreak of smallpox in India. Author(s): Jezek Z, Das MN, Das A, Aggarwal ML, Arya ZS. Source: Indian J Public Health. 1978 January-March; 22(1): 31-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669761&dopt=Abstract

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The last smallpox epidemic in Boston and the vaccination controversy, 1901-1903. Author(s): Albert MR, Ostheimer KG, Breman JG. Source: The New England Journal of Medicine. 2001 February 1; 344(5): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172172&dopt=Abstract

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The level of some smallpox antibodies in selected population groups of several regions of Poland--in the years 1970-1973. Author(s): Potajallo U. Source: Bull Inst Marit Trop Med Gdynia. 1975; 26(3-4): 395-405. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1203603&dopt=Abstract

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The limited role of attenuated smallpox virus in the management of advanced malignant melanoma. Author(s): Milton GW, Brown MM. Source: The Australian and New Zealand Journal of Surgery. 1966 May; 35(4): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4287051&dopt=Abstract

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The mechanism of group differences in the character of the vaccinal process in immunization against natural smallpox. Author(s): Sokhin AA, Lebedinskii AP, Frolov AK, Frolov VK, Sotnik AY, Lysakova VI. Source: J Hyg Epidemiol Microbiol Immunol. 1977; 21(3): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=564370&dopt=Abstract

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The minimum protective level of antibodies in smallpox. Author(s): Sarkar JK, Mitra AC, Mukherjee MK. Source: Bulletin of the World Health Organization. 1975; 52(3): 307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1084801&dopt=Abstract

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The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered. Author(s): Gross CP, Sepkowitz KA. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 1998 July-September; 3(1): 54-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9831677&dopt=Abstract

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The National Commission for Assessment of the Smallpox Eradication Programme in India. Author(s): Basu RN, Khodakevich LN. Source: Indian J Public Health. 1978 January-March; 22(1): 16-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669760&dopt=Abstract

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The national smallpox eradication program: India's struggle against smallpox. Author(s): Kieselstein MJ. Source: Trans Stud Coll Physicians Phila. 1966 October; 34(2): 71-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5977794&dopt=Abstract

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The neurological complications of vaccination against smallpox and measles. Author(s): Osuntokun BO. Source: West Afr Med J Niger Pract. 1968 August; 17(4): 115-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4386473&dopt=Abstract

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The new cell culture smallpox vaccine should be offered to the general population. Author(s): Bicknell W, James K. Source: Reviews in Medical Virology. 2003 January-February; 13(1): 5-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516058&dopt=Abstract

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The next agent of terror? Understanding smallpox & its implications for prehospital crews. Author(s): Brocato CE, Miller GT. Source: J Emerg Med Serv Jems. 2002 March; 27(3): 44-50, 52-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913182&dopt=Abstract

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The ocular complications of smallpox and smallpox immunization. Author(s): Semba RD. Source: Archives of Ophthalmology. 2003 May; 121(5): 715-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742852&dopt=Abstract

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The persistence of complement fixing and haemagglutination-inhibition antibodies after smallpox infection and after smallpox vaccination. Author(s): Siennicki W, Oles A, Kocielska W. Source: J Hyg Epidemiol Microbiol Immunol. 1967; 11(1): 27-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6070331&dopt=Abstract

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The persistence of neutralizing antibodies after revaccination against smallpox. Author(s): el-Ad B, Roth Y, Winder A, Tochner Z, Lublin-Tennenbaum T, Katz E, Schwartz T. Source: The Journal of Infectious Diseases. 1990 March; 161(3): 446-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2155973&dopt=Abstract

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The persistence of smallpox in remote unvaccinated villages during eradication program activities. Author(s): Imperato PJ, Sow O, Benitieni-Fofana. Source: Acta Tropica. 1973; 30(4): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4147875&dopt=Abstract

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The plan to fight smallpox. Author(s): Cowley G. Source: Newsweek. 2002 October 14; 140(16): 44-6, 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389529&dopt=Abstract

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The public and the smallpox threat. Author(s): Blendon RJ, DesRoches CM, Benson JM, Herrmann MJ, Taylor-Clark K, Weldon KJ. Source: The New England Journal of Medicine. 2003 January 30; 348(5): 426-32. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496352&dopt=Abstract

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The Pueblo Indian smallpox epidemic in New Mexico, 1898-1899. Author(s): Frost RH. Source: Bulletin of the History of Medicine. 1990 Fall; 64(3): 417-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2261527&dopt=Abstract

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The recent outbreak of smallpox in Meschede, West Germany. Author(s): Gelfand HM, Posch J. Source: American Journal of Epidemiology. 1971 April; 93(4): 234-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5550338&dopt=Abstract

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The recovery of smallpox virus from patients and their environment in a smallpox hospital. Author(s): Downie AW, Meiklejohn M, St Vincent L, Rao AR, Sundara Babu BV, Kempe CH. Source: Bulletin of the World Health Organization. 1965; 33(5): 615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4285461&dopt=Abstract

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The remaining stocks of smallpox virus should be destroyed. Author(s): Mahy BW, Almond JW, Berns KI, Chanock RM, Lvov DK, Pettersson RF, Schatzmayr HG, Fenner F. Source: Science. 1993 November 19; 262(5137): 1223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8235651&dopt=Abstract

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The return of the smallpox vaccination. Nurses report on plans, concerns. Author(s): Trossman S. Source: The American Nurse. 2003 March-April; 35(2): 1-2, 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815821&dopt=Abstract

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The saga of smallpox eradication: an end and a beginning. Author(s): Henderson DA. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1979 January-February; 70(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=369674&dopt=Abstract

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The scars of smallpox. Author(s): Lee AJ, Norton SA. Source: Archives of Dermatology. 2003 March; 139(3): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622617&dopt=Abstract

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The significance of serological tests in controlling the success of smallpox revaccination. Author(s): Nyerges G, Hollos I, Barsy G. Source: Acta Microbiol Acad Sci Hung. 1966; 13(2): 97-112. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5922218&dopt=Abstract

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The skin and vaccination against smallpox. Author(s): Copeman PW, Banatvala JE. Source: The British Journal of Dermatology. 1971 February; 84(2): 169-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4926866&dopt=Abstract

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The smallpox conundrum. Author(s): Spake A. Source: U.S. News & World Report. 2002 December 23; 133(24): 44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510491&dopt=Abstract

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The smallpox legacy: a history of pediatric immunizations. Author(s): Gregorio L. Source: Pharos Alpha Omega Alpha Honor Med Soc. 1996 Fall; 59(4): 7-13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9130852&dopt=Abstract

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The smallpox saga and the origin(s) of vaccination. Author(s): Cook GC. Source: J R Soc Health. 1996 August; 116(4): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783857&dopt=Abstract

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The smallpox scenario. Author(s): Kher U. Source: Time. 2002 December 16; 160(25): 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510476&dopt=Abstract

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The smallpox story: from variolation to victory. Author(s): Thein MM, Goh LG, Phua KH. Source: Asia Pac J Public Health. 1988; 2(3): 203-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3052542&dopt=Abstract

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The smallpox story: life and death of an old disease. Author(s): Behbehani AM. Source: Microbiol Rev. 1983 December; 47(4): 455-509. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6319980&dopt=Abstract

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The smallpox story: man finally defeats an old adversary. Author(s): Behbehani AM. Source: J Kans Med Soc. 1980 October; 81(10): 447-56, 474. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7014739&dopt=Abstract

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The smallpox vaccine and postvaccinal encephalitis. Author(s): Roos KL, Eckerman NL. Source: Seminars in Neurology. 2002 March; 22(1): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170398&dopt=Abstract

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The smallpox vaccine debate. Author(s): Veenema TG. Source: The American Journal of Nursing. 2002 September; 102(9): 33-8; Quiz 38-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394016&dopt=Abstract

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The speckled monster. Canada, smallpox and its eradication. Author(s): Barreto L, Rutty CJ. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 2002 July-August; 93(4): I1-20, I1-20. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154540&dopt=Abstract

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The spectre of smallpox. Author(s): Mortimer PP. Source: Commun Dis Public Health. 2002 June; 5(2): 92-3. No Abstract Available. Erratum In: Commun Dis Public Health 2002 September; 5(3): 257. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166314&dopt=Abstract

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The survival of smallpox virus (variola minor) in natural circumstances. Author(s): Wolff HL, Croon JJ. Source: Bulletin of the World Health Organization. 1968; 38(3): 492-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4299528&dopt=Abstract

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The threat of bioterrorism returns the fear of smallpox. Author(s): Atlas RM. Source: Current Opinion in Microbiology. 1998 December; 1(6): 719-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10066537&dopt=Abstract

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The threat of bioterrorism: a reason to learn more about anthrax and smallpox. Author(s): Gordon SM. Source: Cleve Clin J Med. 1999 November-December; 66(10): 592-5, 599-600. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10598363&dopt=Abstract

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The threat of smallpox and bioterrorism. Author(s): Berche P. Source: Trends in Microbiology. 2001 January; 9(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166237&dopt=Abstract

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The transmission pattern of smallpox in a West African school population. Author(s): Imperato PJ. Source: Journal of Tropical Pediatrics. 1970 December; 16(4): 204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5313062&dopt=Abstract

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The transmission pattern of smallpox in Eastern Mali. Author(s): Fofana B, Imperato PJ, Nedvideck J. Source: Acta Tropica. 1971; 28(2): 175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4400552&dopt=Abstract

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The United States civilian smallpox vaccination program: have we thought through the whole issue? Author(s): Schwartz MD. Source: Pharmacotherapy. 2003 March; 23(3): 271-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627923&dopt=Abstract

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The US smallpox vaccination plan. Author(s): Abramson JS, McMillan JA, Baltimore RS. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1431-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777565&dopt=Abstract

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The use of smallpox virus as a biological weapon: the vaccination situation in France. Author(s): Levy-Bruhl D, Guerin N; Members of the Eurosurveillance editorial board. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2001 November; 6(11): 171-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891388&dopt=Abstract

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The weight of evidence and the burden of authority: case histories, medical statistics and smallpox inoculation. Author(s): Rusnock AA. Source: Clio Medica (Amsterdam, Netherlands). 1995; 29: 289-315. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7781290&dopt=Abstract

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The world's last endemic case of smallpox: surveillance and containment measures. Author(s): Deria A, Jezek Z, Markvart K, Carrasco P, Weisfeld J. Source: Bulletin of the World Health Organization. 1980; 58(2): 279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6967365&dopt=Abstract

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Thomas Jefferson and smallpox vaccination. Author(s): Leavell BS. Source: Trans Am Clin Climatol Assoc. 1977; 88: 119-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=331644&dopt=Abstract

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Thomas Michael Nowell and his 'Matiere de Boulogne': a neglected figure in the history of smallpox vaccination. Author(s): Meynell E. Source: Journal of the Royal Society of Medicine. 1987 April; 80(4): 232-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3295238&dopt=Abstract

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Thrombocytopenic purpura after smallpox vaccine. Author(s): Burke PJ, Shah NR. Source: Pa Med. 1981 September; 84(9): 49-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7312385&dopt=Abstract

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Throw the switch? New vaccines may not be a reason to keep smallpox stocks. Author(s): Grossman D. Source: Scientific American. 2002 March; 286(3): 21-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11857896&dopt=Abstract

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To be or not to be vaccinated. The smallpox controversy plays out in California hospitals. Author(s): Greene J. Source: Trustee : the Journal for Hospital Governing Boards. 2003 May; 56(5): 14-7, 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774540&dopt=Abstract

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Topical cidofovir for the treatment of dermatologic conditions: verruca, condyloma, intraepithelial neoplasia, herpes simplex and its potential use in smallpox. Author(s): Toro JR, Sanchez S, Turiansky G, Blauvelt A. Source: Dermatologic Clinics. 2003 April; 21(2): 301-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757253&dopt=Abstract

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Topography of variola smallpox virus inverted terminal repeats. Author(s): Massung RF, Knight JC, Esposito JJ. Source: Virology. 1995 August 1; 211(1): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7645234&dopt=Abstract

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Transformation of human blood lymphocytes under the influence of smallpox antigen. Author(s): Gurvich EB, Svet-Moldavskaya IA. Source: Nature. 1968 December 7; 220(171): 1050-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4302756&dopt=Abstract

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Transmission potential of smallpox: estimates based on detailed data from an outbreak. Author(s): Eichner M, Dietz K. Source: American Journal of Epidemiology. 2003 July 15; 158(2): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851223&dopt=Abstract

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Treatment of smallpox and complications of smallpox vaccination. Author(s): Quie PG, Matsen JM. Source: Gp. 1967 October; 36(4): 130-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6054372&dopt=Abstract

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Treatment of smallpox with cytosine arabinoside. Author(s): Hossain MS, Foerster J, Hryniuk W, Israels LG, Chowdhury AS, Biswas MK. Source: Lancet. 1972 December 9; 2(7789): 1230-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4117715&dopt=Abstract

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Treatment of verrucae with smallpox vaccine. Author(s): Hemphill WJ. Source: Jama : the Journal of the American Medical Association. 1969 January 13; 207(2): 368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5818168&dopt=Abstract

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Treatment of verrucae with smallpox vaccine. Author(s): Thompson KW. Source: Jama : the Journal of the American Medical Association. 1969 January 13; 207(2): 368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5818167&dopt=Abstract

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Treatment of verrucae with smallpox vaccine. Author(s): Lawrence KR. Source: J Am Podiatry Assoc. 1971 January; 61(1): 12-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5163447&dopt=Abstract

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Treatment with methisazone of complications following smallpox vaccination. Author(s): Jaroszynska-Weinberger B. Source: Archives of Disease in Childhood. 1970 August; 45(242): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5506947&dopt=Abstract

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Trsmission of smallpox by contact and by aerosol routes in Macaca irus. Author(s): Noble J Jr, Rich JA. Source: Bulletin of the World Health Organization. 1969; 40(2): 279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4308335&dopt=Abstract

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Two cases of smallpox in Byzantium. Author(s): Lascaratos J, Tsiamis C. Source: International Journal of Dermatology. 2002 November; 41(11): 792-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453008&dopt=Abstract

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Two funeral-associated smallpox outbreaks in Sierra Leone. Author(s): Hopkins DR, Lane JM, Cummings EC, Millar JD. Source: American Journal of Epidemiology. 1971 October; 94(4): 341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5110550&dopt=Abstract

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UK awards contract for smallpox vaccine. Author(s): Habeck M. Source: The Lancet Infectious Diseases. 2002 June; 2(6): 321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144887&dopt=Abstract

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UK smallpox vaccine comes under fire from US. Author(s): Dyer O. Source: Bmj (Clinical Research Ed.). 2002 August 10; 325(7359): 298. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169498&dopt=Abstract

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Under scrutiny: smallpox vaccine recommendations. Author(s): Kemper AR, Davis MM. Source: Expert Opinion on Pharmacotherapy. 2003 August; 4(8): 1207-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877631&dopt=Abstract

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Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation. Author(s): Saha K, Mehta R, Misra RC, Chaudhury DS, Ray SN. Source: Scandinavian Journal of Immunology. 1977; 6(6-7): 581-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=198873&dopt=Abstract

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Understanding the threat of smallpox. Author(s): Ridings H, Evans M. Source: Jaapa. 2002 April; 15(4): 41-4, 46. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012586&dopt=Abstract

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Update: adverse events following civilian smallpox vaccination--United States, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 August 29; 52(34): 819-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944880&dopt=Abstract

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Update: cardiac and other adverse events following civilian smallpox vaccination-United States, 2003. Author(s): Centers for Disease Control and Prevention. Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 July 11; 52(27): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855946&dopt=Abstract

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Urban hospital and rural village smallpox in Bangladesh. Author(s): Koplan JP, Azizullah M, Foster SO. Source: Trop Geogr Med. 1978 September; 30(3): 355-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=734762&dopt=Abstract

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US dilutes smallpox vaccine supplies. Author(s): Cimons M. Source: Nature Medicine. 2001 December; 7(12): 1265. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726949&dopt=Abstract

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US draws up plans for smallpox outbreak after terrorist attack. Author(s): Charatan F. Source: Bmj (Clinical Research Ed.). 2002 June 29; 324(7353): 1540. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089080&dopt=Abstract

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US health officials recommend offering smallpox vaccination to all. Author(s): Charatan F. Source: Bmj (Clinical Research Ed.). 2002 October 12; 325(7368): 794. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378724&dopt=Abstract

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US military smallpox vaccination program experience. Author(s): Grabenstein JD, Winkenwerder W Jr. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3278-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824209&dopt=Abstract

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US not ready to destroy smallpox stocks. Author(s): Quirk M. Source: The Lancet Infectious Diseases. 2002 January; 2(1): 2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892491&dopt=Abstract

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US panel advises caution over smallpox vaccination. Author(s): Charatan F. Source: Bmj (Clinical Research Ed.). 2003 August 23; 327(7412): 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933721&dopt=Abstract

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US smallpox vaccine programme stalls as volunteers balk. Author(s): Ault A. Source: Lancet. 2003 May 10; 361(9369): 1626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747889&dopt=Abstract

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US urged to provide smallpox vaccines for emergency crews. Author(s): Check E. Source: Nature. 2002 June 20; 417(6891): 775-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075303&dopt=Abstract

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USA firms up smallpox vaccine plans. Author(s): Senior K. Source: The Lancet Infectious Diseases. 2002 November; 2(11): 649. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409031&dopt=Abstract

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USA to increase smallpox vaccine stockpile. Author(s): Bradbury J. Source: The Lancet Infectious Diseases. 2001 December; 1(5): 290. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871793&dopt=Abstract

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Vaccination against smallpox : is it relevant now? Author(s): Dutta M. Source: Indian J Pediatr. 1981 May-June; 48(392): 257-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7319593&dopt=Abstract

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Vaccination against smallpox in early pregnancy. Author(s): Rajhvajn B, Krznar B, Stoiljkovic C, Orescanin M, Smerdel S. Source: Acta Med Iugosl. 1973; 27(4): 351-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4755152&dopt=Abstract

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Vaccination against smallpox in the plantar surfaces of the feet. Author(s): Helman J. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1978 August 12; 54(7): 264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=715607&dopt=Abstract

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Vaccination against smallpox in the United States--a re-evaluation of the risks and benefits. Author(s): Reeve AM. Source: J Iowa Med Soc. 1971 November; 61(11): 655-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5115181&dopt=Abstract

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Vaccination against smallpox. Author(s): Gully PR, Wood MJ, Bakhshi SS. Source: British Medical Journal (Clinical Research Ed.). 1981 January 3; 282(6257): 70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6778575&dopt=Abstract

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Vaccination against smallpox. Author(s): Jones DT. Source: British Medical Journal. 1980 October 11; 281(6246): 1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7427527&dopt=Abstract

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Vaccination hesitation. Congress, HHS look to tackle safety worries about smallpox vaccinations. Author(s): Piotrowski J. Source: Modern Healthcare. 2003 February 17; 33(7): 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688085&dopt=Abstract

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Vaccination policy against smallpox, 1835-1914: a comparison of England with Prussia and Imperial Germany. Author(s): Hennock EP. Source: Social History of Medicine : the Journal of the Society for the Social History of Medicine / Sshm. 1998 April; 11(1): 49-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11620154&dopt=Abstract

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Vaccines and bioterrorism: smallpox and anthrax. Author(s): Kimmel SR, Mahoney MC, Zimmerman RK. Source: The Journal of Family Practice. 2003 January; 52(1 Suppl): S56-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556279&dopt=Abstract

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Vaccines for smallpox. Author(s): Baxby D. Source: Lancet. 1999 July 31; 354(9176): 422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437892&dopt=Abstract

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Vaccines for smallpox. Author(s): Blanchard T, Smith GL, Whittle H. Source: Lancet. 1999 July 31; 354(9176): 422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437891&dopt=Abstract

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Vaccinia gangrenosum: rare complication of smallpox vaccination. Author(s): Levy JS. Source: Southern Medical Journal. 1969 November; 62(11): 1408-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5366439&dopt=Abstract

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Vaccinia necrosum after smallpox vaccination for herpes labialis. Author(s): Funk EA, Strausbaugh LJ. Source: Southern Medical Journal. 1981 March; 74(3): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7221650&dopt=Abstract

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Vaccinia necrosum following smallpox vaccination for chronic herpetic ulcers. Author(s): Neff JM, Lane JM. Source: Jama : the Journal of the American Medical Association. 1970 July 6; 213(1): 1235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5467961&dopt=Abstract

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Variola virus and immunity in smallpox. II. Recovery of variola-specific soluble antigens from infected rhesus monkey kidney cells. Author(s): Anthony RL, Daniel RW, Cole JL, Heiner GG, McCrumb FR Jr. Source: The Journal of Infectious Diseases. 1971 April; 123(4): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4329345&dopt=Abstract

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Victory over smallpox: interview with Donald A. Henderson. Author(s): Henderson DA. Source: Popul Rep L. 1986 March-April; (5): L172-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3703749&dopt=Abstract

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Vignette of medical history: George Washington and smallpox. Author(s): Miller JM. Source: Md Med J. 1994 May; 43(5): 457-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8052099&dopt=Abstract

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Viraemia in haemorrhagic and other forms of smallpox. Author(s): Mitra AC, Chatterjee SN, Sarkar JK, Manji P, Das AK. Source: J Indian Med Assoc. 1966 August 1; 47(3): 112-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4288107&dopt=Abstract

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Virological evidence for the success of the smallpox eradication programme. Author(s): Arita I. Source: Nature. 1979 May 24; 279(5711): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=221825&dopt=Abstract

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Virological findings during the smallpox outbreak in Stockholm in 1963. Author(s): Espmark A, Biberfeld G, Fagraeus A, Johnsson T, Jonsson J, Magnusson B. Source: Acta Med Scand Suppl. 1966; 464: 71-86. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4290471&dopt=Abstract

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Virological studies of smallpox in an endemic area. I. Evaluation of immunofluorescence staining as a rapid diagnostic procedure in the field. Author(s): Kitamura T, Aoyama Y, Kurata T, Arita M, Imagawa Y. Source: Jpn J Med Sci Biol. 1977 October; 30(5): 215-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=202770&dopt=Abstract

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Virological studies of smallpox in an endemic area. II. Virus content of clinical specimens and typing of virus isolates. Author(s): Kitamura T, Aoyama Y, Kurata T, Arita M, Imagawa Y. Source: Jpn J Med Sci Biol. 1977 October; 30(5): 229-39. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=202771&dopt=Abstract

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Virus content of smallpox scabs. Author(s): Mitra AC, Sarkar JK, Mukherjee MK. Source: Bulletin of the World Health Organization. 1974; 51(1): 106-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4376067&dopt=Abstract

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Virus excretion in smallpox. 1. Excretion in the throat, urine, and conjunctiva of patients. Author(s): Sarkar JK, Mitra AC, Mukherjee MK, De SK, Mazumdar DG. Source: Bulletin of the World Health Organization. 1973 May; 48(5): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4359678&dopt=Abstract

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Virus excretion in smallpox. 2. Excretion in the throats of household contacts. Author(s): Sarkar JK, Mitra AC, Mukherjee MK, De SK. Source: Bulletin of the World Health Organization. 1973 May; 48(5): 523-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4359679&dopt=Abstract

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War or peace: smallpox and the use and abuse of public health. Author(s): Sidel VW. Source: American Journal of Public Health. 1986 October; 76(10): 1189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2944400&dopt=Abstract

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Wart treatment by vaccination with smallpox vaccine: a preliminary report. Author(s): McGee AR. Source: Can Med Assoc J. 1968 July 20; 99(3): 119-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5676076&dopt=Abstract

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What PAs need to know about smallpox. Author(s): Herman L, Toth S, Blanchard E, Larson L, Quigley T, Leger MM, McNellis R. Source: Jaapa. 2003 January; 16(1): 13-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635433&dopt=Abstract

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What should be done about smallpox virus? Author(s): Dumbell K. Source: Lancet. 1987 October 24; 2(8565): 957-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2889871&dopt=Abstract

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What you need to know about the smallpox vaccine. Author(s): Karber S, Fasano N. Source: Nursing. 2003 June; 33(6): 36-42; Quiz 43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799585&dopt=Abstract

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What's next? It could be smallpox, botulism or other equally deadly biological agents. Author(s): Golden F. Source: Time. 2001 November 5; 158(20): 44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11710156&dopt=Abstract

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When do we stop vaccinating against smallpox? Author(s): Millar WS. Source: British Medical Journal. 1977 September 3; 2(6087): 639. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=902017&dopt=Abstract

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WHO advocates investment in global infrastructure for outbreaks such as smallpox. Author(s): Roth CE, Drury P, Andraghetti R, Arthur RR, Ryan MJ, Rodier G. Source: Bmj (Clinical Research Ed.). 2003 February 22; 326(7386): 447. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595391&dopt=Abstract

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Who discovered smallpox vaccination? Edward Jenner or Benjamin Jesty? Author(s): Hammarsten JF, Tattersall W, Hammarsten JE. Source: Trans Am Clin Climatol Assoc. 1979; 90: 44-55. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=390826&dopt=Abstract

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WHO dissenter warns against plans to retain smallpox virus. Author(s): Sharma R. Source: Bmj (Clinical Research Ed.). 2002 January 12; 324(7329): 69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786447&dopt=Abstract

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WHO to wipe out smallpox 'by 2000'. Author(s): Cooper G. Source: The Nursing Journal of India. 1996 August; 87(8): 177. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9004675&dopt=Abstract

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Who will pay for the adverse events resulting from smallpox vaccination? Liability and compensation issues. Author(s): Strongin RJ, Salinsky E. Source: Nhpf Issue Brief. 2003 March 12; (788): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650125&dopt=Abstract

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Why the smallpox virus stocks should not be destroyed. Author(s): Joklik WK, Moss B, Fields BN, Bishop DH, Sandakhchiev LS. Source: Science. 1993 November 19; 262(5137): 1225-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8235652&dopt=Abstract

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Worldwide smallpox eradication: 1977. Author(s): Mahler H. Source: Nord Med. 1977 October; 92(10): 236-240. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=917767&dopt=Abstract

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Yellow-fever before smallpox vaccination. Author(s): Friend HJ. Source: Lancet. 1972 September 2; 2(7775): 493-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4115385&dopt=Abstract

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Zentralblatt fur Bakteriologie--100 years ago: protozoa as causative agents of smallpox, or: Cytoryctes and no end. Author(s): Kohler W. Source: International Journal of Medical Microbiology : Ijmm. 2001 August; 291(3): 1915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11554559&dopt=Abstract

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CHAPTER 2. NUTRITION AND SMALLPOX Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and smallpox.

Finding Nutrition Studies on Smallpox The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “smallpox” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “smallpox” (or a synonym): •

Charles-Marie de la Condamine: early advocate of inoculation for smallpox. Source: Shampo, M A Kyle, R A Mayo-Clin-Proc. 1987 June; 62(6): 486 0025-6196

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Understanding the threat of smallpox. Author(s): University of Kentucky Chandler Medical Center, Lexington, USA. Source: Ridings, Herb Evans, Martin JAAPA. 2002 April; 15(4): 41-4, 46

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND SMALLPOX Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to smallpox. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to smallpox and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “smallpox” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to smallpox: •

“A ring around the rosie” (the rash that was). Author(s): Glickman FS. Source: Journal of the American Academy of Dermatology. 1987 June; 16(6): 1282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3298337&dopt=Abstract

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“Pox Acres” on old Cape Cod. Author(s): Rogers FB. Source: The New England Journal of Medicine. 1968 January 4; 278(1): 21-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4864114&dopt=Abstract

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“The skunk and the smallpox”: mythology and historical reality. Author(s): Feer M.

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Source: Plains Anthropol. 1973; 18: 33-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11630329&dopt=Abstract •

A sermon against the dangerous and sinful practice of inoculation by the English minister Edmond Massey. Author(s): Oda Y. Source: Nippon Ishigaku Zasshi. 1999 March; 45(1): 77-84. Japanese. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11623751&dopt=Abstract

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A small-pox experience in California. February 1912. Author(s): Lee E. Source: The American Journal of Nursing. 2002 February; 102(2): 61, 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953522&dopt=Abstract

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By the London post. The stigma of mental illness--smallpox tragedy--an expedition to Bath. Author(s): Lister J. Source: The New England Journal of Medicine. 1978 December 7; 299(23): 1284-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=213713&dopt=Abstract

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Congruences in Chinese and Western medicine from 1830-1911: smallpox, plague and cholera. Author(s): Summers WC. Source: Yale J Biol Med. 1994 January-April; 67(1-2): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7544052&dopt=Abstract

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Cultural resistance to smallpox vaccination in West Africa. Author(s): Challenor BD. Source: J Trop Med Hyg. 1971 March; 74(3): 57-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5551013&dopt=Abstract

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Lady Mary Wortley Montagu: medical and religious controversy following her introduction of smallpox inoculation. Author(s): Stone AF, Stone WD. Source: J Med Biogr. 2002 November; 10(4): 232-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389051&dopt=Abstract

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Macassans and aboriginal smallpox: the “1789” and “1829” epidemics. Author(s): Butlin NG.

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Source: Hist Stud. 1985; 21: 315-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11617124&dopt=Abstract •

Negotiating with Dharma Pinnu: towards a social history of smallpox in colonial Orissa. Author(s): Pati B. Source: Can Bull Med Hist. 2002; 19(2): 477-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776728&dopt=Abstract

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Observations on variolation practices in Mali. Author(s): Imperato PJ. Source: Trop Geogr Med. 1974 December; 26(4): 429-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4456704&dopt=Abstract

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Popular beliefs about smallpox and other common infectious diseases in South India. Author(s): Mather RJ, John TJ. Source: Trop Geogr Med. 1973 June; 25(2): 190-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4717276&dopt=Abstract

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Public health and the law. Smallpox vaccination and organized religion. Author(s): Curran WJ. Source: American Journal of Public Health. 1971 October; 61(10): 2127-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5096811&dopt=Abstract

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Smallpox and its control in Canada. Author(s): McIntyre JW, Houston CS. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1999 December 14; 161(12): 1543-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624414&dopt=Abstract

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Smallpox and traditional medicine in the developing countries of Africa and Asia. Author(s): Sery V. Source: Z Tropenmed Parasitol. 1973 March; 24(1): 105-18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4733213&dopt=Abstract

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Smallpox and variolisation in the populations on Bulgarian soil. Author(s): Zaprjanov N. Source: Folia Med (Plovdiv). 1967; 9(5): 298-302. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4972397&dopt=Abstract

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Smallpox in aboriginal Australia, 1829-31. Author(s): Campbell J.

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Source: Hist Stud. 1983; 20(81): 536-56. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11617119&dopt=Abstract •

Smallpox in aboriginal Australia, 1829-31. Author(s): Campbell J. Source: Hist Stud. 1983; 20: 536-56. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614617&dopt=Abstract

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Smallpox in aboriginal Australia: the early 1830s. Author(s): Campbell J. Source: Hist Stud. 1985; 21: 336-58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11617125&dopt=Abstract

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Smallpox. “Most terrible of all the ministers of death”. Author(s): Magner LN. Source: International Journal of Dermatology. 1985 September; 24(7): 466-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3902683&dopt=Abstract

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Smallpox: the triumph over the most terrible of the ministers of death. Author(s): Barquet N, Domingo P. Source: Annals of Internal Medicine. 1997 October 15; 127(8 Pt 1): 635-42. Erratum In: Ann Intern Med 1998 May 1; 128(9): 787. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9341063&dopt=Abstract

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State church charity and smallpox: an epidemic crisis in the City of Mexico 1797-98. Author(s): Price R. Source: Journal of the Royal Society of Medicine. 1982 May; 75(5): 356-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7042974&dopt=Abstract

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The African connection. Cotton Mather and the Boston smallpox epidemic of 17211722. Author(s): Brown TH. Source: Jama : the Journal of the American Medical Association. 1988 October 21; 260(15): 2247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3050164&dopt=Abstract

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The goddess Sitala and epidemic smallpox in Bengal. Author(s): Nicholas RW. Source: J Asian Stud. 1981; 41(1): 21-45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614704&dopt=Abstract

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The history and traditional treatment of smallpox in the Sudan. Author(s): Bayoumi A. Source: J East Afr Res Dev. 1976; 1: 1-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614724&dopt=Abstract

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The practice of variolation among the Songhai of Mali. Author(s): Imperato PJ. Source: Trans R Soc Trop Med Hyg. 1968; 62(6): 868-73. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5729574&dopt=Abstract

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Therapy of smallpox vaccination reactions. Author(s): Krynicki FX. Source: J Am Inst Homeopath. 1966 July-August; 59(7): 230-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5952975&dopt=Abstract

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Traditional African medicine and eradication of smallpox. Author(s): Singer P, Vann CR. Source: The New England Journal of Medicine. 1981 April 9; 304(15): 914-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7207532&dopt=Abstract

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Traditional beliefs about smallpox and its treatment in the Republic of Mali. Author(s): Imperato PJ, Traore D. Source: J Trop Med Hyg. 1968 September; 71(9): 224-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5678920&dopt=Abstract

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Treatment of warts with smallpox vaccine. Author(s): Belisario JC. Source: The Medical Journal of Australia. 1971 December 18; 2(25): 1277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5134725&dopt=Abstract

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Variolation in the Rajasthan Desert. Author(s): Davis C. Source: Indian J Public Health. 1978 January-March; 22(1): 134-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=669758&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to smallpox; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Alternative Therapy Color therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON SMALLPOX Overview In this chapter, we will give you a bibliography on recent dissertations relating to smallpox. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “smallpox” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on smallpox, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Smallpox ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to smallpox. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Developing a Quarantine Plan to Respond to a Biological Attack with Smallpox: Using the Delphi Technique in Charlotte-mecklenburg, North Carolina by Waters, John Bennet, Jr. Dha from Medical University of South Carolina - College of Health Professions, 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3082744

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Diseases on the Margin: Morphologies of Tuberculosis and Smallpox in San Francisco, 1860-1940 (california) by Craddock, Susan Leigh, Phd from University of California, Berkeley, 1994, 249 pages http://wwwlib.umi.com/dissertations/fullcit/9529272

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Epidemiology on the Northern Plains: a Cultural Perspective (smallpox, Great Plains, Ethnohistory, Fort Clark, North Dakota) by Trimble, Michael K., Phd from University of Missouri - Columbia, 1985, 345 pages http://wwwlib.umi.com/dissertations/fullcit/8611766

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Experimenting on the Neighbors: Inoculation of Smallpox in Boston in the Context of Eighteenth-century Medicine. by Melchert, Dennis Don, Phd from The University of Iowa, 1973, 290 pages http://wwwlib.umi.com/dissertations/fullcit/7416664

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International Cooperation and Pandemic Diseases: Regimes and the Role of Epistemic Communities in Combating Cholera, Smallpox and Aids (immune Deficiency) by Mcfadden, David Fancher, Phd from The Claremont Graduate University, 1995, 273 pages http://wwwlib.umi.com/dissertations/fullcit/9612315

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Medical Practice and Medical Theory: Smallpox in Britain during the Long Eighteenth Century by Joscelyne, C. E., Phd from University of Essex (united Kingdom), 1990, 350 pages http://wwwlib.umi.com/dissertations/fullcit/D-91149

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Pox Americana: the Great North American Smallpox Epidemic of 1775-1783 by Fenn, Elizabeth Anne, Phd from Yale University, 1999, 475 pages http://wwwlib.umi.com/dissertations/fullcit/9930996

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Pox Britannica: Smallpox Inoculation in Britain, 1721-1830 by Brunton, Deborah Christian, Phd from University of Pennsylvania, 1990, 312 pages http://wwwlib.umi.com/dissertations/fullcit/9112542

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Smallpox and the Disintegration of the Roman Economy after 165 Ad (roman Empire) by Zelener, Yan; Phd from Columbia University, 2003, 230 pages http://wwwlib.umi.com/dissertations/fullcit/3088458

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Smallpox Diffusion between Small and Dispersed Historic Native American Populations by Wolforth, Lynne Mackin, Phd from University of Illinois at Urbanachampaign, 1997, 388 pages http://wwwlib.umi.com/dissertations/fullcit/9717347

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The Search for Vaccinia (smallpox, Jenner, Whitepox, White Pock, Vaccination) by Schibuk, Margaret Danielle, Phd from Harvard University, 1986, 352 pages http://wwwlib.umi.com/dissertations/fullcit/8620531

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND SMALLPOX Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning smallpox.

Recent Trials on Smallpox The following is a list of recent trials dedicated to smallpox.8 Further information on a trial is available at the Web site indicated. •

Dose Safety, Tolerability, and Immunogenicity of a New Smallpox Vaccine in Adults without Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is currently recruiting patients. Sponsor(s): Acambis Purpose - Excerpt: The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053508

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Dressing Preparation Comparison for Smallpox Vaccination Sites Condition(s): Smallpox Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to find out the risk of spread of the vaccine virus, vaccinia, from the sore when different types of bandages are used to cover

8

These are listed at www.ClinicalTrials.gov.

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the site. This study will also look at how each bandage type affects the healing of the sore. In order to find out if the vaccine virus can be spread through the air, like a cold, the study staff will also look at throat cultures. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063856 •

Phase I Trial of Smallpox Vaccine Condition(s): Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety of an experimental vaccine called Modified Vaccinia Virus Ankara (MVA) for use against the smallpox virus. It will also investigate how many injections of MVA are needed to produce immunity against vaccinia virus, which is closely related to the smallpox virus. An effective smallpox vaccine exists, but it can cause side effects that, on rare occasions, can be life-threatening. The FDA gave new license approval for Dryvax on 10/25/02, but has not been used in the general population since smallpox was eradicated worldwide. Both the MVA and Dryvax(r) (Registered Trademark) vaccines are made using the vaccinia virus, however the MVA vaccine contains a more attenuated, or weakened, form of the virus. [http://www.fda.gov/cber/products/smalwye102502.htm] Healthy normal volunteers between 18 and 30 years of age, who have never been vaccinated with a smallpox vaccine, may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential. MVA, placebo and Dryvax(r) (Registered Trademark) will be administered by different methods. The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax(r) (Registered Trademark) vaccine is administered, as it was for many years, with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and is evidence of the development of immunity. The development of a take suggests that an individual will be protected against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work. Participants will be assigned to groups, as well as, product randomly. For instance, the first study participant could be enrolled into group 3. The Dryvax(r) (Registered Trademark) dose is given as a challenge to see if the person has a take. A reduced take response or no take, could suggest that MVA is able to produce an immune response. The dosing schedules vary from 12 to 24 weeks and volunteers are in the study a total of 24 to 36 weeks, depending on the number of injections. Participants will be observed for at least 1 hour after each injection. They will come to the clinic a week after MVA or placebo injections and at least twice a week after Dryvax(r) (Registered Trademark) for about 21 days to have the injection site evaluated and photographed. At each visit, participants will be asked about how they are feeling and if they are taking any medications. Blood and urine tests will be done on injection days and at follow up visits scheduled 1 and 4 weeks after each immunization as well as 12

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weeks after the Dryvax(r) (Registered Trademark) challenge dose. Additional tests may be done between visits if medically necessary. Phase(s): Phase I; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046397 •

Phase I/II Trial of Modified Vaccinia Virus Ankara (MVA) Vaccine against Smallpox Condition(s): Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety of an experimental vaccine called modified vaccinia virus ankara (MVA) and determine if it confers protection against the smallpox virus (variola). There is an existing vaccine, called Dryvax(r) (Registered Trademark), which is effective against smallpox; however, this vaccine can cause various side effects, including some that, on rare occasions, can be life-threatening. Dryvax(r) (Registered Trademark) has not been used in the United States since childhood vaccination was stopped in 1971, and though it is given to certain healthcare and laboratory workers, and some people in the armed forces, it is not recommended for the general population. Both the MVA and Dryvax(r) (Registered Trademark) vaccines are made using the vaccinia virus, which is closely related to variola. Healthy normal volunteers between 31 and 60 years of age who have been vaccinated with a smallpox vaccine more than 10 years before entering the study may be eligible for this protocol. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential. Participants will receive MVA vaccine or placebo, followed by a dose of Dryvax(r) (Registered Trademark). The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax(r) (Registered Trademark) vaccine is administered with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and will protect against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work. Study participants will be randomly assigned to one of the following dosing groups: 1) one injection of MVA; 2) one injection of placebo; 3) two injections of MVA 4 weeks apart; or 4) two injections of placebo 4 weeks apart. All participants will receive a challenge dose of Dryvax(r) (Registered Trademark) 12 weeks after their last injection of MVA or placebo to determine if the MVA vaccine has conferred immunity. A take, that occurs in response to the Dryvax(r) (Registered Trademark) dose indicates lack of prior immunity, and thus tells whether one or two doses of MVA is needed to produce an immune response. Participants will be observed for at least 1 hour after each injection. They will come to the clinic at least once a week after MVA or placebo injections and at least twice a week after Dryvax(r) (Registered Trademark) to have the injection site evaluated and photographed. At each visit, participants will be asked how they are feeling and what medications, if any, they are taking. Blood and urine tests will be done according to the following schedule: - Before each injection; - 1 week after each injection; - 4 weeks after the MVA or placebo

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injections are finished; - At the time of the Dryvax(r) (Registered Trademark) dose; - 4 weeks after the Dryvax(r) (Registered Trademark) dose; - 12 weeks after the Dryvax(r) (Registered Trademark) dose. Additional laboratory tests may be done between visits if medically necessary. Phase(s): Phase I; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053742 •

APSV in vaccinia naive adults Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The study seeks to define, with precision, the safety and efficacy of APSV, two dose potencies of one lot in vaccinia-naive adults. The ability of this vaccine to induce a classic "take" as defined by formation of a lesion at the injection site consistent with the "Jennerian" process (see Appendix A) and vaccine specific immune responses will be assessed. The local cutaneous lesion is considered to be a surrogate for clinical effectiveness of live, replicating smallpox vaccines. Neutralizing antibody formation has been correlated with takes for the Dryvax vaccine and is considered to be cross-protective for other orthopoxviruses, including variola. The study also seeks to characterize preliminarily the cell mediated immune (CMI) response to APSV (as compared to Dryvax). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050518

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Assessment of dryvax in previously vaccinated adults Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The primary objective is to define the proportion of individuals who respond to vaccination 6 to 8 days after vaccination. Immune studies will be performed. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032708

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Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults With Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is no longer recruiting patients.

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Sponsor(s): Acambis Purpose - Excerpt: The objective of this study is to determine the minimum dose of ACAM2000 needed to produce a cutaneous reaction in at least 90% of a population of healthy adults at least 28 years of age and previously vaccinated against smallpox. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053482 •

Dryvax vaccine immunogenicity in previously vaccinated Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The study seeks to further 1) evaluate safety in previously vaccinated adults between the ages of 32-70 who are vaccinated with undiluted Dryvax, and 1:5 and 1:10 dilutions; 2) define with very high precision the proportion of individuals who respond with a "take" 6-11 days after vaccination with undiluted Dryvax and Dryvax diluted 1:5; 3) define with good precision the proportion of individuals who respond with a "take" with a 1:10 dilution of Dryvax and; 4) explore correlations between "takes/no takes" and immune responses in all vaccine dilution groups. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050505

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Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): Acambis Purpose - Excerpt: The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053495

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Human Immune Response to Smallpox Vaccine Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)

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Purpose - Excerpt: The purpose of this study is to attempt to identify the immune response of healthy adults to an investigational dilution of the Dryvax smallpox vaccine. In addition, we will try to determine whether certain genetic characteristics influence the size of the sore around the vaccination site, and use blood samples from subjects in the study to make a new form of antibody that could be given to people wtih vaccine side effects. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068198 •

Study of Reactogenicity, Safety, Immunogenicity, and Pock Lesion Formation of a Cell-Cultured Smallpox Vaccine Compared to Dryvax(r) Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): DynPort Vaccine Company Purpose - Excerpt: This study will evaluate the safety and efficacy of both Dryvax(r) and the new cell-cultured vaccine (CCSV) in a comparative fashion. Across 3 cohorts, 150 vaccinia-naive volunteers will be randomly assigned to receive either CCSV (100 volunteers) or Dryvax(r) (50 volunteers) in a blinded fashion. Subjects will be followed closely for up to 6 months and a subgroup of volunteers will be followed up to 3 years in order to evaluate the duration of immunity following vaccination. Another cohort will enroll 100 vaccinia-experienced volunteers and randomly assign them to receive either CCSV (50 volunteers) or Dryvax(r) (50 volunteers) and a sub group will be followed up to 3 years. A fifth cohort will enroll 100 vaccinia-naive volunteers and randomly assign them to receive different dilutions of CCSV (1:1, 1:5, 1:25, and 1:50). Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042094

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Vaccinia virus vaccine (APSV) in vaccinia- naive subjects: PILOT Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: To define the safety of vaccination with APSV as determined by the reactogenicity of the vaccine and the development of expected and un-expected adverse events associated with vaccination. To assess the proportion of individuals who respond to vaccination with a "take" (those who form a visible lesion at the injection site) 6 to 8 days after the vaccination. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038987

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A Comparative Phase I Clinical Study of HIVAC-1e and Smallpox (Vaccinia) Vaccines in Previously (Vaccinia) Vaccinated and Unvaccinated Volunteers Condition(s): HIV Infections Study Status: This study is completed. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: To determine the physiological and immunological responses in healthy HIV seronegative adult volunteers vaccinated with a) the HIVAC-1e (vacciniaHIV) vaccine expressing the envelope glycoproteins of HIV and b) the Wyeth smallpox vaccine. The parameters to be studied will include: 1. The course of physiological responses to vaccination, including (a) lesion development, progression, and resolution; (b) physiological changes such as temperature, malaise, itching at the site, etc. and (c) any observable AE. 2. The appearance, identity, quantity, and duration of humoral antibodies against HIV and vaccinia virus. 3. The appearance, identity, quantity, and duration of cell-mediated immunity against HIV and vaccinia virus. 4. The adequacy of a procedure using a special dressing to contain viral shedding from the vaccination site. 5. The safety, humoral and cellular immune responses of a booster injection of the recombinant subunit gp160 vaccine (MicroGeneSys) in HIVAC-1e recipients. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002261

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A Study of Dryvax Vaccine Against Smallpox in Previously Unvaccinated Adults Condition(s): Smallpox Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see how many people respond to a smallpox vaccine when a sore forms where the shot was given. The world was declared free of smallpox in 1980. General routine vaccinations for smallpox were stopped in the U.S. in 1971. In 1976, the recommendation for routine vaccination of healthcare workers was also discontinued. The only people who presently receive this vaccine are people who work with vaccinia virus or monkeypox virus. Because the world was considered free of smallpox infections, this vaccine was no longer produced; there is a limited supply available in the United States. Because of the limited amount of Dryvax vaccine (vaccinia virus) against smallpox, this study will look at the ability to dilute the vaccine making more doses available in the event of a smallpox outbreak. The study seeks to characterize a strategy of vaccination against smallpox with various doses of Dryvax, followed by revaccination with the same dose, if required, in volunteers 18-32 years of age with a negative history of smallpox vaccination. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026611

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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “smallpox” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON SMALLPOX Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “smallpox” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on smallpox, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Smallpox By performing a patent search focusing on smallpox, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

204 Smallpox

will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on smallpox: •

Attenuated smallpox vaccine strain Inventor(s): Ooi; Kiyoshi (Tokyo, JP), Morita; Michio (Chiba, JP), Suzuki; Kazuyoshi (Ichikawa, JP), Hashizume; Soh (Chiba, JP), Yoshizawa; Hanako (Funabashi, JP) Assignee(s): Chiba Prefectural Government (Chiba, JP) Patent Number: 4,567,147 Date filed: December 20, 1984 Abstract: The present invention discloses an attenuated smallpox vaccine strain exhibiting antibody production similar to conventional strains but without postvaccinal side effects. The vaccine is prepared by attenuating a Lister strain of a vaccinia virus by cell culture and selecting a suitable strain therefrom showing relatively small and uniform pocks on the chorioallantoic membrane of an embryonated egg. Excerpt(s): This invention relates to a vaccine strain exhibiting a similar antibody productivity to that of conventional strains and little postvaccinal side effects, which is prepared by attenuating a Lister strain of a vaccinia virus by cell culture. The original strain (i.e. Lister strain) was subcultured in rabbit Kidney cells over 36 generations at 30.degree. C. and then plaque-purified thrice to isolate 50 clones. From these 50 clones, a temperature-sensitive variant which showed the worst growth at 40.degree. C. in Vero cells established from green monkey (Coropithecus aethiops) Kidney cells was selected. Compared with the original strain, the temperature-sensitive variant grew better in rabbit Kidney cells but worse in rabbit central nervous system cells. In the central nervous system of a monkey, it exhibited a pathogenicity which was similar to that of DI.sub.s strain, i.e. an attenuated micropock variant prepared from Dairen I strain, and extremely lower than that of the original strain. Accordingly an inoculation test was carried out with the use of a small number of subjects. Consequently it was found that the foregoing variant would result in a light systemic reaction with a febrility ratio of 14% followed by somewhat slow formation of crust. Therefore it was attempted to isolate a clone showing a poor skin growth capacity. As a marker in the isolation of the foregoing clone, the size of pocks on the chorioallantoic membrane of an embryonated egg was employed. That is, the temperature-sensitive variant was subcultured in rabbit Kidney cells over six generations and plaque-purified twice to isolate a clone showing relatively small and uniform pocks on the chorioallantoic membrane of an embryonated egg. The clone was further subcultured in rabbit Kidney cells over additional three generations at 30.degree. C. to isolate a clone showing extremely small pocks on the chorioallantoic membrane of an embryonated egg to thereby prepare an attenuated smallpox vaccine strain. Properties of the strain of the present invention are summarized in Table 1 compared with those of the original strain (i.e. Lister strain). Web site: http://www.delphion.com/details?pn=US04567147__

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Smallpox inhibitor of complement enzymes (SPICE) protein and methods of inhibiting complement activation Inventor(s): Rosengard; Ariella M. (Gladwyne, PA), Ahearn; Joseph M. (Pittsburgh, PA) Assignee(s): The Trustees of the University of Pennsylvania (), The University of Pittsburgh of the Commonwealth of Pennsylvania () Patent Number: 6,551,595 Date filed: September 1, 2000 Abstract: The invention provides a complement inhibitor derived from variola, called smallpox inhibitor of complement enzymes (SPICE) and SPICE-related proteins, such as fusion proteins. These proteins are useful in the treatment of complement-mediated conditions, such as hyperacutc rejection of xenografts. Excerpt(s): The field of the invention is inhibition of complement activation. The complement system plays a fundamental role in both the innate and acquired immune responses. As such, it also participates in the majority of diseases characterized by acute and/or chronic inflammation. For example, a critical role of the complement system has been demonstrated in rheumatoid arthritis, post-myocardial infarction reperfusion injury, post-bowel ischemia reperfusion injury, and systemic lupus erythematosus. These specific disorders are simply representative of most inflammatory states in which similar or identical molecular pathways result in complement activation and concomitant tissue injury. Hyperacute rejection of xenografts has also been shown to result from activation of the human complement system. The utilization of organs obtained from nonhuman donors is an appealing solution to the increasing shortage of organs available for clinical transplantation. Although xenotransplantation using organs obtained from primate donors has been performed with limited clinical success, the use of distantly related species, such as pigs or sheep, avoids ethical dilemmas, potential virus transmission, and limited availability associated with the use of primates as xenograft donors. However, the use of organs from distantly related species for xenotransplantation is impractical due to hyperacute rejection (hyperacute rejection), a process that leads to irreversible xenograft damage and organ loss within minutes to hours. In xenotransplantation of vascularized tissues, hyperacute rejection is thought to be mediated by the binding of naturally occurring recipient antibodies to the endothelium of the xenograft. Web site: http://www.delphion.com/details?pn=US06551595__

Patent Applications on Smallpox As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to smallpox:

10

This has been a common practice outside the United States prior to December 2000.

206 Smallpox

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Effective monitoring system for anthrax smallpox, or other pathogens Inventor(s): Lu, Peter S. (Mountain View, CA), Sherlock, Thomas M. (Los Altos, CA), Byerly, Joseph; (Pebble Beach, CA) Correspondence: David Garman; 772 Lucerne Drive; Sunnyvale; CA; 94085; US Patent Application Number: 20030153021 Date filed: December 6, 2002 Abstract: A device and method for detecting anthrax or other pathogens are disclosed. Individual self-contained monitoring devices of a monitoring system can be portable or stationary (e.g. installed in air ducts or plumbing of buildings) and can be part of a network of devices. Monitoring devices may be used for the detection of a variety of airborne or surface pathogens, including but not limited to anthrax, smallpox, and Salmonella. Bioamplification-coupled proteomics assays provide rapid and reliable detection of pathogens, with self-checking capabilities reducing or eliminating false positives and false negatives. Sample preservation capability allows pathogen samples to be preserved after detection for further testing. The device of the invention can be remotely operated by minimally trained technicians or security personnel. The pathogen monitoring device of the invention provides a more compact, accurate, rapid, and costeffective alternative to other anthrax detectors, and an effective weapon against bioterrorism. Excerpt(s): The rapid detection of microorganisms, particularly highly virulent pathogens, is required for the timely treatment of serious infections. Contamination of air or water by pathogenic microorganisms can occur naturally, can be the result of unintended human interference, or can occur as a result of intentional use of biological warfare agents against military and civilian populations. Because of the ability of pathogens to disseminate and infect human populations rapidly, a detection system requires speed, versatility and, preferably, portability. Early detection and identification of pathogens in patients allows a health care worker to diagnose and appropriately treat a patient. Remote sampling and detection of microorganisms can limit exposure to biological agents through the identification of contaminated areas. These areas can then be quarantined and decontaminated by appropriately trained individuals. However, in spite of the need for rapid detection of pathogens, detection equipment in current use has significant shortcomings. Manipulating and interpreting pathogen detection devices in the field is a hazardous duty, and can be made more difficult by cumbersome protective clothing worn by health care or military personnel. Thus, remote and automated sensing is required to address both safety and efficiency concerns. To be truly effective as a monitoring system, it also must be widely distributed, such that detection of bioterrorism induced or natural outbreaks can be rapidly identified and controlled. In turn, the need for a widespread early warning network demands that any detection device be accurate, automated and relatively inexpensive. There are several methods commonly used to detect pathogens in collected samples, but not all of these methods are rapid, readily automatable or of low cost. These include (i) amplification of pathogen-specific nucleic acid sequences, including methods for amplifying pathogenspecific nucleic acid sequences requiring numerous time-consuming steps that are difficult to automate and often produce false positives or false negatives; (ii) culture of pathogens on appropriate growth media, followed by isolation and either timeconsuming biochemical or histological assays; (iii) mass spectrometer-based detection of pathogen-specific components, in which each detection unit is expensive to produce; and (iv) serological-based assays, which have limited sample size and can only detect pathogens in an infected individual.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with smallpox, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “smallpox” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on smallpox. You can also use this procedure to view pending patent applications concerning smallpox. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON SMALLPOX Overview This chapter provides bibliographic book references relating to smallpox. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on smallpox include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “smallpox” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on smallpox: •

AIDS, Fear, and Society: Challenging the Dreaded Disease Contact: Taylor & Francis, Publishers, 1101 Vermont Ave Ste 200, Washington, DC, 20005-3521, (202) 289-2174. Summary: This book examines the fear and dread invoked by AIDS and the stigma associated with the disease that attaches to patients, their families, and their caregivers. The book takes the position that this and other diseases are more than medical phenomena or individual catastrophes but are profound social events that change societal conditions. The first section of the book reviews the nature and history of other "dreaded" diseases over history such as leprosy, tuberculosis, cancer, and smallpox. The second section considers AIDS as the archetype of the dreaded disease, examining the panic and fear associated with its diagnosis.

210 Smallpox

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “smallpox” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “smallpox” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “smallpox” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

2002 Bioterrorism After the Anthrax Attacks: Complete Revised Guide to Biological Weapons and Germ Warfare ¿ Anthrax, Smallpox, Medicines, Treatment, Preparedness, White House, Homeland Security, CDC, HHS, FDA, NIH, Military Manuals by U. S. Government; ISBN: 1931828229; http://www.amazon.com/exec/obidos/ASIN/1931828229/icongroupinterna

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2002 Smallpox Bioterrorism: Complete Revised Guide to Government Response Plan and Guidelines, Vaccines, Treatment, Preparedness with CDC, FDA, and NIH Documents plus Military Manuals by PM Medical Health News; ISBN: 1592480306; http://www.amazon.com/exec/obidos/ASIN/1592480306/icongroupinterna

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21st Century Bioterrorism and Germ Weapons - U.S. Army Field Manual for the Treatment of Biological Warfare Agent Casualties (Anthrax, Smallpox, Plague, Viral Fevers, Toxins, Delivery Methods, Detection, Symptoms, Treatment, Equipment) by Department of Defense; ISBN: 1931828105; http://www.amazon.com/exec/obidos/ASIN/1931828105/icongroupinterna

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21st Century Collection Centers for Disease Control (CDC) Emerging Infectious Diseases (EID) - Comprehensive Collection from 1995 to 2002 with Accurate and Detailed Information on Dozens of Serious Virus and Bacteria Illnesses - Hantavirus, Influenza, AIDS, Malaria, TB, Pox, Bioterrorism, Smallpox, Anthrax, Vaccines, Lyme Disease, Rabies, West Nile Virus, Hemorrhagic Fevers, Ebola, Encephalitis (Core Federal Information Series) by U.S. Government; ISBN: 1592480675; http://www.amazon.com/exec/obidos/ASIN/1592480675/icongroupinterna

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21st Century Smallpox Digest: Government Information on Biological Warfare and Bioterrorism, Symptoms, Vaccines, and Treatment by U.S. Government; ISBN: 1931828148; http://www.amazon.com/exec/obidos/ASIN/1931828148/icongroupinterna

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A Destroying Angel: The Conquest of Smallpox in Colonial Boston. by Ola Elizabeth. Winslow; ISBN: 0395184533; http://www.amazon.com/exec/obidos/ASIN/0395184533/icongroupinterna

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Assessment of Future Scientific Needs for Live Variola Virus (Compass Series) by National Research Council, Institute of Medicine (1999); ISBN: 0309064414; http://www.amazon.com/exec/obidos/ASIN/0309064414/icongroupinterna

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Bioterrorism of Smallpox Variola Virus: Index of New Information and Guide-Book for Consumers, Reference and Research by John C., Dr Bartone (2001); ISBN: 0788325884; http://www.amazon.com/exec/obidos/ASIN/0788325884/icongroupinterna

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Bioterrorism Smallpox by Daniel Farb; ISBN: 193263410X; http://www.amazon.com/exec/obidos/ASIN/193263410X/icongroupinterna

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Clinical Description and Epidemiology of Bioterroism Agents: Anthrax, Smallpox, and Plague by Terri Rebmann, et al; ISBN: 0972666028; http://www.amazon.com/exec/obidos/ASIN/0972666028/icongroupinterna

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Conqueror of Smallpox: Dr. Edward Jenner by Israel E. Levine; ISBN: 0671638882; http://www.amazon.com/exec/obidos/ASIN/0671638882/icongroupinterna

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Contagion: Epidemics, History and Culture - From Smallpox to Anthrax by Alison Bashford (Editor), Claire Hooker (Editor) (2002); ISBN: 1864031816; http://www.amazon.com/exec/obidos/ASIN/1864031816/icongroupinterna

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Cotton Mather and American science and medicine : with studies and documents concerning the introduction of inoculation or variolation; ISBN: 0405125569; http://www.amazon.com/exec/obidos/ASIN/0405125569/icongroupinterna

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Dr. Jenner and the Speckled Monster: The Search for the Smallpox Vaccine by Albert Marrin (2002); ISBN: 0525469222; http://www.amazon.com/exec/obidos/ASIN/0525469222/icongroupinterna

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Edward Jenner and Smallpox Vaccination by Eberle; ISBN: 0531008878; http://www.amazon.com/exec/obidos/ASIN/0531008878/icongroupinterna

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Germ Warriors: Stories of the Men and Women Who Fight the World's Worst Plagues from Tuberculosis to Smallpox (Adrenaline Series) by Clint Willis (Editor) (2004); ISBN: 1560255609; http://www.amazon.com/exec/obidos/ASIN/1560255609/icongroupinterna

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Guide to the Laboratory Diagnosis of Smallpox for Eradication Programmes; ISBN: 9241540206; http://www.amazon.com/exec/obidos/ASIN/9241540206/icongroupinterna

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Hospital Handbook on Smallpox Vaccinations by American Health Consulants (2003); ISBN: 193110753X; http://www.amazon.com/exec/obidos/ASIN/193110753X/icongroupinterna

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Invisible Invaders: Smallpox and Other Diseases in Aboriginal Australia 1780-1880 by Judy Campbell; ISBN: 0522849393; http://www.amazon.com/exec/obidos/ASIN/0522849393/icongroupinterna

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Jenner's Smallpox Vaccine: The Riddle of Vaccina Virus and Its Origin by Derrick Baxby; ISBN: 0435540572; http://www.amazon.com/exec/obidos/ASIN/0435540572/icongroupinterna

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Memorandum on the control of outbreaks of smallpox; ISBN: 0114913897; http://www.amazon.com/exec/obidos/ASIN/0114913897/icongroupinterna

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Memorandum on vaccination against smallpox; ISBN: 0113204892; http://www.amazon.com/exec/obidos/ASIN/0113204892/icongroupinterna

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Memorandum on vaccination against smallpox; ISBN: 0113205376; http://www.amazon.com/exec/obidos/ASIN/0113205376/icongroupinterna

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Microorganisms: From Smallpox to Lyme Disease by Thomas D. Brock (Editor); ISBN: 0716720841; http://www.amazon.com/exec/obidos/ASIN/0716720841/icongroupinterna

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Pox Americana: The Great Smallpox Epidemic of 1775-82 by Elizabeth A. Fenn; ISBN: 080907821X; http://www.amazon.com/exec/obidos/ASIN/080907821X/icongroupinterna

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Princes and Peasants: Smallpox in History by Donald R. Hopkins; ISBN: 0226351769; http://www.amazon.com/exec/obidos/ASIN/0226351769/icongroupinterna

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Report of the Committee on Inquiry into the Smallpox Outbreak in London in March and April 1973; ISBN: 0101562608; http://www.amazon.com/exec/obidos/ASIN/0101562608/icongroupinterna

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Rotting Face: Smallpox and the American Indian by R. G. Robertson; ISBN: 0870044192; http://www.amazon.com/exec/obidos/ASIN/0870044192/icongroupinterna

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Russia, Iraq, and Other Potential Sources of Anthrax, Smallpox and Other Bioterrorist Weapons: Hearing Before the Committee on International Relations, U.S. House of Representatives by Henry J. Hyde (Editor) (2003); ISBN: 0756729157; http://www.amazon.com/exec/obidos/ASIN/0756729157/icongroupinterna

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Scourge: The Once and Future Threat of Smallpox by Jonathan B. Tucker; ISBN: 0871138301; http://www.amazon.com/exec/obidos/ASIN/0871138301/icongroupinterna

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Smallpox (Deadly Diseases and Epidemics) by Chelsea House Publications; ISBN: 0791073076; http://www.amazon.com/exec/obidos/ASIN/0791073076/icongroupinterna

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Smallpox (Diseases and Disorders) by Barbara Saffer (2004); ISBN: 1590183010; http://www.amazon.com/exec/obidos/ASIN/1590183010/icongroupinterna

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Smallpox (Epidemics) by Tom Ridgway (2001); ISBN: 0823933466; http://www.amazon.com/exec/obidos/ASIN/0823933466/icongroupinterna

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Smallpox and Its Eradication (History of International Public Health, No. 6) by Frank Fenner (Editor), Numerous; ISBN: 9241561106; http://www.amazon.com/exec/obidos/ASIN/9241561106/icongroupinterna

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Smallpox and the American Indian (World Disasters) by Arthur Diamond; ISBN: 1560060182; http://www.amazon.com/exec/obidos/ASIN/1560060182/icongroupinterna

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Smallpox and the Iroquois Wars: An Ethnohistorical Study of the Influence of Disease and Demographic Change in Iroquoian Culture History, 1630-1700 by Stephen Clark, Steven Martin Clark (1981); ISBN: 155567027X; http://www.amazon.com/exec/obidos/ASIN/155567027X/icongroupinterna

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Smallpox in colonial America; ISBN: 0405098804; http://www.amazon.com/exec/obidos/ASIN/0405098804/icongroupinterna

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Smallpox in the New World (Peters, Stephanie True, Epidemic!,) by Stephanie True Peters; ISBN: 0761416374; http://www.amazon.com/exec/obidos/ASIN/0761416374/icongroupinterna

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Smallpox Inoculation: An Eighteenth Century Mathematical Controversy by L. Bradley (1971); ISBN: 0902031236; http://www.amazon.com/exec/obidos/ASIN/0902031236/icongroupinterna

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Smallpox Is Dead by Arnold Sanderson, Sue Harrison (Illustrator); ISBN: 1850830134; http://www.amazon.com/exec/obidos/ASIN/1850830134/icongroupinterna

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Smallpox Story : In Words and Pictures by Abbas M. Behbehani (1988); ISBN: 0685240223; http://www.amazon.com/exec/obidos/ASIN/0685240223/icongroupinterna

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Smallpox Strikes!: Cotton Mather's Bold Experiment (American Adventure) by Norma Jean Lutz; ISBN: 0791050475; http://www.amazon.com/exec/obidos/ASIN/0791050475/icongroupinterna

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Smallpox, When Should Routine Vaccination Be Discontinued (The Umap Expository Monograph Series) by James C. Frauenthal (1981); ISBN: 3764330422; http://www.amazon.com/exec/obidos/ASIN/3764330422/icongroupinterna

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Smallpox: Cholera by Vasile Tudor; ISBN: 0856260924; http://www.amazon.com/exec/obidos/ASIN/0856260924/icongroupinterna

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Smallpox: Clinical Description & Recommendations for a Vaccination Program by Centers for the Study of Bioterrorism, Emerging Infections (2003); ISBN: 0972666052; http://www.amazon.com/exec/obidos/ASIN/0972666052/icongroupinterna

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Smallpox: The Fight to Eradicate a Global Scourge by David A. Koplow; ISBN: 0520237323; http://www.amazon.com/exec/obidos/ASIN/0520237323/icongroupinterna

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Surgeons, Smallpox, and the Poor: A History of Medicine and Social Conditions in Nova Scotia, 1749-1799 by Allan Everett Marble (1993); ISBN: 0773509887; http://www.amazon.com/exec/obidos/ASIN/0773509887/icongroupinterna

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The Conquest of Smallpox by Peter Razzell; ISBN: 0904573036; http://www.amazon.com/exec/obidos/ASIN/0904573036/icongroupinterna

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The Eradication of Smallpox: Organizational Learning and Innovation in Intellectual Health (Westview Special Studies in Health Care and Medical Scie) by Jack W. Hopkins; ISBN: 0813377293; http://www.amazon.com/exec/obidos/ASIN/0813377293/icongroupinterna

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The global eradication of smallpox : final report of the Global Commission for the Certification of Smallpox Eradication, Geneva, December 1979; ISBN: 9241560657; http://www.amazon.com/exec/obidos/ASIN/9241560657/icongroupinterna

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The Greatest Killer: Smallpox in History, With a New Introduction by Donald R. Hopkins (2002); ISBN: 0226351688; http://www.amazon.com/exec/obidos/ASIN/0226351688/icongroupinterna

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The Invisible Fire: The Story of Mankind's Victory over the Ancient Scourge of Smallpox by Joel N. Shurkin (2001); ISBN: 0595168671; http://www.amazon.com/exec/obidos/ASIN/0595168671/icongroupinterna

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The Management of Smallpox Eradication in India: A Case Study and Analysis by Lawrence B. Brilliant; ISBN: 0472100599; http://www.amazon.com/exec/obidos/ASIN/0472100599/icongroupinterna

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The Smallpox Slayer by Alan Brown; ISBN: 0340787732; http://www.amazon.com/exec/obidos/ASIN/0340787732/icongroupinterna

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The Speckled Monster: A Historical Tale of Battling Smallpox by Jennifer Lee Carrell (2003); ISBN: 0525947361; http://www.amazon.com/exec/obidos/ASIN/0525947361/icongroupinterna

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Toward a Containment Strategy for Smallpox Bioterror: An Individual-Based by Joshua M. Epstein (Editor), et al (2003); ISBN: 0815724551; http://www.amazon.com/exec/obidos/ASIN/0815724551/icongroupinterna

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Vaccination Against Smallpox (Great Minds Series) by Edward Jenner (1996); ISBN: 1573920649; http://www.amazon.com/exec/obidos/ASIN/1573920649/icongroupinterna

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Vaccinations: From Smallpox to Cancer (Single Title: Science: Health and Human Disease) by Margaret O. Hyde, Elizabeth H., M.D. Forsyth (2000); ISBN: 0531117464; http://www.amazon.com/exec/obidos/ASIN/0531117464/icongroupinterna

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When Plague Strikes : The Black Death, Smallpox, AIDS by James Cross Giblin (Author), David Frampton (Illustrator) (1997); ISBN: 0064461955; http://www.amazon.com/exec/obidos/ASIN/0064461955/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “smallpox” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A guide for the evaluation of the national smallpox eradication programme at the district level, by S. P. Ramakrishnan and H. M. Gelfand. Author: Ramakrishnan, S. P.; Year: 1964; New Delhi, Ministry of Health, 1964

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A note on smallpox in the Philippine Islands Author: Heiser, Victor George,; Year: 1965; Washington, D. C.: Government Printing Office, 1911

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An essay on the animal oeconomy: together with observations upon the smallpox Author: Helvétius, Jean Claude Adrien,; Year: 1926; London: Printed for W. and J. Innys., 1723

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Further investigations on the variola-vaccinia flocculation reaction, by James Craigie and W. J. Tulloch. Author: Craigie, James.; Year: 1911; London, H. M. Stationery off., 1931

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Guide to the laboratory diagnosis of smallpox for smallpox eradication programmes. Author: World Health Organization.; Year: 1963; Geneva, 1969

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Memorandum on vaccination against smallpox. Author: Great Britain. Ministry of Health.; Year: 1964; London, H. M. Stationery Off., 1967

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National smallpox eradication programme in India; planning, organization and execution, problems encountered, approach to their solution. Author: India. Ministry of Health and Family Welfare.; Year: 1960; New Delhi, 1966

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Procedures for prevention or containment of an outbreak of smallpox. Author: United States. Public Health Service. Interbureau Committee on Disease Control.; Year: 2003; [Washington] Bureau of State Services, Public Health Service, 1961

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Proceedings. Symposium on Smallpox, 2 & 3 September 1969, and Symposium on Acute Respiratory Diseases, 1 & 2 October 1969. Editor: Branimir Gusi´c. Author: Gusi´c, Branimir.; Year: 1951; Zagreb, Yugoslav Academy of Sciences and Arts, 1969

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Questions and answers on smallpox and vaccination. Author: Leake, James Payton,; Year: 1951; [Washington, 1946]

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Report on the evaluation of the independent assessment of national smallpox eradication programme in Chingleput district. Author: India (Republic) Ministry of Health.; Year: 1964; New Delhi, 1964

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Report on the evaluation of the independent assessment of national smallpox eradication programme in Mysore district. Author: India (Republic) Ministry of Health.; Year: 1963; New Delhi, 1964

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Report on the evaluation of the independent assessment of national smallpox eradication programme in Palghat district. Author: India (Republic) Ministry of Health.; Year: 1702; New Delhi, 1964

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Requirements for biological substances. 5. Requirements for smallpox vaccine. Report. Author: World Health Organization. Study Group on Requirements for Smallpox Vaccine.; Year: 1965; Geneva, 1959

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Smallpox Author: ECRI (Organization); Year: 1964; Plymouth Meeting, PA: ECRI, c2003

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Smallpox or variola. Author: Leake, James Payton,; Year: 1951; [Philadelphia? 1943]

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Smallpox. Author: Rao, A. R.,; Year: 1966; Bombay, Kothari Book Depot, 1972

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Studies of smallpox vaccination by jet injection in Brazil. Author: Millar, John Donald,; Year: 1936; Washington, Pan American Health Organization, 1965

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The "philosophes" and the propaganda for inoculation of smallpox in eighteenthcentury France. Author: Rowbotham, Arnold H.; Year: 1961; [Berkeley, Univ. of California Press, 1935]

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The diagnosis of smallpox. Author: Dixon, Cyril William.; Year: 1965; [Leeds, Lumby, 1951]

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Variola virus; a survey and analysis of the literature [by] Mary S. Watson. Author: U.S. Army Biological Laboratories.; Year: 1963; Fort Detrick, Md., U. S. Army Biological Laboratories, Virus and Rickettsia Division, 1960

Chapters on Smallpox In order to find chapters that specifically relate to smallpox, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and smallpox using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “smallpox” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on smallpox: •

Viral Diseases Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 88-123.

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Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: Many viral diseases present with oral lesions. This lengthy chapter, from a textbook on diseases of the oral mucosa and the lips, discusses the etiology, clinical features, histopathology, diagnosis, and differential diagnosis for a variety of viral diseases. Diseases covered include herpes simplex, primary herpetic gingivostomatitis, recurrent herpes simplex, eczema herpeticum, varicella, herpes zoster, herpangina, acute lymphonodular pharyngitis, hand-foot-and-mouth disease, hoof-and-mouth disease, vesicular stomatitis, smallpox, vaccinia, orf, measles, rubella, infectious mononucleosis, mumps, human papillomavirus, oral squamous papilloma, verruca vulgaris, condyloma acuminatum, focal epithelial hyperplasia (Heck's disease), molluscum contagiosum, Kawasaki's disease, HIV infections, and AIDS. Full-color photographs illustrate the chapter; references are provided for each section. 56 figures. 189 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON SMALLPOX Overview In this chapter, we show you how to keep current on multimedia sources of information on smallpox. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Smallpox The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in smallpox (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on: •

Clinical management of adverse events following smallpox vaccination [videorecording]: a national training initiative Source: Centers for Disease Control and Prevention, Public Health Training Network; produced for the Bioterrorism Preparedness and Response P; Year: 2003; Format: Videorecording; Carrollton, TX: PRIMEDIA Workplace Learning, 2003

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Complications of smallpox vaccination [slide] Source: Center for Disease Control, Bureau of Training, Instructional Systems Division; Year: 1968; Format: Slide; [Atlanta: The Center, 1968?]

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Decision point for the smallpox vaccine candidate [videorecording] Source: produced for Centers for Disease Control and Prevention; Year: 2003; Format: Videorecording; [Atlanta, Ga.?]: U.S. Dept. of Health & Human Services, Public Health Service, CDC, Centers for Disease Control and Prevention, 2003

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Overview of smallpox preparedness and response [videorecording]: communications with public and stakeholders and considerations for hospitals Source: produced for Office of Terrorism Preparedness and Response [and] National Immunization Program, Centers for Di; Year: 2002; Format: Videorecording; [Atlanta, GA]: CDC, 2002

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Public health scares [videorecording]: smallpox Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2003; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2003

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Smallpox [electronic resource]: a city on the edge of disaster. Source: Gerstner, Patsy, 1933-; Year: 1997; Format: Electronic resource; Cleveland: Dittrick Medical History Center, c1997

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Smallpox [electronic resource]: a great and terrible scourge Source: Public Health Service Historian [and] History of Medicine Division, National Library of Medicine, National Institutes of Health; Year: 2002; Format: Electronic resource; Bethesda, MD: National Library of Medicine, National Institutes of Health, Dept. of Health and Human Services, 2002

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Smallpox [motion picture] Source: United States Army; Year: 1967; Format: Motion picture; [Washington]: The Army; [Atlanta: for loan by National Medical Audiovisual Center, 1967]

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Smallpox [slide] Source: Center for Disease Control, Bureau of Training, Instructional Systems Division; Year: 1963; Format: Slide; [Atlanta: The Center, 1963?]

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Smallpox [videorecording] Source: Waring Library Society; produced by Medical University of South Carolina, Health Communications Network; Year: 1993; Format: Videorecording; Charleston, S.C.: The Society, 1993

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Smallpox [videorecording]: the secret killer Source: Produced by Canadian Broadcasting Corporation; Year: 2003; Format: Videorecording; New York, NY: Filmakers Library, 2003

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Smallpox [videorecording]: what every clinician should know Source: U.S. Public Health Service, CDC, Centers for Disease Control & Prevention, Public Health Training Network; produced for Office of Bioterrorism Preparedness and Response, National Center for I; Year: 2001; Format: Videorecording; [Atlanta, Ga.]: Centers for Disease Control and Prevention, [2001]

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Smallpox and vaccinia laboratory testing [videorecording]: a national training initiative Source: U.S. Public Health Service, CDC, Centers for Disease Control and Prevention, Public Health Training Network; produced by Division of Professional Development and; Year: 2003; Format: Videorecording; Carrollton, TX: PWPL, [2003]

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Smallpox preparedness [videorecording]: considerations for response team volunteers Source: produced by Public Health Training Network, Division of Professional Development and Evaluation, Public Health Practice Program Office, Centers for Disease Control and; Year: 2002; Format: Videorecording; [Atlanta, GA]: CDC, 2002

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Smallpox vaccination [motion picture]: should our policy be changed? Source: [presented by] the U.S. Department of Health, Education, and Welfare, Public Health Service; a National Medical Audiovisual Center production; Year: 1969; Format: Motion picture; [United States]: The Center, 1969

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Smallpox vaccination procedure [motion picture] Source: United States Army; produced by Walter Reed Army Institute of Research, Division of Medical Audio Visual Services; Year: 1972; Format: Motion picture; [Washington]: The Army: [for loan by Armed Forces Institute of Pathology Audiovisual Support Center], 1972

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Smallpox vaccine [videorecording]: issues for clinicians Source: produced for Office of Terrorism Preparedness and Response [and] National Immunization Program, Centers for Disease Control and Prevention; produced by Public Health Training Network, Division o; Year: 2002; Format: Videorecording; [Atlanta, GA]: CDC, 2002

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Smallpox vaccine administration [videorecording] Source: produced by Public Health Training Network, Division of Professional Development and Evaluation, Public Health Practice Program Office, Centers for Disease Control and Prevention; produced for Bioterrori; Year: 2002; Format: Videorecording; [Atlanta, Ga.]: CDC, Dept. of H&HS, 2002

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Smallpox vaccine operational issues [videorecording] Source: produced for Office of Terrorism Preparedness and Response [and] National Immunization Program, Centers for Disease Control and Prevention; produced by Public Health Training Network, Division of Pro; Year: 2002; Format: Videorecording; [Atlanta, GA]: CDC, 2002

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The smallpox vaccine [videorecording]: are you ready? Source: Envision Incorporated; APIC, Association for Professionals in Infection Control and Epidemiology, Inc; Year: 2002; Format: Videorecording; Nashville, TN: Envision, [2002?]

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The status of global smallpox eradication [videorecording] Source: Brooke Army Medical Center; Year: 1972; Format: Videorecording; Fort Sam Houston, Tex.: Academy of Health Sciences, 1972

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Toward a containment strategy for smallpox bioterror [electronic resource]: an individual-based computational approach Source: Joshua M. Epstein. [et al.]; Year: 2002; Format: Electronic resource; [Washington, D.C. Baltimore, Md.: Center on Social and Economic Dynamics, 2002]

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CHAPTER 9. PERIODICALS AND NEWS ON SMALLPOX Overview In this chapter, we suggest a number of news sources and present various periodicals that cover smallpox.

News Services and Press Releases One of the simplest ways of tracking press releases on smallpox is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “smallpox” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to smallpox. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “smallpox” (or synonyms). The following was recently listed in this archive for smallpox: •

Heart problems not tied to smallpox vaccine Source: Reuters Health eLine Date: October 02, 2003

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Concerns about sequelae of smallpox vaccine, anthrax cleared up Source: Reuters Medical News Date: October 02, 2003

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Anti-viral inhaler may protect against smallpox Source: Reuters Health eLine Date: September 26, 2003

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US gives more cash to Danish smallpox vaccine firm Source: Reuters Industry Breifing Date: September 25, 2003

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Study suggests smallpox vaccine may fight AIDS Source: Reuters Health eLine Date: September 12, 2003

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Prior smallpox vaccination may have protective effect against HIV infection Source: Reuters Industry Breifing Date: September 12, 2003

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California firm gets license to make smallpox drug Source: Reuters Health eLine Date: September 12, 2003

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Acambis shares jump on AIDS hopes for smallpox jab Source: Reuters Industry Breifing Date: September 12, 2003

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Canada hosts 8-nation test on smallpox "outbreak" Source: Reuters Health eLine Date: September 08, 2003

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UK firm says it has shipped half US smallpox doses Source: Reuters Health eLine Date: August 27, 2003

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UK firm says has shipped half U.S. smallpox doses Source: Reuters Industry Breifing Date: August 27, 2003

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Voluntary smallpox vaccination programs may provide inadequate immunity Source: Reuters Medical News Date: August 21, 2003

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Smallpox vaccination would fall short if voluntary Source: Reuters Health eLine Date: August 21, 2003

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Vaccinia immunoglobulin may lower smallpox risks in HIV-infected patients Source: Reuters Medical News Date: August 20, 2003

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Old smallpox vaccination probably still protective Source: Reuters Health eLine Date: August 18, 2003

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Most people given smallpox vaccine in past probably still immune Source: Reuters Industry Breifing Date: August 18, 2003

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U.S. Panel recommends against smallpox vaccination for general public Source: Reuters Medical News Date: August 12, 2003

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No need for general U.S. smallpox shots: report Source: Reuters Health eLine Date: August 12, 2003

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ViroPharma compounds active against smallpox in preclinical studies Source: Reuters Industry Breifing Date: July 31, 2003

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New compounds show promise as smallpox drugs Source: Reuters Health eLine Date: July 31, 2003

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Viropharma shrs surge on smallpox prospects Source: Reuters Industry Breifing Date: July 30, 2003

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UK goes abroad to boost smallpox vaccine supplies Source: Reuters Industry Breifing Date: July 30, 2003

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Bavarian to test its smallpox vaccine against rival Source: Reuters Industry Breifing Date: July 15, 2003

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Weakened smallpox vaccine is safer, research shows Source: Reuters Industry Breifing Date: July 14, 2003

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New smallpox vaccine looks safe in tests Source: Reuters Health eLine Date: July 14, 2003

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Antibody response to new attenuated virus protects against smallpox Source: Reuters Industry Breifing Date: July 14, 2003

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Smallpox vaccination may reduce asthma risk Source: Reuters Industry Breifing Date: July 07, 2003

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Pfizer to discuss SARS, malaria, smallpox research Source: Reuters Industry Breifing Date: June 25, 2003

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U.S. studies weigh safety of smallpox vaccinations Source: Reuters Health eLine Date: June 24, 2003

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Diluted smallpox vaccine safe and effective after previous immunization Source: Reuters Industry Breifing Date: June 24, 2003

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U.S. urges smallpox vaccine for monkeypox exposure Source: Reuters Health eLine Date: June 11, 2003

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U.S. bans rodent transport and advises smallpox vaccine to limit monkeypox Source: Reuters Medical News Date: June 11, 2003

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Panel: More data before smallpox shots expanded Source: Reuters Health eLine Date: May 27, 2003

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Advisers reiterate need to wait before giving smallpox vaccine to first responders Source: Reuters Medical News Date: May 27, 2003

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US to buy new smallpox vaccine once available Source: Reuters Industry Breifing Date: May 23, 2003

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US plans to buy new smallpox vaccine once available Source: Reuters Health eLine Date: May 23, 2003

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Smallpox vaccine-related myopericarditis and encephalomyelitis cases under investigation Source: Reuters Industry Breifing Date: May 22, 2003

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CDC: Case of brain swelling after smallpox shot Source: Reuters Health eLine Date: May 22, 2003

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Smallpox immunity lasts decades, study shows Source: Reuters Health eLine Date: May 20, 2003

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Acambis gets fresh smallpox boost Source: Reuters Industry Breifing Date: May 08, 2003

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U.S. states receive $100 million for smallpox vaccination programs Source: Reuters Industry Breifing Date: May 05, 2003

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Smallpox vaccine candidates often fail to recall skin disorders Source: Reuters Industry Breifing Date: May 05, 2003

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Smallpox shot refusers say compensation a concern Source: Reuters Health eLine Date: May 02, 2003

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Smallpox vaccine refusers cite compensation concerns, low threat of attack Source: Reuters Industry Breifing Date: May 01, 2003

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Report: Smallpox program too slow to evaluate Source: Reuters Health eLine Date: May 01, 2003

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CDC reports 103 pregnancies in smallpox vaccinees Source: Reuters Health eLine Date: May 01, 2003

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CDC reports 103 pregnancies among smallpox vaccinees Source: Reuters Industry Breifing Date: May 01, 2003

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US smallpox vaccine campaign linked with 45 serious adverse events Source: Reuters Medical News Date: April 24, 2003

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CDC says 33,400 in U.S. given smallpox shots Source: Reuters Health eLine Date: April 24, 2003

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DynPort smallpox vaccine shows fewer side effects than Dryvax in phase I study Source: Reuters Medical News Date: April 17, 2003 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “smallpox” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “smallpox” (or synonyms). If you know the name of a company that is relevant to smallpox, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “smallpox” (or synonyms).

Academic Periodicals covering Smallpox Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to smallpox. In addition to these sources, you can search for articles covering smallpox that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for smallpox. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with smallpox. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

228 Smallpox

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to smallpox: Antihistamines •

Systemic - U.S. Brands: Aller-Chlor; AllerMax Caplets; Aller-med; Atarax; Banophen; Banophen Caplets; Benadryl; Benadryl Allergy; Bromphen; Calm X; Chlo-Amine; Chlorate; Chlor-Trimeton; Chlor-Trimeton Allergy; Chlor-Trimeton Repetabs; Claritin; Claritin Reditabs; Compoz; Conta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202060.html

Antihistamines and Decongestants •

Systemic - U.S. Brands: A.R.M. Maximum Strength Caplets; Actagen; Actifed; Actifed Allergy Nighttime Caplets 20; Alcomed; Alcomed 2-60; Allent; Allercon; Allerest Maximum Strength; Allerfrim; Allerphed; Amilon; Anamine; Anamine T.D. Andec; Andec-TR; Aprodrine; Atrofed; Atrohi http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202061.html

Antihistamines, Decongestants, and Analgesics •

Systemic - U.S. Brands: Aclophen; Actifed Cold & Sinus; Actifed Cold & Sinus Caplets; Actifed Sinus Nighttime; Actifed Sinus Nighttime Caplets; Alka-Seltzer Plus Allergy Medicine Liqui-Gels; Alka-Seltzer Plus Cold Medicine; Alka-Seltzer Plus Cold Medicine Liqui-Gels; Allerest http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202062.html

Antihistamines, Decongestants, and Anticholinergics •

Systemic - U.S. Brands: Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202653.html

Antihistamines, Phenothiazine-Derivative •

Systemic - U.S. Brands: Anergan 25; Anergan 50; Antinaus 50; Pentazine; Phenazine 25; Phenazine 50; Phencen-50; Phenergan; Phenergan Fortis; Phenergan Plain; Phenerzine; Phenoject-50; Pro-50; Promacot; Pro-Med 50; Promet; Prorex-25; Prorex-50; Prothazine; Prothazine Plain; Sho http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202063.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

Researching Medications 229

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “smallpox” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “smallpox” (or synonyms) into the “For these words:” box. The following is a sample result: •

AIDSCOM: Reducing HIV Transmission, Lessons From the Past Contact: Academy for Educational Development, 1255 23rd St NW, Washington, DC, 20037, (202) 884-8000. Summary: This report summarizes what is known about how education programs can reduce the transmission of Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS); identifies evaluation problems; and suggests areas for future research and investment. The report outlines early AIDS prevention programs and discusses possible correlations to reduced sexual transmission of HIV. It analyzes existing national AIDS health programs and lessons learned about HIV prevention. Finally, it compares HIV prevention efforts to those directed against other lifestyle diseases, including other Sexually transmitted diseases (STD's), cancer, heart disease, family planning and contraception, child survival, and smallpox survival. Major findings indicate that current evidence cannot prove a direct correlation between educational intervention and reduced HIV seroconversion, but there is a probable link between information and risk reduction. The report also states that personal loss seems to correlate with risk reduction, changes in knowledge are easier to produce than changes in behavior or attitude, information source credibility is significant in the success of behavior modification, and changes in drug use have been more difficult to produce than changes in sexual behavior. Effective education goes beyond information to include service delivery, counseling, needle exchange, and condom distribution, it states, while external competition has reduced the effectiveness of positive education campaigns, and people selectively believe AIDS information for illogical reasons. Continuing programs are needed to sustain behavior modification. The report outlines principles of effective HIV prevention education: Programs must be based on factual, scientific information; prevention messages must be consistent, clear, and effective; programs must reflect the awareness spectrum; programs must enable people to modify their behavior and maintain those changes over time; and HIV prevention must build a community consensus.

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The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “smallpox” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 6224 780 26 14 2 7046

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “smallpox” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI 15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on smallpox can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to smallpox. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to smallpox. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “smallpox”:

240 Smallpox

•

Guides on smallpox Smallpox http://www.nlm.nih.gov/medlineplus/smallpox.html

•

Other guides Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Monkeypox Virus Infections http://www.nlm.nih.gov/medlineplus/monkeypoxvirusinfections.html

Within the health topic page dedicated to smallpox, the following was listed: •

General/Overviews Smallpox Questions and Answers: The Disease and the Vaccine Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/overview/faq.asp Update on Smallpox Source: Food and Drug Administration http://www.fda.gov/fdac/features/2003/203_smallpox.html

•

Alternative Therapy Bioterrorism and CAM (Complementary and Alternative Medicine): What the Public Needs To Know Source: National Center for Complementary and Alternative Medicine http://nccam.nih.gov/health/alerts/bioterrorism/

•

Specific Conditions/Aspects Pre-Event Screening Worksheet for Smallpox Vaccine: Important Interim Supplementary Information http://www.bt.cdc.gov/agent/smallpox/vaccination/pdf/screeningworksheet2.pdf Smallpox: Health Information for International Travel, 2001-2002 Source: Centers for Disease Control and Prevention http://www.cdc.gov/travel/diseases/smallpox.htm

•

Children What Is Smallpox? Source: Nemours Foundation http://kidshealth.org/kid/misc/smallpox.html

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•

From the National Institutes of Health NIAID Study Results Support Diluting Smallpox Vaccine Stockpile to Stretch Supply Source: Dept. of Health and Human Services http://www.nih.gov/news/pr/mar2002/hhs-28.htm

•

Latest News Anti-Viral Inhaler May Protect Against Smallpox Source: 09/26/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14111 .html Heart Problems Not Tied to Smallpox Vaccine Source: 10/02/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14168 .html

•

Law and Policy CDC's Smallpox Preparation and Response Activities Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/prep/cdc-prep.asp Medical Society Supports 'Ring Vaccination' in Case of Smallpox Outbreak Source: American Academy of Pediatrics http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZBWB3A27D &sub_cat=2 Smallpox Emergency Personnel Protection Act of 2003: Benefits Compensation for Smallpox Vaccine Injuries Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/bene-comp.asp

and

Smallpox Questions and Answers: Section 304 of the Homeland Security Act Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/section-304-qa.asp •

Men Pregnancy and Breastfeeding Mean You Should Not Get Smallpox Vaccine Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/preg-contra.asp Smallpox Vaccination Information for Women Who Are Pregnant Breastfeeding Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/preg-factsheet.asp

•

Organizations Johns Hopkins University, Center for Civilian Biodefense Strategies http://www.hopkins-biodefense.org/

or

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National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ Public Health Emergency Preparedness and Response Program Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/ WHO/OMS: World Health Organization Source: World Health Organization http://www.who.int/en/ •

Pictures/Diagrams Smallpox Disease Images Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/Agent/Smallpox/SmallpoxImages.asp Vaccine Reaction Images Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/Agent/Smallpox/VaccineImages.asp

•

Prevention/Screening Caring for the Smallpox Vaccination Site Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/site-care-pub.asp Frequently Asked Questions: Smallpox Source: White House http://www.whitehouse.gov/news/releases/2002/12/20021213-3.html Information on Live Virus Vaccines and Vaccinia Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/live-virus.asp List of Medications Contraindicating Receipt of Smallpox Vaccine Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/immuno_suppress_meds.as p People Who Should NOT Get the Smallpox Vaccine (Unless They Are Exposed to Smallpox) Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/contraindications-public.asp Reactions after Smallpox Vaccination Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/reactions-vacc-public.asp Smallpox and Vaccinia Source: National Center for Biotechnology Information http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View.ShowSection&rid=v acc.chapter.3 Smallpox Vaccination and the Patient with HIV/AIDS Source: Johns Hopkins University, Center for Civilian Biodefense Strategies http://www.hopkins-biodefense.org/pages/resources/bartlett.html

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Smallpox Vaccination: An Important Decision Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/important-decision.asp Smallpox Vaccine Overview Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/facts.asp Someone You Are Close to Is Getting the Vaccine: What You Should Know and Do Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/close-contacts.asp •

Research NIAID Study Results Support Diluting Smallpox Vaccine Stockpile to Stretch Supply Source: Dept. of Health and Human Services http://www.nih.gov/news/pr/mar2002/hhs-28.htm Recall of Skin Diseases That Disqualify People from Preexposure Smallpox Vaccination Source: American College of Physicians http://www.annals.org/cgi/content/full/139/1/I-32 Smallpox Vaccinations: People with Cancer Could Have Problems Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_2_1x_Smallpox_Vaccination s_People_With_Cancer_Could_Have_Problems.asp

•

Statistics Smallpox Vaccination Program Status by State Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/spvaccin.htm Smallpox Vaccine Adverse Event Rates Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccine-safety/adverse-events-chart.asp Smallpox Vaccine Shipment Numbers Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/smallpox.htm

•

Teenagers What Is Smallpox? Source: Nemours Foundation http://kidshealth.org/teen/misc/smallpox.html

•

Women Pregnancy and Breastfeeding Mean You Should Not Get Smallpox Vaccine Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/preg-contra.asp

244 Smallpox

Smallpox Vaccination Information for Women Who Are Pregnant Breastfeeding Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/smallpox/vaccination/preg-factsheet.asp

or

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on smallpox. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

In the Old Days It Was Measles, TB and Smallpox, Now It's AIDS Contact: Feather of Hope Aboriginal AIDS Prevention Society, 10242 105th St Ste 702, Edmonton, (780) 488-5773. Summary: This brochure, written by native Aboriginal people in Canada, uses a question-and-answer format to discuss the danger AIDS poses to Aboriginal people. It describes ways HIV is transmitted, suggests methods of preventing HIV, and emphasizes the use of condoms. The brochure describes the Feather of Hope organization and explains its position on AIDS. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “smallpox” (or synonyms). The following was recently posted: •

(1) Smallpox as a biological weapon: medical and public health management. (2) Smallpox as a biological weapon. (Addendum) Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 1999 June 9 (addendum published 2002); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3612&nbr=2838&a mp;string=smallpox

•

Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program. Supplemental recommendations of the Advisory Committee on

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Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 26; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3623&nbr=2849&a mp;string=smallpox •

Smallpox vaccination and adverse reactions. Guidance for clinicians Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 January 24; 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3597&nbr=2823&a mp;string=smallpox

•

Smallpox vaccine Source: American Academy of Pediatrics - Medical Specialty Society; 2002 September; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3451&nbr=2677&a mp;string=smallpox

•

Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 April 4; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3727&nbr=2953&a mp;string=smallpox

•

Updated interim CDC guidance for use of smallpox vaccine, cidofovir, and vaccinia immune globulin (VIG) for prevention and treatment in the setting of an outbreak of monkeypox infections Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 June 12 (revised 2003 Jun 25); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3851&nbr=3066&a mp;string=smallpox

•

Vaccinia (smallpox) vaccine Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 June; 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2850&nbr=2076&a mp;string=smallpox

246 Smallpox

Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Bioterrorism: U.S. Food and Drug Administration Summary: This bioterrorism page from the FDA provides general information about anthrax, smallpox, botulism and other biological agents. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6375

•

Information About Anthrax and Bioterrorism: Morbidity and Mortality Weekly Report Summary: This document is a compilation of current and previous Morbidity and Mortality Weekly Reports covering anthrax, bioterrorism, and other biological agents such as smallpox. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6374

•

JAMA Consensus Statement: Smallpox As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of smallpox, its microbiology and virulence, clinical manifestations, epidemiology, diagnosis, prophylaxis, and treatment. Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6388

•

Smallpox Summary: This smallpox page from CDC has the latest smallpox vaccine recommendations, public health response plan, factsheets, and clinical information about smallpox. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6323

•

Smallpox Basics Summary: This is a brief factsheet about smallpox and the smallpox vaccine. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6971

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•

Smallpox Information from the U.S. Department of Health and Human Services Summary: This smallpox page presents basic information about smallpox and the smallpox vaccine and features information for specific audiences: kids, teens, parents, primary health care providers, public Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7076 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to smallpox. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on smallpox can be purchased from NORD for a nominal fee. Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

248 Smallpox

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to smallpox. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with smallpox. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about smallpox. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “smallpox” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “smallpox”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “smallpox” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “smallpox” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 253

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

254 Smallpox

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 255

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

256 Smallpox

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

257

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on smallpox: •

Basic Guidelines for Smallpox Smallpox Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001356.htm

•

Signs & Symptoms for Smallpox Backache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003108.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm

258 Smallpox

Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Skin rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm •

Diagnostics and Tests for Smallpox Platelet count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm White blood cell count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

259

SMALLPOX DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically

260 Smallpox

active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test

Dictionary 261

new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Anthrax Vaccines: Vaccines or candidate vaccines used to prevent anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the

262 Smallpox

pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH]

Dictionary 263

Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Warfare: Warfare involving the use of living organisms or their products as disease etiologic agents against people, animals, or plants. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomedical Technology: The application of technology to the solution of medical problems. [NIH]

Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH]

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Bispecific antibodies: Antibodies developed in the laboratory to recognize more than one protein on the surface of different cells. Examples include bispecific antibodies 2B1, 520C9xH22, mDX-H210, and MDX447. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Groups: The classification systems (or schemes) of the different antigens located on erythrocytes.The antigens are the phenotypic expression of the genetic differences characteristic of specific blood groups. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Brucellosis: Infection caused by bacteria of the genus Brucella mainly involving the reticuloendothelial system. This condition is characterized by fever, weakness, malaise, and weight loss. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be

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found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Capping: A 7-methyl guanosine cap attached to the 5'-end of eucaryotic mRNAs by a phosphodiester linkage. The cap is believed to increase the stability of the message, since most nucleases require a 5'-3'or 3'-5'bond in order to cleave the RNA. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]

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Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Chorioallantoic membrane: The membrane in hen's eggs that helps chicken embryos get enough oxygen and calcium for development. The calcium comes from the egg shell. [NIH]

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Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Civilization: The distinctly human attributes and attainments of a particular society. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The

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remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU]

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Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact Tracing: Identification of those persons (or animals) who have had such an association with an infected person, animal, or contaminated environment as to have had the opportunity to acquire the infection. Contact tracing is a generally accepted method for the control of sexually transmitted diseases. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH]

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Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin A: A 33-kD protein identical to adenovirus E1A-associated protein p60. Cyclin A regulates p33cdk2 and p34cdc2, and is necessary for progression through the S phase of the cell cycle. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure.

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The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a

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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Dracunculiasis: Infection with nematodes of the genus Dracunculus. One or more worms may be seen at a time, with the legs and feet being the most commonly infected areas. Symptoms include pruritus, nausea, vomiting, diarrhea, or asthmatic attacks. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Ectromelia: Gross hypo- or aplasia of one or more long bones of one or more limbs. The concept includes amelia, hemimelia, and phocomelia. [NIH] Ectromelia Virus: A species of orthopoxvirus infecting mice and causing a disease that involves internal organs and produces characteristic skin lesions. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is

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based on the results of a randomized control trial. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species

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designated "human enterovirus". [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelioma: A neoplasm of epithelial origin, ranging from benign (adenoma and papilloma) to malignant (carcinoma). [EU] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU]

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Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements.

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Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Antibody Technique: Test for tissue antigen using either a direct method by conjugation of antibody with fluorescent dye or an indirect method by formation of antigenantibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody. The tissue is then examined by fluorescence microscopy. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fowlpox: A poxvirus infection of poultry and other birds characterized by the formation of wart-like nodules on the skin and diphtheritic necrotic masses (cankers) in the upper digestive and respiratory tracts. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored

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in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and

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used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanine: One of the four DNA bases. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH]

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Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic Fever with Renal Syndrome: An acute febrile disease occurring predominately in Asia. It is characterized by fever, prostration, vomiting, hemorrhagic phenonema, shock, and renal failure. It is caused by any one of several closely related species of the genus Hantavirus. The most severe form is caused by Hantaan virus whose natural host is the rodent Apodemus agrarius. A milder form is caused by Seoul virus and related species and transmitted by the rodents Rattus rattus and R. norvegicus. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small

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intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]

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Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence)

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or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inosine Monophosphate: Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role

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in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that

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surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol,

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and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphotoxin: Soluble substance released by lymphocytes activated by antigens or T-cell mitogens, that is cytotoxic to other cells. It is involved in allergies and chronic inflammatory diseases. Lymphotoxin is antigenically distinct from tumor necrosis factor-alpha (tumor necrosis factor), though they both share a common receptor, biological activities, and significant amino acid sequences. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean

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islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammogram: An x-ray of the breast. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Methisazone: An antiviral agent effective against pox viruses. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

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arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monkeypox Virus: A species of orthopoxvirus causing an epidemic disease among captive primates. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where

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all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH]

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Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH]

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Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Occupational Health Nursing: The practice of nursing in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Orthopoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirninae, comprising many species infecting mammals. Viruses of this genus cause generalized

Dictionary 291

infections and a rash in some hosts. The type species is Vaccinia virus. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

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Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perianal: Located around the anus. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phocomelia: Congenital deformity that leaves the child without legs. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild

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rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poliomyelitis: An acute viral disease, occurring sporadically and in epidemics, and characterized clinically by fever, sore throat, headache, and vomiting, often with stiffness of the neck and back. In the minor illness these may be the only symptoms. The major illness, which may or may not be preceded by the minor illness, is characterized by involvement of the central nervous system, stiff neck, pleocytosis in the spinal fluid, and perhaps paralysis. There may be subsequent atrophy of groups of muscles, ending in contraction and permanent deformity. The major illness is called acute anterior p., infantile paralysis and Heine-Medin disease. The disease is now largely controlled by vaccines. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Postal Service: The functions and activities carried out by the U.S. Postal Service, foreign postal services, and private postal services such as Federal Express. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Poxviridae: A family of double-stranded DNA viruses infecting mammals (including humans), birds and insects. There are two subfamilies: Chordopoxvirinae, poxviruses of vertebrates, and Entomopoxvirinae, poxviruses of insects. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government

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agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary vaccination: First or principal vaccination ( = introduction of a vaccine into the body for the purpose of inducing immunity). [EU] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

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Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]

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Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Redux: Appetite suppressant. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic

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obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rinderpest: A viral disease of cloven-hoofed animals caused by Morbillivirus. It may be acute, subacute, or chronic with the major lesions characterized by inflammation and ulceration of the entire digestive tract. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and

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spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rural Health: The status of health in rural populations. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shame: An emotional attitude excited by realization of a shortcoming or impropriety. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

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one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Small-pox: A generalized virus infection with a vesicular rash. [NIH] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Change: Social process whereby the values, attitudes, or institutions of society, such as education, family, religion, and industry become modified. It includes both the natural process and action programs initiated by members of the community. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]

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Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH] Spirochete: Lyme disease. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Stabilization: The creation of a stable state. [EU] Sterile: Unable to produce children. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the

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nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Technology Transfer: Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH]

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Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH]

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Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH]

304 Smallpox

Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Variola Virus: A species of Orthopoxvirus causing infections in humans. No infections have been reported since 1977 and the virus is now believed to be virtually extinct. [NIH] Variolation: Inoculation with the virus of smallpox. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral Proteins: Proteins found in any species of virus. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a

Dictionary 305

protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virologist: A specialist of the study of viruses and viral disease. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Virus Shedding: The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (disease transmission, vertical). [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] War: Hostile conflict between organized groups of people. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH]

306 Smallpox

Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

307

INDEX A Acceptor, 26, 259, 291 Acquired Immunodeficiency Syndrome, 134, 141, 259 Adenoma, 259, 274 Adenovirus, 18, 159, 259, 270 Adjuvant, 7, 13, 25, 34, 37, 259 Adverse Effect, 31, 51, 259, 298 Aerosol, 5, 10, 25, 45, 47, 173, 259 Affinity, 4, 13, 15, 20, 26, 259 Agar, 259, 293 Agonist, 13, 259 Algorithms, 28, 49, 69, 259, 263 Alimentary, 259, 291 Alkaline, 259, 265 Alkylating Agents, 259, 303 Alleles, 29, 31, 260 Alternative medicine, 225, 260 Amino acid, 4, 40, 260, 261, 267, 275, 277, 285, 290, 292, 294, 297, 302, 303 Amino Acid Sequence, 260, 261, 275, 277, 285 Amplification, 9, 35, 206, 260 Amyloid, 24, 260 Anaesthesia, 260, 282 Anal, 260, 275 Analog, 52, 260 Analogous, 260, 272, 302 Anaphylatoxins, 260, 268 Anemia, 260, 278, 286 Anergy, 14, 260 Animal model, 8, 16, 24, 33, 37, 51, 260 Anions, 261, 283, 298, 300 Anthrax Vaccines, 47, 261 Antibacterial, 261, 271, 299 Antibiotic, 8, 261, 299 Anticoagulant, 261, 294 Antigen, 13, 14, 18, 23, 25, 33, 37, 39, 42, 43, 44, 47, 50, 55, 56, 102, 172, 259, 261, 262, 268, 270, 276, 279, 280, 281, 282, 296 Antigen-Antibody Complex, 261, 268, 276 Antigen-presenting cell, 261, 270 Antimetabolite, 261, 297 Antiserum, 261, 262 Antiviral, 6, 10, 14, 18, 19, 21, 25, 38, 39, 46, 50, 56, 59, 70, 122, 123, 151, 261, 283, 286, 297 Anxiety, 261, 291

Aplasia, 261, 272 Apoptosis, 11, 14, 41, 261 Applicability, 113, 262 Aqueous, 262, 263, 270, 273, 280, 284 Archaea, 262, 287 Arterial, 262, 294 Arteries, 262, 264, 269, 287, 288 Artery, 262, 264, 269, 288, 295, 297, 304 Articular, 121, 262 Artificial Organs, 262, 297 Assay, 11, 19, 21, 26, 35, 38, 48, 50, 54, 55, 57, 72, 262, 296, 303 Asymptomatic, 92, 262 Atopic, 40, 145, 262 Atrophy, 262, 293 Attenuation, 4, 17, 262 Atypical, 262, 282 Autoimmune disease, 9, 262, 288 Autoimmunity, 33, 127, 262 Autonomic, 262, 288 Avidity, 25, 262 B Bacillus, 8, 16, 18, 35, 36, 48, 261, 262, 303 Bacteria, 210, 261, 262, 263, 264, 269, 272, 273, 275, 287, 293, 298, 299, 302, 303 Bacteriophage, 263, 293, 305 Bacterium, 263, 269, 303 Base, 10, 263, 270, 276, 277, 282, 284, 301, 303 Benign, 259, 263, 274, 277, 278, 289, 291, 296, 297 Beta-pleated, 260, 263 Bile, 263, 276, 280, 285 Bilirubin, 158, 263 Bioavailability, 20, 263 Biochemical, 27, 30, 34, 41, 49, 54, 55, 57, 206, 260, 261, 263, 276, 284 Biogenesis, 27, 263 Biological response modifier, 263, 283 Biological Warfare, 35, 81, 118, 206, 210, 263 Biomarkers, 11, 12, 40, 263 Biomedical Technology, 48, 263 Biopsy, 263, 292 Biotechnology, 48, 59, 61, 63, 94, 214, 225, 235, 242, 263 Bioterrorism, 4, 6, 10, 14, 15, 18, 19, 22, 29, 30, 32, 35, 37, 38, 39, 42, 44, 45, 47, 48,

308 Smallpox

49, 53, 56, 60, 70, 71, 74, 75, 92, 118, 135, 141, 144, 149, 151, 169, 170, 176, 206, 210, 213, 217, 218, 240, 246, 263 Bispecific antibodies, 26, 264 Bladder, 264, 281, 294, 303 Blastocyst, 264, 268 Blister, 194, 195, 264 Blood Cell Count, 264, 278 Blood Coagulation, 264, 265, 301 Blood Groups, 67, 123, 129, 264 Blood pressure, 264, 287 Blood vessel, 264, 266, 273, 283, 285, 292, 300, 301, 304 Body Fluids, 263, 264, 303 Bone Marrow, 264, 277, 281, 285, 287 Bowel, 205, 260, 264, 271, 283 Bowel Movement, 264, 271 Brachytherapy, 264, 283, 295, 305 Branch, 255, 264, 278, 281, 285, 291, 295, 299, 301 Brucellosis, 48, 264 Buccal, 264, 285, 300 C Calcification, 77, 127, 264 Calcineurin, 9, 265 Calcium, 9, 264, 265, 266, 268, 287, 288, 299 Calmodulin, 265 Cancer vaccine, 149, 265 Capping, 38, 39, 265 Capsid, 265, 305 Capsular, 37, 265 Carbohydrate, 39, 265, 293 Carbon Dioxide, 265, 275, 297, 304 Carcinogenic, 260, 265, 282, 290, 294 Carcinoma, 73, 265, 274 Cardiac, 60, 76, 77, 174, 265, 288 Carrier Proteins, 265, 296 Case report, 77, 78, 117, 146, 265, 275 Cause of Death, 157, 265 Cell Death, 261, 266 Cell membrane, 23, 30, 265, 266, 275 Cell Size, 266, 276 Central Nervous System, 204, 265, 266, 277, 278, 293 Cerebral, 24, 266, 286, 301 Cerebral Cortex, 24, 266 Cerebrospinal, 111, 266 Cerebrospinal fluid, 111, 266 Cerebrum, 266, 301 Cervical, 266, 297 Character, 165, 266, 270

Chemokines, 13, 30, 43, 58, 266 Chemotactic Factors, 266, 268 Chemotherapeutic agent, 5, 266 Chickenpox, 78, 84, 91, 162, 266 Chin, 90, 134, 266, 286 Cholera, 9, 186, 192, 213, 266, 298, 304 Chorioallantoic membrane, 204, 266 Chromatin, 262, 267 Chromosomal, 70, 78, 260, 267, 293, 301 Chromosome, 54, 78, 267, 269, 284, 298, 301, 302 Chronic, 111, 130, 177, 205, 267, 271, 282, 284, 285, 297, 300, 301, 305 Chronic lymphocytic leukemia, 130, 267 Cidofovir, 5, 18, 57, 120, 171, 245, 267 CIS, 53, 267 Civilization, 35, 267 Cleave, 265, 267 Clinical Medicine, 72, 107, 267, 294 Clinical trial, 3, 6, 7, 18, 24, 35, 41, 193, 200, 235, 267, 272, 295, 296 Clone, 204, 267 Cloning, 57, 263, 267, 284 Coagulation, 104, 264, 267 Codon, 22, 267, 277 Cofactor, 267, 294, 301 Collagen, 260, 267 Colon, 267, 272, 284 Combinatorial, 14, 38, 268 Complement, 10, 21, 26, 31, 44, 52, 60, 82, 166, 205, 260, 268, 277, 285 Complement Activation, 44, 52, 205, 260, 268 Complementary and alternative medicine, 185, 190, 268 Complementary medicine, 185, 268 Complementation, 56, 268 Computational Biology, 48, 235, 268 Conception, 94, 268, 269, 275 Concomitant, 84, 205, 268 Condoms, 244, 269 Condyloma, 171, 216, 269 Conjugated, 269, 276 Conjugation, 269, 276 Conjunctiva, 111, 178, 269, 282 Connective Tissue, 264, 267, 269, 277, 285, 297, 301 Constriction, 269, 283 Consumption, 269, 271, 297 Contact Tracing, 77, 269 Contraception, 236, 269 Contraindications, ii, 62, 85, 86, 242, 269

Index 309

Coordination, 15, 269 Cornea, 269, 298, 306 Coronary, 269, 286, 288 Coronary Thrombosis, 269, 287, 288 Cowpox, 10, 19, 22, 29, 39, 50, 269, 270, 304 Cowpox Virus, 22, 50, 269, 270, 304 Critical Care, 137, 270 Crossing-over, 270, 296 Curative, 270, 301 Cutaneous, 39, 81, 86, 88, 107, 110, 132, 149, 196, 197, 261, 270, 283, 284, 285, 304 Cyclin, 33, 270 Cyclin A, 33, 270 Cytokine, 10, 28, 30, 44, 270 Cytoplasm, 54, 56, 262, 266, 270, 278, 287, 297 Cytosine, 101, 172, 270 Cytotoxic, 9, 28, 56, 125, 270, 285, 296, 299 Cytotoxicity, 11, 29, 270 D Data Collection, 270, 276 Defense Mechanisms, 28, 270 Degenerative, 270, 279 Dehydration, 266, 270 Deletion, 46, 262, 270 Dementia, 259, 270 Dendrites, 270, 271, 289 Dendritic, 13, 23, 43, 270, 286 Dendritic cell, 13, 43, 270 Density, 24, 270, 276, 285, 290 Dentate Gyrus, 270, 279 Dermal, 40, 271 Dermatitis, 40, 145, 271, 272 Developed Countries, 70, 271 Developing Countries, 187, 271, 301 Diagnostic procedure, 178, 203, 225, 271, 298 Diarrhea, 257, 271, 272 Digestion, 259, 263, 264, 271, 283, 285, 300, 304 Digestive system, 200, 271 Digestive tract, 271, 297 Dilatation, 271, 294 Dilution, 11, 38, 197, 198, 271 Diphtheria, 127, 128, 271 Diploid, 268, 271, 293 Direct, iii, 22, 25, 34, 40, 90, 227, 236, 267, 271, 276, 291, 296, 301 Discrete, 13, 271, 306 Disease Progression, 271, 304 Disease Transmission, 271, 305

Disease Transmission, Vertical, 271, 305 Disinfection, 100, 271 Dissociation, 259, 271 Double-blind, 101, 272 Dracunculiasis, 113, 272 Drug Design, 19, 272 Drug Interactions, 228, 229, 272 Drug Resistance, 51, 272 Drug Tolerance, 272 Dyes, 260, 272, 276 Dysentery, 9, 272 E Ectromelia, 8, 16, 19, 25, 30, 45, 46, 52, 272 Ectromelia Virus, 8, 16, 19, 45, 52, 272 Eczema, 17, 39, 50, 82, 114, 216, 272 Effector, 29, 40, 268, 272 Efficacy, 4, 7, 12, 13, 19, 20, 23, 24, 25, 26, 30, 31, 40, 42, 50, 51, 94, 196, 198, 272 Electrocoagulation, 267, 273 Emaciation, 259, 273 Embryo, 264, 273, 275, 282 Emulsion, 273, 275 Encephalitis, 17, 36, 48, 81, 95, 169, 210, 273 Encephalitis, Viral, 273 Encephalomyelitis, 146, 224, 273 Endemic, 51, 68, 96, 112, 118, 170, 178, 266, 273, 285 Endogenous, 272, 273, 294 Endothelial cell, 273, 279, 301 Endothelium, 205, 273 Endothelium, Lymphatic, 273 Endothelium, Vascular, 273 Endotoxin, 273, 303 Enterovirus, 84, 273 Entorhinal Cortex, 274, 279 Environmental Health, 234, 236, 274 Enzymatic, 48, 57, 260, 265, 268, 274 Enzyme, 14, 35, 38, 40, 272, 274, 275, 277, 284, 286, 288, 293, 294, 295, 299, 300, 301, 305, 306 Enzyme Inhibitors, 38, 274 Epidemic, 46, 61, 81, 90, 96, 140, 156, 162, 164, 167, 188, 192, 211, 212, 274, 287 Epidemiological, 70, 96, 160, 274, 275 Epidermal, 274, 286, 304 Epidermis, 264, 274, 295 Epithelial, 23, 216, 259, 274, 279, 291 Epithelioma, 74, 274 Epithelium, 269, 273, 274, 291, 306 Epitope, 6, 11, 12, 16, 31, 107, 274 Erythrocyte Indices, 264, 274

310 Smallpox

Erythrocytes, 26, 260, 264, 274 Esophagus, 271, 274, 292, 300 Ethanol, 274, 275 Ether, 18, 262, 274 Eukaryotic Cells, 56, 274, 290, 303 Excitation, 274, 276, 289 Exhaustion, 275, 286 Exocytosis, 9, 275 Exogenous, 272, 273, 275, 294 Exon, 13, 275 External-beam radiation, 275, 283, 295, 305 Extracellular, 26, 36, 44, 260, 269, 275 Eye Infections, 259, 275 F Facial, 125, 275 Family Planning, 235, 236, 275 Fatal Outcome, 275, 295 Febrile, 47, 275, 279, 286 Fermentation, 14, 275 Fetal Development, 55, 275 Fetus, 275 Filtration, 27, 275 Fixation, 31, 275 Fixatives, 127, 275 Flow Cytometry, 12, 58, 276 Fluorescence, 9, 34, 276 Fluorescent Antibody Technique, 99, 276 Fluorescent Dyes, 276 Focus Groups, 33, 276 Fold, 14, 16, 276 Follicles, 276 Folliculitis, 102, 276 Fovea, 275, 276 Fowlpox, 25, 276 Fractionation, 27, 276 Frameshift, 276, 303 Frameshift Mutation, 276, 303 Fungi, 269, 275, 276, 287, 300, 305 G Gallbladder, 271, 276 Ganglia, 277, 289 Ganglion, 277, 306 Gangrenous, 277, 298 Gene Expression, 28, 38, 40, 47, 51, 55, 56, 59, 277 Gene Therapy, 18, 49, 259, 277 Generator, 23, 277 Genetic Code, 277, 290 Genetic Engineering, 263, 267, 277 Genetic testing, 48, 277

Genetics, 14, 40, 53, 55, 70, 123, 269, 277, 281 Genital, 277, 305 Genomics, 15, 30, 47, 48, 59, 277 Genotype, 277, 292 Glucuronic Acid, 277, 279 Glycine, 260, 277, 289 Glycoprotein, 33, 278, 301, 303 Goats, 278, 290 Governing Board, 171, 278, 294 Grade, 18, 76, 278 Graft, 278, 280, 281, 288 Graft Rejection, 278, 281 Granule, 9, 271, 278, 297 Granulocytes, 278, 288, 299, 305 Guanine, 38, 278 H Habitual, 266, 278 Haematological, 105, 278 Haematology, 278 Hair follicles, 276, 278, 305 Half-Life, 29, 278 Haplotypes, 31, 278 Haptens, 259, 278, 296 Headache, 257, 278, 282, 293, 303 Hematocrit, 264, 274, 278 Heme, 263, 278 Hemoglobin, 260, 264, 274, 278, 279 Hemoglobinopathies, 277, 279 Hemorrhage, 119, 273, 278, 279, 288, 295, 300 Hemorrhagic Fever with Renal Syndrome, 12, 279 Heparin, 52, 279 Heparin-binding, 52, 279 Hepatitis, 34, 279, 282 Hepatocytes, 279 Hepatomegaly, 279, 282 Heredity, 277, 279 Herpes, 113, 115, 129, 171, 177, 216, 279 Herpes Zoster, 115, 216, 279 Heterogeneity, 259, 279 Hippocampus, 24, 270, 279, 300 Homologous, 10, 23, 46, 50, 52, 260, 270, 277, 279, 288, 298, 302 Hormonal, 262, 279, 292 Hormone, 279, 282, 297, 299 Human papillomavirus, 216, 280 Humoral, 17, 18, 24, 33, 39, 41, 42, 44, 45, 50, 81, 107, 159, 199, 278, 280 Humour, 280 Hybrid, 267, 280

Index 311

Hybridization, 35, 280 Hydrogen, 259, 263, 265, 280, 287, 289, 290, 291, 300 Hydrogen Peroxide, 280, 300 Hydrolysis, 34, 280, 295 Hydroxyproline, 260, 267, 280 Hyperplasia, 216, 280 Hyperreflexia, 280, 301 Hypersensitivity, 130, 280, 297 Hypertrophy, 280 Hypoxanthine, 280, 282 I Id, 182, 190, 244, 245, 247, 254, 256 Immune adjuvant, 13, 280 Immune function, 44, 280 Immune Sera, 155, 280, 281 Immune system, 9, 13, 41, 45, 261, 262, 280, 281, 285, 289, 292, 303, 305 Immunocompromised, 5, 20, 26, 38, 42, 44, 45, 281 Immunocompromised Host, 20, 44, 45, 281 Immunodeficiency, 4, 26, 41, 42, 134, 141, 236, 259, 281 Immunodeficiency syndrome, 236, 281 Immunofluorescence, 178, 281 Immunogen, 54, 281 Immunogenetics, 8, 17, 57, 281 Immunogenic, 25, 281, 296 Immunoglobulin, 26, 108, 155, 222, 261, 276, 281, 287, 298 Immunologic, 6, 31, 41, 51, 57, 173, 266, 281, 296 Immunology, 12, 14, 15, 23, 27, 28, 30, 33, 39, 41, 56, 57, 86, 130, 141, 145, 151, 164, 173, 259, 276, 281 Immunophilin, 265, 281 Immunosuppressive, 25, 41, 265, 281 Immunosuppressive therapy, 281 Immunotherapy, 7, 36, 281 Impairment, 275, 281, 286 Implant radiation, 281, 283, 295, 305 Implantation, 268, 281 In situ, 21, 281 In vitro, 6, 13, 14, 16, 19, 28, 36, 38, 49, 51, 54, 55, 56, 277, 281, 302 In vivo, 6, 13, 15, 20, 36, 42, 44, 46, 50, 51, 52, 277, 279, 281 Incontinence, 281, 288 Indicative, 210, 282, 291, 304 Induction, 33, 34, 125, 282 Infancy, 114, 282

Infarction, 282, 297 Infection Control, 67, 74, 128, 162, 219, 245, 282 Infectious Mononucleosis, 216, 282 Infiltration, 104, 282, 306 Influenza, 9, 47, 86, 210, 282 Infusion, 18, 282, 288 Ingestion, 261, 282 Inhalation, 259, 282 Initiation, 55, 282 Inoculum, 22, 282 Inosine Monophosphate, 39, 282 Insight, 34, 40, 46, 58, 282 Insulin, 282, 297 Interferon, 4, 28, 33, 49, 58, 125, 283 Interferon-alpha, 283 Internal radiation, 283, 295, 305 Interstitial, 264, 283, 296, 305 Intestinal, 273, 283, 305 Intestine, 264, 280, 283, 284 Intoxication, 15, 283 Intracellular, 9, 26, 27, 36, 282, 283, 299, 305 Intraepithelial, 171, 283 Intramuscular, 283, 291 Intravenous, 18, 282, 283, 291 Intrinsic, 259, 283 Invasive, 281, 283 Ions, 263, 265, 272, 280, 283 Irradiation, 46, 283, 305 Irritants, 272, 283 Ischemia, 205, 262, 283, 288, 297 J Joint, 143, 262, 283, 301 K Kb, 54, 234, 284 Kinetic, 38, 284 L Labile, 268, 284 Laceration, 284, 301 Large Intestine, 271, 283, 284, 296 Latency, 33, 284 Latent, 33, 111, 284 Lectin, 30, 284 Leishmaniasis, 53, 284 Lens, 265, 284 Leprosy, 85, 209, 284 Lethal, 7, 18, 23, 40, 43, 46, 284 Leukemia, 277, 284 Leukocytes, 264, 266, 278, 283, 284, 287, 303 Library Services, 254, 284

312 Smallpox

Life cycle, 20, 54, 59, 276, 284 Ligands, 11, 13, 30, 284 Ligase, 46, 284 Linkage, 265, 284 Lipid, 18, 283, 284 Lipoprotein, 284, 305 Liver, 263, 271, 273, 276, 277, 279, 285 Local Government, 36, 164, 285 Localized, 104, 271, 275, 282, 285, 288, 293, 301 Lupus, 9, 90, 285, 301 Lymph, 31, 88, 99, 266, 273, 280, 282, 285, 297 Lymph node, 266, 285, 297 Lymphadenopathy, 31, 282, 285 Lymphatic, 273, 282, 285, 297, 301 Lymphatic system, 285, 297, 301 Lymphocyte, 12, 28, 47, 56, 259, 261, 285 Lymphocyte Count, 259, 285 Lymphocytic, 285 Lymphoid, 261, 285 Lymphotoxin, 34, 285 Lytic, 9, 285, 298, 305 M Major Histocompatibility Complex, 56, 278, 285 Malaise, 199, 258, 264, 285 Malaria, 7, 23, 53, 210, 223, 285, 286 Malaria, Falciparum, 285, 286 Malaria, Vivax, 285, 286 Malignant, 115, 116, 125, 164, 259, 274, 286, 289, 296 Mammogram, 264, 286, 287 Mastitis, 286, 298 Measles Virus, 80, 286 Mediate, 29, 43, 286 MEDLINE, 235, 286 Melanocytes, 286 Melanoma, 110, 125, 133, 164, 286 Membrane, 9, 10, 27, 34, 204, 266, 268, 269, 274, 275, 286, 288, 289, 290, 297, 299, 302 Memory, 6, 11, 24, 28, 39, 41, 58, 270, 286 Meninges, 266, 286 Mental, iv, 3, 186, 201, 234, 237, 266, 270, 272, 286, 290, 295 Mental Disorders, 201, 286, 295 Mental Health, iv, 3, 201, 234, 237, 286, 290, 295 Mercury, 276, 286 Methisazone, 62, 101, 126, 173, 286 Methyltransferase, 38, 286 MI, 32, 87, 113, 117, 258, 286

Microbe, 287, 302 Microcalcifications, 264, 287 Microorganism, 6, 267, 287, 291, 305 Microscopy, 95, 100, 276, 287 Migration, 11, 13, 39, 287 Mitochondria, 287, 288, 290 Mitosis, 262, 287 Modeling, 32, 117, 272, 287 Modification, 236, 260, 277, 287 Molecular, 3, 14, 22, 28, 30, 35, 40, 43, 46, 49, 53, 54, 55, 57, 58, 59, 205, 235, 238, 263, 265, 268, 270, 272, 279, 287, 300, 302, 303 Monitor, 7, 287, 290 Monkeypox Virus, 36, 39, 199, 240, 287 Monoclonal, 8, 13, 16, 20, 24, 26, 29, 36, 41, 45, 283, 287, 295, 305 Monoclonal antibodies, 8, 13, 16, 20, 29, 36, 45, 287 Monocytes, 13, 284, 287, 288 Mononuclear, 282, 287, 303 Morbillivirus, 286, 287, 297 Morphogenesis, 27, 38, 54, 288 Morphology, 262, 278, 288 Mucocutaneous, 284, 288 Mucosa, 215, 216, 285, 288, 300 Mucus, 272, 288 Multivalent, 262, 288 Mutate, 40, 288 Myalgia, 282, 288 Myelitis, 67, 288 Myeloid Cells, 13, 288 Myocardial infarction, 205, 269, 286, 288 Myocardial Reperfusion, 288, 297 Myocardial Reperfusion Injury, 288, 297 Myocarditis, 117, 271, 288 Myocardium, 286, 288 Myosin, 265, 288 N Naive, 11, 19, 28, 31, 43, 57, 58, 102, 117, 196, 198, 289 Nasal Mucosa, 282, 289 Natural selection, 263, 289 Nausea, 272, 289 NCI, 1, 200, 233, 267, 289 Needs Assessment, 33, 289 Neonatal, 55, 118, 289 Neoplasia, 171, 289 Neoplasm, 274, 289, 291, 303 Nerve, 122, 266, 270, 277, 289, 298, 300, 306 Nervous System, 204, 266, 289, 295

Index 313

Networks, 28, 32, 36, 109, 289 Neural, 28, 260, 280, 289, 292 Neurologist, 149, 289 Neurons, 270, 271, 277, 289, 300 Neurotransmitter, 260, 278, 289, 299 Neutralization, 15, 25, 26, 40, 45, 52, 58, 86, 289 Neutrons, 283, 289, 295 Nitrogen, 275, 290 Nuclear, 269, 274, 277, 290 Nuclei, 47, 269, 277, 287, 289, 290, 297 Nucleic acid, 5, 206, 265, 270, 277, 280, 290, 297, 305 Nucleic Acid Hybridization, 280, 290 Nucleus, 56, 262, 267, 270, 274, 287, 289, 290, 300 O Occupational Health, 93, 124, 146, 290 Occupational Health Nursing, 124, 290 Ocular, 100, 119, 166, 290 Oncogenic, 33, 290 Opacity, 270, 290 Open Reading Frames, 30, 290 Ophthalmologist, 118, 290 Ophthalmology, 71, 118, 119, 122, 166, 275, 290 Opportunistic Infections, 259, 290 Orf, 10, 216, 290 Organ Culture, 290, 302 Organ Transplantation, 9, 290 Organelles, 27, 270, 286, 287, 290, 293 Oropharynx, 152, 290 Orthopoxvirus, 10, 19, 30, 39, 41, 123, 270, 272, 287, 290, 304 Ovum, 284, 291, 306 Oxidation, 259, 291 P Palate, 291, 300 Palliative, 291, 301 Pancreas, 263, 271, 282, 291, 303 Panic, 209, 291 Papilloma, 216, 269, 274, 291 Papillomavirus, 291 Paradoxical, 28, 291 Paralysis, 291, 293 Parasite, 291 Parasitic, 53, 272, 291, 302 Parasitic Diseases, 53, 291 Parenteral, 8, 16, 291 Pathogen, 5, 6, 8, 15, 22, 30, 35, 36, 37, 49, 56, 70, 206, 282, 291

Pathogenesis, 8, 10, 15, 16, 33, 36, 38, 40, 44, 45, 49, 52, 59, 122, 291 Pathologic, 262, 263, 269, 275, 280, 291 Pathologic Processes, 262, 291 Pathophysiology, 28, 291 Patient Education, 244, 252, 254, 258, 291 Penis, 269, 292 Peptide, 12, 24, 28, 260, 292, 294, 295 Percutaneous, 78, 79, 292 Perfusion, 292, 302 Perianal, 269, 292 Pericardium, 292, 301 Periodicity, 70, 292 Peripheral blood, 47, 58, 283, 292 Phagocyte, 11, 292 Phagocytosis, 11, 292 Phallic, 275, 292 Pharmacokinetic, 50, 292 Pharmacologic, 278, 292, 302 Pharyngitis, 216, 292 Pharynx, 111, 282, 290, 292 Phenotype, 29, 268, 292 Phocomelia, 272, 292 Phosphorus, 265, 292 Photocoagulation, 267, 292 Physical Examination, 194, 195, 292 Physiologic, 259, 275, 278, 292, 296 Plague, 16, 35, 71, 186, 210, 211, 214, 292, 303 Plants, 263, 265, 284, 288, 293, 300, 302 Plaque, 38, 86, 204, 293 Plasma, 9, 10, 26, 123, 261, 266, 273, 279, 293, 298, 302, 304 Plasma cells, 261, 293 Plasmid, 23, 38, 54, 293, 304 Plastids, 290, 293 Pneumonia, 269, 293 Poliomyelitis, 98, 293 Polymerase, 21, 40, 54, 55, 56, 293 Polymorphism, 29, 293 Polyneuritis, 271, 293 Polysaccharide, 261, 293 Postal Service, 18, 293 Potentiate, 34, 293 Poxviridae, 39, 56, 290, 293 Practice Guidelines, 237, 244, 293 Precipitation, 99, 103, 124, 294 Preclinical, 13, 15, 20, 51, 223, 294 Precursor, 109, 272, 274, 294 Prevalence, 58, 294 Primary vaccination, 7, 29, 99, 125, 134, 159, 294

314 Smallpox

Probe, 9, 34, 294 Progression, 107, 199, 260, 270, 294 Progressive, 15, 52, 270, 272, 278, 294, 296, 303 Projection, 270, 294 Promoter, 57, 294 Prophylaxis, 15, 25, 29, 36, 37, 51, 126, 246, 294, 303 Prospective study, 31, 64, 294 Prostate, 263, 294, 303 Protease, 40, 294 Protective Clothing, 206, 294 Protein Binding, 294, 302 Protein C, 34, 57, 260, 263, 267, 284, 294, 295, 304 Protein S, 38, 214, 263, 277, 294, 297 Proteolytic, 268, 295 Proteome, 49, 295 Protocol, 15, 18, 19, 25, 195, 295 Protozoa, 8, 180, 269, 272, 284, 287, 295, 300, 302 Protozoan, 285, 295 Pruritic, 272, 295 Pruritus, 272, 295 Psychiatry, 275, 295 Psychic, 286, 295 Public Policy, 235, 295 Pulmonary, 7, 47, 77, 127, 264, 269, 295, 304 Pulse, 22, 23, 287, 295 Purpura, 71, 171, 295 R Rabies, 24, 210, 295 Race, 287, 295 Radiation, 275, 276, 281, 283, 295, 296, 305 Radiation therapy, 275, 276, 283, 295, 305 Radioactive, 278, 280, 281, 283, 287, 290, 295, 296, 305 Radioimmunoassay, 89, 296 Radiolabeled, 283, 295, 296, 305 Radiological, 292, 296 Radiopharmaceutical, 277, 296 Radiotherapy, 264, 283, 295, 296, 305 Randomized, 273, 296 Reagent, 20, 54, 296 Receptor, 10, 13, 16, 26, 28, 33, 261, 285, 296, 299 Recombinant, 4, 7, 17, 37, 40, 42, 47, 51, 54, 199, 296, 304 Recombination, 59, 269, 277, 296 Rectum, 264, 268, 271, 282, 284, 294, 296 Recur, 292, 296

Recurrence, 292, 296 Redux, 140, 296 Refer, 1, 264, 268, 275, 276, 279, 289, 296, 302 Reference Values, 58, 296 Refraction, 296, 299 Regimen, 272, 296 Renal failure, 279, 296 Reperfusion, 205, 288, 296, 297 Reperfusion Injury, 205, 297 Research Design, 27, 51, 297 Respiration, 265, 287, 297 Retroviral vector, 277, 297 Reversion, 297, 303 Rheumatism, 297 Rheumatoid, 205, 297 Rheumatoid arthritis, 205, 297 Rhinitis, 297, 298 Ribavirin, 5, 297 Ribosome, 297, 302 Rinderpest, 4, 297 Risk factor, 26, 294, 297 Risk patient, 39, 297 Robotics, 50, 297 Rubella, 87, 216, 297 Rural Health, 32, 63, 298 Rural Population, 67, 72, 129, 298 S Salivary, 271, 298 Salivary glands, 271, 298 Sanitation, 9, 46, 298 Sclera, 269, 298 Screening, 10, 13, 19, 22, 27, 38, 50, 240, 242, 267, 298 Sebaceous, 283, 298, 305 Segregation, 296, 298 Sensory loss, 288, 298 Sepsis, 8, 16, 298 Septicaemia, 298 Seroconversion, 236, 298 Serologic, 74, 79, 99, 134, 298 Serologic Tests, 74, 298 Serotypes, 16, 298 Serous, 273, 298 Serum, 58, 64, 81, 104, 108, 158, 159, 163, 260, 261, 268, 280, 296, 298, 303 Serum Albumin, 296, 298 Sexually Transmitted Diseases, 269, 298 Shame, 109, 298 Shedding, 31, 51, 199, 298, 305 Shock, 279, 298

Index 315

Side effect, 23, 26, 35, 194, 195, 198, 204, 225, 227, 259, 298, 302 Signal Transduction, 265, 299 Skeleton, 283, 299 Skin test, 299, 303 Skull, 299, 301 Small-pox, 186, 299 Sneezing, 298, 299 Social Change, 107, 299 Solvent, 27, 274, 299 Somatic, 280, 287, 299 Specialist, 248, 299, 305 Specificity, 20, 29, 31, 38, 46, 48, 50, 55, 259, 299, 302 Spectrometer, 206, 299 Spectrum, 50, 236, 299 Sperm, 267, 300 Spinal cord, 266, 273, 277, 286, 288, 289, 300 Spinal Cord Vascular Diseases, 288, 300 Spirochete, 300, 301 Splenomegaly, 282, 300 Spores, 282, 300 Squamous, 216, 300 Stabilization, 34, 300 Sterile, 300, 303 Stimulus, 274, 284, 300 Stomach, 271, 274, 279, 289, 292, 300 Stomatitis, 216, 300 Strand, 59, 293, 300 Stress, 289, 297, 300 Stroke, 201, 234, 300 Subacute, 282, 297, 300 Subclinical, 84, 282, 300 Subcutaneous, 79, 108, 277, 291, 300 Subiculum, 279, 300 Subspecies, 299, 300, 304 Substrate, 274, 300 Suction, 275, 300 Superoxide, 41, 300 Superoxide Dismutase, 41, 300 Synapse, 9, 300 Synergistic, 12, 301 Syphilis, 74, 301 Systemic, 7, 35, 204, 205, 228, 264, 271, 282, 283, 295, 300, 301, 302, 304, 305 Systemic lupus erythematosus, 205, 301 T Technology Transfer, 36, 301 Telencephalon, 266, 301 Telomere, 38, 54, 301 Temporal, 162, 279, 301

Tenesmus, 272, 301 Terminator, 267, 301 Tetani, 301 Tetanic, 301 Tetanus, 122, 301 Therapeutics, 5, 7, 8, 13, 14, 15, 16, 24, 25, 36, 49, 123, 229, 301 Thrombin, 294, 301 Thrombomodulin, 294, 301 Thrombosis, 294, 300, 301 Thymus, 281, 285, 301 Tissue, 14, 18, 20, 30, 38, 50, 205, 261, 262, 263, 264, 266, 267, 269, 272, 273, 276, 277, 278, 280, 281, 282, 283, 284, 285, 286, 288, 289, 292, 296, 297, 298, 301, 302, 303 Tissue Culture, 14, 20, 30, 38, 302 Tissue Distribution, 18, 302 Toxic, iv, 52, 260, 269, 270, 271, 273, 281, 302 Toxicity, 7, 35, 272, 286, 302 Toxicology, 7, 19, 20, 236, 302 Toxin, 15, 35, 271, 273, 301, 302 Toxoid, 47, 302 Toxoplasma, 53, 302 Trachea, 292, 302 Transfection, 49, 263, 277, 302 Transfer Factor, 133, 281, 302 Translating, 48, 302 Translation, 12, 49, 50, 260, 302 Translational, 12, 36, 48, 51, 302 Translocate, 34, 302 Translocation, 34, 302 Transplantation, 205, 281, 285, 302 Triage, 32, 302 Tropism, 28, 302 Tubercle, 303 Tuberculin, 94, 127, 128, 303 Tuberculin Test, 94, 303 Tularemia, 8, 16, 35, 48, 71, 303 Tumor marker, 263, 303 Tumor Necrosis Factor, 34, 285, 303 Tumour, 111, 277, 303 Tunica, 288, 303 TYPHI, 9, 303 Typhimurium, 8, 303 Typhoid fever, 9, 303 U Ubiquitin, 46, 303 Ulceration, 290, 297, 303 Unconscious, 270, 303 Uracil, 54, 303

316 Smallpox

Urethra, 292, 294, 303 Urine, 111, 178, 194, 195, 264, 281, 303 V Vaccine adjuvant, 13, 303 Vacuoles, 290, 304 Varicella, 33, 216, 304 Variola, 4, 6, 8, 11, 14, 16, 17, 20, 21, 22, 23, 27, 28, 30, 35, 39, 40, 41, 42, 43, 45, 46, 49, 50, 51, 52, 56, 60, 61, 69, 71, 72, 104, 124, 127, 156, 169, 171, 177, 195, 196, 205, 210, 214, 215, 304 Variola Virus, 4, 14, 17, 21, 23, 27, 30, 35, 39, 43, 45, 49, 50, 51, 56, 72, 210, 304 Variolation, 64, 91, 109, 121, 168, 187, 189, 211, 304 Vascular, 273, 282, 300, 304 Vector, 8, 16, 18, 19, 49, 57, 59, 291, 304 Vein, 283, 290, 304 Venereal, 301, 304 Venous, 26, 264, 294, 304 Venous blood, 264, 304 Ventricle, 279, 295, 304 Verruca, 171, 216, 304 Vesicular, 216, 279, 299, 304 Veterinary Medicine, 235, 304 Vibrio, 9, 266, 304 Vibrio cholerae, 266, 304 Viral Load, 6, 28, 304 Viral Proteins, 11, 27, 33, 46, 52, 304 Viral vector, 18, 304

Virion, 38, 51, 304 Virologist, 5, 305 Virulence, 4, 8, 25, 28, 40, 46, 49, 51, 52, 124, 246, 302, 305 Virulent, 15, 25, 30, 206, 305 Virus Replication, 38, 45, 305 Virus Shedding, 11, 305 Visceral, 284, 305 Vitro, 16, 50, 279, 305 Vivo, 13, 16, 45, 305 Vulgaris, 216, 305 W War, 109, 138, 162, 179, 305 Wart, 179, 276, 305 White blood cell, 258, 261, 267, 282, 284, 285, 288, 293, 305 Windpipe, 292, 305 X Xenograft, 205, 261, 305 X-ray, 30, 276, 283, 286, 290, 295, 296, 305 X-ray therapy, 283, 305 Y Yeasts, 276, 292, 305 Yellow Fever, 69, 305 Z Zoonoses, 295, 306 Zoster, 113, 306 Zygote, 268, 269, 306 Zymogen, 294, 306

Index 317

318 Smallpox

Index 319

320 Smallpox

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