The 2002 Official Patient's Sourcebook on Lyme Disease

THE 2002 OFFICIAL PATIENT’S SOURCEBOOK

on

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 Ó2002 by ICON Group International, Inc. Copyright Ó2002 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: Tiffany LaRochelle 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 as a substitute for consultation with your physician. All matters regarding your health require medical supervision. 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, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking 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., 1960The 2002 Official Patient’s Sourcebook on Lyme Disease: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83169-6 1. Lyme Disease-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 or as a substitute for consultation with licensed medical professionals. 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, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. 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 sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of Lyme disease.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to Lyme disease. All of the Official Patient’s Sourcebooks 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 sourcebook. 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 LaRochelle 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 the Official Patient’s Sourcebook series published 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 the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to Lyme disease, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Acne

·

The Official Patient's Sourcebook on Acne Rosacea

·

The Official Patient's Sourcebook on Atopic Dermatitis

·

The Official Patient's Sourcebook on Behçet Syndrome

·

The Official Patient's Sourcebook on Epidermolysis Bullosa

·

The Official Patient's Sourcebook on Lichen Sclerosus

·

The Official Patient's Sourcebook on Psoriasis

·

The Official Patient's Sourcebook on Raynaud's Phenomenon

·

The Official Patient's Sourcebook on Scleroderma

·

The Official Patient's Sourcebook on Sjogren's Syndrome

·

The Official Patient's Sourcebook on Vitiligo

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

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON LYME DISEASE: GUIDELINES........... 9

Overview............................................................................................................... 9 What Is Lyme Disease?....................................................................................... 10 How Lyme Disease Became Known.................................................................... 11 Symptoms of Lyme Disease ................................................................................ 12 How Lyme Disease Is Diagnosed........................................................................ 13 How Lyme Disease Is Treated ............................................................................ 16 Lyme Disease Prevention ................................................................................... 17 More Guideline Sources ..................................................................................... 20 Vocabulary Builder............................................................................................. 27

CHAPTER 2. SEEKING GUIDANCE ....................................................... 31

Overview............................................................................................................. 31 Associations and Lyme Disease .......................................................................... 31 Finding More Associations................................................................................. 38 Finding Doctors.................................................................................................. 40 Finding a Dermatologist..................................................................................... 41 Selecting Your Doctor ........................................................................................ 42 Working with Your Doctor ................................................................................ 42 Broader Health-Related Resources ..................................................................... 44 Vocabulary Builder............................................................................................. 44

CHAPTER 3. CLINICAL TRIALS AND LYME DISEASE ........................... 47

Overview............................................................................................................. 47 Recent Trials on Lyme Disease........................................................................... 50 Benefits and Risks............................................................................................... 56 Keeping Current on Clinical Trials.................................................................... 59 General References.............................................................................................. 59 Vocabulary Builder............................................................................................. 60

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 63 CHAPTER 4. STUDIES ON LYME DISEASE ............................................ 65

Overview............................................................................................................. 65 The Combined Health Information Database ..................................................... 65 Federally-Funded Research on Lyme Disease..................................................... 75

viii Contents

E-Journals: PubMed Central .............................................................................. 84 The National Library of Medicine: PubMed ...................................................... 89 Vocabulary Builder............................................................................................. 90

CHAPTER 5. PATENTS ON LYME DISEASE ........................................... 95

Overview............................................................................................................. 95 Patents on Lyme Disease .................................................................................... 96 Patent Applications on Lyme Disease .............................................................. 113 Keeping Current ............................................................................................... 113 Vocabulary Builder........................................................................................... 113

CHAPTER 6. BOOKS ON LYME DISEASE............................................. 115

Overview........................................................................................................... 115 Book Summaries: Federal Agencies .................................................................. 115 Book Summaries: Online Booksellers ............................................................... 121 The National Library of Medicine Book Index ................................................. 125 Chapters on Lyme Disease................................................................................ 129 General Home References ................................................................................. 133 Vocabulary Builder........................................................................................... 134

CHAPTER 7. MULTIMEDIA ON LYME DISEASE .................................. 139

Overview........................................................................................................... 139 Video Recordings .............................................................................................. 139 Bibliography: Multimedia on Lyme Disease .................................................... 140 Vocabulary Builder........................................................................................... 143

CHAPTER 8. PERIODICALS AND NEWS ON LYME DISEASE ............... 145

Overview........................................................................................................... 145 News Services & Press Releases ....................................................................... 145 Newsletter Articles ........................................................................................... 156 Academic Periodicals covering Lyme Disease .................................................. 158 Vocabulary Builder........................................................................................... 159

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 161

Overview........................................................................................................... 161 NIH Guidelines................................................................................................. 161 NIH Databases.................................................................................................. 162 Other Commercial Databases ........................................................................... 168 The Genome Project and Lyme Disease............................................................ 168 Specialized References....................................................................................... 173 Vocabulary Builder........................................................................................... 174

CHAPTER 10. DISSERTATIONS ON LYME DISEASE ............................ 175

Overview........................................................................................................... 175 Dissertations on Lyme Disease......................................................................... 175 Keeping Current ............................................................................................... 176

PART III. APPENDICES .................................................. 179 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 181

Contents

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Overview........................................................................................................... 181 Your Medications: The Basics .......................................................................... 182 Learning More about Your Medications .......................................................... 183 Commercial Databases...................................................................................... 187 Contraindications and Interactions (Hidden Dangers) ................................... 188 A Final Warning .............................................................................................. 189 General References............................................................................................ 190 Vocabulary Builder........................................................................................... 191

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 193

Overview........................................................................................................... 193 What Is CAM? ................................................................................................. 193 What Are the Domains of Alternative Medicine?............................................ 194 Can Alternatives Affect My Treatment? ......................................................... 197 Finding CAM References on Lyme Disease ..................................................... 198 Additional Web Resources................................................................................ 203 General References............................................................................................ 206 Vocabulary Builder........................................................................................... 207

APPENDIX C. RESEARCHING NUTRITION ......................................... 209

Overview........................................................................................................... 209 Food and Nutrition: General Principles........................................................... 210 Finding Studies on Lyme Disease .................................................................... 214 Federal Resources on Nutrition........................................................................ 217 Additional Web Resources................................................................................ 218 Vocabulary Builder........................................................................................... 219

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 223

Overview........................................................................................................... 223 Preparation ....................................................................................................... 223 Finding a Local Medical Library ...................................................................... 224 Medical Libraries Open to the Public............................................................... 224

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 231

Overview........................................................................................................... 231 Your Rights as a Patient................................................................................... 231 Patient Responsibilities .................................................................................... 235 Choosing an Insurance Plan............................................................................. 236 Medicare and Medicaid .................................................................................... 238 NORD’s Medication Assistance Programs ..................................................... 241 Additional Resources ........................................................................................ 242

ONLINE GLOSSARIES.................................................... 243 Online Dictionary Directories.......................................................................... 252

LYME DISEASE GLOSSARY.......................................... 253 INDEX................................................................................... 271

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Contents

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, 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.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

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Lyme Disease

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Lyme Disease has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to Lyme disease, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on Lyme disease. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on Lyme disease should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching Lyme disease (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to Lyme disease. It also gives you sources of information that can help you find a doctor in your local area specializing in treating Lyme disease. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with Lyme disease. Part II moves on to advanced research dedicated to Lyme disease. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on Lyme disease. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “freeto-use” options. Part III provides appendices of useful background reading for all patients with Lyme disease or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with Lyme disease. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with Lyme disease.

Scope While this sourcebook covers Lyme disease, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that Lyme disease is often considered a synonym or a condition closely related to the following: ·

Acrodermatitis Chronica Atrophicans

·

Bannworth's Syndrome

·

Lyme Arthritis

4

Lyme Disease

·

Lyme Borreliosis

In addition to synonyms and related conditions, physicians may refer to Lyme disease using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for Lyme disease:4 ·

088.81 lyme disease

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to Lyme disease. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with Lyme disease will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with Lyme 4 This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

5

disease is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of Lyme disease, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

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PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on Lyme disease. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of Lyme disease to you or even given you a pamphlet or brochure describing Lyme disease. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

CHAPTER 1. GUIDELINES

9

THE ESSENTIALS ON LYME DISEASE:

Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on Lyme disease. 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. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on Lyme disease 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.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on Lyme disease. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Lyme Disease

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with Lyme disease and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc. ) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines at http://www.nih.gov/niams/healthinfo/

Among those listed above, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is especially noteworthy. The mission of NIAMS, a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS provides the following guideline concerning Lyme disease.6

What Is Lyme Disease?7 In the early 1970s, a mysterious clustering of arthritis cases occurred among children in Lyme, Connecticut, and surrounding towns. Medical researchers soon recognized the illness as a distinct disease, which they called Lyme disease. They subsequently described the clinical features of Lyme disease, established the usefulness of antibiotic therapy in its treatment, identified the deer tick as the key to its spread, and isolated the bacterium that caused it. 6This and other passages are adapted from the NIH and NIAMS (http://www.niams.nih.gov/hi/index.htm). “Adapted” signifies that the text is reproduced with attribution, with some or no editorial adjustments. 7 Adapted from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.niaid.nih.gov/publications/lyme/contents.htm.

Guidelines 11

Lyme disease is still mistaken for other ailments, and it continues to pose many other challenges: it can be difficult to diagnose because of the inadequacies of today's laboratory tests, and it can be troublesome to treat in its later phases. Development of a vaccine to prevent Lyme disease is underway.

How Lyme Disease Became Known Lyme disease was first recognized in 1975 after researchers investigated why unusually large numbers of children were being diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut, and two neighboring towns. The investigators discovered that most of the affected children lived near wooded areas that harbored ticks. They also found that the children's first symptoms typically started in the summer months coinciding with the height of the tick season. Several of the patients interviewed reported having a skin rash just before developing their arthritis, and many also recalled being bitten by a tick at the rash site. Further investigations resulted in the discovery that tiny deer ticks infected with a spiral-shaped bacterium or spirochete (which was later named Borrelia burgdorferi) were responsible for the outbreak of arthritis in Lyme.

Ticks that Most Commonly Transmit B. burgdorferi in the U.S. These ticks are all quite similar in appearance: ·

Ixodes scapularis -most common in the northeast and midwest. Also found in the south and southeast.

·

Ixodes pacificus -found on west coast.

In Europe, a skin rash similar to that of Lyme disease had been described in medical literature dating back to the turn of the century. Lyme disease may have spread from Europe to the United States in the early 1900s but only recently was recognized as a distinct illness. The ticks most commonly infected with B. burgdorferi usually feed and mate on deer during the adult part of their life cycle. The recent resurgence of the deer population in the northeast and the influx of suburban developments into rural areas where deer ticks are commonly found have probably contributed to the disease's rising prevalence.

12 Lyme Disease

The number of reported cases of Lyme disease, as well as the number of geographic areas in which it is found, has been increasing. Lyme disease has been reported in nearly all states in this country, although most cases are concentrated in the coastal northeast, mid-Atlantic states, Wisconsin and Minnesota, and northern California. Lyme disease is endemic in large areas of Asia and Europe.

Symptoms of Lyme Disease Erythema Migrans In most people, the first symptom of Lyme disease is a red rash known as erythema migrans (EM). The telltale rash starts as a small red spot at the site of the tick bite. The spot expands over a period of days or weeks, forming a circular or ovalshaped rash. Sometimes the rash resembles a bull's eye, appearing as a red ring surrounding a clear area with a red center. The rash, which can range in size from that of a dime to the entire width of a person's back, appears within a few weeks of a tick bite and usually occurs at the site of a bite. As infection spreads, rashes can appear at different sites on the body. Erythema migrans is often accompanied by symptoms such as fever, headache, stiff neck, body aches, and fatigue. Although these flu-like symptoms may resemble those of common viral infections, Lyme disease symptoms tend to persist or may occur intermittently.

Arthritis After several months of being infected by B. burgdorferi, slightly more than half of those people not treated with antibiotics develop recurrent attacks of painful and swollen joints that last a few days to a few months. The arthritis can shift from one joint to another; the knee is most commonly affected. About 10 to 20 percent of untreated patients will go on to develop chronic arthritis.

Neurological Symptoms Lyme disease can also affect the nervous system, causing symptoms such as stiff neck and severe headache (meningitis), temporary paralysis of facial muscles (Bell's palsy), numbness, pain or weakness in the limbs, or poor

Guidelines 13

motor coordination. More subtle changes such as memory loss, difficulty with concentration, and a change in mood or sleeping habits have also been associated with Lyme disease. Nervous system abnormalities usually develop several weeks, months, or even years following an untreated infection. These symptoms often last for weeks or months and may recur. Heart Problems Fewer than one out of ten Lyme disease patients develops heart problems, such as an irregular heartbeat, which can be signalled by dizziness or shortness of breath. These symptoms rarely last more than a few days or weeks. Such heart abnormalities generally surface several weeks after infection.

Other Symptoms Less commonly, Lyme disease can result in eye inflammation, hepatitis, and severe fatigue, although none of these problems is likely to appear without other Lyme disease symptoms being present.

How Lyme Disease Is Diagnosed Lyme disease may be difficult to diagnose because many of its symptoms mimic those of other disorders. In addition, the only distinctive hallmark unique to Lyme disease-the erythema migrans rash-is absent in at least onefourth of the people who become infected. The results of recent studies indicate that an infected tick must be attached to a person's skin for at least 2 days to transmit the Lyme bacteria. Although a tick bite is an important clue for diagnosis, many patients cannot recall having been bitten recently by a tick. This is not surprising because the tick is tiny, and a tick bite is usually painless. When a patient with possible Lyme disease symptoms does not develop the distinctive rash, a physician will rely on a detailed medical history and a careful physical examination for essential clues to diagnosis, with laboratory tests playing a supportive role.

14 Lyme Disease

Most Common Symptoms of Lyme Disease Early infection: ·

EM Rash (erythema migrans)

·

Muscle and joint aches

·

Headache

·

Fever

·

Fatigue

Early disseminated infection: ·

Multiple EM lesions

·

Facial paralysis (Bell's palsy)

·

Meningitis

·

Radiculitis (numbness, tingling, burning)

·

Brief episodes of joint pain and swelling

Late infection: ·

Arthritis, intermittent or chronic

·

Encephalopathy (mild to moderate confusion)

Less Common Symptoms of Lyme Disease ·

Heart abnormalities

·

Eye problems such as conjunctivitis

·

Chronic skin disorders

·

Encephalomyelitis (limb weakness, motor coordination)

Blood Tests Unfortunately, the Lyme disease microbe itself is difficult to isolate or culture from body tissues or fluids. Most physicians look for evidence of antibodies against B. burgdorferi in the blood to confirm the bacterium's role as the cause of a patient's symptoms. Antibodies are molecules or small substances tailor-made by the immune system to lock onto and destroy specific microbial invaders.

Guidelines 15

Some patients experiencing nervous system symptoms may also undergo a spinal tap. Using this procedure, doctors can detect brain and spinal cord inflammation and can look for antibodies or genetic material of B. burgdorferi in the spinal fluid. The inadequacies of the currently available diagnostic tests may prevent physicians from firmly establishing whether the Lyme disease bacterium is causing a patient's symptoms. In the first few weeks following infection, antibody tests are not reliable because a patient's immune system has not produced enough antibodies to be detected. Antibiotics given to a patient early during infection may also prevent antibodies from reaching detectable levels, even though the Lyme disease bacterium is the cause of the patient's symptoms. The antibody test used most often is called an ELISA test. When an ELISA is positive, it should be confirmed with a second, more specific test, called a Western blot. Physicians must rely on their clinical judgment in diagnosing someone with Lyme disease even though the patient does not have the distinctive erythema migrans rash. Such a diagnosis would be based on the time of year, history of a tick bite, the patient's symptoms, and a thorough ruling out of other diseases that might cause those symptoms. Doctors may consider such factors as an initial appearance of symptoms during the summer months when tick bites are most likely to occur, and outdoor exposure in an area where Lyme disease is common. New Tests Under Development To improve the accuracy of Lyme disease diagnosis, NIH-supported researchers are developing a number of new tests that promise to be more reliable than currently available procedures. NIH scientists are developing tests that use the highly sensitive genetic engineering technique, known as polymerase chain reaction (PCR), to detect extremely small quantities of the genetic material of the Lyme disease bacterium in body tissues and fluids. A bacterial protein, outer surface protein (Osp) C, is proving useful for the early detection of specific antibodies in people with Lyme disease.

16 Lyme Disease

How Lyme Disease Is Treated Nearly all Lyme disease patients can be effectively treated with an appropriate course of antibiotic therapy. In general, the sooner such therapy is begun following infection, the quicker and more complete the recovery. Antibiotics, such as doxycycline, cefuroxime axetil, or amoxicillin taken orally for a few weeks, can speed the healing of the erythema migrans rash and usually prevent subsequent symptoms such as arthritis or neurological problems. Doxycycline will also effectively treat most other tick-borne diseases. Patients younger than 9 years or pregnant or lactating women with Lyme disease are treated with amoxicillin, cefuroxime axetil, or penicillin because doxycycline can stain the permanent teeth developing in young children or unborn babies. Patients allergic to penicillin are given erythromycin. Lyme disease patients with neurological symptoms are usually treated with the antibiotic ceftriaxone given intravenously once a day for a month or less. Most patients experience full recovery. Lyme arthritis may be treated with oral antibiotics. Patients with severe arthritis may be treated with ceftriaxone or penicillin given intravenously. To ease these patients' discomfort and further their healing, the physician might also give anti-inflammatory drugs, draw fluid from affected joints, or surgically remove the inflamed lining of the joints. Lyme arthritis resolves in most patients within a few weeks or months following antibiotic therapy, although it can take years to disappear completely in some people. Some Lyme disease patients who are untreated for several years may be cured of their arthritis with the proper antibiotic regimen. If the disease has persisted long enough, however, it may irreversibly damage the structure of the joints. Physicians prefer to treat Lyme disease patients experiencing heart symptoms with antibiotics such as ceftriaxone or penicillin given intravenously for about 2 weeks. If these symptoms persist or are severe enough, patients may also be treated with corticosteroids or given a temporary internal cardiac pacemaker. People with Lyme disease rarely experience long-term heart damage. Following treatment for Lyme disease, some people still have muscle achiness, neurologic symptoms such as problems with memory and

Guidelines 17

concentration, and persistent fatigue. NIH-sponsored researchers are conducting studies to determine the cause of these symptoms and how to best treat them. Researchers are also currently conducting studies to assess the optimal duration of antibiotic therapy for the various manifestations of Lyme disease. Investigators are also testing newly developed antibiotics for their effectiveness in countering the Lyme disease bacterium. Unfortunately, a bout with Lyme disease is no guarantee that the illness will be prevented in the future. The disease can strike more than once in the same individual if he or she is reinfected with the Lyme disease bacterium.

Lyme Disease Prevention Avoid Ticks At present, the best way to avoid Lyme disease is to avoid deer ticks. Although generally only about one percent of all deer ticks are infected with the Lyme disease bacterium, in some areas more than half of them harbor the microbe. Most people with Lyme disease become infected during the summer, when immature ticks are most prevalent. Except in warm climates, few people are bitten by deer ticks during winter months. Deer ticks are most often found in wooded areas and nearby shady grasslands, and are especially common where the two areas merge. Because the adult ticks feed on deer, areas where deer are frequently seen are likely to harbor sizable numbers of deer ticks. To help prevent tick bites, people entering tick-infested areas should walk in the center of trails to avoid picking up ticks from overhanging grass and brush. To minimize skin exposure to ticks, people outdoors in tick-infested areas should wear long pants and long-sleeved shirts that fit tightly at the ankles and wrists. As a further safeguard, people should wear a hat, tuck pant legs into socks, and wear shoes that leave no part of the feet exposed. To make it easy to detect ticks, people should wear light-colored clothing.

18 Lyme Disease

To repel ticks, people can spray their clothing with the insecticide permethrin, which is commonly found in lawn and garden stores. Insect repellents that contain a chemical called DEET (N,N-diethyl-M-toluamide) can also be applied to clothing or directly onto skin. Although highly effective, these repellents can cause some serious side effects, particularly when high concentrations are used repeatedly on the skin. Infants and children may be especially at risk for adverse reactions to DEET. Pregnant women should be especially careful to avoid ticks in Lyme disease areas because the infection can be transferred to the unborn child. Although rare, such a prenatal infection may make the woman more likely to miscarry or deliver a stillborn baby.

Check for Ticks Once indoors, people should check themselves and their children for ticks, particularly in the hairy regions of the body. The immature deer ticks that are most likely to cause Lyme disease are only about the size of a poppy seed, so they are easily mistaken for a freckle or a speck of dirt. All clothing should be washed. Pets should be checked for ticks before entering the house, because they, too, can develop symptoms of Lyme disease. In addition, a pet can carry ticks into the house. These ticks could fall off without biting the animal and subsequently attach to and bite people inside the house. If a tick is discovered attached to the skin, it should be pulled out gently with tweezers, taking care not to squeeze the tick's body. An antiseptic should then be applied to the bite. Studies by NIH-supported researchers suggest that a tick must be attached for at least 48 hours to transmit the Lyme disease bacterium, so prompt tick removal could prevent the disease. The risk of developing Lyme disease from a tick bite is small, even in heavily infested areas, and most physicians prefer not to treat patients bitten by ticks with antibiotics unless they develop symptoms of Lyme disease.

Vaccine Development Because Lyme disease is difficult to diagnose and sometimes does not respond to treatment, researchers are trying to create a vaccine that will protect people from the disorder. Vaccines work in part by prompting the body to generate antibodies. These custom-shaped molecules lock onto

Guidelines 19

specific proteins made by a virus or bacterium-often those proteins lodged in the microbe's outer coat. Once antibodies attach to an invading microbe, other immune defenses are evoked to destroy it. Development of an effective vaccine for Lyme disease has been difficult for a number of reasons. Scientists need to find out how the immune system protects against the bacterium. However, a vaccine based on the outer surface protein A (OspA) of the Lyme bacterium has been tested in people living in the northeastern United States, and preliminary results are encouraging.

Tips for Personal Protection ·

Avoid tick-infested areas, especially in May, June, and July.8

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Wear light-colored clothing so that ticks can be easily spotted.

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Wear long-sleeved shirts and closed shoes and socks.

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Tuck pant legs into socks or boots and tuck shirt into pants.

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Apply insect repellent containing permethrin to pants, socks, and shoes, and compounds containing DEET on exposed skin. Do not overuse these products.

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Walk in the center of trails to avoid overgrown grass and brush.

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After being outdoors in a tick-infested area, remove, wash, and dry clothing.

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Inspect the body thoroughly and remove carefully any attached ticks.

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Check pets for ticks.

How to Remove a Tick ·

Tug gently but firmly with blunt tweezers near the “head” of the tick until it releases its hold on the skin.

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To lessen the chance of contact with the bacterium, try not to crush the tick's body or handle the tick with bare fingers.

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Swab the bite area thoroughly with an antiseptic to prevent bacterial infection.

Local health departments and park or agricultural extension services may have information on the seasonal and geographic distribution of ticks in your area. 8

20 Lyme Disease

Tick Eradication In the meantime, researchers are trying to develop an effective strategy for ridding areas of deer ticks. Studies show that spraying of pesticide in wooded areas in the spring and fall can substantially reduce for more than a year the number of adult deer ticks residing there. Spraying on a large scale, however, may not be economically feasible and may prompt environmental or health concerns. Scientists are also pursuing biological control of deer ticks by introducing tiny stingerless wasps, which feed on immature ticks, into tick-infested areas. Researchers are currently assessing the effectiveness of this technique. Successful control of deer ticks will probably depend on a combination of tactics. More studies are needed before wide-scale tick control strategies can be implemented.

Research - The Key to Progress Although Lyme disease poses many challenges, they are challenges the medical research community is well equipped to meet. New information on Lyme disease is accumulating at a rapid pace, thanks to the scientific research being conducted around the world.

More Guideline Sources The guideline above on Lyme disease is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to Lyme disease. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with Lyme disease. 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.

Guidelines 21

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html.

If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material 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 Lyme disease and related conditions. One of the advantages of CHID over other sources is that it 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: ·

Poster Guide to Lyme Disease Source: Hartford, CT: Lyme Disease Foundation. 1998. 8 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail: [email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This pamphlet provides people who have Lyme disease (LD) with information on this bacterial infection caused by a spirochete named Borrelia burgdorferi. The pamphlet presents the general signs and symptoms of LD, as well as those specific to the skin, brain, heart and

22 Lyme Disease

blood vessels, lungs, eyes, joints and muscles, liver, gastrointestinal system, and spleen. Other topics include the antibody and direct detection tests used to help diagnose LD, treatment, examples of LD rashes, and guidelines on reducing the risk of tick bites and removing a tick properly. The pamphlet concludes with information about the Lyme Disease Foundation. 10 figures. ·

Lyme Disease Source: Atlanta, GA: Arthritis Foundation. 1997. 10 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 30009-1616. (800) 207-8633. Fax (credit card orders only) (770) 4429742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call 800-283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This brochure for people with Lyme disease provides information on this bacterial infection that is transmitted by the bite of an infected tick. In the early stage, the disease may cause only mild flulike symptoms, but then a large, expanding red skin rash may develop around the bite. Joint or muscle pain can also follow. In later stages, Lyme disease can cause nervous system problems as well as arthritis, and immune system difficulties. It explains how early treatment with antibiotics can prevent more serious problems from developing. People can minimize exposure by wearing protective clothing, checking for ticks after being outdoors, keeping pets from roaming outside when ticks are active, and clearing brush and cutting long grass near the house. In addition, the brochure identifies sources of additional information. 3 figures.

·

Guide to Lyme Disease Source: Hartford, CT: Lyme Disease Foundation. 1997. 8 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail: [email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This pamphlet provides the general public with information about Lyme disease (LD), a bacterial infection caused by a spirochete called Borrelia burgdorferi. The spirochetes live in animals in nature. When certain ticks bite infected animals, they ingest the bacteria, then transmit the infection through subsequent feedings to other hosts, including humans and pets. The pamphlet explains how LD affects the brain, eyes, skin, heart and blood vessels, joints, liver, lungs, muscles,

Guidelines 23

gastrointestinal system, spleen, and fetus. It identifies antibody and direct detection tests that may be used to help diagnose LD and explains how it is treated. The pamphlet offers tips on removing a tick and reducing the chances of getting a tick bite. In addition, the pamphlet provides information on the Lyme Disease Foundation and lists many of the free services it offers. 6 figures. ·

Lyme Disease and Pets Source: Hartford, CT: Lyme Disease Foundation. 1997. 6 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail: [email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This pamphlet provides the general public with information about the occurrence of Lyme disease (LD) in pets. LD is an infectious, zoonotic disease transmitted by the bite of a blood-sucking arthropod, usually a tick. Ticks become infected with the LD spirochete, Borrelia burgdorferi, by feeding on infected host animals. The pamphlet explains the typical mode of transmission, highlights theoretical methods of transmission, and notes unlikely methods. The pamphlet outlines the symptoms of LD in cats, dogs, cattle, and horses and discusses the diagnosis, treatment, and prevention of LD in domestic animals.

·

Frequently Asked Questions About Lyme Disease Source: Hartford, CT: Lyme Disease Foundation. 1997. 6 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail: [email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This pamphlet uses a question and answer format to provide the general public with information about Lyme disease (LD). The pamphlet describes the features of the LD rash and discusses the possible transmission of LD to an unborn child during pregnancy. Various tests may be used to help diagnose LD, such as immune system-based tests (the lymphocyte stimulation assay, antibody tests, and the Western blot test) and direct detection-based tests (the antigen capture assay and the polymerase chain reaction test). The pamphlet provides reasons for falsenegative and false-positive antibody test results. Other topics include relapse, sexual transmission of LD, treatment methods, and reasons for early treatment.

24 Lyme Disease

·

Understanding Lyme Disease: Prevention and Treatment Source: San Bruno, CA: StayWell Company. 1997. 6 p. Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 94066-3030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This illustrated pamphlet provides the general public with information on the prevention and treatment of Lyme disease and the proper removal of a tick. Lyme disease is caused by bacteria that can be passed into the bloodstream through the bite of certain ticks. Common symptoms include a red, round rash; tiredness; sore or painful joints; headaches; and stiffness. Ways to prevent Lyme disease include avoiding areas infected with ticks, dressing with care, using insect repellent, staying on paved or cleared paths and trails, checking pets for ticks, and inspecting the body for ticks before going indoors. Diagnosis is based on a medical history, a physical examination, and, sometimes, a blood test. Antibiotics are used to treat the disease.

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 their site located at http://www.guideline.gov by using the keyword “Lyme disease” or synonyms. The following was recently posted: ·

Guidelines for laboratory evaluation in the diagnosis of Lyme disease. Source: American College of Physicians-American Society of Internal Medicine.; 1997 December 15; 5 pages (guideline); 14 pages (background paper) http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0272&sSearch_string=Lyme+disease

·

Practice guidelines for the treatment of Lyme disease. Source: Infectious Diseases Society of America.; 2000 July; 14 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1898&sSearch_string=Lyme+disease

Guidelines 25

·

Recommendations for the use of Lyme disease vaccine. Source: Centers for Disease Control and Prevention.; 1999 June; 30 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1204&sSearch_string=Lyme+disease

Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which 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: ·

Getting Lyme Disease To Take A Hike Summary: This document gives consumers advice on how to protect themselves from tick bites, which may result in lyme disease, during outdoor activity. Source: Office of Consumer Affairs, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2123

·

Lyme Disease Research Efforts of NIAID Summary: NIAID is committed to research on Lyme borreliosis or Lyme disease. Basic and clinical research efforts funded by the this Institute encompass many different aspects of this disease. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=231

·

Lyme Disease; The facts, The Challenge Summary: In the early 1970s, a mysterious clustering of arthritis occured among children in Lyme, Connecticut, and surrounding towns. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=131

26 Lyme Disease

·

New Vaccine Targets for Lyme Disease Summary: The Food and Drug Administration licensed the first vaccine to help prevent Lyme disease -- LYMErix. This FDA Consumer article discusses the drug LYMErix and its usage. Source: U.S. Food and Drug Administration, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4484

·

Spotlight on Lyme Disease Summary: This page provides information about this tick-borne disease for consumers and health care professionals. Includes consumer information fact sheet and brochure and case studies. Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2402

·

The Neurological Sequelae Of Lyme Disease Summary: A general overview of neurological sequelae of lyme disease that includes a description of the disorder, treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=3799

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. 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 Lyme disease. 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

Guidelines 27

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.

PEDBASE PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of conditions covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites that often link to government sites are available to the public. 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

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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Amoxicillin:

A broad-spectrum semisynthetic antibiotic similar to

28 Lyme Disease

ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Antibody: An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] 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 Tlymphocytes, 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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Borrelia: A genus of gram-negative, anaerobic, helical bacteria, various species of which produce relapsing fever in man and other animals. [NIH] Cardiac: Pertaining to the heart. [EU] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long halflife and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to betalactamase. It has been proposed for infections with gram-negative and grampositive organisms, gonorrhea, and haemophilus. [NIH] Chronic: Persisting over a long period of time. [EU] Confusion: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU]

Guidelines 29

Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] deet: A compound used as a topical insect repellent that may cause irritation to eyes and mucous membranes, but not to the skin. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [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] Encephalopathy: Any degenerative disease of the brain. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Erythema: A name applied to redness of the skin produced by congestion of the capillaries, which may result from a variety of causes, the etiology or a specific type of lesion often being indicated by a modifying term. [EU] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Hepatitis: Inflammation of the liver. [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] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU]

30 Lyme Disease

Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Rheumatoid: Resembling rheumatism. [EU] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Wasps: Any of numerous winged hymenopterous insects of social as well as solitary habits and having formidable stings. [NIH]

Seeking Guidance 31

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with Lyme disease. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with Lyme disease. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Lyme Disease As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9

32 Lyme Disease

influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

Lyme Disease Foundation Address: Lyme Disease Foundation 1 Financial Plaza 18th Floor, Hartford, CT 06103 Telephone: (860) 525-2000 Toll-free: (800) 886-5963 Fax: (860) 525-8425 Email: [email protected] Web Site: http://www.lyme.or Background: The Lyme Disease Foundation, Inc. (LDF) is a voluntary not-for-profit organization dedicated to finding the solutions to Lyme Disease and other tick-borne disorders. Established in 1988, the Lyme Disease Foundation funds research on Lyme Disease (LD), conducts international scientific conferences, and publishes a peer-reviewed scientific journal. It has successfully lobbied Congress for federal funds dedicated to Lyme Disease education and research. In addition, the Lyme Disease Foundation provides appropriate referrals, promotes patient advocacy, and supports the development of educational programs for affected individuals, family members, the medical and scientific communities, and the public. The Lyme Disease Foundation's many educational and support materials include a monthly self-help newsletter and a Lyme Disease Awareness Pack. A Lyme Disease Scientific Pack includes reprints of medical articles, scientific slide show information, and guidelines for establishing and conducting a self-help group. In addition, the Foundation distributes educational program materials for students, workplace and community education program materials, poster sets, brochures, and videotapes. Relevant area(s) of interest: Lyme Disease

Seeking Guidance 33

·

Lyme Disease Foundation (LDF) Address: e Disease Foundation (LDF). 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (203) 525-2000 or (800) 886-5963; FAX (203) 525-8435. Telephone: 02 221 2456 Toll-free: (800) 876-5963 Background: This resource sheet lists publications, media aids, T- shirts, pamphlets, and public awareness bulletins that focus on Lyme disease. Topics include community education planning; general information about Lyme disease including diagnosis, treatment, and prevention; and Lyme disease information for children. Information is also included about the donation categories of the Lyme Disease Foundation (LDF).

·

Lyme Disease Resource Center Address: Lyme Disease Resource Center P.O. Box 1423, Ukiah, CA 95482 Telephone: (707) 468-8460 Toll-free: (800) 886-5963 Email: [email protected] Web Site: http://www.lymedisease.or Background: The Lyme Disease Resource Center is a voluntary not-forprofit education and communication center dedicated to supporting people affected by Lyme Disease, the public, physicians, and any others interested in this disorder. Established in 1990, the Lyme Disease Resource Center educates the public about Lyme Disease, its risks, and preventive measures. It provides a forum for physicians and other health care professionals to exchange ideas and information concerning symptoms, diagnosis, and treatments for Lyme Disease and functions as a communication center for individuals and groups who assist people with Lyme Disease. The Center also has a network of Lyme Disease support groups; engages in patient advocacy; and provides referrals to medical professionals or support groups. The Resource Center offers a variety of educational and support materials through its directory, audio visual aids, brochures, Spanish language brochure, and regular newsletter. Relevant area(s) of interest: Lyme Disease

·

American Lyme Disease Foundation, Inc Address: American Lyme Disease Foundation, Inc. Mill Pond Offices, 293 Route 100, Somers, NY 10589 Telephone: (914) 277-6970 Toll-free: (800) 876-5963 Fax: (914) 277-6974 Email: [email protected]

34 Lyme Disease

Web Site: http://www.aldf.co Background: The American Lyme Disease Foundation, Inc. (ALDF) is a nonprofit organization that is dedicated to advancing treatment, research, prevention, and public awareness of Lyme disease and other tickborne illnesses. Lyme disease is an infectious tick-transmitted disorder characterized by an early skin lesion and, subsequently, a growing red area on the skin (i.e., 'bull's eye' rash). In some cases, later symptoms may include joint, neurological, and/or heart problems. Established in 1990, the Foundation's work focuses on public and professional education and support of research. ALDF publishes a semi- annual newsletter and several brochures, including 'A Homeowner's Guide to the Ecology and Environmental Management of Lyme Disease,' 'A Quick Guide to Lyme Disease,' and a 'National Clinical Conference on Lyme Disease' supplement to the American Journal of Medicine (April 1995). Other educational materials include reports, videos, and a selection of audiovisual aids. The Foundation also provides a toll-free informational number and a physician referral service. Relevant area(s) of interest: Lyme Arthritis, Lyme Borreliosis, Lyme Disease ·

Arthritis Foundation of Australia Address: Arthritis Foundation of Australia 33 Bligh Street, Suite 902A, Sydney, New South Wales, 2000, Australia Telephone: 02 221 2456 Toll-free: (800) 876-5963 Fax: 02 232 2538 Web Site: http://www.span.com.au/arthritis Background: The Arthritis Foundation of Australia is a not-for-profit organization that is committed to providing care, education, and research for people affected by arthritis and other musculoskeletal disorders. The term arthritis, meaning inflammation of the joints, may encompass several conditions or disease states, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and others. The Arthritis Foundation of Australia, which was founded in 1949, is dedicated to promoting research into the causes, control, and cure of arthritis; supporting the professional education and training of physicians and allied health professionals; and enhancing community awareness of the needs of those affected by arthritis. The Foundation's additional objectives include representing people with arthritis nationally and internationally, serving as national secretariat of affiliated state and territory foundations, and assisting affiliated foundations in promoting self-management programs for people with arthritis. The Arthritis

Seeking Guidance 35

Foundation of Australia currently consists of eight state and territory affiliates. These affiliated foundations offer a wide range of services to their members and represent their interests to their own state and territory governments. Each affiliated foundation may also provide the addresses of a wide network of branches and self-help groups in each state. Relevant area(s) of interest: Lyme Disease ·

Back Pain Association of America, Inc Address: Back Pain Association of America, Inc. P.O. Box 135, Pasadena, MD 21123-0135 Telephone: (410) 255-3633 Toll-free: (800) 886-5963 Fax: (410) 255- 7338 Email: [email protected] Background: The Back Pain Association of America, Inc. (BPAA) is a national nonprofit organization dedicated to providing information and support to people who are affected by back and neck pain, their family members, friends, and health care professionals. Established in 1991 and consisting of nearly 4,000 members, BPAA offers programs and information to help affected individuals learn more about their spinal disorders and ways to cope with them. The organization also has a program to help individuals prevent back injuries. BPAA publishes a self-titled quarterly newsletter that helps readers stay informed of updated information and new forms of treatment. The organization's 'Friends Across America' networking program enables affected individuals to exchange information and support via telephone. BPAA also has a physician referral service as well as an information service for physicians who treat back and neck pain. In addition, the Association also promotes research and offers a variety of fact sheets including 'The Relationship Between Nerve Damage and Leg Pain,' 'Urinary Problems and Diseases of the Spine,' 'Arachnoiditis, Questions and Answers,' and 'A Guide to Abdominal and Stretching Exercises.'. Relevant area(s) of interest: Lyme Disease

·

American Association of Equine Practitioners Address: 4075 Iron Works Parkway Lexington, KY 40511 Telephone: (606) 233-0147; (800) 433-0177 Fax: (606) 233-1968 Web Site: http://www.aaep.org

36 Lyme Disease

Background: The American Association of Equine Practitioners (AAEP) exists to improve the health and welfare of horses, to further the professional development of its members, and to provide resources and leadership for the benefit of the equine industry. Each year the AAEP awards grant money to selected veterinarians and researchers with an eye toward understanding and reducing injuries and illnesses. Educational efforts are directed toward informing and supporting horse owners, trainers, event organizers and veterinarians regarding preventive medicine. The organization seeks to assure responsible training and the humane treatment of horses. Regarding horses in competition, the AAEP advocates ethical and humane conditions and handling which includes proper housing, transportation and nutrition. Publication(s): Legal Status of Horses Debated; Congenital Cleft Palate in Horses; Deep Digital Flexor Tenotomy as a Treatment for Chronic Laminitis; Lyme Disease in Horses; Overo Lethal White Syndrome; Vesicular Stomatitis. Relevant area(s) of interest: Continuing education; Equine care; Equine welfare; Horses; Veterinary medicine ·

Ball State University Department of Physiology and Health Science Public Health Entomology Laboratory Address: 2000 University Avenue Muncie, IN 47306-0510 Telephone: (765) 285-1504; (765) 285-5961 Fax: (765) 285-1624 Email: [email protected] Web Site: http://www.bsu.edu/csh/phs/phel.html Background: Funded in part by the State of Indiana, the Public Health Entomology Laboratory conducts research and provides public service in the field of medical and public health entomology. Primary interests of the Laboratory currently center on ticks and tick-borne diseases. The Laboratory's collection includes 10,000 specimens of ticks, 2,400 specimens of mosquitoes, 1,700 specimens of domestic flies of Indiana, and other insects of medical importance. The Library staff answers inquiries; provides advisory and current-awareness services; makes referrals to other sources of information; lends specimens; and permits onsite use of collections. Services are provided free to private citizens of Indiana and at cost to others. Publication(s): Mosquitoes of Indiana (pamphlet); Ticks and Disease in Indiana (pamphlet); scientific papers.

Seeking Guidance 37

Relevant area(s) of interest: Canine heartworm disease; Ehrlichiosis; Entomology; Insect vectors; Lyme Disease; Mosquitoes; Public health; Rocky Mountain spotted fever; Ticks ·

College of Veterinary Medicine Cornell University Diagnostic Laboratory, Department of Population Medicine and Diagnostic Service Address: Ithaca, NY 14851-5786 PO Box 5786 Upper Tower Road Telephone: (607) 253-3900 Fax: (607) 253-3943 Background: The Diagnostic Laboratory, Department of Population Medicine and Diagnostic Service a diagnostic laboratory; established in 1926, is an integral unit of New York State College of Veterinary Medicine at Cornell University, a statutory college of State University of New York. Sources of support: New York State Department of Agriculture and Markets, U.S. government, foundations and industry. The staff includes research and supporting professionals and technicians that research animal health, virology, toxicology, analytical chemistry, serology, parasitology, bacteriology, epidemiology, endocrinology, and clinical pathology. The laboratory provides support and diagnostic services for the New York State Department of Agriculture and Markets, practicing veterinarians, and animal industries. It also provides various research, agricultural, companion animals, exotic wildlife laboratory animals, and health-care delivery programs; and it conducts training programs, and extension service and field programs. Research findings are published in journal articles, books and reports. Publication(s): research findings are published in journal articles, books and reports General Notes Maintains anaerobic laboratory, mycoplasma laboratory, Lyme disease laboratory, mycobacteriosis laboratory; contagious equine metritis unit; bovine Mastitis laboratory, an analytical toxicology laboratory; nutritional laboratory; and comparative coagulation laboratory and a field service unit. Relevant area(s) of interest: Animal health; Diagnostic laboratory; Endocrinology; Epidemiology; Parasitology; Serology; Toxicology; Veterinary medicine; Virology

·

Environmental Health Los Angeles County Department of Health Services Vector Management Program Address: 2525 Corporate Place, Room 150 Monterey Park, CA 91754 Telephone: (323) 881-4046

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Web Site: http://lapublichealth.org/eh/progs/consumer/vecman.htm Background: Rhe Vector Mangement Prograam consists of three units: Vector-Borne Disease Surveillance, Entomology and Vector Control. The historic objectives of the Vector-Borne Disease Surveillance Unit have always been the reduction of the risks of exposure to the pathogens of vector-borne disease through early detection and abatement of those factors which enhance the transmission of disease to humans. Routine surveillance of such diseases as sylvatic plague, murine typhus, Lyme borreliosis, the various hantaviruses and arenaviruses is conducted. The Entomology Unit performs the taxonomic duties which identify those arthropods responsible for transmission of the etiologic agents of disease and defines the biology, life history, and the complex transmission cycles which permit the transference of these diseases to the human population. Vector Control is responsible for rodent abatement activities and licensed animal keeper premises inspection and enforcement throughout Los Angeles County (except for the Mountain & Rural Program and District Environmental Services-Antelope Valley Districts). The unit continues to survey and manage the rodent populations within the Los Angeles metropolitan area as part of it's response to the historic Downtown Project. Relevant area(s) of interest: Disease vectors; Entomology; Pesticides; Vector control

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations. 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 Lyme disease. 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.

Seeking Guidance 39

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Lyme disease” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

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 “Lyme disease”. 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.” By making these selections and typing in “Lyme disease” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with Lyme disease. You should check back periodically with this database since it is updated every 3 months. 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 specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “Lyme disease” (or a synonym) in the search box. Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site:

40 Lyme Disease

http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·

Lyme Disease Network www.lymenet.org

·

NOAH www.noah-health.org/english/support.html

·

Lyme Alliance www.lymealliance.org

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with Lyme disease must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:11 ·

If you are in a managed care plan, check the plan's list of doctors first.

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

·

Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

·

Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

11

Check with the associations listed earlier in this chapter.

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 41

·

Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

·

The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 12 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.

·

You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Finding a Dermatologist To find a dermatologist in your area, you can use the “Find a Dermatologist” search engine provided by the American Academy of Dermatology. With a membership of 13,000, the American Academy of Dermatology represents virtually all practicing dermatologists in the United States and Canada. Type the following Web address into your browser to begin your search: http://www.aad.org/DermSearch/index.html. To search for dermatologists by U.S. state, enter your state into the search box and click “Search.” To search for dermatologists practicing outside the U.S., select “international members.” Enter your country and click the “Search” button.

While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified. 12

42 Lyme Disease

Selecting Your Doctor13 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about Lyme disease?

·

Really listen to my questions?

·

Answer in terms I understood?

·

Show respect for me?

·

Ask me questions?

·

Make me feel comfortable?

·

Address the health problem(s) I came with?

·

Ask me my preferences about different kinds of treatments for Lyme disease?

·

Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor14 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

13 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 14 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 43

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don't, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

·

After leaving the doctor's office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

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Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:15 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

·

Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

·

Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Anaerobic: 1. lacking molecular oxygen. 2. growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Ehrlichiosis: A tick-borne disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In humans the disease is caused by ehrlichia chaffeensis, in dogs it is caused by E. canis, and in horses, E. equi. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

15

Seeking Guidance 45

Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH]

Osteoarthritis: Noninflammatory degenerative joint disease occurring chiefly in older persons, characterized by degeneration of the articular cartilage, hypertrophy of bone at the margins, and changes in the synovial membrane. It is accompanied by pain and stiffness, particularly after prolonged activity. [EU] Pathogen: Any disease-producing microorganism. [EU] Plague: An acute infectious disease caused by yersinia pestis that affects humans, wild 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] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] 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] 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] Vesicular: 1. composed of or relating to small, saclike bodies. 2. pertaining to or made up of vesicles on the skin. [EU] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH]

Clinical Trials 47

CHAPTER 3. CLINICAL TRIALS AND LYME DISEASE Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning Lyme disease.

What Is a Clinical Trial?16 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for Lyme disease is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

16

48 Lyme Disease

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on Lyme disease.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for Lyme disease compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors' offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on Lyme disease carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on Lyme disease. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This

Clinical Trials 49

treatment, like a placebo, has no effect on Lyme disease and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how Lyme disease develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for Lyme disease. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial's investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo

50 Lyme Disease

surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Lyme Disease The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to Lyme disease.17 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Brain Imaging and Retreatment Study of Persistent Lyme Disease Condition(s): Lyme Disease; Lyme Neuroborreliosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to determine whether patients with persistent memory problems after Lyme disease benefit from an additional longer course of IV antibiotic therapy; to use modern brain imaging technology to determine whether the problem in the central nervous system is primarily one of poor blood flow or one of impaired nerve cell functioning; and to try to identify biological markers prior to treatment that will identify patients who are more or less likely to respond to the study treatment. Phase(s): Phase III Study Type: Interventional

17

These are listed at www.ClinicalTrials.gov.

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Contact(s): Kathy Corbera, M.D. (212) 543-6508 [email protected] Tani Viera (212) 543-6510 [email protected]; New York; Columbia Presbyterian Medical Center, New York, New York, 10032, United States; Recruiting; Tani Viera 212-543-6510 [email protected]; Brian Fallon, M.D., Principal Investigator. Study chairs or principal investigators: Brian Fallon, M.D., Principal Investigator; Columbia University, College of Physicians and Surgeons, Lyme Disease Research Program Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00037479 ·

Evaluation of Lyme Disease: Immunological Characteristics

Clinical,

Microbiological

and

Condition(s): Chronic Disease; Healthy; Lyme Arthritis; Lyme Disease; Multiple Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will determine whether patients who have been infected with the Lyme bacteria, Borrelia burgdorferi, and treated with antibiotics still have the bacteria alive inside them and whether it is causing their symptoms. The information from this study may serve as a basis for developing stringent diagnostic criteria for Lyme disease and the establishment of future treatment trials. Individuals in the following categories may be eligible for this study: chronic Lyme disease; chronic Lyme arthritis; seropositive control (are infected with the bacteria that causes Lyme disease but do not have disease symptoms); recovered control (have been sick with Lyme disease but were treated successfully and are currently well); control with multiple sclerosis (patients with multiple sclerosis); and healthy volunteers. Patients in the chronic Lyme disease category must be between 13 and 65 years of age; all others must be between 18 and 65 years of age. Candidates will be screened with blood and urine tests. Participants will have a physical examination and the following tests: Blood tests - Includes HLA-typing, a genetic test of immune system markers; Leukapheresis - Collection of large numbers of white blood cells Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through another needle in the other arm. (Alternatively, patients will 100 cc (about 7 tablespoons) of blood drawn.); Lumbar puncture (spinal tap) - Collection of cerebrospinal fluid (CSF, fluid that bathes the brain and spinal cord). A local anesthetic is administered and a needle is inserted in the space between the bones in the lower back where the

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cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle; Magnetic resonance imaging (MRI) of the brain - Imaging of the brain using a strong magnetic field and radio waves instead of X-rays. During the scan, the patient lies on a table in a narrow cylinder containing a magnetic field. He or she can speak with a staff member via an intercom at all times during the procedure; Neuropsychologic testing; Some participants may also have a hearing test and urine collection. Participants whose test results are positive for Borrelia burgdorferi will be followed at NIH at intervals of 3 to 6 months until it is determined whether there is infection. Those who are infected will be offered treatment with the antibiotic ceftriaxone. Following treatment, patients will return to the NIH Clinical Center for follow-up visits 1 week after treatment and again at 3, 6 and 12 months. The lumbar puncture, hearing examination, blood and urine tests will be repeated at these visits to evaluate the response to treatment, and the leukapheresis will be repeated for research purposes. Patients whose MRI was abnormal during therapy will have a repeat MRI at the 3-month, 6-month and 1-year visits. All participants with chronic Lyme disease, chronic Lyme arthritis, seropositive controls and recovered controls may be reevaluated at intervals of 6 to 12 months. Study Type: Observational Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00001539 ·

Evaluation, Treatment, and Follow-up of Patients with Lyme Disease Condition(s): Lyme Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study is designed to establish a population of patients with Lyme disease for evaluation, treatment and follow-up to learn more about the infection. Patients with active Lyme disease may be eligible for this study. Participants will have a medical history and physical examination and diagnostic evaluations as appropriate to their individual condition. Laboratory tests may include routing blood and urine tests, X-rays, or other imaging studies, body fluid or tissue cultures, skin biopsy and tests for allergic or immune responses. Treatment will include only medications approved by the Food and Drug Administration, given according to accepted dose schedules and ways of

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taking the medicines. All diagnostic tests and treatments will be according to standard medical practice for the disease. No experimental procedures will be offered under this protocol. Patients will be followed as needed for evaluation and treatment of their condition. In general, they will be asked to return at the end of therapy, then 3, 6 and 12 months later, and then every 6 to 12 months. More frequent visits may be required or less frequent visits may be allowed, depending on the individual's condition. Participants may be asked to undergo the following additional procedures for research purposes: - Extra blood draws to study Lyme disease and other inflammatory conditions. Blood will be drawn from arm veins. The total amount drawn during any 6week period will not exceed 450 cc (30 tablespoons) for adults and 7 cc (1/2 tablespoon) per kilogram (2.2 pounds) of body weight for children under 18 years of age. - Leukapheresis to collect large numbers of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body through the same needle. Only adults 18 years of age and older will be asked to undergo leukapheresis. Study Type: Observational Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00028080 ·

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients with Seronegative Chronic Lyme Disease Condition(s): Lyme Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in an acute and chronic form. The purpose of this study is to determine the safety and effectiveness, in seronegative patients, of intensive antibiotic treatment in eliminating symptoms of Chronic Lyme Disease (CLD). Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in a chronic form and be the result of: 1) persistent infection by B. burgdorferi; 2) damage caused by the original infectious process; or 3)

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the presence of co-infection with another organism transmitted by Ixodes ticks. Phase(s): Phase III Study Type: Observational Contact(s): Massachusetts; Mark Klempner, Boston, Massachusetts, 02111, United States Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00000938 ·

Lyme Disease Prevention Program Condition(s): Lyme Disease; Tick-Borne Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Centers for Disease Control and Prevention Purpose - Excerpt: This is a large study of an educational program on Lyme disease prevention for passengers on ferry boats going to Nantucket Island during the period from Memorial Day until Labor Day. Some boats provide passengers with the experimental program and the other boats provide a "control" program that the researchers can compare to the experimental program. The experimental program uses live performances by entertainers to teach people about Lyme disease prevention, and also uses additional printed materials. People on the control boats receive education on injury prevention and road safety while bicycling, rollerblading, and using mopeds. The main result we will look for is Lyme disease identified by a followup survey and confirmed by reviewing medical records. We will also ask some people to take part in a smaller study of behavior change. In this study, we will ask people to complete forms on self-efficacy (a person's belief in his or her ability to reach a certain goal), their plans to take preventive steps, and actual prevention behaviors. We also ask participants who report doctor visits or illness to provide confirmation of their use of health services. Phase(s): Phase III Study Type: Interventional Contact(s): Charlotte Phillips, M.P.H. 617-732-5083 [email protected]; Massachusetts; Steamship Authority ferry boats to Nantucket Island, Hyannis, Massachusetts, 02601, United States. Study chairs or principal investigators: Matthew H. Liang, M.D., M.P.H., Principal Investigator; Brigham & Women's Hospital Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00000432

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·

Study and Treatment of Post Lyme Disease (STOP-LD) Condition(s): Lyme Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see how well antibiotics work in reducing chronic fatigue symptoms, such as tiredness, in patients that were treated for Lyme Disease. Fatigue is a common symptom of Lyme Disease. When fatigue does not improve after treatment, patients are considered to have Post Lyme Syndrome (PLS). The chronic fatigue seen in these patients appears to be related to the initial infection which causes Lyme Disease. It is believed, but not proven, that treatment with antibiotics may be effective in relieving chronic fatigue in PLS patients. Phase(s): Phase III Study Type: Observational Contact(s): New York; Lauren Krupp, Stony Brook, New York, 117948121, United States Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00000937

·

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of the Safety and Efficacy of Ceftriaxone and Doxycycline in the Treatment of Patients with Seropositive Chronic Lyme Disease Condition(s): Lyme Disease Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Lyme disease is the most common tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. It may exist in a chronic form and be the result of: 1) active infection by B. burgdorferi; 2) damage caused by the original infectious process; or 3) the presence of co-infection with another organism transmitted by Ixodes ticks. The purpose of this study is to determine the safety and effectiveness, for seropositive patients, of intensive antibiotic treatment in eliminating symptoms of Chronic Lyme Disease (CLD). Phase(s): Phase III Study Type: Observational Contact(s): Massachusetts; Mark Klempner, Boston, Massachusetts, 02111, United States Web Site: http://clinicaltrials.gov/ct/gui/c/w2r/show/NCT00001101

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Benefits and Risks18 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for Lyme disease. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

·

If the treatment is effective, then it may improve health or prevent diseases or disorders.

·

Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with Lyme disease. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial's risks and benefits, the researcher’s expectations of you, and your rights as a patient.

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 18

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receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

·

Know how the researchers plan to carry out the study, for how long, and where.

·

Know what is expected of you.

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Know any costs involved for you or your insurance provider.

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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

·

Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

·

Receive any new information about the new treatment.

·

Continue to ask questions and get answers.

58 Lyme Disease

·

Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for Lyme disease? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

·

What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

·

How long will the treatment last? How often will I have to come back for follow-up exams?

·

What are the treatment's possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

·

Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

·

How will my health be monitored?

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Where will I need to go for the clinical trial? How will I get there?

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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

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·

Will I be able to see my own doctor? Who will be in charge of my care?

·

Will taking part in the study affect my daily life? Do I have time to participate?

·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with 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 their Web site (www.clinicaltrials.gov) and search by “Lyme disease” (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/

·

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library.

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These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

·

A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

·

The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

·

The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

·

Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

·

Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU]

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Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Physiologic: Normal; not pathologic; characteristic of or conforming to the normal functioning or state of the body or a tissue or organ; physiological. [EU]

Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on Lyme disease. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on Lyme disease. In Part II, as in Part I, our objective is not to interpret the latest advances on Lyme disease or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with Lyme disease is suggested.

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CHAPTER 4. STUDIES ON LYME DISEASE Overview Every year, academic studies are published on Lyme disease or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on Lyme disease. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on Lyme disease and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Lyme disease, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in 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

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format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “Lyme disease” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Arthritis 101: Lyme Disease Source: Arthritis Today. 14(2): 34-35. March-April 2000. Summary: This journal article provides the general public and people who have arthritis with information on Lyme disease. This tick borne disease causes symptoms that can mimic those of mononucleosis, meningitis, multiple sclerosis, rheumatoid arthritis, and other diseases. The early localized stage of Lyme disease occurs 7 to 10 days after infection and is characterized by an expanding red rash and viral type symptoms. The early disseminated stage occurs after several weeks or months of infection. Additional symptoms, including nervous system problems, may appear. The late stage of the disease can occur from months to years after the initial infection. In this stage, arthritis pain and swelling may occur in a few large joints. Lyme disease is usually diagnosed from the signs and symptoms in the earlier stages. A blood test may help confirm the diagnosis. Treatment involves taking antibiotics. Although two vaccines have been developed, people should still take precautions such as clearing brush from a yard, wearing long sleeved shirts and long pants tucked into socks when walking through woods or high grasses, checking exposed skin regularly, and removing a tick gently. 2 figures.

·

Taking a Bite Out of Lyme Disease: Preventive Vaccine Is Now Available Source: Consultant. 39(2): 527-529. February 1999. Summary: This journal article provides health professionals with information on a vaccine for Lyme disease, the most common tick borne illness in the United States. Lyme disease is endemic to the Northeast, upper Midwest, and Pacific coastal States. It is a multisystem, multistage disorder typically presenting as a red papule that expands to an enlarging patch of erythema migrans. Flu like symptoms often accompany the rash. If the disease is left untreated neurologic and myocardial abnormalities may develop within weeks or months of infection. Arthritis occurs in approximately half of those with untreated

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Lyme disease. The first vaccine, LYMErix, was recently approved for marketing by the Food and Drug Administration. The vaccine is formulated from a lipoprotein, OspA, that stimulates the production of antibodies against Borrelia burgdorferi in vaccinated patients. A 20 month randomized, multicenter, placebo controlled trial of the vaccine indicated a 78 percent efficacy rate against definite Lyme disease and a 100 percent effectiveness rate against asymptomatic infection. The article provides information on dosage and reactions, identifies candidates for vaccination, and outlines precautions people should take to prevent tick bites. 1 figure, 1 table, and 5 references. ·

New Vaccine Targets Lyme Disease: New Hope for Diminishing the 'Great Masquerader' Source: FDA Consumer. 33(3): 12-17. May-June 1999. Summary: This journal article provides the general public with information on a vaccine for Lyme disease, a bacterial infection transmitted by tick bites. In December 1998, the Food and Drug Administration licensed the first vaccine, known as LYMErix, to help prevent Lyme disease. The vaccine stimulates the human immune system to produce antibodies against Borrelia burgdorferi, but unlike the process with typical vaccines that fight bacteria in a person's body, the antibodies from a vaccinated person enter the tick and kill the bacteria there. The vaccine is not 100 percent effective, so people still need to take preventive measures against infection. The article explains how ticks become infected with the Lyme disease bacteria and how the disease is transmited to humans. Symptoms, including a skin rash called erythema migrans and flu-like symptoms, are identified. The article also discusses the diagnosis of Lyme disease using an enzyme-linked immunosorbent assay technique and the PreVue B. burgdorferi Antibody Detection Assay, treatment with antibiotics, and prevention. In addition, the article provides guidelines on removing and disposing of ticks and protecting household pets from Lyme disease. 5 figures.

·

Questions and Answers About the Lyme Disease Vaccine Source: Patient Care. 33(11): 209. June 15, 1999. Summary: This patient information sheet uses a question and answer format to provide the public with information about the Lyme disease vaccine, which has been approved only for people over 15 years old. The vaccine is suggested for those who are at high or moderate risk of getting Lyme disease. Factors placing people at high risk include living in a county where Lyme disease is common, having deer on residential property, and working or spending leisure time outdoors on a frequent

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or prolonged basis where Lyme disease is common. The vaccine should be given in three doses. The first dose should be followed by a second one a month later. The third dose should be administered 12 months after the second one. The vaccine is very effective, but it may not protect everyone. Therefore, people who receive the vaccine should still take precautions to protect themselves against tick bites. ·

Musculoskeletal and Neurologic Outcomes in Patients With Previously Treated Lyme Disease Source: Annals of Internal Medicine. 131(12): 919-926. December 21, 1999. Summary: This journal article provides health professionals with information on a population based, retrospective cohort study that determined clinical and functional outcomes in persons who were treated for Lyme disease in the late 1980s. The study population consisted of 186 Nantucket Island, MA, residents who had a history of Lyme disease and 167 residents who did not. Measurements included a standardized medical history, a physical examination, a functional status measure, a mood state assessment, neurocognitive tests, and a serologic examination. The study found that the prevalence of Lyme disease among adults on Nantucket Island was estimated to be 14.3 percent. In multivariate analyses, persons with previous Lyme disease had more joint pain, more symptoms of memory impairment, and poorer functional status due to pain than persons without previous Lyme disease. However, on physical examination, case patients and controls did not differ in musculoskeletal abnormalities, neurologic abnormalities, or neurocognitive performance. Persons with previous Lyme disease who had persistent symptoms after receiving treatment were more likely than those who had completely recovered to have had fever, headache, photosensitivity, or neck stiffness during their acute illness; however, the performance of the two groups on neurocognitive tests did not significantly differ. The article concludes that, although musculoskeletal and neurocognitive outcomes seem to be favorable among persons with previous Lyme disease, long term impairment of functional status can occur. 1 figure, 5 tables, and 39 references. (AA-M).

·

Lyme Disease Update: Current Approach to Early, Disseminated, and Late Disease Source: Postgraduate Medicine. 103(5): 51-54,57-59,63-64,70. May 1998. Summary: This journal article provides health professionals with information on the clinical manifestations, and diagnosis of Lyme disease, as well as its treatment. This disease, which is a tick-borne multisystem infectious syndrome, is the most frequently reported vector-

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borne illness in the United States. The causative organism, Borrelia burgdorferi, is a flagellated spirochete transmitted from small-mammal reservoirs to humans through bites from infected ixodid ticks. The symptoms of Lyme disease are categorized according to organ system involvement and duration of infection. The hallmark of early localized Lyme disease is an expanding erythematous patch or ring appearing within 30 days after the infected tick inoculates the skin with the spirochete. A minority of patients with the erythematous patch also report various systemic symptoms. Supportive laboratory data can help confirm the diagnosis. Serologic testing is the only routinely available laboratory diagnostic aid for Lyme disease. After a period of localized skin infection at the site of the tick bite, infection may spread hematogenously to various target organs. Disseminated Lyme disease occurs 1 to 4 months after an infected tick bite. Features may include cutaneous, rheumatic, neurologic, and cardiac manifestations. Serologic testing should be used only in patients who are considered to be at risk epidemiologically and have clinical features truly suggestive of disseminated Lyme disease. Late Lyme disease is used for manifestations occurring more than 4 months after disease onset. Features include persistent skin inflammation, encephalopathy, and chronic inflammatory arthritis. All stages of Lyme disease are treated with an antibiotic regimen. Antibiotic therapy should be tailored to the extent of the disease and should be limited to 4 weeks. The article includes a discussion of issues in disease management. 3 figures, 2 tables, and 29 references. ·

Guidelines for Serologic Testing of Lyme Disease Source: Journal of Musculoskeletal Medicine. 15(8): 19-25. August 1998. Summary: This journal article provides health professionals with information on laboratory tests available to help the clinician confirm the diagnosis of Lyme disease. A variety of laboratory tests detect specific antibodies to the spirochete Borrelia burgdorferi. Incorrect use of serologic tests for Lyme disease often results in overdiagnosis and overtreatment. Serologic testing is indicated only when the patient demonstrates clinical findings suggestive of Lyme disease, and it is most likely to be useful when done at 6 weeks after the tick bite. It is not indicated when the patient has erythema migrans or nonspecific symptoms. Determining the pretest probability of Lyme disease requires consideration of various factors, including geography, time of year, and previous tick bite. The most accurate and widely available and used are the enzyme-linked immunosorbent assay (ELISA) and the immunoblot (Western blot) analysis. The ELISA test can measure immunoglobulin (Ig) G or IgM antibodies either individually or combined. Several weeks after

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infection, specificity increases but sensitivity declines. There are currently no standard criteria for a positive test result. The Western blot is more sensitive than ELISA for detecting the presence of antibodies, but may be less sensitive for establishing the diagnosis and is used to corroborate positive or equivocal ELISA results. A positive result on the Western blot confirms infection and is an indication for treatment; a negative result greatly decreases the probability of Lyme disease. The immunoblot assay identifies specific antibodies against different Borrelia proteins. Clinical indications for serologic testing include history of tick bite more than 4 to 6 weeks earlier and neurologic, cardiac, and musculoskeletal symptoms. Physicians need to consider other explanations for patient symptoms before considering a diagnosis of Lyme disease. 1 figure, 3 tables, and 18 references. (AA-M). ·

Recognition and Management of Lyme Disease Source: American Family Physician. 56(2):427,430-436. August 1997. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 9066000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article for health professionals provides guidelines for recognizing and managing Lyme disease. This multisystem disorder, which is the most common tick-borne illness in the United States, has an annual incidence of 0.5 percent in endemic areas. It most commonly occurs in the Northeast and upper Midwest, in areas that encourage and harbor the deer tick. The tick transmits an infection of the spirochete Borrelia burgdorferi that typically manifests as a localized skin lesion, erythema migrans. Rarely, Lyme disease manifests as localized arthritis, heart block, or disease of the nervous system. Lyme disease is a clinical diagnosis, and laboratory tests should only be used to clarify diagnostic issues. The current standard for laboratory diagnosis includes a two-step approach using an initial immunoassay with a confirmatory Western blot. Treatment includes 10 to 21 days of oral doxycycline in nonpregnant adults or a similar course of amoxicillin in children or pregnant women. Overdiagnosis and overtreatment of Lyme disease have become common. 37 references, 5 figures, and 3 tables. (AA-M).

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Lyme Disease in Children in Southeastern Connecticut Source: New England Journal of Medicine. 335(17):1270-1274; October 24, 1996. Summary: This journal article for health professionals describes a prospective, longitudinal, community-based cohort study of 201 children

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with Lyme disease in an area of southeastern Connecticut in which the disease is highly endemic. The researchers obtained clinical and demographic information and performed serial antibody tests and followup evaluations. Results indicate that the initial clinical manifestations of Lyme disease were a single erythema migrans lesion in 66 percent of the patients, multiple erythema migrans lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent, aseptic meningitis in 2 percent, and carditis in 0.5 percent. At presentation, 37 percent of the patients with a single erythema migrans lesion and 89 percent of those with multiple erythema migrans lesions had antibodies against Borrelia burgdoferi. All but 3 of the 201 patients were treated for 2 to 4 weeks with conventional antimicrobial therapy, which was administered orally to 96 percent of the patients. All had prompt clinical responses. After 4 weeks, 94 percent were completely asymptomatic. At followup, none of the patients had evidence of either chronic or recurrent Lyme disease. Six patients subsequently had a new episode of erythema migrans. The article concludes that the prognosis for children with early Lyme disease who are treated with appropriate antimicrobial therapy is excellent. An appendix lists members of the Pediatric Lyme Disease Study Group. 29 references and 2 tables. (AA-M). ·

Diagnosis of Lyme Disease Source: Hospital Practice. p. 35-36. August 15, 1996. Summary: This letter to the editor responds to Leonard H. Sigal's editorial entitled Lyme Disease Over-diagnosis: Causes and Cure, which focused on the overdiagnosis of Lyme disease within the nonpsychiatric context, and as a result of this overdiagnosis (diagnosis by exclusion), subjecting patients to long-term and unnecessary antibiotic therapy. The letter's author indicates that there is a closed system of thinking that contributes to diagnostic error and that there is actually more underdiagnosis than overdiagnosis. Such underdiagnosis is laying the ground work for a large scale epidemic of neuropsychiatric Lyme disease in the future. Dr. Sigal responds that while diagnosis by exclusion may be imprecise, and that he does not known of any of the psychiatric signs and symptoms described by the letter's author, he suggests the only way to settle the questions raised is to perform scientific studies to demonstrate that the form of Lyme disease described in the author's letter does actually exist. 8 references.

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Lyme Disease: 10 Questions Physicians Often Ask Source: Consultant. 36(10):2252-2254,2260-2263; October 1996.

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Summary: This journal article for health professionals answers 10 questions that physicians often ask about Lyme disease. This condition, which has been reported in 48 States, is fairly easy to cure, and serious complications rarely develop when the disease is treated promptly. Questions address issues related to the diagnosis and treatment of Lyme disease. Diagnosis is complicated by the fact that the pathognomonic skin lesion, erythema migrans, is absent in up to 40 percent of infected persons. Also roughly half of patients with erythema migrans are seronegative at the time of presentation. All specimens submitted for testing should be evaluated in two steps: if results of ELISA or IFA testing are negative, no further testing is needed, but if results are borderline or positive, Western blot analysis is needed to confirm the diagnosis. Prophylactic therapy with amoxicillin or doxycycline should be considered if a tick has been attached more than 24 hours and the patient was exposed in an area with an infectivity rate of more than 30 percent. In addition, other questions deal with the risk, diagnosis, and prevention of reinfection; the treatment of a pregnant woman who has Lyme disease; the management of patients who continue to be symptomatic after being treated for Lyme disease; the reduction of the risk of Lyme disease; and the progress made in the development of a vaccine. 19 references, 1 figure, and 1 table. (AA-M). ·

Identifying and Managing Lyme Disease in Children Source: Journal of Musculoskeletal Medicine. 13(7):28-33; July 1996. Summary: This journal article for health professionals offers guidelines for identifying and managing pediatric Lyme disease and its complications. The evaluation of a child with new onset of joint swelling for the possibility of Lyme disease should include consideration of the epidemiology of the disease, the history other than joint involvement, the type of joint disease, and laboratory data. The fact the Lyme disease is much more common in certain geographic areas affects the level of clinical suspicion when a child presents with typical complaints. The only pathognomonic feature is the erythematous ring-shaped skin lesion that appears 1 to 3 weeks following tick attachment and can expand to a large diameter within hours. An acute flu-like illness develops 1 to 4 weeks after the tick bite. The most common late complication is join inflammation. Inflammation may be classically episodic and monarticular, which may cause a delay is diagnosis. One third of children present with an acute arthritis. Various laboratory tests may useful in evaluating patients, including serologic tests and synovial fluid analysis. Treatment options include oral antibiotic agents for manifestations of uncomplicated disease. 24 references, 1 figure, and 2 tables. (AA- M).

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Differentiation of Orofacial Pain Related to Lyme Disease from Other Dental and Facial Pain Disorders Source: Dental Clinics of North America. 41(2): 243-258. April 1997. Contact: Available from W.B. Saunders. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.wbsaunders.com. Summary: This article discusses ways to differentiate orofacial pain related to Lyme disease from other dental and facial pain disorders. The author notes that the facial pain of Lyme disease may simulate dental pathology, temporomandibular joint or masticatory muscle pain, headache, and neuropathic disorders. The author discusses the cause and diagnosis of odontogenic pain, normal and pathologic function of the temporomandibular joints, myofascial trigger points, and pain referral patterns. A screening examination of the odontogenic and masticatory structures as well as a summary of headache disorders is provided. These conditions are compared with their presentation in a patient with Lyme disease to facilitate the diagnostic process. 11 tables. 32 references.

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Now You Can Prevent Lyme Disease Source: Patient Care. 33(11): 180-182,187-188,191-192,194,197-200,205. June 15, 1999. Summary: This journal article provides health professionals with information on a LYMErix, the newly approved Lyme disease vaccine. The vaccine is given in three doses over 1 year to achieve maximum efficacy. The initial dose should be followed by a second dose 1 month later and the third dose 12 months after the second. Although the duration of protection following the third dose has not yet been established, it is likely that boosters will be needed at 1 to 2 year intervals. Unresolved concerns about the vaccine include its safety and efficacy in children and the elderly, its link to Lyme arthritis, and its effect on laboratory tests used to detect Lyme disease. Physicians need to ask patients to assess their risk for Lyme disease based on their place of residence; the terrain of their property; and their occupational, recreational, and leisure activities. Despite progress made on the vaccination front, detecting Lyme disease often remains a challenge. Early recognition is important because progression can lead to serious complications. Early localized infection is characterized by erythema migrans, which develops about 1 to 4 weeks after a tick bite. Early disseminated infection may develop within weeks to months in untreated patients. Late persistent infection may develop months to years after the initial infection. To determine whether serologic testing is warranted,

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physicians should first assess the pretest probability of disease and the predictive value of the serologic test results. For most patients, antibiotic therapy is an effective cure, and when used early, it prevents progression to more serious complications. 5 figures, 4 tables, and 7 references. ·

Musculoskeletal Manifestations of Lyme Disease Source: Rheumatic Disease Clinics of North America. 24(2): 323-351. May 1998. Summary: This journal article provides health professionals with information on the musculoskeletal manifestations of Lyme arthritis. The article begins by briefly reviewing the history of Lyme disease in the United States and Europe and the evolution of investigators' sense of Lyme disease in the United States and Europe. This is followed by a discussion of the ecology and epidemiology of Lyme disease, the life cycle of ixodid ticks, and the types of proteins expressed after Borrelia burgdorferi is transmitted into the mammalian host. The article then presents the features of early localized, early disseminated, and late Lyme disease. The hallmark of early localized Lyme disease is an expanding erythematous patch or ring appearing within roughly a week after an infected tick inoculates the skin with the spirochete. After a period of localized skin infection at the site of the bite, infection may spread hematogenously to various target organs. The symptoms of disseminated Lyme disease include cardiac and neurologic manifestations. The features of late Lyme disease are encephalopathy, axonal polyneuropathy, and leukoencephalitis. The musculoskeletal features of untreated Lyme disease are arthralgia, intermittent episodes of arthritis, or chronic arthritis. Other topics include B. burgdorferi as a cause of reactive arthritis, the radiographic features of Lyme arthritis, its occurrence in children, and the development of fibromyalgia in patients with Lyme disease. The article describes some of the techniques used in laboratory evaluation, including the enzyme-linked immunosorbent assay, the Western blot analysis, polymerase chain reaction, and the borreliacidal antibody assay. Tests of unproven value in Lyme disease include urinary antigen detection, T cell proliferative responses, and autoantibody testing. The article presents caveats on the use of testing in Lyme disease, discusses treatment with antibiotics, and comments on prevention strategies. In addition, the article identifies factors in the immunopathogenesis of Lyme disease, examines the potential role of autoimmunity in the pathogenesis of Lyme neurologic disease, and discusses psychopathogenetic factors that may have a role in chronic Lyme disease. The article concludes with recommendations on diagnosis and treatment. 4 tables and 141 references.

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Federally-Funded Research on Lyme Disease The U.S. Government supports a variety of research studies relating to Lyme disease and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 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. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to Lyme disease and related conditions. 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 Lyme disease and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for Lyme disease: ·

Project Title: Chronic Lyme Arthritis--Is This Autoimmunity? Principal Investigator & Institution: Huber, Brigitte T.; Professor; Pathology; Tufts University Boston 136 Harrison Ave Boston, Ma 02111 Timing: Fiscal Year 2000; Project Start 0-SEP-1998; Project End 9-SEP-2001 Summary: Lyme disease is a multi-faceted illness, initiated upon infection with the spirochete borrelia burgdorferi (Bb). One manifestation of the disease is arthritis, which can result in treatment-resistant chronic arthritis in a small subset of exposed individuals. The prevalence of HLA.DR4 related alleles in these patients is an indication of an autoimmune process. They have explored the role of T helper cells in the development of Lyme arthritis, and the investigators hypothesize that patients with these particular HLA.DR alleles are at risk of developing chronic disease as a result of a vigorous inflammatory Th response to Bb. The interferon gamma production by these activated Thl cells, as well as the presence of Bb, itself leads to upregulation of MHC class II, LFA-1 and ICAM-1 expression predisposing for an autoimmune process by

19 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).

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molecular mimicry. Based upon homology to a highly antigenic epitope of outer surface protein A (Osp A) of Bb, the applicants have identified a candidate autoantigen, hLFA-1. The aim of this application is to verify this hypothesis by creating in vitro and in vivo test systems. I. The functional similarity between the homologous epitopes and Osp A Bb and human LFA-1, but not mouse LFA-1, will be analyzed by three in vitro approaches: (a) T cell hybridomas will be generated from DR4 transgenic mice after immunization with Osp A, and the resulting clones will be tested for reactivity to human LFA-1. If double-reactive hybridomas are identified, the antigenic epitopes will be mapped; (b) synovial fluid T cells from chronic Lyme patients will be transformed and tested at the single-cell level for reactivity to Osp A and human LFA-1; (c) Osp A will be tested for binding to ICAM-1. Competition assays will be performed between Osp A and LFA-1. II. Murine models for treatmentresistant chronic Lyme arthritis will be generated by two approaches; (a) LFA-1/DR4 double transgenic mice on an MHC class II-/-background will be created and tested for the development of chronic Lyme arthritis after exposure to Bb. This is based on the observation that mouse LFA-1 does not express the Osp A cross-reactive epitope; (b) Hu-SCID-beige mice will be generated with PBMCs from patients with chronic Lyme arthritis. These mice will contain the non-immune lymphocytes of the susceptible genotype, allowing a detailed analysis of the acquisition of chronic Lyme arthritis after injection with Bb. These investigations, they propose, should provide a vigorous test of their working hypothesis, and will lead to new insights into the mechanism of treatment-resistant chronic Lyme arthritis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Incomplete Recovery Following Lyme Disease Principal Investigator & Institution: Shadick, Nancy A.; ; Brigham and Women's Hospital 75 Francis St Boston, Ma 02115 Timing: Fiscal Year 2000; Project Start 1-AUG-1997; Project End 0-JUN2002 Summary: The candidate is an Instructor in Medicine in the Division of Rheumatology/Immunology and a clinical investigator in the Multipurpose Arthritis and Musculoskeletal Diseases Center at the Brigham and Women's Hospital, who coordinates the Nantucket Island Lyme disease cohort study. Her goal is to become a clinical researcher, focusing on the epidemiology, prognosis and management of Lyme disease. The applicant's sponsor, Dr. Matthew Liang, Director, Multipurpose Arthritis and Musculoskeletal Diseases Center and Professor of Medicine at Harvard Medical School, has acted as her

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mentor and will continue to do so for this proposal. This project, combined with course work and regular participation in conferences, will prepare her for a career as an independent clinical investigator. The Division of Rheumatology/Immunology and the Multipurpose Arthritis and Musculoskeletal Diseases Center have faculty with expertise in epidemiology and health services research including survey techniques, forms design, statistical programming and analyses. Computer facilities in the Center's Biometry Core are available to the candidate. The resources of the Brigham and Women's Hospital allow the opportunity to collaborate with members of other departments and to participate in graduate school courses at the Harvard School of Public Health. The overall goal of the present study is to improve our understanding of the long term outcomes of Lyme disease. Specific aims include l) determination of the chronicity of musculoskeletal and neurologic impairment in a well characterized population-based cohort of individuals with prior Lyme disease and 2) development of a predictive model of chronic Lyme disease with particular attention to potentially modifiable biological and psychosocial risk factors in order to define an intervention strategy to reduce chronic Lyme disease. A retrospective cohort of 349 Lyme subjects and community controls on Nantucket Island, MA, will receive a standardized and blinded physical examination, symptom review, health status measure, psychometric test battery, and serologic analysis at a three year follow-up interval to assess outcomes. Baseline clinical and psychosocial variables will be evaluated as risk factors for objective and subjective morbidity. This study will help develop better treatment and management guidelines for people with Lyme disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurobehavioral Syndromes of Chronic Lyme Disease Principal Investigator & Institution: Krupp, Lauren B.; ; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2000 Summary: Chronic neurologic Lyme disease has emerged as the major health care issue concerning B. burgdorferi infection, the most rapidly growing vector borne infection in the United States. Encephalopathy is the core syndrome of chronic neurologic Lyme disease. The primary goal of this project is to characterize Lyme encephalopathy. Chronic Lyme patients (n=100) will be assessed on neurobehavioral measures, as compared to controls drawn from the community (n=100) and CSF measures, as compared to an Other Neurologic Disease (OND) group (n=50). We will test specific hypotheses related to the major clinical

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features and pathogenesis of chronic neurologic Lyme disease. A longitudinal design over an 18 month period will allow the course and key risk factors of Lyme encephalopathy to be defined. Specific Aim 1. To define the neurobehavioral and psychological sequelae of chronic Lyme disease Specific Aim 2. To determine the pathogenesis for neurobehavioral deficits in chronic Lyme disease Specific Aim 3. To identify the clinical and laboratory factors which predict health outcome in chronic Lyme disease Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurologic Aspects of Lyme Disease in North America Principal Investigator & Institution: Coyle, Patricia K.; Associate Professor; Neurology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2000; Project Start 1-APR-1997; Project End 1-MAR2002 Summary: Lyme disease is a major emerging infection in the United States, and has become a significant health issue in terms of public awareness, health care costs, and medical practice standards. Neurologic involvement is now recognized as the major morbidity of Lyme disease, but has not been studied in a systematic fashion. This Program Project has assembled an interdisciplinary team of investigators to study neurologic Lyme disease. They will utilize the clinical and laboratory resources of the Lyme Disease Center at Stony Brook. All components of this Program Project are linked by shared methodologies, conceptual frameworks, and common Cores. The three Clinical Projects will provide materials for the Pathogenesis Project: Project 1 will look at the role of host factors (the T cell response) and organism factors (neurotropism, antigenic variation). Project 2 will determine the frequency, correlates, and outcome of central nervous system invasion in early Lyme disease. Project 3 will characterize the neurobehavioral syndromes of chronic Lyme disease. Project 4 will study neurologic Lyme disease in children. The supporting Cores are: A) an Administrative Center Core; B) a Data Management Core; C) a Central Laboratory Core; D) a Neuropsychology Core. The primary scientific goals of this Program Project are 1) to identify and characterize prospectively the neurologic, neuropsychologic, and psychosocial manifestations of Lyme disease in children and adults; and 2) to identify pathogenetic mechanisms involved in neurologic Lyme disease. The secondary goals are 3) to characterize associated cerebrospinal fluid changes; and 4) to identify risk factors for poor outcome. This Program Project will support a structured interdisciplinary effort to study the neurologic aspects of Lyme disease. It will provide

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information to guide development of rational and cost-effective public health policy for this important infection. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Neurologic Involvement in Pediatric Lyme Disease Principal Investigator & Institution: Belman, Anita L.; ; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2000 Summary: Lyme disease, due to the tick borne spirochete Borrelia burgdorferI (Bb), is a major emerging infection. It was originally recognized in children, and children continue to have a high rate of infection. Major issues concerning neurologic aspects of the disease in children and adolescents remain unresolved. Failure to understand the full spectrum of neurologic features has led to health care practices which may be both costly and ineffective. The objective of this proposal is to characterize the neurologic, cognitive, and behavioral aspects of pediatric disseminated Lyme disease. Three groups of children will be evaluated in a prospective longitudinal 18 month study. Case Group 1 [N=50] will meet Centers for Disease Control and Prevention (CDC) surveillance criteria for neurologic Lyme disease. Case Group 2 [N=50] will meet the CDC surveillance criteria for extraneural Lyme disease [Lyme arthritis, carditis or multifocal erythema migrans. Control Group 3 [N=50] will be composed of an age- sex- and IQ- matched group of healthy Bb seronegative controls. All three groups will have comprehensive neurologic, neuropsychologic, behavioral. and psychosocial evaluations at entry. Subjects with neurologic involvement will have cerebrospinal fluid [CSF] studies. Disseminated Lyme disease subjects will receive currently recommended antibiotic treatment. All three groups will be followed prospectively with full re-evaluation at 18 months. SPECIFIC AIM 1: To delineate the neurologic and CSF features of disseminated Lyme disease in children. Hypothesis 1: Neurologic involvement is common in pediatric disseminated Lyme disease. SPECIFIC AIM 2: To delineate the behavioral and neurocognitive features of disseminated Lyme disease in children. Hypothesis 2: Behavioral changes [dysphoria, irritability, fatigue] and cognitive problems [deficits of attention and memory] are frequent in children with neurologic Lyme disease. These problems will have remitted by 18 month follow up. SPECIFIC AIM 3: To identify specific risk factors for persistent post treatment behavioral and neurocognitive complaints. Hypothesis 3: Persistent post-treatment complaints at the 18 month follow-up are more common in children with psychosomatic problems, and those with parents who reinforce illnessrelated behavior. This project will: (A) establish the relative frequency,

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severity, and progression of neurologic and neurobehavioral disturbances associated with pediatric Lyme disease; (B) provide needed data to optimize diagnosis, evaluation, and management of neurologic Lyme syndromes in children. thereby helping to standardize care and reduce medical costs; (C) increase our understanding of underlying pathophysiologic mechanisms of this disorder. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Nucleic Acid-Based Diagnostic Probes for Lyme Disease Principal Investigator & Institution: Schwartz, Ira S.; Professor; Biochem and Molecular Biology; New York Medical College Elmwood Hall Valhalla, Ny 10595 Timing: Fiscal Year 2000; Project Start 0-SEP-1991; Project End 0-JUN2005 Summary: (Adapted from the Applicant's Abstract): Lyme disease is the most common vector-borne disease in the United States. It is caused by the bite of a tick infected with the spirochete, Borrelia burgdorferi, the etiologic agent of the disease. Evaluation of the potential for development of disease from a tick bite is complicated by incomplete knowledge of the diversity of spirochete genotypes in nature and their pathogenic capacities. Furthermore, current laboratory diagnosis rests on a number of serologic tests of varying degrees of sensitivity and reliability, which limits the rapid and specific diagnosis of the disease immediately following a tick bite. During the previous grant period significant progress was made in the molecular typing of B. burgdorferi clinical isolates. In particular, the investigators observed an unequal distribution of genotypes between skin and blood; a particular genotype which is readily cultured from skin was significantly less frequently found in blood. This suggests that the capacity for hematogenous dissemination may vary among different B. burgdorferi genotypes. In addition, progress in the application of a polymerase chain reaction (PCR)-based assay for detection of B. burgdorferi in skin, blood, and synovial fluid was achieved. The investigators propose to extend these findings by pursuing the following specific aims: l) They hypothesize that there is significant genotypic diversity among B. burgdorferi in nature, with the greatest diversity in wildlife hosts and the least in human patients. Molecular typing of B. burgdorferi in ticks and various wildlife hosts will be carried out by PCR-RFLP analysis and DNA sequencing and the number and distribution of genotypes in reservoir hosts, ticks and patients will be compared. 2) Dissemination of different RFLP types will be tested directly in a murine model. I. scapularis colonies infected with single, clonal B. burgdorferi genotypes will be established and potential

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phenotypic variation will be explored with regard to dissemination, acquisition and transmission. 3) The potential of PCR as a modality for diagnosis of early Lyme disease and Lyme arthritis, particularly in patient blood and synovial fluid specimens, will be further explored. A number of variables will be systematically evaluated with the goal of designing a PCR-based approach which can be effectively employed for reliable diagnosis of Lyme disease. The proposed experiments will provide for a more complete understanding of the infection dynamics of B. burgdorferi. This will contribute to a better appreciation of the risk of contracting Lyme disease from a tick bite. In addition, a reliable PCRbased method for detection of B. burgdorferi in patient blood and synovial should improve accurate diagnosis of early Lyme disease and Lyme arthritis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Pathogenesis of Neurologic Lyme Disease Principal Investigator & Institution: Luft, Benjamin J.; ; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2000 Summary: The goal of this project is to identify Borrelial and host-specific factors involved in the invasion of and persistence within the central nervous system (CNS). This will be done by identifying those strains of B. burgdorferi which are neurotropic; by determining strain antigenic variation associated with neurotropism and persistence; by defining the relationship between neurotropism ,antigenic variability, and early and late neurologic Lyme syndromes; and by examining the role of host T-cell responses in dissemination and perpetuation-of disease. This project will use erythema migrans skin biopsy, cerebrospinal fluid, and blood samples from early Lyme disease patients (Project 2), and cerebrospinal fluid and blood samples from late Lyme disease patients (Project 3). Techniques to be used include polymerase chain reaction (PCR), singlestranded conformational polymorphism and cytokine assays. The following specific aims will be addressed. Specific Aim 1: To identify neurotropic strains of B. burgdorferi. Specific Aim 2: To test the hypothesis that T-cell cytokine production (Th1 vs Th2) in response to B. burgdorferi, correlates with clinical outcome. The following predictions will be tested: A. Early Lyme patients show a predominant Th2 T-cell response, while late/chronic Lyme patients show a predominant Th1 response. B. Early Lyme patients with a predominant Th1 T-cell response are more likely to develop chronic sequelae than early Lyme disease patients with a predominant Th2 response. This will be tested by correlating cytokine production of early Lyme disease patients with

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clinical outcome at 18 months. C. Early Lyme patients with neurologic symptoms have a predominant Th1 response, while early Lyme patients with a single lesion of erythema migrans and no systemic symptoms have a predominant Th2 response. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: T Cell Specificity and Function in Lyme Synovitis Principal Investigator & Institution: Vincent, Michael S.; ; Brigham and Women's Hospital 75 Francis St Boston, Ma 02115 Timing: Fiscal Year 2000; Project Start 0-SEP-1996; Project End 1-AUG2001 Summary: A research career development plan is proposed encompassing laboratory investigations on the role of gamma/delta T cells in Lyme synovitis and a curriculum in immunology, autoimmunity, and the conduct of responsible, clinically relevant research. The candidate will train at the University of Vermont College of Medicine and is a Board-eligible internist with a Ph.D in pharmacology who will be an independent investigator focusing the majority of his efforts on basic research in autoimmunity upon completion of the program. The laboratory project will investigate chronic Lyme arthritis, which presents a model human T lymphocyte infiltrative disease resembling rheumatoid arthritis clinicopathologically, but providing the advantage that the inciting agent, Borrelia burgdorferi, is known. The T lymphocyte infiltrates in Lyme synovitis and rheumatoid arthritis include a striking abundance of gamma/delta T lymphocytes, but the role of this subset in the synovial inflammation remains unclear. Previous work from our laboratory suggests that Lyme synovial gamma/delta T cells proliferate in response to Borrelia burgdorferi and manifest cytolytic activity toward CD4+ T lymphocytes in a Fas-dependent manner. The hypothesis of the research proposal is that Lyme synovial y& cells react to components of B. burgdorferi and modulate the inflammatory response by expression of high and sustained levels of Fas ligand (FasL). This results in cytolytic activity towards activated Fas/high lymphocytes in the inflamed synovium, influencing the in situ immune response. The specific aims of the research portion of this project are to: 1) define the antigen presenting cells and molecules for borrelia-reactive gamma/delta T cell clones derived from Lyme synovial fluid, and identify the component(s) of B. burgdorferi recognized by these clones, 2) characterize the cytokine phenotype of borrelia-reactive gamma/delta T cell clones. and 3) further characterize the effector function of these clones by measuring the kinetics and stimuli for FasL expression, defining their target cell specificity, and defining any change in the cytokine profile of the

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synovium that results from differential susceptibility to Fas-mediated cytolysis of various T cell subsets. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Vector Competence for Malaria in Anopheles Quadri Maculatusspecies Complex Principal Investigator & Institution: Cogswell, Frank B.; ; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2000; Project Start 1-JUN-1978; Project End 0-APR2002 Summary: Objectives To develop reagents for the improved diagnostic serology of Lyme disease. Results A segment (P7-1) of the variable domain of VlsE, the variant surface antigen of the spirochete Borrelia burgdorferi sensu lato was cloned and sequenced. and a conserved, immunodominant region of 26 amino acids (IR6) was identified. A 26mer peptide (C6) was synthesized on the basis of the IR6 sequence and a peptide ELISA was developed for serodiagnosis of Lyme disease. Ten rhesus monkeys were infected with Borrelia burgdorferi strains JD1 or B31 by either tick or needle inoculation. Blood samples were periodically collected for up to 3 years post-infection (PI) until the animals were sacrificed, and serum samples were assessed for antibody responses to C6. Anti-C6 antibody was detectable in 6 monkeys as early as week 2 and in the remaining animals between weeks 3 and 5 PI. Antibody persisted at high levels for as long as serum samples were monitored. Forty-one serum samples from patients the majority of which had cultureconfirmed, acute Lyme borreliosis, were obtained from the Centers for Disease Control and Prevention (CDC) and assessed with the C6 ELISA. Sensitivity was 85% (35/41), whereas with a commercially available Lyme disease ELISA it was 78% (32/41), and 49% (20/41) with a commercially available IgG Lyme immunoblot, 51% (21/41) with an IgM immunoblot, and 78% (32/41) by the combination of both IgG and IgM immunoblots. Of a group of 99 randomly collected serum samples from hospital patients in Louisiana, where Lyme disease is not endemic, only 2 were positive with the C6 ELISA. In addition, serum samples from 9/9 relapsing fever patients and 12/12 syphilitic patients also had no detectable anti-C6 antibodies. On the basis of the small number of serum samples tested thus far, the C6 peptide-based ELISA permits sensitive, specific and simple serodiagnosis of Lyme disease.. Future directions To extend our survey of crossreactivity; samples from patients with autoim mune diseases will be tested. FUNDING PUBLICATIONS None Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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E-Journals: PubMed Central20 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).21 Access to this growing archive of e-journals is free and unrestricted.22 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “Lyme disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Lyme disease in the PubMed Central database: ·

A European Multicenter Study of Immunoblotting in Serodiagnosis of Lyme Borreliosis by J. Robertson, E. Guy, N. Andrews, B. Wilske, P. Anda, M. Granstrom, U. Hauser, Y. Moosmann, V. Sambri, J. Schellekens, G. Stanek, and J. Gray; 2000 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86736&ren dertype=external

·

Archaeal-type lysyl-tRNA synthetase in the Lyme disease spirochete Borrelia burgdorferi by Michael Ibba, James L. Bono, Patricia A. Rosa, and Dieter Soll; 1997 December 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24988

·

Borrelia burgdorferi B31 Erp Proteins That Are Dominant Immunoblot Antigens of Animals Infected with Isolate B31 Are Recognized by Only a Subset of Human Lyme Disease Patient Sera by Jennifer C. Miller, Nazira El-Hage, Kelly Babb, and Brian Stevenson; 2000 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86492&ren dertype=external

·

Characterization of a Borrelia burgdorferi VlsE Invariable Region Useful in Canine Lyme Disease Serodiagnosis by Enzyme-Linked Immunosorbent Assay by Fang Ting Liang, Richard H. Jacobson, Reinhard K. Straubinger, Amy Grooters, and Mario T. Philipp; 2000 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87557&ren dertype=external

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 21 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. 22 The value of PubMed Central, in addition to its role as an archive, lies 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. 20

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·

Characterization of Lyme Borreliosis Isolates from Patients with Erythema Migrans and Neuroborreliosis in Southern Sweden by Katharina Ornstein, Johan Berglund, Ingrid Nilsson, Ragnar Norrby, and Sven Bergstrom; 2001 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87927&ren dertype=external

·

Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab by Hong Li, John J. Dunn, Benjamin J. Luft, and Catherine L. Lawson; 1997 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20483

·

Direct Molecular Typing of Borrelia burgdorferi Sensu Lato Species in Synovial Samples from Patients with Lyme Arthritis by B. Jaulhac, R. Heller, F. X. Limbach, Y. Hansmann, D. Lipsker, H. Monteil, J. Sibilia, and Y. Piemont; 2000 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86617&ren dertype=external

·

Dogs as Sentinels for Human Lyme Borreliosis in The Netherlands by H. A. T. Goossens, A. E. van den Bogaard, and M. K. E. Nohlmans; 2001 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87839&ren dertype=external

·

Evaluation of Whole-Cell and OspC Enzyme-Linked Immunosorbent Assays for Discrimination of Early Lyme Borreliosis from OspA Vaccination by Chad A. Wieneke, Steven D. Lovrich, Steven M. Callister, Dean A. Jobe, Jennifer A. Marks, and Ronald F. Schell; 2000 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88715&ren dertype=external

·

Genetic Diversity of Borrelia burgdorferi in Lyme Disease Patients as Determined by Culture versus Direct PCR with Clinical Specimens by Dionysios Liveris, Shobha Varde, Radha Iyer, Seth Koenig, Susan Bittker, Denise Cooper, Donna McKenna, John Nowakowski, Robert B. Nadelman, Gary P. Wormser, and Ira Schwartz; 1999 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84470&ren dertype=external

·

Granulocytic Ehrlichiae in Ixodes persulcatus Ticks from an Area in China Where Lyme Disease Is Endemic by Wu-Chun Cao, Qiu-Min Zhao, Pan-He Zhang, J. Stephen Dumler, Xi-Tan Zhang, Li-Qun Fang, and Hong Yang; 2000 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87564&ren dertype=external

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·

Infection with Agents of Human Granulocytic Ehrlichiosis, Lyme Disease, and Babesiosis in Wild White-Footed Mice (Peromyscus leucopus) in Connecticut by Kirby C. Stafford, III, Robert F. Massung, Louis A. Magnarelli, Jacob W. Ijdo, and John F. Anderson; 1999 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85405&ren dertype=external

·

Integrin [alpha]IIb[beta]3 Mediates Binding of the Lyme Disease Agent Borrelia burgdorferi to Human Platelets by J Coburn, JM Leong, and JK Erban; 1993 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47075

·

Isolation and Characterization of Borrelia burgdorferi Sensu Lato Strains in an Area of Italy Where Lyme Borreliosis Is Endemic by Lorenzo Ciceroni, Simonetta Ciarrochi, Alessandra Ciervo, Valeria Mondarini, Francesco Guzzo, Giuseppe Caruso, Rossella Murgia, and Marina Cinco; 2001 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88120&ren dertype=external

·

Isolation and Transmission of the Lyme Disease Spirochete from the Southeastern United States by JH Oliver, Jr, FW Chandler, Jr, MP Luttrell, AM James, DE Stallknecht, BS McGuire, HJ Hutcheson, GA Cummins, and RS Lane; 1993 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47139

·

Isolation of Lyme Disease Borrelia from Puffins (Fratercula arctica) and Seabird Ticks (Ixodes uriae) on the Faeroe Islands by Asa Gylfe, Bjorn Olsen, Darius Strasevicius, Nuria Marti Ras, Pal Weihe, Laila Noppa, Yngve Ostberg, Guy Baranton, and Sven Bergstrom; 1999 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84640&ren dertype=external

·

Lyme Disease: A Growing Threat to Urban Populations by AC Steere; 1994 March 29 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43375

·

Monoclonal Antibodies Specific for the Outer Surface Protein A (OspA) of Borrelia burgdorferi Prevent Lyme Borreliosis in Severe Combined Immunodeficiency (Scid) Mice by UE Schaible, MD Kramer, K Eichmann, M Modolell, C Museteanu, and MM Simon; 1990 May 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53984

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·

Note:Comparison of the Yields of Blood Cultures Using Serum or Plasma from Patients with Early Lyme Disease by Gary P. Wormser, Susan Bittker, Denise Cooper, John Nowakowski, Robert B. Nadelman, and Charles Pavia; 2000 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86513&ren dertype=external

·

Note:Effects of OspA Vaccination on Lyme Disease Serologic Testing by Maria E. Aguero-Rosenfeld, Janet Roberge, Carol A. Carbonaro, John Nowakowski, Robert B. Nadelman, and Gary P. Wormser; 1999 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85737&ren dertype=external

·

Note:One-Step Reverse Transcriptase PCR Method for Detection of Borrelia burgdorferi mRNA in Mouse Lyme Arthritis Tissue Samples by F. X. Limbach, B. Jaulhac, Y. Piemont, J. L. Kuntz, H. Monteil, and J. Sibilia; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85022&ren dertype=external

·

Note:Phenotypic and Genetic Characterization of a Novel Borrelia burgdorferi Sensu Lato Isolate from a Patient with Lyme Borreliosis by Guiqing Wang, Alje P. van Dam, and Jacob Dankert; 1999 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85444&ren dertype=external

·

Note:Rapid Typing of Borrelia burgdorferi Sensu Lato Species in Specimens from Patients with Different Manifestations of Lyme Borreliosis by Jan D. Lunemann, Silvia Zarmas, Susanne Priem, Juliane Franz, Rolf Zschenderlein, Elisabeth Aberer, Rolf Klein, Leo Schouls, Gerd R. Burmester, and Andreas Krause; 2001 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87886&ren dertype=external

·

Quantitative Approach for the Serodiagnosis of Canine Lyme Disease by the Immunoblot Procedure by Marta A. Guerra, Edward D. Walker, and Uriel Kitron; 2000 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86982&ren dertype=external

·

Recombinant Chimeric Borrelia Proteins for Diagnosis of Lyme Disease by Maria J. C. Gomes-Solecki, John J. Dunn, Benjamin J. Luft, Jonathan Castillo, Daniel E. Dykhuizen, Xiaohua Yang, John D. Glass, and Raymond J. Dattwyler; 2000 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86960&ren dertype=external

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·

Recombinant Flagellin A Proteins from Borrelia burgdorferi Sensu Stricto, B. afzelii, and B. garinii in Serodiagnosis of Lyme Borreliosis by Jaana Panelius, Pekka Lahdenne, Harri Saxen, Tero Heikkila, and Ilkka Seppala; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88480&ren dertype=external

·

Sensitive and Specific Serodiagnosis of Lyme Disease by EnzymeLinked Immunosorbent Assay with a Peptide Based on an Immunodominant Conserved Region of Borrelia burgdorferi VlsE by Fang Ting Liang, Allen C. Steere, Adriana R. Marques, Barbara J. B. Johnson, James N. Miller, and Mario T. Philipp; 1999 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85863&ren dertype=external

·

Serologic Diagnosis of Lyme Borreliosis by Using Enzyme-Linked Immunosorbent Assays with Recombinant Antigens by Louis A. Magnarelli, Jacob W. Ijdo, Steven J. Padula, Richard A. Flavell, and Erol Fikrig; 2000 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86574&ren dertype=external

·

Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete, Borrelia burgdorferi, during the Chain of Infection in Ticks and Mice by Tom G. Schwan and Joseph Piesman; 2000 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88728&ren dertype=external

·

The Borrelia burgdorferi 37-Kilodalton Immunoblot Band (P37) Used in Serodiagnosis of Early Lyme Disease Is the flaA Gene Product by Robert D. Gilmore, Jr., Rendi L. Murphree, Angela M. James, Sarah A. Sullivan, and Barbara J. B. Johnson; 1999 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84463&ren dertype=external

·

Therapeutic passive vaccination against chronic Lyme disease in mice by Weimin Zhong, Thomas Stehle, Crisan Museteanu, Annette Siebers, Lise Gern, Michael Kramer, Reinhard Wallich, and Markus M. Simon; 1997 November 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=25028

·

Use of Serum Immune Complexes in a New Test That Accurately Confirms Early Lyme Disease and Active Infection with Borrelia burgdorferi by Michael Brunner and Leonard H. Sigal; 2001 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88321&ren dertype=external

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Validity of Interpretation Criteria for Standardized Western Blots (Immunoblots) for Serodiagnosis of Lyme Borreliosis Based on Sera Collected throughout Europe by Ulrike Hauser, Gisela Lehnert, and Bettina Wilske; 1999 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85128&ren dertype=external

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. 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 the public.23 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 Lyme disease, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “Lyme disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “Lyme disease” (hyperlinks lead to article summaries): ·

Lyme disease. Author(s): Brier SR. Source: Journal of Manipulative and Physiological Therapeutics. 1990 July-August; 13(6): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=2394950&dopt=Abstract

·

Prevention of Lyme disease. Author(s): Couch P, Johnson CE.

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.

23

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Source: Am J Hosp Pharm. 1992 May; 49(5): 1164-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1595748&dopt=Abstract

Vocabulary Builder Adenoma: A benign epithelial tumour in which the cells form recognizable glandular structures or in which the cells are clearly derived from glandular epithelium. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Antigens: Substances that are recognized by the immune system and induce an immune reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Arthralgia: Pain in a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Asymptomatic: Showing or causing no symptoms. [EU] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH]

Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biometry: The use of statistical methods to analyze biological observations and phenomena. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Collagen: The protein substance of the white fibres (collagenous fibres) of

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skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Cutaneous: Pertaining to the skin; dermal; dermic. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] 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 health-related event occurring in such outbreaks. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Fatal: Causing death, deadly; mortal; lethal. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Flagellin: A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU] Glomerulonephritis: A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Haplotypes: The genetic constitution of individuals with respect to one

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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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Pertaining to the liver. [EU] Hepatomegaly: Enlargement of the liver. [EU] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Immunization: The induction of immunity. [EU] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] 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] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or

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divides a space or organ. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Myopathy: Any disease of a muscle. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoporosis: Reduction in the amount of bone mass, leading to fractures after minimal trauma. [EU] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] 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] Peromyscus: A genus of the subfamily Hesperomyinae consisting of 49 species. Two of these are widely used in medical research. They are P. leucopus, or the white-footed mouse, and P. maniculatus, or the deer mouse. [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] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280-400 mm. There are two main types : photoallergy and photoxicity. [EU] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Pulmonary: Pertaining to the lungs. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not

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found together in either parent; usually applied to linked genes. [EU] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Respiratory: Pertaining to respiration. [EU] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] 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] Synovial: Of pertaining to, or secreting synovia. [EU] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox vaccine, the term has come to mean any immunizing procedure in which vaccine is injected. [EU]

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CHAPTER 5. PATENTS ON LYME DISEASE Overview You can learn about innovations relating to Lyme disease by reading recent patents and patent applications. 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.24 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 to patients with Lyme disease 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 to patients with Lyme disease. 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.

24Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Lyme Disease By performing a patent search focusing on Lyme disease, 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 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 Lyme disease: ·

Tick (Ixodes scapularis) vector saliva-induced Lyme disease spirochete (Borrelia burgdorferi) antigens as vaccine candidates Inventor(s): Nelson; David R. (Wakefield, RI), Mather; Thomas N. (Wakefield, RI), Scorpio; Angelo (Columbia, MD) Assignee(s): The Board of Governors for Higher Education, State of Rhode Island (Providence, RI), Providence Plantations (Providence, RI) Patent Number: 6,312,915 Date filed: January 29, 1997 Abstract: The invention relates to a method by which new antigens from vector-borne pathogens may be discovered and analyzed by incubating the viable pathogens in the saliva of their vector host. Three such antigens, proteins with the approximate molecular weights of 19, 22 and 24 kDa, have been discovered and analyzed from a strain of B. burgdorferi T-15. The proteins provide a route for the development of immunodiagnostics for Lyme disease and related disorders. The proteins and related amino acids and DNA sequences may also be used for the immunization, for the detection of B. burgdorfei in human or body fluids, and also for the generation of specific antibodies for use in diagnosis, epidemiology, prevention of and treatment of Lyme disease. Excerpt(s): The present invention relates to the use of the saliva of a member of the family Ixodidae to induce the expression of proteins by Borrelia burgdorferi. Novel tick saliva-induced B. burgdorferi proteins can be used for the potential development of a vaccine against Lyme disease and for improved diagnostic kits for the detection of Lyme disease. ... Borrelia burgdorferi, a spirochete, is the causative agent of Lyme disease. It is a vector borne pathogen, transmitted by ticks of the Ixodes scapularis and Ixodes pacificus complexes in the United States.

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Burgdorfer W., B. burgdorferi: Its Relationships to Tick Vectors, In Staken (ed): Lyme Borreliosis, II, Zbl Bakt Supplement 18, Stuttgart-New York, Gustav Fischer, 8-13, 1989. Infection with B. burgdorferi is the most common tick-borne infectious disease in the United States. In endemic areas, between 30 and 90% of Ixodes ticks are infected with this organism. ... The illness caused by B. burgdorferi is a multisystem infection that affects the skin, central nervous system, peripheral nerves, the heart and the joints, with nerve and joint involvement being the most common. Steere, A. C., S. E. Malawista, J. A. Hardin, S. Ruddy, W. Askenase, and W. A. Andiman, Erythema Chronicum Migrans and Lyme Arthritis: the Enlarging Spectrum, Ann Intern Med. 86:685-698, 1977a. The dissemination of spirochetes over time from the site of infection has been documented in a mouse model. Barthold, S. W., D. H. Persing, A. L. Armstrong, and R. A. Peeples, Kinetics of B. burgdorferi Dissemination and Evolution of Disease after Intradermal Inoculation of Mice, AM J. Pathol, 139:263-273, 1991. In these experiments it was shown that the spirochetes were multifocal in distribution with a predilection for collagenous connective tissue of joints, heart, arteries, nerves, muscles, skin and other tissues. In humans, nerve, joint and heart involvement is usually manifested when the disease reaches a chronic state. The pathogensis to a chronic state of nerve involvement, termed neuroborreliosis, is unclear, but may be due to a direct effect of the spirochetes at the site of infection, the host response to B. burgdorferi, or the host response to tissue antigens that may mimic those of Borrelia burgdorferi. Fikrig, E., R. Berland, M. Chen, S. Williams, L. H. Signal, and R. A. Flavell, Serological Response to B. burgdorferi Flagellin Demonstrates an Epitope Common to a Neuroblastoma Cell Line, Proc. Natl. Acad. Sci. 90:183-187, 1993. For example, spirochetes can be detected in the cerebrospinal fluid of patients with neuroborreliosis with a corresponding high level of antigen specific T-cells which suggests that a local immune response may be involved in the disease. However, the presence of spirochetes has yet to be demonstrated in biopsy specimens of affected nerve tissue suggesting that clinical manifestations may be due to some type of molecular mimicry. Indeed, it has been shown that antibodies reactive to a certain epitope of the B. burgdorferi flagellin molecule cross react with a neuroblastoma cell line. Fikrig, E., R. Berland, , M. Chen, S. Williams, L. H. Sigal , and R. A. Flavell, Serological Response to B. burgdorferi Flagellin Demonstrates an Epitope Common to a Neuroblastoma Cell Line, Proc. Natl. Acad. Sci. 90:183-187, 1993. Development of arthritic symptoms is similarly complex. Patients who develop arthritis usually show involvement of the knee joint with an increase of polymorphonuclear granulocytes in the synovial fluid. Steere, A. C., S. E. Malawista, and D. R. Snydman, Lyme Arthritis: An Epidemic

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of oligoarticular Arthritis in Children and Adults in Three Connecticut Communities, Arthritis Rheum. 20:7-17, 1977. It has been hypothesized that spirochetes trigger a local immune response with autoreactive features in the joint, symptoms which may continue after the organisms no larger are viable. Girouard, L., D. C. Laux, S. Jindal, and D. R. Nelson, Immune Recognition of Human Hsp60 by Lyme Disease Patient Sra, Microb. Pathog. 14:287-297, 1993; and Steere, A. C., J. Feld, and R. Winchester, Association of Chronic Lyme Arthritis with Increased Frequencies of DR4 and 3, Arthritis Rheum. 31:98 (Abstract), 1988. As with nerve biopsies, culturing of spirochetes from synovial fluid of the joints is exceedingly difficult, being reported only twice, and direct observation is also rare. These phenomena are especially true as the disease progresses. Recent advances in the ability to detect small amounts of DNA using polymerase chain reaction (PCR) has led to conflicting results regarding the presence of spirochetes in the joint. Nocton, J. J., F. Dressler, B. J. Rutledge, P. N. Rys, D. H. Persing, and A. C. Steere, Detection of B. burgdorferi DNA by Polymerase Chain Reaction in Synovial Fluid in Lyme Arthritis, N. Engl. J. Med. (In press); and Malawista, S. E., T. L. Moore, D. E. Dodge, T. J. White, R. T. Schoen, and D. H. Persing, Failure of Multitarget Detection of Borrelia burgdorferiAssociated DNA Sequences in Synovial Fluids of Patients with Juvenile Rheumatoid Arthritis: A Cautionary Note, Arthritis Rheum. 35:246-247, 1992. Thus, as with neuroborreliosis, there appear to be two possibilities: septic arthritis with live organisms in the joint, and reactive arthritis where a microbial antigen at a remote site stimulates an immune response involving either antibodies or cytotoxic mononuclear cells that cross-react with a compartment of host tissue. Web site: http://www.delphion.com/details?pn=US06312915__ ·

Compositions and methods for the prevention and diagnosis of Lyme disease Inventor(s): Flavell; Richard A. (Killingworth, CT), Kantor; Fred S. (Orange, CT), Barthold; Stephen W. (Madison, CT), Fikrig; Erol (Guilford, CT) Assignee(s): Yale University (New Haven, CT) Patent Number: 6,197,301 Date filed: May 31, 1995 Abstract: Methods and compositions for the prevention and diagnosis of Lyme disease. OspA and OspB polypeptides and serotypic variants thereof, which elicit in a treated animal the formation of an immune

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response which is effective to treat or protect against Lyme disease as caused by infection with B. burgdorferi. Anti-OspA and anti-OspB antibodies that are effective to treat or protect against Lyme disease as caused by infection with B. burgdorferi. A screening method for the selection of those OspA and OspB polypeptides and anti-OspA and antiOspB antibodies that are useful for the prevention and detection of Lyre disease. Diagnostic kits including OspA and OspB polypeptides or antibodies directed against such polypeptides. Excerpt(s): This invention relates to compositions and methods useful for the prevention, treatment and diagnosis of Lyme disease in humans and other animals. More particularly, this invention relates to OspA and OspB polypeptides which are able to elicit in a treated patient, the formation of an immune response which is effective to treat or protect against Lyme disease. This invention also relates to a screening method for selecting the OspA and OspB polypeptides of this invention which are able to elicit such an immune response. Also within the scope of this invention are antibodies directed against the OspA and OspB polypeptides and diagnostic kits comprising the antibodies or the polypeptides. ... Lyme borreliosis is the most common vectorborne infection in the United States [S. W. Barthold, et al., "An Animal Model For Lyme Arthritis", Ann. N.Y. Acad. Sci., 539, pp. 264-73 (1988)]. It has been reported in every continent except Antarctica. The clinical hallmark of Lyme Disease is an early expanding skin lesion known as erythema migrans, which may be followed weeks to months later by neurologic, cardiac, and joint abnormalities. ... The causative agent of Lyme disease is a recently recognized spirochete known as Borrelia burgdorferi, transmitted primarily by ixodes ticks that are part of the Ixodes ricinus complex. B. burgdorferi has also been shown to be carried in other species of ticks and in mosquitoes and deer flies, but it appears that only ticks of the I. ricinus complex are able to transmit the disease to humans. Web site: http://www.delphion.com/details?pn=US06197301__ ·

Nucleic acid amplification oligonucleotides and probes to Lyme disease associated Borrelia Inventor(s): Hogan; James J. (Coronado, CA), Yang; Yeasing (San Diego, CA), Carter; Nick (San Diego, CA) Assignee(s): Gen-Probe Incorporated (San Diego, CA) Patent Number: 6,074,826 Date filed: October 17, 1997

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Abstract: The present invention discloses hybridization assay probes, amplification primers, nucleic acid compositions and methods useful for detecting Borrelia nucleic acids. Hybridization assay probes and amplification primers that selectively detect Lyme disease-associated Borrelia and distinguish those Borrelia from Borrelia hermsii are disclosed. Other hybridization probes selectively detect Borrelia hermsii and not Lyme disease-associated Borrelia are also described. Excerpt(s): The inventions described and claimed herein relate to the design and use of amplification oligonucleotides and nucleic acid probes to Borrelia organisms associated with Lyme disease, which allow detection of the organism in test samples, e.g., from tissue samples and body fluids, and from cultures. ... Lyme disease is a frequently diagnosed human disease and is the most prevalent tick-borne disease in North America, Europe and other parts of the world with a moderate climate. See, A. G. Barbour & D. Fish, Science 260:1610-16 (1993); J. F. Anderson, Rev. Insect Dis. 11:51451-59 (1989); A. C. Steere, N. Engl. J. Med., 331:58696 (1989). Lyme disease or Lyme borreliosis is a multistage infection caused by Borrelia spirochetes. The Borrelia organism is transmitted to humans and animals by infected Ixodes ticks. White-tailed deer and the white-footed mouse, Peromyscus leucopus, serve as primary reservoirs in nature for the adult tick and larval forms, respectively. ... Cultivation of Borrelia organisms from body fluids is difficult, making microbiological diagnosis of lyme borreliosis by culturing unsatisfactory. Serological tests to detect B. burgdorferi have been developed including enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence assay (IFA) and western blotting. See, M. G. Golightly, Am. J. Clin. Pathol., 99:168-74 (1993). However, poor standardization, false-positive and false-negative results do occur with these serologic tests and limit their usefulness. See, Barbour, Ann. Intern. Med., 110:504 (1989). Patients with early (Stage I) or Stage II infections may not yet have developed detectable levels of antibodies and cross reactions with Treponema or other Borrelia not associated with Lyme disease may occur. Treatment with antibiotics may also prevent or delay the development of detectable antibodies in patients with Lyme borreliosis. Together these deficiencies limit the usefulness and reliability of serologic tests in diagnosis and treatment of Lyme borreliosis. Web site: http://www.delphion.com/details?pn=US06074826__

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Modified western blot membrane and method for detecting lyme disease and other tick-borne diseases Inventor(s): Levin; Andrew E. (Wellesley, MA) Assignee(s): Immunetics, Incorporated (Cambridge, MA) Patent Number: 6,013,460 Date filed: September 12, 1997 Abstract: Modified Western blot membranes and methods of using same are provided which allow confirmation of Lyme disease and screening for at least one additional tick-borne disease. The membranes and methods of the present invention may thus be used to screen for the presence of tick-borne diseases which may be transferred along with Lyme disease. A Western blot assay may also be employed to confirm the presence of such additional tick-borne disease. Excerpt(s): The present invention relates generally to a diagnostic method for detecting tick-borne disease and more specifically, a modified Western blot membrane and method of using same for detecting Lyme disease as well as other tick-borne diseases which may accompany Lyme disease during its transmission. In particular, the modified Western blot membrane and method of the present invention may be used to simultaneously confirm Lyme disease and screen for at least one additional tick-borne disease. ... Lyme disease is a progressive, systemic infection caused by the spirochete Borrelia burgdorferi. The disease is transmitted to man by the bite of the deer tick (Ixodes scapularis and other species). Diagnostic tests for Lyme disease rely mainly on the detection of human antibodies to spirochetal antigens. The principal test used for screening human sera for antibodies to the Lyme spirochete is enzyme-linked immunosorbent assay (ELISA). Due to the significant inaccuracies inherent in ELISA, sera which are ELISA-positive or indeterminate are often subjected to a confirmatory test. The confirmatory test now in most common use and officially recommended by the U.S. Centers for Disease Control (CDC) is the Western blot. In a conventional Western blot assay, antigens of a given pathogen are resolved into discrete bands on the surface of a paper-like nitrocellulose membrane. The serum to be tested is allowed to react with the antigen bands, and serum antibodies which bind specific bands are detected with a labeled anti-human antibody reagent. Typically, results of the Western blot test appear as a series of bands on a membrane strip. The pattern of bands is compared with the band pattern of known positive sera to produce a diagnostic result. The exact position of bands, and the number of bands which correlate with positivity, differ depending on the pathogen. ... Considerable effort has been expended to develop new and

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improved diagnostic tests for Lyme disease. For example, U.S. Pat. No. 5,187,065 discloses methods of detecting Lyme disease in mammals that otherwise show seronegativity due to the generation of immune complexes which "hide" the antibodies raised to the spirochete; disassociation of such complexes followed by immunological assay procedures such as ELISA are described. U.S. Pat. No. 5,470,712 provides bioassays which incorporate non-flaggellar B. burgdorferi proteins, or antibodies raised to such proteins, to create an assay where such proteins or antibodies are bound to a surface and form complexes with certain components of the serum. Similarly, U.S. Pat. No. 5,308,753 teaches the formation of assays which may be used to diagnose Lyme and other diseases which induce primary or secondary IgM antibody-mediated immunity. U.S. Pat. No. 5,217,872 teaches a method of detecting B. burgdorferi antigens through an assay which utilizes vesicle proteins released from the spirochete, while U.S. Pat. Nos. 5,494,797 and 5,324,630 teach the detection of the Lyme spirochete via oligonucleotide probes. U.S. Pat. No. 4,888,276 describes a reliable, noninvasive method for detecting antigens of B. burgdorferi from the urine of affected individuals and U.S. Pat. No. 5,155,022 teaches an improved method of assaying for Lyme disease by eliminating crossreacting antibodies. Both U.S. Pat. Nos. 4,859,419 and 5,100,626 provide apparati that are able to assay multiple samples for a specific disease such as Lyme. However, none of these patents teach a method of simultaneously assaying for Lyme disease and other diseases. Web site: http://www.delphion.com/details?pn=US06013460__ ·

Control of lyme disease spirochete Inventor(s): Poche ; Richard M. (Ft. Collins, CO) Assignee(s): Genesis Laboratories, Inc. (Wellington, CO) Patent Number: 5,932,437 Date filed: April 13, 1998 Abstract: A method is described for controlling the spread of Lyme Disease spirochete from rodents which have been infected. The method involves orally administering to the rodents a composition which includes an antibiotic (e.g., tetracycline) which is capable of killing the spirochete. Bait compositions are described which include an antibiotic. The bait compositions may be solid or liquid. Excerpt(s): This invention relates to methods and techniques for controlling Lyme Disease spirochete in rodents. ... In recent times, Lyme Disease has emerged as an increasing public health threat. The Center for

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Disease Control has reported that the number of Lyme Disease cases has increased steadily from 1982 to 1995 with 47 of 50 states reporting at least one case of Lyme Disease. In the United States, three ticks of the Ixodes genus, Ixodes scapularis and Ixodes dammini in the East and Ixodes pacificus in the West commonly carry the spirochete that causes the disease and are in a two year enzootic cycle with rodents and deer. ... There has not heretofore been described an effective technique for controlling the Lyme disease spirochete Borrelia burgdorferi in rodents. Web site: http://www.delphion.com/details?pn=US05932437__ ·

Hybridomas producing antibodies specific for lyme disease antigens OspA and OspB Inventor(s): Simon; Markus M. (Freiburg, DE), Schaible; Ulrich E. (Freiburg, DE), Eichmann; Klaus (Freiburg, DE), Kramer; Michael (Heidelberg, DE), Reinhard; Wallich (Heidelberg, DE) Assignee(s): Max-Planck-Gesellschaft zur Forderung der Wissenschaften (Heidelberg, DE) Patent Number: 5,856,447 Date filed: February 23, 1998 Abstract: The present invention provides a vaccine against Lyme disease, wherein it contains one or more monoclonal antibodies which are specific for the 31 kD antigen (OspA) or the 34 kD antigen (OspB) of Borrelia burgdorferi.The present invention also provides a process for obtaining this vaccine, as well as new monoclonal antibodies, hybridomas and antigens. Excerpt(s): The present invention is concerned with a vaccine against Lyme disease, with a process for obtaining said vaccine, with new monoclonal antibodies, with new antigens and with new recombinant DNA's and vectors. ... Lyme borreliosis is the most common infectious disease transmitted by ticks in the temperate regions. It is caused by the spirochete Borrelia burgdorferi which is transmitted to humans in particular by ticks of the genus Ixodes. The disease is a chronic, progressive infection which attacks many organs, such as the skin, the central and peripheral nervous system, the heart, the liver, the kidneys and musculoskeletal system. Since a reliable treatment of this disease by therapy with antibiotics is difficult, at the moment great efforts are being made to investigate the pathogen itself and the immune response of the host to infection with Borrelia burgdorferi. In the case of persons afflicted by Lyme disease, there is admittedly ascertained a high titre of antibodies against Borrelia burgdorferi which, however, do not provide any

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protection against the infection. It is assumed that the pathogen passes over very quickly from the blood circulation into the tissues and can there no longer be directly reached by the immune system. This would mean that a protection by antibodies is only possible immediately after commencement of the infection, i.e. as long as the pathogen is still present in the blood circulation. ... The fact that a natural infection with Borrelia burgdorferi has been found in various kinds of animals has led to attempts to establish laboratory models for Lyme disease. This also took place with limited success. Thus, in the case of experiments which had the object of inducing in mice a specific immune response for Borrelia burgdorferi, it was found that the infection of inbred mouse strains with a prolonged cultured isolate of Borrelia burgdorferi led to moderate but significant pathomorphological changes in various organs, such as the brain, the heart, the lungs and the kidneys, which were comparable to those which are to be observed in patients with Lyme disease (see Schaible et al., Infect. Immun., 1, 41/1988). The development of a serious aspect of the disease in animals was presumably prevented either by the immune defence of the host and/or by the reduced virulence of spirochetes cultured in vitro for a comparatively long period of time (see Johnson et al., J. Clin. Microbiol., 20, 747/1984; Schwan et al., Infect. and Immun., 56, 1837/1988). Web site: http://www.delphion.com/details?pn=US05856447__ ·

Passive vaccine against Lyme disease Inventor(s): Simon; Markus M. (Freiburg, DE), Schaible; Ulrich E. (Freiburg, DE), Eichmann; Klaus (Freiburg, DE), Kramer; Michael (Heidelberg, DE), Reinhard; Wallich (Heidelberg, DE) Assignee(s): Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V. (Gottingen, DE), Deutsches Krebsforschun Zentrum Stiftung des Offentlichen Rechts (Heidelberg, DE) Patent Number: 5,780,030 Date filed: March 20, 1995 Abstract: The present invention provides a vaccine against Lyme disease, wherein it contains one or more monoclonal antibodies which are specific for the 31 kD antigen (OspA) or the 34 kD antigen (OspB) of Borrelia burgdorferi. The present invention also provides a process for obtaining this vaccine, as well as new monoclonal anti-bodies and antigens. Excerpt(s): The present invention is concerned with a vaccine against Lyme disease, with a process for obtaining said vaccine, with new monoclonal antibodies, with new antigens and with new recombinant

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DNA's and vectors. ... Lyme borreliosis is the most common infectious disease transmitted by ticks in the temperate regions. It is caused by the spirochete Borrelis burgdorferi which is transmitted to humans in particular by ticks of the genus Ixodes. The disease is a chronic, progressive infection which attacks many organs, such as the skin, the central and peripheral nervous system, the heart, the liver, the kidneys and musculoskeletal system. Since a reliable treatment of this disease by therapy with antibiotics is difficult, at the moment great efforts are being made to investigate the pathogen itself and the immune response of the host to infection with Borrelia burgdorferi. In the case of persons afflicted by lyme disease, there is admittedly ascertained a high titre of antibodies against Borrelia burgdorferi which, however, do not provide any protection against the infection. It is assumed that the pathogen passes over very quickly from the blood circulation into the tissues and can there no longer be directly reached by the immune system. This would mean that a protection by antibodies is only possible immediately after commencement of the infection, i.e. as long as the pathogen is still present in the blood circulation. ... The fact that a natural infection with Borrelia burgdorferi has been found in various kinds of animals has led to attempts to establish laboratory models for Lyme disease. This also took place with limited success. Thus, in the case of experiments which had the object of inducing in mice a specific immune response for Borrelia burgdorferi, it was found that the infection of inbred mouse strains with a prolonged cultured isolate of Borrelia burgdorferi led to moderate but significant pathomorphological changes in various organs, such as the brain, the heart, the lungs and the kidneys, which were comparable to those which are to be observed in patients with Lyme disease (see Schaible et al., Infect. Immun., 1, 41/1988). The development of a serious aspect of the disease in animals was presumably prevented either by the immune defense of the host and/or by the reduced virulence of spirochetes cultured in vitro for a comparatively long period of time (see Johnson et al., J. clin licrobiol.20, 747/1984; Schwan et al., Infect . and Immun., 56, 1837/1988). Web site: http://www.delphion.com/details?pn=US05780030__

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Nucleic acid molecule encoding antigen associated with lyme disease Inventor(s): Simon; Markus M. (Freiburg, DE), Schaible; Ulrich E. (Freiburg, DE), Eichmann; Klaus (Freiburg, DE), Kramer; Michael (Heidelberg, DE), Reinhard; Wallich (Heidelberg, DE) Assignee(s): Max-Planck-Gesellschaft zur Forderung der Wissenscaften E.V. (Gottingen, DE), Deutsches Krebsforschun Zentrum Stiftung des Offentlichen Rechts (Heidelberg, DE) Patent Number: 5,686,267 Date filed: March 20, 1995 Abstract: A vaccine against Lyme disease, wherein it contains one or more monoclonal antibodies which are specific for the 31 kD antigen (OspA) or the 34 kD antigen (OspB) of Borrelia burgdorferi. The present invention also provides a process for obtaining this vaccine, as well as new monoclonal antibodies and antigens. Excerpt(s): The present invention is concerned with a vaccine against Lyme disease, with a process for obtaining said vaccine, with new monoclonal antibodies, with new antigens and with new recombinant DNA's and vectors. ... Lyme borreliosis is the most common infectious disease transmitted by ticks in the temperate regions. It is caused by the spirochete Borrelia burgdorferi which is transmitted to humans in particular by ticks of the genus Ixodes. The disease is a chronic, progressive infection which attacks many organs, such as the skin, the central and peripheral nervous system, the heart, the liver, the kidneys and musculoskeletal system. Since a reliable treatment of this disease by therapy with antibiotics is difficult, at the moment great efforts are being made to investigate the pathogen itself and the immune response of the host to infection with Borrelia burgdorferi. In the case of persons afflicted by Lyme disease, there is admittedly ascertained a high titre of antibodies against Borrelia burgdorferi which, however, do not provide any protection against the infection. It is assumed that the patbogen passes over very quickly from the blood circulation into the tissues and can there no longer be directly reached by the immune system. This would mean that a protection by antibodies is only possible immediately after commencement of the infection, i.e. as long as the pathogen is still present in the blood circulation. ... The fact that a natural infection with Borrelia burgdorferi has been found in various kinds of animals has led to attempts to establish laboratory models for Lyme disease. This also took place with limited success. Thus, in the case of experiments which had the object of inducing in mice a specific immune response for Borrelia burgdorferi, it was found that the infection of inbred mouse strains with a prolonged cultured isolate of Borrelia burgdorferi led to

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moderate but significant pathomorphological changes in various organs, such as the brain, the heart, the lungs and the kidneys, which were comparable to those which are to be observed in patients with Lyme disease (see Schaible et al., Infect. Immun., 1, 41/1988). The development of a serious aspect of the disease in animals was presumably prevented either by the immune defence of the host and/or by the reduced virulence of spirochetes cultured in vitro for a comparatively long period of time (see Johnson et al., J. Clin. Microbiol., 20, 747/1984; Schwan et al., Infect. and Immun., 56, 1837/1988). Web site: http://www.delphion.com/details?pn=US05686267__ ·

Methods for diagnosing early Lyme disease Inventor(s): Padula; Steven J. (Simsbury, CT) Assignee(s): University of Connecticut (Storrs, CT) Patent Number: 5,620,862 Date filed: November 24, 1993 Abstract: The invention relates to DNA encoding Borrelia burgdorferi sensu stricto outer surface protein C. Purified and recombinant forms of a 23 kDa protein from a Connecticut isolate of B. burgdorferi are described. The 23 kDa protein, referred to as p23 or OspC, can be used for immunodiagnostic assays for detection of early Lyme disease. The protein, amino acid coding for the protein and DNA sequences can be used to prevent Lyme disease, to diagnose/detect B. burgdorferi in human or animal tissues or body fluids. Antibodies specific for the protein can also be generated. Excerpt(s): Lyme disease is a multisystem infection caused by the tickborne spirochete, B. burgdorferi (Steere, 1989). Because of the low yield of both culture and direct visualization techniques for identification of this organism, the diagnosis of Lyme disease has relied on serologic confirmation in patients with characteristic clinical findings. ... Recognizing Lyme disease in the early stages can be difficult, however, because patients may not manifest the characteristic rash or may have only non-specific flu-like symptoms. This difficulty of diagnosis is compounded by the delayed emergence of a humoral response to the spirochete as detected by available serologic tests (Steere, 1989). These tests, which currently lack standardization, also do not readily distinguish between reactivity to B. burgdorferi proteins and crossreactive proteins from commensual or other pathogenic organisms (Hansen et al., 1988; Magnarelli et al., 1987). Delay in establishing the diagnosis of Lyme disease in its early stages is clinically important

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because timely institution of appropriate antibiotic treatment can prevent the serious sequelae from this potentially chronic infection (Dattwyler et al., 1990; Steere et al., 1983). ... Initial studies with immunoblot analysis of patients from North America with the early manifestations of Lyme disease found IgM reactivity predominantly against the 41 kDa flagellar protein of B. burgdorferi (Barbour et al., 1986; Craft et al., 1986). In hope of improving the level of detection of the antibody response in early Lyme disease, studies have utilized enriched preparations and recombinant forms of the 41 kDa flagellar protein as target antigen for serologic testing (Magnarelli et al., 1992; Coleman et al., 1987). This approach was prompted by the initial immunoblot studies with B. burgdorferi lysates in which an early and predominant IgM antibody response to the flagellar protein was demonstrated by Craft et al., 1986. Use of the flagellar protein-based serologic tests may be problematic because of the relatively frequent finding of cross-reactive antibodies to conserved flagellar epitopes from commonly occurring commensual and pathogenic spirochetes, such as those found in the mouth (Magnarelli et al., 1990; Russell et al., 1984). Web site: http://www.delphion.com/details?pn=US05620862__ ·

Flagellin-based polypeptides for the diagnosis of lyme disease Inventor(s): Flavell; Richard A. (Killingworth, CT), Fikrig; Erol (Guilford, CT), Berland; Robert (Kingston, NY) Assignee(s): Yale University (New Haven, CT) Patent Number: 5,618,533 Date filed: December 10, 1993 Abstract: Diagnostic means and methods for Lyme disease comprising B. burgdorferi flagellin polypeptides and antibodies. Compositions and methods comprising neuroborreliosis-associated antigens useful for the detection, treatment and prevention of neuroborreliosis, arthritis, carditis and other manifestations of Lyme disease. Excerpt(s): This invention relates to flagellin-based compositions and methods useful for the diagnosis and treatment of Lyme disease. More particularly, this invention relates to flagellin polypeptides which are useful to detect the presence of B. burgdorferi in humans and other animals, and which are useful to diagnose and treat neuroborreliosis, arthritis, carditis and other manifestations of Lyme disease. Also within the scope of this invention are antibodies directed against the flagellin polypeptides and diagnostic kits comprising the antibodies or polypeptides. ... Lyme borreliosis is the most common vector-borne

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infection in the United States [S. W. Barthold, et al., "An Animal Model For Lyme Arthritis", Ann. N.Y. Acad. Sci., 539, pp. 264-73 (1988)]. It has been reported in every continent except Antarctica. The clinical hallmark of Lyme Disease is an early expanding skin lesion known as erythema migrans (ECM), which may be followed weeks to months later by neurologic, cardiac, and joint abnormalities. ... The causative agent of Lyme disease is a spirochete known as Borrelia burgdorferi, transmitted primarily by ixodes ticks that are part of the Ixodes ricinus complex. B. burgdorferi has also been shown to be carried in other species of ticks and in mosquitoes and deer flies, but it appears that only ticks of the I. ricinus complex are able to transmit the disease to humans. Web site: http://www.delphion.com/details?pn=US05618533__ ·

Method for detecting lyme disease Inventor(s): McCann; Daisy S. (Ontario, CA), Chuba; Paul (Detroit, MI) Assignee(s): McCann Associates, Inc. (Wayne, MI) Patent Number: 5,494,797 Date filed: July 8, 1994 Abstract: Described is a method of detecting the presence of Lyme Disease organism comprising the steps of (a) combining a sample with an oligonucleotide probe for the organism; (b) hybridizing the probe with the organism; and (c) determining the presence of the organism hybridized with the probe. Also described is a kit containing a hybridization buffer, a labeled probe, and filter assemblies on which the hybridized product may be placed during the hybridization reaction. The kit may also contain positive and negative control filters to assist in the evaluation of unknown specimens. Excerpt(s): This invention relates to Lyme disease. ... Lyme disease is a systemic tick-borne illness generally characterized as a reddish or purplish target rash radiating around the tick bite. Lyme disease is generally characterized as being caused by a spirochete bacteria Borrelia burgdorferi. Various sub-species and strains of this organism have been identified, but their inter-relationship is not finally determined. ... The diagnostic acumen for Lyme Disease is poor. The ability to quickly and reliably detect the presence of Borrelia burgdorferi in patients suspected of having Lyme Disease is of great medical importance. The in-vitro culture of Borrelia burgdorferi is currently the most effective technique but is an impractical method of diagnosis. Web site: http://www.delphion.com/details?pn=US05494797__

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Specific and sensitive diagnostic test for Lyme disease Inventor(s): Simpson; Warren J. (Hamilton, MT), Schwan; Tom (Hamilton, MT), Garon; Claude (Hamilton, MT) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,489,511 Date filed: December 27, 1993 Abstract: A sensitive DNA probe for detecting infection by Borrelia burgdorferi, the causative agent of Lyme disease, is provided. Excerpt(s): The present invention is related generally to diagnostic tests. More particularly, the present invention is related to providing specific and sensitive diagnostic probes for detecting infection by Borrelia burgdorferi, the causative agent of Lyme disease. Web site: http://www.delphion.com/details?pn=US05489511__

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Nucleic acid probes for the detection of Lyme disease spirochetes Inventor(s): Weisburg; William G. (Milford, MA) Assignee(s): Amoco Corporation () Patent Number: 5,466,577 Date filed: October 27, 1993 Abstract: Nucleic acid probes are described for detecting bacteria capable of causing Lyme disease. These probes complement the ribosomal ribonucleic acid sequences unique to Borrelia spirochetes, and as such can detect the rRNA, rDNA, or polymerase chain reaction amplification products of these genes. These probes, plus the described amplification primers, can be used to detect the etiological agent of Lyme disease in human or veterinary samples, and for determining the infective potential of Ixodes ticks. Excerpt(s): This invention relates to detection of bacteria belonging to the species Borrelia burgdorferi and related species of tick-borne spirochetes capable of causing human and veterinary disease. More specifically, it provides nucleic acid probes and compositions along with methods for their use for the specific detection of Lyme disease causing bacteria. ... Lyme borreliosis, Lyme disease, Lyme arthritis, Bannwarth's syndrome, or erythema chronicum migrans (ECM) are synonymous designations for a zoonotic spirochetal infection transmitted by the bite of ticks of the genus Ixodes. Although the disease was known in Europe for quite some

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time, it was not discovered in the United States until a 1975 arthritis epidemic occurred in Connecticut. A presumptive etiological agent was isolated from a tick in 1982 (Burgdorfer et. al, Science 216:1317-1319, 1982). In 1984, the spirochete was shown to be a member of the genus Borrelia, and formally named Borrelia burgdorferi (Johnson et. al, Int. J. Syst. Bacteriol. 34:496-497, 1984). As such, it is an evolutionary relative of Borrelia hermsii, Borrelia turicatae, Borrelia anserina, and other members of this arthropod associated genus of spiral bacteria. ... Lyme disease is a serious chronic borrelial infection characterized by a diversity of symptoms at various stages. Approximately 3 to 14 days following the initiating tick bite, symptoms may include fever, flu-like illness, and the appearance of the ECM skin rash. Stage two, occurring weeks to months after the initial bite includes further skin involvement, arthritis, nervous system complaints, and cardiac pathology. Stage three is characterized by more severe arthritis and nervous system complications. Web site: http://www.delphion.com/details?pn=US05466577__ ·

Sensitive diagnostic test for lyme disease Inventor(s): Rosa; Patricia A. (Hamilton, MT) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,279,938 Date filed: May 18, 1992 Abstract: The nucleotide sequence of a recombinant clone containing a specific segment of Borrelia burgdorferi DNA which enables the identification of the spirochetes causing Lyme disease has been provided. A diagnostic kit containing oligonucleotide primers derived from this sequence, suitable for the detection of Borrelia burgdoferi in a PCR assay, as well as the cloned DNA of the present invention, allows the detection of Lyme disease with sensitivity and specificity not heretofore attained by any other test. Excerpt(s): The present invention relates generally to diagnostic tests, particularly to assays and kits. More particularly, the present invention relates to a diagnostic kit comprising containers containing various components for performing a sensitive and specific assay for detecting the presence of Lyme disease spirochetes. ... Diagnosis of Lyme disease is often not straightforward. There exist well-documented cases of Lyme disease where knowledge of tick bite, skin rash or positive serology are missing (Magnarelli, et al, 1987, J. Infect. Dis, 156: 183-187; Craft et al, 1984, J. Infect. Dis., 149: 789-795; Dattwyler et al, 1988, N. Engl. J. Med.,

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319: 1441-1446). Most of the systemic manifestations of advanced Lyme disease are not unique and demonstration of spirochetes in patients is extremely difficult (Steere, et al, 1983, N. Engl. J. Med., 308: 733-740). Considering the debilitating nature of the advanced stages of the disease, an accurate diagnostic tool remains a critical need. ... It is an additional object of the present invention to provide a diagnostic test for Lyme disease. Web site: http://www.delphion.com/details?pn=US05279938__ ·

Method and materials for detecting lyme disease Inventor(s): Schutzer; Steven E. (21 Canterbury Rd., Great Neck, NY 11021) Assignee(s): none reported Patent Number: 5,187,065 Date filed: December 22, 1989 Abstract: A method for detecting the onset or presence of Lyme disease in a mammal, which comprises isolating a biological sample from the mammal, isolating from said biological sample any circulating immune complexes suspected to contain antibody reactive to Borrelia burgdorferi, dissociating the immune complexes so isolated, and examining the dissociated immune complexes for the presence of antibody. The present method offers a simple and reliable means for detecting Borrelia antibodies. Test kits and related methodology are also disclosed. Excerpt(s): The Applicant is author or co-author of articles, submitted or to be submitted for publication, directed to the subject matter of the present invention: (e.g. "Sequestration of Antibody to Borrelia burgdorferi in Immune Complexes in Seronegative Lyme Disease" (submitted for publication). The above listed articles are incorporated herein by reference. ... The present invention relates to the detection of Lyme disease, and particularly to the clinically reliable examination and detection of Lyme disease in instances of seronegativity in mammals and particularly in humans. ... Seronegativity is one of the major obstacles to diagnosis of Lyme disease as well as a common unexplained feature of the disease. Lyme disease, etiologically linked to the spirochete, Borrelia burgdorferi, may present acutely or develop insidiously. Its manifestations are protean and may specifically involve the musculoskeletal, cardiovascular, cutaneous, and nervous systems. Some cases begin with a characteristic cutaneous lesion, erythema chronicum migrans (ECM), following a deer tick bite. However, many others are unaware of a tick bite or skin lesion, making diagnosis difficult, yet

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develop features of Lyme disease. Diagnosis is also complicated when symptomatic individuals are negative for Borrelia burgdorferi antibody despite sensitive serological assays. Untreated patients as well as patients who have received early antibiotic therapy may remain seronegative even when symptoms of infection persist. Web site: http://www.delphion.com/details?pn=US05187065__

Patent Applications on Lyme Disease As of December 2000, U.S. patent applications are open to public viewing.25 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years).

Keeping Current In order to stay informed about patents and patent applications dealing with Lyme disease, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “Lyme disease” (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 Lyme disease. You can also use this procedure to view pending patent applications concerning Lyme disease. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Arteries: The vessels carrying blood away from the heart. [NIH] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They 25

This has been a common practice outside the United States prior to December 2000.

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are divided into three groups: neutrophils, eosinophils, and basophils. [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] 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] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Ricinus: An euphorbiaceous plant with very toxic seeds. The castor bean, castor oil, ricin, and other lectins are its most important products. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Treponema: A genus of microorganisms of the order spirochaetales, many of which are pathogenic and parasitic for man. [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]

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CHAPTER 6. BOOKS ON LYME DISEASE Overview This chapter provides bibliographic book references relating to Lyme disease. You have many options to locate books on Lyme disease. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on Lyme disease include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is 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 to 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 “Lyme disease” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on Lyme disease:

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Sick and Tired of Feeling Sick and Tired: Living With Invisible Chronic Illness Source: New York, NY: W.W. Norton and Company, Inc. 2000. 306 p. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 6709292. Fax (301) 670-9486. Website: www.lupus.org/lupus. PRICE: $8.95 for 1-9 copies; $6.50 for 10-25 copies. ISBN 0393320650. Summary: This book offers hope and coping strategies to people who suffer from invisible chronic illnesses (ICIs) such as chronic fatigue and chronic pain. Part 1 focuses on the experience of having an ICI. Chapter 1 serves as an introduction to ICI. Chapter 2 describes some forms of ICI, including arthritis, Charcot-Marie-Tooth disease, chronic fatigue immune dysfunction syndrome, endometriosis, fibromyalgia, human immunodeficiency virus, inflammatory bowel disease, irritable bowel syndrome, lupus erythematosus, Lyme disease, migraine, multiple sclerosis, post polio syndrome, premenstrual syndrome, and thyroid illnesses. Chapter 3 explores the psychological consequences of ICI, focusing on self doubt, self dislike, uncertainty, fear of mental illness, fear of the course of illness, giving in to illness, interpersonal insecurity, loss of self esteem, guilt, and roller coaster feelings. Chapter 4 examines the dimensions of ICI and their psychological impact, focusing on the social acceptability of the illness, the clarity of diagnosis, and the potential severity of the illness. Chapters 5 through 8 deal with adjusting to and accepting a constant state of unwellness; seeking answers; consulting a doctor; and relating to family, friends, and colleagues. Part 2 focuses on coping with ICI. Chapters deal with living in the present, thinking clearly, handling irrational thinking, using imagery to confront irrational thinking, identifying one's life story and the role played in the story, getting and keeping the attention of the health care system, coping with ICI in the family, saying what one feels, hearing what is said, and managing the stress associated with ICI. The book includes a general reading list on illnesses and a list of illness associations. Numerous references.

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Everything You Need To Know About Lyme Disease and Other TickBorne Disorders Source: Somerset, NJ: John Wiley and Sons, Inc. 1997. 256 p. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail: [email protected]. Website: catalog.wiley.com. PRICE: $14.95 plus shipping and handling. Also

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available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525TICK. E-mail: [email protected]. Website: www.lyme.org. PRICE: $18.00; bulk orders available at cost. Summary: This book provides the general public and people who have Lyme disease with comprehensive information about this tick-borne illness. The book begins with a chapter on the public health threat posed by Lyme disease. This chapter provides an overview of progression, diagnosis, and treatment; an explanation of the science of Lyme disease; and a description of other tick-borne disorders. Chapter two discusses ticks' life cycle and method of feeding. Other topics include the forces that have converged to increase the threat of ticks, factors influencing the likelihood of becoming ill from a tick bite, and types of ticks. The next chapter presents significant events in the history of Lyme disease. Chapter four presents the signs and symptoms of localized and disseminated Lyme disease. The fifth chapter discusses the diagnosis of Lyme disease in terms of getting a diagnosis and undergoing antibody tests to detect Borrelia burgdorferi, as well as types of antibody and direct detection tests. Chapter six addresses treatment, focusing on choosing health professionals, taking antibiotics, persuading an insurer to pay for treatment, and obtaining emotional support. This is followed by a chapter that describes other tick-borne disorders, including babesiosis, ehrlichiosis, Rocky Mountain spotted fever, Colorado tick fever, tularemia, relapsing fever, Powassan encephalitis, and tick paralysis. Subsequent chapters provide guidelines on using proper equipment to remove a tick, protecting oneself and family members from ticks, and modifying property to create tick-free zones. Final chapters report on the promise of a vaccine for Lyme disease and discuss the risks of tick bites to animals. 6 appendixes, 28 figures, 1 table, and numerous references. ·

Lyme Disease: The Cause, the Cure, the Controversy Source: Baltimore, MD: Johns Hopkins University Press. 1996. 274 p. Contact: Johns Hopkins University Press, 2715 North Charles Street, Baltimore, MD 21218-4319. Summary: This book for the general public or individuals with Lyme disease presents a comprehensive discussion of what is known about Lyme disease. Chapters explain what Lyme disease is and how it is spread; describe the symptoms and consequences of Lyme disease; identify all of the diagnostic tests for Lyme disease and discuss the meaning of test results; examine proven and unproven treatments for Lyme disease, focusing on antibiotic therapy and alternative medicines; compare Lyme disease with other conditions, such as fibromyalgia and

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chronic fatigue syndrome; discuss depression; and offer guidelines for preventing Lyme disease. Case reports of four individuals are used throughout the book to illustrate the varying course of Lyme disease in different individuals. A report demonstrates the problems confronting individuals who test negative for Lyme disease but are convinced that Lyme disease explains their symptoms. A list of resources is included. 7 figures and 3 photographs. ·

Guidelines for Perinatal Care Source: Guidelines for Perinatal Care; 3rd edition, 1992. Contact: American College of Obstetricians and Gynecologists, PO Box 96920, Washington, DC, 20090-6920, (202) 638-5577, http://www.acog.com. American Academy of Pediatrics, Department of Maternal Child and Adolescent Health, Committee on Pediatric AIDS, 141 NW Point Blvd, Elk Grove Village, IL, 60007-1098, (847) 434-4000, http://www.aap.org. Summary: This book chapter focuses on the clinical management of viral and bacterial perinatal infections. These include cytomegalovirus, herpes simplex, the human immunodeficiency virus (HIV), human papillomavirus, human parvovirus, rubella, varicella-zoster, group B streptococcal, listeriosis, syphilis, lyme disease, and chlamydia infection. For each of these infections, guidelines are provided on treatment and counseling during pregnancy, obstetric management, management of exposed newborns, nursery management, and early diagnosis. The section on HIV focuses on diagnostic criteria for adults, children, and infants; prevention; and management after delivery.

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Essentials of Musculoskeletal Care. 2nd ed Source: Rosemont, IL: American Academy of Orthopaedic Surgeons (AAOS). 2001. 756 p. Contact: Available from American Academy of Orthopaedic Surgeons (AAOS). 6300 North River Road, Rosemont, IL 60018-4262. (800) 626-6726 (toll-free) or (847) 823-7186. Fax (800) 823-8025 (toll-free) or (847) 8238025. E-mail: [email protected]. Website: www.aaos.org. PRICE: $105.00 for nonmembers; $90.00 AAOS members; $80.00 for residents; plus shipping and handling. ISBN 0892032170. Summary: This book serves as a guide and easy reference to provide health professionals with information on the diagnosis and management of common musculoskeletal conditions. The book begins with a section on general orthopedics. This section presents information on the principles of evaluating and examining a patient with musculoskeletal

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complaints and discusses pharmacological and nonpharmacological modes of treatment. In addition, the section describes various musculoskeletal conditions, including amputations, rheumatoid arthritis, osteoarthritis, septic arthritis, compartment syndrome, crystalline deposition diseases, diffuse idiopathic skeletal hyperostosis, falls and other injuries, fibromyalgia syndrome, fractures, Lyme disease, osteomyelitis, osteoporosis, overuse syndromes, reflex sympathetic dystrophy and complex regional pain syndromes, seronegative spondyloarthropathies, sprains and strains, soft tissue and bone tumors, and venous thrombosis. This is followed by sections that deal with common conditions affecting the shoulder girdle, elbow and forearm, hand and wrist, hip and thigh, knee and lower leg, foot and ankle, and spine, including acute and chronic or repetitive injuries and degenerative, inflammatory, or idiopathic conditions. Information in these sections includes synonyms for and red flags associated with each condition; the definition, clinical symptoms, diagnosis, differential diagnosis, adverse outcomes, and treatment of the condition; diagnostic tests; and adverse treatment outcomes. The final section focuses on pediatric orthopedics. The book includes a glossary of ICD-9 codes, a list of common orthopedic terms and their definitions, and a subject index. Numerous figures and 36 tables. ·

Delicate Balance: Living Successfully with Chronic Illness Source: New York, NY: Plenum Press. 1998. 289 p. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 6105308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $22.00 plus shipping and handling. Summary: This book offers a look at the lives of people with chronic and largely invisible illnesses, such as lupus, Sjogren's syndrome, fibromyalgia, chronic fatigue syndrome, inflammatory bowel disorders (IBD), Lyme disease, interstitial cystitis, and multiple sclerosis. Instead of focusing on a specific illness, this book candidly examines the experience of living with chronic disease through in depth, personal interviews with patients, care providers, and family members. The author follows 21 individuals in the quest to find a comprehensive diagnosis; locate a capable and caring health care provider; research and try traditional or alternative treatments; make sense of their powerful emotions; strengthen relationships with family and friends; make significant career decisions; and reflect on how illness changes their overall lives. The book includes practical advice, including how to use the Internet for information and support, how to seek reasonable accommodations under the Americans

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with Disabilities Act (ADA), how to apply for Social Security Disability Insurance, and how to make the most of the doctor patient relationship in an era of managed care. The author also examines some of the most current research on the mind body connection and its relation to chronic physical illness. The book concludes with a section of endnotes, a list of resources, a glossary of terms, and a subject index. ·

Safety and environmental health Source: Kent, OH: American School Health Association. [1993?]. ca. 50 pp. Contact: Available from Publications Department, American School Health Association, P.O. Box 708, Kent, OH 44240-0708. Telephone: (330) 678- 1601 / fax: (330) 678-4526 / e-mail: [email protected] / Web site: http://www.ashaweb.org. $8.75 members, $10.25 nonmembers; plus $3.00 shipping and handling. Summary: This American School Health Association topical package on safety and environmental health contains selected reprints from the 'Journal of School Health' from 1984 to 1992. The topics addressed in the articles include: a high school safety belt incentive program; the safety of lawn chemicals on school grounds; radon in schools; an earthquake preparedness program; sunscreens and skin cancer; evaluating pedestrian safety education materials for children ages five to nine; psychological health and well-being in school; Lyme disease; school bus safety; student accidents; and alcohol and drug use and automobile safety.

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Oral and Cutaneous Manifestations of Hematogenously Disseminated Systemic Infections: A Monograph Source: Research Triangle Park, NC: Glaxo, Inc. 1993. 79 p. Contact: Available from Glaxo-Wellcome Education Resource Center. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free. Stock Number GVL251. Summary: This monograph describes oral and dermatologic manifestations resulting from systemic infections. Written as a continuing education tool for physicians, the monograph features 26 sections, each of which includes a description of dermatologic manifestations, other clinical features, laboratory findings, and epidemiologic factors. Diseases covered include AIDS, blastomycosis, candidiasis, coccidioidomycosis, cryptococcoses, erythema infectiousum (Fifth disease), gonococcemia, gram-negative bacterial sepsis, hand-foot-and-mouth disease, infectious mononucleosis, infective endocarditis, Kawasaki syndrome, leprosy,

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lyme disease, meningococcemia, Rocky Mountain spotted fever, roseola, rubella (German measles), rubeola (measles), scarlet fever, secondary (disseminated) syphilis, staphylococcal scalded skin syndrome, toxic shock syndrome, typhoid fever, varicella (chickenpox), and Vibrio vulnificus infection. Each section is illustrated with full-color photographs depicting patients with manifestations of the disease under consideration. The monograph includes a glossary of illustrations to help with diagnosis and classification. The monograph concludes with a selftest and instructions for receiving continuing medical education credits. A subject index is also included. 12 references.

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 PrintÒ). The following have been recently listed with online booksellers as relating to Lyme disease (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

Lyme Disease : Selected Articles from New England Journal of Medicine, Mmwr, and Massachusetts Medicine. (1987); ISBN: 0910133220; http://www.amazon.com/exec/obidos/ASIN/0910133220/icongroupin terna

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Lyme Borreliosis : Proceedings of the Second International Symposium on Lyme Disease and Related Disorders, Vienna 1985 by Gerold Stanek, et al (1988); ISBN: 0895742306; http://www.amazon.com/exec/obidos/ASIN/0895742306/icongroupin terna

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Lyme Disease and Related Disorders (Annals of the New York Academy of Sciences, Vol 539) by Jorge L. Benach, Edward M. Bosler (Editor) (1988); ISBN: 0897664744; http://www.amazon.com/exec/obidos/ASIN/0897664744/icongroupin terna

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Lyme Disease : An Annotated Bibliography (1989); ISBN: 9992998512; http://www.amazon.com/exec/obidos/ASIN/9992998512/icongroupin terna

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Lyme Borreliosis II (Zentralblatt Fur Bakteriologie Supplement 18) by Gerold Stanek (Editor) (1989); ISBN: 089574306X; http://www.amazon.com/exec/obidos/ASIN/089574306X/icongroupi nterna

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Microorganisms : From Smallpox to Lyme Disease by Thomas D. Brock (Editor) (1989); ISBN: 0716720841; http://www.amazon.com/exec/obidos/ASIN/0716720841/icongroupin terna

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Protect Yourself from Lyme Disease (1989); ISBN: 9993652539; http://www.amazon.com/exec/obidos/ASIN/9993652539/icongroupin terna

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Protect Yourself from Lyme Disease : The New York Medical College Guide to Prevention, Detection, and Treatment by Diana Benzaia (1989); ISBN: 0440204372; http://www.amazon.com/exec/obidos/ASIN/0440204372/icongroupin terna

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Lyme Disease by Elaine Landau (1990); ISBN: 0788190555; http://www.amazon.com/exec/obidos/ASIN/0788190555/icongroupin terna

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Learning About Lyme Disease by Jo Ann Heltzel (1990); ISBN: 0963304100; http://www.amazon.com/exec/obidos/ASIN/0963304100/icongroupin terna

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Lyme Disease the Great Imitator: How to Prevent and Cure It by Alvin Silverstein, et al (1990); ISBN: 0962365386; http://www.amazon.com/exec/obidos/ASIN/0962365386/icongroupin terna

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Lyme Disease (1991); ISBN: 0962266906; http://www.amazon.com/exec/obidos/ASIN/0962266906/icongroupin terna

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Lyme Disease and the Nervous System by Louis Reik (1991); ISBN: 0865773947; http://www.amazon.com/exec/obidos/ASIN/0865773947/icongroupin terna

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Cicm 1 : 4 Lyme Disease by Fessia (1991); ISBN: 0812113381; http://www.amazon.com/exec/obidos/ASIN/0812113381/icongroupin terna

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Lyme Disease : My Search for a Diagnosis by Linda Hanner, et al (1991); ISBN: 0962266914;

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http://www.amazon.com/exec/obidos/ASIN/0962266914/icongroupin terna ·

Lyme Disease : Molecular and Immunologic Approaches (Current Communications in Cell & Molecular Biology, Vol. 6) by Steven E. Schutzer (Editor) (1992); ISBN: 0879693770; http://www.amazon.com/exec/obidos/ASIN/0879693770/icongroupin terna

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Ecology and Management of Tick and Lyme Disease at Fire Island National Seashore and Selected Eastern National Parks (Scientific Monograph, 92/20) by Howard S. Ginsberg (1992); ISBN: 9992743204; http://www.amazon.com/exec/obidos/ASIN/9992743204/icongroupin terna

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Lyme Disease 1991 (1992); ISBN: 0963234803; http://www.amazon.com/exec/obidos/ASIN/0963234803/icongroupin terna

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Aspects of Lyme Borreliosis by K. Weber, W. Borgdorfer (Editor) (1992); ISBN: 0387556281; http://www.amazon.com/exec/obidos/ASIN/0387556281/icongroupin terna

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Lyme Disease 1991 : Patient Physician Perspectives from the U S and Canada by Lora Mermin (Editor) (1992); ISBN: 096323482X; http://www.amazon.com/exec/obidos/ASIN/096323482X/icongroupi nterna

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Lyme Disease by Patricia K., MD Coyle (1993); ISBN: 1556643659; http://www.amazon.com/exec/obidos/ASIN/1556643659/icongroupin terna

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Lyme Disease : A Mother's Perspective by Karen Angotti (1993); ISBN: 0963390236; http://www.amazon.com/exec/obidos/ASIN/0963390236/icongroupin terna

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Ecology and Environmental Management of Lyme Disease by Howard S. Ginsberg (Editor) (1993); ISBN: 0813519284; http://www.amazon.com/exec/obidos/ASIN/0813519284/icongroupin terna

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Lyme Disease (1993); ISBN: 9992643552; http://www.amazon.com/exec/obidos/ASIN/9992643552/icongroupin terna

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Lyme Disease by Ronald L. Hoffman (1994); ISBN: 0879836172; http://www.amazon.com/exec/obidos/ASIN/0879836172/icongroupin terna

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Lyme Borreliosis (NATO Asi Series A: Life Sciences, Vol 260) by John S. Axford, David H.E. Rees (Editor) (1994); ISBN: 0306446642; http://www.amazon.com/exec/obidos/ASIN/0306446642/icongroupin terna

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Lyme Disease by Anderson (1995); ISBN: 0787215082; http://www.amazon.com/exec/obidos/ASIN/0787215082/icongroupin terna

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Lyme Disease : The Cause, the Cure, the Controversy (Johns Hopkins Health Book) by Alan G. Barbour (1996); ISBN: 0801852242; http://www.amazon.com/exec/obidos/ASIN/0801852242/icongroupin terna

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The Widening Circle: A Lyme Disease Pioneer Tells Her Story by Polly Murray (1996); ISBN: 0312140681; http://www.amazon.com/exec/obidos/ASIN/0312140681/icongroupin terna

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Coping With Lyme Disease : A Practical Guide to Dealing With Diagnosis and Treatment by Denise Lang, et al (1997); ISBN: 0805047751; http://www.amazon.com/exec/obidos/ASIN/0805047751/icongroupin terna

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Rabies, Lyme Disease, Hanta Virus : And Other Animal-Borne Human Diseases in the United States and Canada by E. Lendell Cockrum (1997); ISBN: 1555611389; http://www.amazon.com/exec/obidos/ASIN/1555611389/icongroupin terna

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Lyme Disease -- The Untold Story by Dennis Lakin (1998); ISBN: 189062215X; http://www.amazon.com/exec/obidos/ASIN/189062215X/icongroupi nterna

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Applied Neuropsychology : Special Issue : Neuropsychological Aspects of Lyme Disease : 1999 by Richard F. Kaplan (Editor) (1999); ISBN: 0805898174; http://www.amazon.com/exec/obidos/ASIN/0805898174/icongroupin terna

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Surviving Lyme Disease Using Alternative Medicine by David A., Dr. Jernigan, D.C., B.S. Dr. David A. Jernigan (1999); ISBN: 0967462304; http://www.amazon.com/exec/obidos/ASIN/0967462304/icongroupin terna

Books 125

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Lyme Borreliosis : Biology, Epidemiology, and Control by J. S. Gray (Editor), et al (2002); ISBN: 0851996329; http://www.amazon.com/exec/obidos/ASIN/0851996329/icongroupin terna

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Lyme Disease (My Health) by Alvin Silverstein, et al (2002); ISBN: 0531165620; http://www.amazon.com/exec/obidos/ASIN/0531165620/icongroupin terna

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 “Lyme disease” (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:26 ·

Aspects of Lyme borreliosis. Author: K. Weber, W. Burgdorfer (eds.); coeditor, G. Schierz; Year: 1993; Berlin; New York: Springer-Verlag, c1993; ISBN: 3540556281 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/3540556281/icongroupin terna

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Biography of a germ. Author: Arno Karlen; Year: 2000; New York: Pantheon Books, c2000; ISBN: 0375401997 http://www.amazon.com/exec/obidos/ASIN/0375401997/icongroupin terna

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Ecology and environmental management of lyme disease. Author: edited by Howard S. Ginsberg; Year: 1993; New Brunswick, NJ: Rutgers University Press, c1993; ISBN: 0813519284 (cloth)

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is 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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126 Lyme Disease

http://www.amazon.com/exec/obidos/ASIN/0813519284/icongroupin terna ·

Ecology and management of ticks and lyme disease at Fire Island National Seashore and selected eastern national parks. Author: Howard S. Ginsberg; Year: 1992; Denver, CO: U.S. Dept. of the Interior, National Park Service, 1992

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Handbook of Lyme borreliosis. Author: Wendy P. Feaga, ed; Year: 1991; Madison, Wis.: <STRONG>Lyme Resource Group of Madison/South Central Wisconsin, [1991]

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Lyme borreliosis 1990: proceedings of the IV International Conference on Lyme Borreliosis, held in Stockholm, Sweden, June 18-21, 1990. Author: guest editors, Birgit Sköldenberg, Göran Stiernstedt; Year: 1991; Stockholm, Sweden: Almqvist & Wiksell International, [1991]

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Lyme borreliosis and tick-borne encephalitis. Author: [Patrick Oschmann ... et al. (eds.)]; Year: 1999; Bremen, Germany: UNI-MED Verlag, c1999; ISBN: 3895994499

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Lyme borreliosis II: based on the contribution to the First European Update on Lyme Borreliosis, Baden near Vienna 1987. Author: sponsored by the Hygiene Institute of the University of Vienna and by the Austrian Society for Hygiene, Microbiology, and Preventive; Year: 1989; Stuttgart; New York: G. Fischer Verlag, 1989; ISBN: 089574306X (U.S.) http://www.amazon.com/exec/obidos/ASIN/089574306X/icongroupi nterna

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Lyme borreliosis. Author: edited by John S. Axford and David H.E. Rees; Year: 1994; New York: Plenum Press, c1994; ISBN: 0306446642 http://www.amazon.com/exec/obidos/ASIN/0306446642/icongroupin terna

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Lyme disease: a pediatric perspective. Author: Lawrence S. Zemel; Year: 1992; Toronto, Ont.: Journal of Rheumatology Pub. Co., c1992

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Lyme disease: a summary of the occupational health concern. Author: James A. Baxter; Year: 1989; Hamilton, Ont.: Canadian Centre for Occupational Health and Safety, [1989]; ISBN: 066013246X

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Lyme disease: an annotated bibliography 1989. Author: Zemel, Lawrence S; Year: 1989; Bethesda, MD (Box AMS, Bethesda 20892): National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse, 1989

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Lyme disease: HHS programs and resources: report to congressional requesters. Author: United States General Accounting Office; Year: 2001; Washington, D.C.: The Office, [2001]

Books 127

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Lyme disease: January 1985 through December 1988: 850 citations. Author: prepared by Kristine Scannell and Fritz P. Gluckstein; Year: 1989; Bethesda, Md.: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section; Washington, D.C.: Sold by the Supt. of Docs., U.S. G.P.O., [1989]

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Lyme disease: molecular and immunologic approaches. Author: edited by Steven E. Schutzer; Year: 1992; Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1992; ISBN: 0879693770 http://www.amazon.com/exec/obidos/ASIN/0879693770/icongroupin terna

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Lyme disease: selected articles from the New England Journal of Medicine, MMWR, and Massachusetts medicine. Author: European Update on Lyme Borreliosis (1st: 1987: Baden, Austria); Year: 1987; Waltham, Mass.: Massachusetts Medical Society, 1987; ISBN: 0910133220 (pbk.) http://www.amazon.com/exec/obidos/ASIN/0910133220/icongroupin terna

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Lyme disease: the cause, the cure, the controversy. Author: Alan G.Barbour; Year: 1996; Baltimore: Johns Hopkins University Press, 1996; ISBN: 0801852242 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0801852242/icongroupin terna

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Lyme disease 1991: patient. Author: physician perspectives from the U.S. & Canada / Lora Mermin, editor; Year: 1992; Madison, WI: Education Project, Inc., c1992; ISBN: 096323482X (pbk.) http://www.amazon.com/exec/obidos/ASIN/096323482X/icongroupi nterna

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Lyme disease and related disorders. Author: edited by Jorge L. Benach and Edward M. Bosler; Year: 1988; New York, N.Y.: New York Academy of Sciences, 1988; ISBN: 0897664744 http://www.amazon.com/exec/obidos/ASIN/0897664744/icongroupin terna

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Lyme disease and the nervous system. Author: Louis Reik, Jr; Year: 1991; New York: Thieme Medical Publishers, 1991; ISBN: 0865773947 (TMP) http://www.amazon.com/exec/obidos/ASIN/0865773947/icongroupin terna

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Lyme disease. Author: Karlen, Arno; Year: 1990; New York, N.Y.: American Council on Science and Health, 1990

128 Lyme Disease

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Lyme disease. Author: [edited by] Patricia K. Coyle; Year: 1993; St. Louis: Mosby Year Book, c1993; ISBN: 1556643659 http://www.amazon.com/exec/obidos/ASIN/1556643659/icongroupin terna

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Lyme disease. Author: [edited by] Daniel W. Rahn, Janine Evans; Year: 1998; Philadelphia, Pa.: American College of Physicians, c1998; ISBN: 0943126584 (