THE OFFICIAL PATIENT’S SOURCEBOOK
on
ANTAVIRUS ULMONARY YNDROME 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 Official Patient’s Sourcebook on Hantavirus Pulmonary Syndrome: 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: 0-597-83054-1 1. Hantavirus Pulmonary Syndrome-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 Hantavirus pulmonary syndrome.
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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Adenoviruses
·
The Official Patient's Sourcebook on Arenaviridae
·
The Official Patient's Sourcebook on Chronic Fatigue Syndrome
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The Official Patient's Sourcebook on Ebola Hemorrhagic Fever
·
The Official Patient's Sourcebook on Filoviruses
·
The Official Patient's Sourcebook on Human Ehrlichiosis
·
The Official Patient's Sourcebook on Human Parainfluenza Viruses
·
The Official Patient's Sourcebook on Influenza Viruses
·
The Official Patient's Sourcebook on Lassa Fever
·
The Official Patient's Sourcebook on Lymphocytic Choriomeningitis
·
The Official Patient's Sourcebook on Marburg Hemorrhagic Fever
·
The Official Patient's Sourcebook on Q Fever
·
The Official Patient's Sourcebook on Rabies
·
The Official Patient's Sourcebook on Respiratory Syncytial Virus
·
The Official Patient's Sourcebook on Rift Valley Fever
·
The Official Patient's Sourcebook on Rocky Mountain Spotted Fever
·
The Official Patient's Sourcebook on Rotavirus
·
The Official Patient's Sourcebook on Viral Hemorrhagic Fevers
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 HANTAVIRUS PULMONARY SYNDROME: GUIDELINES ...................................................................... 9
Overview............................................................................................................... 9 What Is the Hantavirus? .................................................................................... 11 History of Hantavirus Pulmonary Syndrome.................................................... 11 How Is Hantavirus Transmitted? The Rodent Connection ............................... 17 Transmission: How Does “Aerosolization” Really Work? ................................ 21 Who Is at Risk of Getting HPS, and Why?........................................................ 22 What Are the Symptoms of HPS?...................................................................... 23 How Do I Prevent HPS? .................................................................................... 25 Tips For Preventing HPS: Prevention Indoors and Outdoors........................... 25 Common Signs of Rodent Infestation................................................................. 26 Safety Precautions for Cleaning Up Infested Areas ........................................... 29 What Is the Treatment for HPS?........................................................................ 34 More Guideline Sources ..................................................................................... 34 Vocabulary Builder............................................................................................. 37
CHAPTER 2. SEEKING GUIDANCE ....................................................... 41
Overview............................................................................................................. 41 Associations and Hantavirus Pulmonary Syndrome......................................... 41 Finding Doctors.................................................................................................. 43 Selecting Your Doctor ........................................................................................ 45 Working with Your Doctor ................................................................................ 45 Broader Health-Related Resources ..................................................................... 47
CHAPTER 3. CLINICAL TRIALS AND HANTAVIRUS PULMONARY SYNDROME........................................................................................... 49
Overview............................................................................................................. 49 Recent Trials on Hantavirus Pulmonary Syndrome.......................................... 52 Benefits and Risks............................................................................................... 53 Keeping Current on Clinical Trials.................................................................... 56 General References.............................................................................................. 57 Vocabulary Builder............................................................................................. 58
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 59
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CHAPTER 4. STUDIES ON HANTAVIRUS PULMONARY SYNDROME .... 61
Overview............................................................................................................. 61 Federally-Funded Research on Hantavirus Pulmonary Syndrome ................... 61 E-Journals: PubMed Central .............................................................................. 73 The National Library of Medicine: PubMed ...................................................... 74 Vocabulary Builder............................................................................................. 75
CHAPTER 5. PATENTS ON HANTAVIRUS PULMONARY SYNDROME ... 81
Overview............................................................................................................. 81 Patents on Hantavirus Pulmonary Syndrome................................................... 82 Patent Applications on Hantavirus Pulmonary Syndrome............................... 90 Keeping Current ................................................................................................. 90 Vocabulary Builder............................................................................................. 90
CHAPTER 6. BOOKS ON HANTAVIRUS PULMONARY SYNDROME ...... 93
Overview............................................................................................................. 93 Book Summaries: Online Booksellers ................................................................. 93 The National Library of Medicine Book Index ................................................... 94 Chapters on Hantavirus Pulmonary Syndrome................................................. 95 General Home References ................................................................................... 96
CHAPTER 7. MULTIMEDIA ON HANTAVIRUS PULMONARY SYNDROME ............................................................................................................. 97
Overview............................................................................................................. 97 Bibliography: Multimedia on Hantavirus Pulmonary Syndrome ..................... 97
CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES ..................... 99
Overview............................................................................................................. 99 NIH Guidelines................................................................................................... 99 NIH Databases.................................................................................................. 100 Other Commercial Databases ........................................................................... 104 Specialized References....................................................................................... 105
CHAPTER 9. DISSERTATIONS ON HANTAVIRUS PULMONARY SYNDROME......................................................................................... 107
Overview........................................................................................................... 107 Dissertations on Hantavirus Pulmonary Syndrome........................................ 107 Keeping Current ............................................................................................... 108
PART III. APPENDICES .................................................. 109 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 111
Overview........................................................................................................... 111 Your Medications: The Basics .......................................................................... 112 Learning More about Your Medications .......................................................... 114 Commercial Databases...................................................................................... 115 Contraindications and Interactions (Hidden Dangers) ................................... 116 A Final Warning .............................................................................................. 117 General References............................................................................................ 118
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Vocabulary Builder........................................................................................... 118
APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 119
Overview........................................................................................................... 119 What Is CAM? ................................................................................................. 119 What Are the Domains of Alternative Medicine?............................................ 120 Can Alternatives Affect My Treatment? ......................................................... 123 Finding CAM References on Hantavirus Pulmonary Syndrome.................... 124 Additional Web Resources................................................................................ 125 General References............................................................................................ 126
APPENDIX C. RESEARCHING NUTRITION ......................................... 129
Overview........................................................................................................... 129 Food and Nutrition: General Principles........................................................... 129 Finding Studies on Hantavirus Pulmonary Syndrome ................................... 134 Federal Resources on Nutrition........................................................................ 136 Additional Web Resources................................................................................ 137 Vocabulary Builder........................................................................................... 137
APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 139
Overview........................................................................................................... 139 Preparation ....................................................................................................... 139 Finding a Local Medical Library ...................................................................... 140 Medical Libraries Open to the Public............................................................... 140
APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 147
Overview........................................................................................................... 147 Your Rights as a Patient................................................................................... 147 Patient Responsibilities .................................................................................... 151 Choosing an Insurance Plan............................................................................. 152 Medicare and Medicaid .................................................................................... 155 NORD’s Medication Assistance Programs ..................................................... 158 Additional Resources ........................................................................................ 158
APPENDIX F. MORE ON HANTAVIRUS: TECHNICAL INFORMATION 161
Overview........................................................................................................... 161 HPS Case Definition ........................................................................................ 162 Clinical Disease Manifestations ....................................................................... 163 Disease Development........................................................................................ 165 Differential Diagnosis....................................................................................... 166 Radiologic Findings .......................................................................................... 167 Treatment.......................................................................................................... 168 Histopathology.................................................................................................. 169 Pathology and Pathogenesis ............................................................................. 170 Diagnostics ....................................................................................................... 171 Epidemiology .................................................................................................... 173 Ecology.............................................................................................................. 174 Virology ............................................................................................................ 177 Prevention Information .................................................................................... 181
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Suspected HPS Specimen Submission Guidelines ........................................... 183 Guidelines for Submitting Specimens to the Special Pathogens Branch ......... 184 HPS Clinical Update, 1999 Satellite Conference ............................................. 185
ONLINE GLOSSARIES.................................................... 197 Online Dictionary Directories.......................................................................... 198
HANTAVIRUS PULMONARY SYNDROME GLOSSARY ......................................................................... 199 General Dictionaries and Glossaries ................................................................ 214
INDEX................................................................................... 216
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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Hantavirus Pulmonary Syndrome
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 Hantavirus Pulmonary Syndrome 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 Hantavirus pulmonary syndrome, 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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome 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.
Introduction
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Deciding on appropriate 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 Hantavirus pulmonary syndrome (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 Hantavirus pulmonary syndrome. It also gives you sources of information that can help you find a doctor in your local area specializing in treating Hantavirus pulmonary syndrome. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with Hantavirus pulmonary syndrome. Part II moves on to advanced research dedicated to Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome. 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 “free-to-use” options. Part III provides appendices of useful background reading for all patients with Hantavirus pulmonary syndrome or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome.
Scope While this sourcebook covers Hantavirus pulmonary syndrome, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that Hantavirus pulmonary syndrome is often considered a synonym or a condition closely related to the following:
4
Hantavirus Pulmonary Syndrome
·
Four Corners Hantavirus (fcv)
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Hantavirus Pulmonary Syndrome
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Hantavirus-associated Respiratory Distress Syndrome (hards)
In addition to synonyms and related conditions, physicians may refer to Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome:4 ·
079.99 infection, viral, unspecified nature or site
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 Hantavirus pulmonary syndrome. 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.
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.”
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Introduction
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Why “Internet age”? All too often, patients diagnosed with Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome, 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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome to you or even given you a pamphlet or brochure describing Hantavirus pulmonary syndrome. 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. THE ESSENTIALS ON PULMONARY SYNDROME: GUIDELINES
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HANTAVIRUS
Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. 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
5
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
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physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine. 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 Hantavirus pulmonary syndrome 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 Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
·
Centers for Disease Control and Prevention: various fact sheets on infectious diseases at http://www.cdc.gov/health/diseases.htm
Among the above, the National Institute of Allergy and Infectious Diseases (NIAID) is particularly noteworthy. The mission of the NIAID is to provide support for scientists conducting research aimed at developing better ways to diagnose, treat, and prevent the many infectious, immunologic and allergic diseases that afflict people worldwide.6 The NIAID is composed of four extramural divisions: the Division of AIDS; the Division of Allergy, Immunology and Transplantation; the Division of Microbiology and Infectious Diseases; and the Division of Extramural Activities. In addition, NIAID scientists conduct intramural research in laboratories located in Bethesda, Rockville and Frederick, Maryland, and in Hamilton, Montana. The following patient guideline was recently published by the NIAID on Hantavirus pulmonary syndrome.
This paragraph has been adapted from the NIAID: http://www.niaid.nih.gov/facts/overview.htm. “Adapted” signifies that a passage has been reproduced exactly or slightly edited for this book.
6
Guidelines 11
What Is the Hantavirus?7 Small But Deadly Hantavirus pulmonary syndrome (HPS) has been recognized as a disease only recently in North America. So far, it’s also fairly uncommon and the chances of becoming infected are low. However, HPS is potentially deadly and immediate intensive care is essential once symptoms appear.
The Mouse That Roared Hantaviruses that cause HPS are carried by rodents, especially the deer mouse. You can become infected by exposure to their droppings, and the first signs of sickness (especially fever and muscle aches) appear 1 to 5 weeks later, followed by shortness of breath and coughing. Once this phase begins, the disease progresses rapidly, necessitating hospitalization and often ventilation within 24 hours. Prevention is the best strategy, and it simply means taking some very practical steps to minimize your contact with rodents. HPS is not contagious from person to person in the United States.
History of Hantavirus Pulmonary Syndrome The “First” Outbreak In May 1993, an outbreak of an unexplained pulmonary illness occurred in the southwestern United States, in an area shared by Arizona, New Mexico, Colorado and Utah known as “The Four Corners.” A young, physically fit Navajo man suffering from shortness of breath was rushed to a hospital in New Mexico and died very rapidly. While reviewing the results of the case, medical personnel discovered that the young man’s fiancee had died a few days before after showing similar symptoms, a piece of information that proved key to discovering the disease. As Dr. James Cheek of the Indian Health Service (IHS) noted, “I think if it hadn’t been for that initial pair of people that became sick within a week of each other, we never would have discovered the illness at all.” Adapted from The Centers for Disease Control and Prevention (CDC): http://www.cdc.gov/ncidod/diseases/hanta/hps/index.htm.
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12 Hantavirus Pulmonary Syndrome
An investigation combing the entire Four Corners region was launched by the New Mexico Office of Medical Investigations (OMI) to find any other people who had a similar case history. Within a few hours, Dr. Bruce Tempest of IHS, working with OMI, had located five young, healthy people who had all died after acute respiratory failure. A series of laboratory tests had failed to identify any of the deaths as caused by a known disease, such as bubonic plague. At this point, the CDC Special Pathogens Branch was notified. CDC, the state health departments of New Mexico, Colorado and Utah, the Indian Health Service, the Navajo Nation, and the University of New Mexico all joined together to confront the outbreak. During the next few weeks, as additional cases of the disease were reported in the Four Corners area, physicians and other scientific experts worked intensively to narrow down the list of possible causes. The particular mixture of symptoms and clinical findings pointed researchers away from possible causes, such as exposure to a herbicide or a new type of influenza, and toward some type of virus. Samples of tissue from patients who had gotten the disease were sent to CDC for exhaustive analysis. Virologists at CDC used several tests, including new methods to pinpoint virus genes at the molecular level, and were able to link the pulmonary syndrome with a virus, in particular a previously unknown type of Hantavirus.
Researchers Launch Investigations to Pin Down the Carrier of the New Virus Researchers knew that all other known Hantaviruses were transmitted to people by rodents, such as mice and rats. Therefore, an important part of their mission was to trap as many different species of rodents living in the Four Corners region as possible to find the particular type of rodent that carried the virus. From June through mid-August of 1993, all types of rodents were trapped inside and outside homes where people who had Hantavirus pulmonary syndrome had lived, as well as in piñon groves and summer sheep camps where they had worked. Additional rodents were trapped for comparison in and around nearby households as well. Taking a calculated risk, researchers decided not to wear protective clothing or masks during the trapping process. “We didn’t want to go in wearing respirators, scaring...everybody,” John Sarisky, an Indian Health Service environmental disease specialist said. However, when the
Guidelines 13
almost 1,700 rodents trapped were dissected to prepare samples for analysis at CDC, protective clothing and respirators were worn.
Protective gear, such as gloves, gown, and respirator, were worn during activities that required dissection of rodents.
Peromyscus maniculatus, the deer mouse.
Among rodents trapped, the deer mouse (Peromyscus maniculatus) was found to be the main host to a previously unknown type of Hantavirus. Since the deer mouse often lives near people in rural and semi-rural areas— in barns and outbuildings, woodpiles, and inside people’s homes— researchers suspected that the deer mouse might be transmitting the virus to humans. About 30% of the deer mice tested showed evidence of infection with Hantavirus. Tests also showed that several other types of rodents were infected, although in lesser numbers. The next step was to pin down the connection between the infected deer mice and households where people who had gotten the disease lived. Therefore, investigators launched a case-control investigation. They compared “case” households, where people who had gotten the disease lived, with nearby “control” households. Control households were similar to those where the case-patients lived, except for one factor: no one in the control households had gotten the disease. The results? First, investigators trapped more rodents in case households than in control households, so more rodents may have been living in close
14 Hantavirus Pulmonary Syndrome
contact with people in case households. Second, people in case households were more likely than those in control households to do cleaning around the house or to plant in or hand-plow soil outdoors in fields or gardens. However, it was unclear if the risk for contracting HPS was due to performing these tasks, or with entering closed-up rooms or closets to get tools needed for these tasks. In November 1993, the specific Hantavirus that caused the Four Corners outbreak was isolated. The Special Pathogens Branch at CDC used tissue from a deer mouse that had been trapped near the New Mexico home of a person who had gotten the disease and grew the virus from it in the laboratory. Shortly afterwards and independently, the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) also grew the virus, from a person in New Mexico who had gotten the disease as well as from a mouse trapped in California. The new virus was called Muerto Canyon virus—later changed to Sin Nombre virus (SNV)—and the new disease caused by the virus was named Hantavirus pulmonary syndrome, or HPS. The isolation of the virus in a matter of months was remarkable. This success was based on close cooperation of all the agencies and individuals involved in investigating the outbreak, years of basic research on other Hantaviruses that had been conducted at CDC and USAMRIID, and on the continuing development of modern molecular virologic tests. To put the rapid isolation of the Sin Nombre virus in perspective, it took several decades for the first Hantavirus discovered, the Hantaan virus, to be isolated.
Thin-section electron micrograph of Sin Nombre virus isolate, a causative agent of Hantavirus pulmonary syndrome (HPS). From the 1993 outbreak of HPS in the southwestern United States. Electron micrograph.
Guidelines 15
HPS Not Really a New Disease As part of the effort to locate the source of the virus, researchers located and examined stored samples of lung tissue from people who had died of unexplained lung disease. Some of these samples showed evidence of previous infection with Sin Nombre virus—indicating that the disease had existed before the “first” known outbreak—it simply had not been recognized! Other early cases of HPS have been discovered by examining samples of tissue belonging to people who had died of unexplained adult respiratory distress syndrome. By this method, the earliest known case of HPS that has been confirmed has been the case of a 38-year-old Utah man in 1959. Interestingly, while HPS was not known to the epidemiologic and medical communities, there is evidence that it was recognized elsewhere. The Navajo Indians, a number of whom contracted HPS during the 1993 outbreak, recognize a similar disease in their medical traditions, and actually associate its occurrence with mice. As strikingly, Navajo medical beliefs concur with public health recommendations for preventing the disease. Why Did the Outbreak Occur in the Four Corners Area? But why this sudden cluster of cases? The key answer to this question is that, during this period, there were suddenly many more mice than usual. The Four Corners area had been in a drought for several years. Then, in early 1993, heavy snows and rainfall helped drought-stricken plants and animals to revive and grow in larger-than-usual numbers. The area’s deer mice had plenty to eat, and as a result they reproduced so rapidly that there were ten times more mice in May 1993 than there had been in May of 1992. With so many mice, it was more likely that mice and humans would come into contact with one another, and thus more likely that the Hantavirus carried by the mice would be transmitted to humans.
Person-to-Person Spread of HPS Decided Unlikely “Although person-to-person spread [of HPS] has not been documented with any of the other known Hantaviruses, we were concerned [during this outbreak] because we were dealing with a new agent,” said Charles Vitek, a CDC medical investigator.
16 Hantavirus Pulmonary Syndrome
Researchers and clinicians investigating the ongoing outbreak were not the only groups concerned about the disease. Shortly after the first few HPS patients died and it became clear that a new disease was affecting people in the area, and that no one knew how it was transmitted, the news media began extensive reporting on the outbreak. Widespread concern among the public ensued. Unfortunately, the first victims of the outbreak were Navajo. News reports focused on this fact, and the misperception grew that the unknown disease was somehow linked to Navajos. As a consequence, Navajos found themselves at the center of intense media attention and the objects of the some people’s fears. By later in the summer of 1993, the media frenzy had quieted somewhat, and the source of the disease was pinpointed. Researchers determined that, like other Hantaviruses, the virus that causes HPS is not transmitted from person to person the way other infections, such as the common cold, may be. To date, no cases of HPS have been reported in the United States in which the virus was transmitted from one person to another. In fact, in a study of health care workers who were exposed to either patients or specimens infected with related types of Hantaviruses (which cause a different disease in humans), none of the workers showed evidence of infection or illness.
HPS Since the First Outbreak After the initial outbreak, the medical community nationwide was asked to report any cases of illness with symptoms similar to those of HPS that could not be explained by any other cause. As a result, additional cases have been reported. Since 1993, researchers have discovered that there is not just one Hantavirus that causes HPS, but several. In June 1993, a Louisiana bridge inspector who had not traveled to the Four Corners area developed HPS. An investigation was begun. The patient’s tissues were tested for the presence of antibodies to Hantavirus. The results led to the discovery of another Hantavirus, named Bayou virus, which was linked to a carrier, the rice rat (Oryzomys palustris). In late 1993, a 33-year-old Florida man came down with HPS symptoms; he later recovered. This person also had not traveled to the Four Corners area. A similar investigation revealed yet another Hantavirus, named the Black Creek Canal virus, and its carrier, the cotton rat (Sigmodon hispidus). Another case occurred in New York. This time, the Sin Nombre-like virus
Guidelines 17
was named New York-1, and the white-footed mouse, Peromyscus leucopus, was implicated as the carrier. More recently, cases of HPS stemming from related Hantaviruses have been documented in Argentina, Brazil, Canada, Chile, Paraguay, and Uruguay, making HPS a pan-hemispheric disease.
How Is Hantavirus Transmitted? The Rodent Connection So just how do people get Hantavirus pulmonary syndrome (HPS)? It all starts with rodents, like the deer mouse and cotton rat, which carry Hantaviruses.
The Basic Transmission Cycle The short story is that some rodents are infected with a type of Hantavirus that causes HPS. In the United States, deer mice (plus cotton rats and rice rats in the southeastern states and the white-footed mouse in the Northeast) are the rodents carrying Hantaviruses that cause Hantavirus pulmonary syndrome. These rodents shed the virus in their urine, droppings and saliva. The virus is mainly transmitted to people when they breathe in air contaminated with the virus. This happens when fresh rodent urine, droppings or nesting materials are stirred up. When tiny droplets containing the virus get into the air, this process is known as “aerosolization.” There are several other ways rodents may spread Hantavirus to people: ·
If a rodent with the virus bites someone, the virus may be spread to that person—but this is very rare.
·
Researchers believe that you may be able to get the virus if you touch something that has been contaminated with rodent urine, droppings or saliva, and then touch your nose or mouth.
·
Researchers also suspect that if virus-infected rodent urine, droppings or saliva contaminates food that you eat, you could also become sick.
18 Hantavirus Pulmonary Syndrome
These possibilities demonstrate why disinfecting rodent-infested areas is so important in preventing transmission of the virus. Transmission can happen any place that infected rodents have infested. (Remember, by “carrier rodent” we mean deer mice plus cotton rats and rice rats in the Southeast, and the white-footed mouse in the Northeast. Common house mice do not carry Hantavirus.) This could be barns or sheds or other outbuildings, warehouses or summer cottages closed up for the season. But carrier rodents infest homes as well! Therefore, the most sensible way to avoid contact with rodents is to prevent rodents from infesting the places where you live and work, and to follow safety precautions if you do stumble into a rodent-infested area.
Can You Get Hantavirus from Another Person? The types of Hantavirus that cause HPS in the United States cannot be transmitted from one person to another. For example, you cannot get the virus from touching or kissing a person who has HPS, or from a health care worker who has treated someone with the disease. Finally, you cannot get the virus from a blood transfusion in which the blood came from a person who became ill with HPS and survived.
Can You Get Hantavirus from Animals Other Than Rodents, or from Insects? What About Pets? No—the Hantaviruses that cause HPS in the United States are not known to be transmitted by any types of animals other than certain species of rodents. You cannot get Hantavirus from farm animals, such as cows, chickens or sheep, or from insects, such as mosquitoes. Dogs and cats are not known to carry Hantavirus. However, they may bring infected rodents into contact with people if they catch such animals and carry them home. Guinea pigs, hamsters, gerbils and other such pets are not known to carry Hantavirus.
Summing Up: How Hantavirus is Transmitted ·
Exposure to infected rodent (deer mouse, white-footed mouse, cotton rat, rice rat)
·
Rodent saliva/droppings dry up, are “aerosolized” and breathed in
·
No transmission from one person to another, in the United States
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·
No known transmission from other animals or insects
Rodents That Carry the Types of Hantavirus Which Cause HPS in the U.S.
The Deer Mouse (Peromyscus maniculatus) is a deceptively cute animal, with big eyes and big ears. Its head and body are normally about 2 - 3 inches long, and the tail adds another 2 - 3 inches in length. You may see it in a variety of colors, from gray to reddish brown, depending on its age. The underbelly is always white and the tail has sharply defined white sides. The deer mouse is found almost everywhere in North America. Usually, the deer mouse likes woodlands, but also turns up in desert areas.
The Cotton Rat (Sigmodon hispidus), which you’ll find in the southeastern United States (and way down into Central and South America), has a bigger body than the deer mouse—head and body about 5 - 7 inches, and another 3 - 4 inches for the tail. The hair is longer and coarser, of a grayish brown color, even grayish black. The cotton rat prefers overgrown areas with shrubs and tall grasses.
20 Hantavirus Pulmonary Syndrome
The Rice Rat (Oryzomys palustris) is slightly smaller than the cotton rat, having a head and body 5 - 6 inches long, plus a very long, 4- to 7-inch tail. Rice rats sport short, soft, grayish brown fur on top, and gray or tawny underbellies. Their feet are whitish. As you might expect from the name, this rat likes marshy areas and is semiaquatic. It’s found in the southeastern United States and in Central America.
The White-footed Mouse (Peromyscus leucopus) is hard to distinguish from the deer mouse. The head and body together are about four inches long. Note that its tail is normally shorter than its body (about 2 - 4 inches long). Topside, its fur ranges from pale brown to reddish brown, while its underside and feet are white. The white-footed mouse is found through southern New England, the Mid-Atlantic and southern states, the midwestern and western states, and Mexico. It prefers wooded and brushy areas, although sometimes it will live in more open ground. Sometimes, a “Country Mouse” Becomes a “City Mouse” Both the deer mouse and the cotton rat usually live in rural areas, but can also be found in cities when conditions are right, such as easy availability of food, water and shelter.
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Other Rodents May Also Carry Hantavirus Other rodents carry strains of Hantavirus that cause HPS, but they have not yet been identified. In addition, other rodent species may play host to other types of Hantaviruses that cause a different type of infection, hemorrhagic fever with renal syndrome, or HFRS. It is wise, therefore, to avoid close contact with rodents in general.
Transmission: How Does “Aerosolization” Really Work? For a Hantavirus to cause HPS, the virus must travel from the rodents that carry it to a person. A common way this happens is when a person breathes in the Hantavirus from the air. Let’s create an imaginary scenario and go through the process step by step. Say you have a storage room in your home that you hardly ever enter. You keep old furniture there, old newspapers and magazines, and so on. At some point, a group of deer mice find their way into the room, looking for places to build nests. They found their way into the room through a crack— deer mice can squeeze through holes as small as a shirt button! Some mice chew through the fabric of an old armchair and build a nest inside it. Other mice shred bits of magazines and build nests under the shredded pieces. A few of these mice are infected with the Hantavirus. The infected mice don’t show any signs of being sick. In fact, the virus does not seem to make them ill at all; it simply lives in their bodies. However, the virus is shed continuously from them: into the droppings and urine they leave around the room, and into their saliva, which dries on anything they have chewed, such as nesting material. Out in the environment like this, the virus can live for several days. Meanwhile, you decide to clean up your storage room. You go inside, spend a few minutes moving boxes and furniture. The mice hear you coming and scurry away, leaving a trail of fresh urine! Because you find mouse droppings and some of the furniture stuffing the mice have used as nesting material, you get a broom and sweep up the mess. As you move around and sweep, tiny particles of fresh urine, droppings and saliva, with the virus in them, get kicked up into the air. This is the
22 Hantavirus Pulmonary Syndrome
aerosolization. It is these tiny particles that you breathe in—and this is the beginning of becoming sick with HPS. Because the virus is spread when virus-containing particles are stirred up into the air, an essential HPS prevention tactic in areas showing signs of rodents is to avoid actions that raise dust and to carefully wet the area down with disinfectant. The less chance the virus has to get into the air, the less chance it will be breathed in!
Who Is at Risk of Getting HPS, and Why? HPS Was Discovered in the Southwest, but It’s NOT an “Indian Disease” You can be old or young, male or female, of any race, living anywhere in almost any part of the Americas. Healthy, active people are more likely to become infected because their activities often put them in contact with the virus. By the way, in the United States, you cannot get HPS from another person.
What Kind of Activities Are Risky? Anything that puts you in contact with rodent droppings, urine or nesting materials can place you at risk for infection. These include such activities as opening up cabins and sheds or cleaning outbuildings that have been closed during the winter—such as barns, garages or storage facilities for farm and construction equipment. Both activities mean you may directly touch rodents or their droppings and/or “stir up the dust,” and when you touch or inhale them, you’re at risk for infection. Hikers and campers can also be exposed when they use infested trail shelters or camp in other rodent habitats. Overall, the chance of being exposed to Hantavirus is greatest when people work, play or live in closed spaces where rodents are actively living. However, recent research results show that many people who have become ill with HPS got the disease after having been in frequent contact with rodents and/or their droppings for some time. In addition, many people who have become ill reported that they had not seen rodents or their droppings—at all. Therefore, if you live in an area where the carrier rodents such as the deer mouse are known to live, take sensible precautions before
Guidelines 23
you do activities like those described above—even if you don’t see any rodents or their droppings.
Summing Up: Conditions That Put You at Risk ·
Closed up rooms, cabins, warehouses
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Housecleaning activities
·
Really stirring up dust
·
Large populations of rodents—so don’t invite them to live around you by leaving food out or allowing them easy access to your home
What Are the Symptoms of HPS? Early Symptoms Early symptoms include fatigue, fever and muscle aches, especially the large muscle groups—thighs, hips, back, sometimes shoulders. These symptoms are universal. There may also be headaches, dizziness, chills and/or abdominal problems, such as nausea, vomiting, diarrhea and abdominal pain. About half of all HPS patients experience these symptoms.
How long could it be between the time you get the virus, and the time you start showing these symptoms? Because there have been so few cases of HPS, it isn’t quite clear what this “incubation time” is. However, on the basis of limited information, it appears that symptoms may develop between 1
24 Hantavirus Pulmonary Syndrome
and 5 weeks after exposure to potentially infected rodents and their droppings. Another important point to remember from the data that the CDC Special Pathogens Branch keeps on all reported cases of HPS, it appears that many people who have become ill were in a situation where they didn’t see rodents or rodent droppings. Other people have had frequent contact with rodents and their droppings before becoming ill. This apparent inconsistency makes it very difficult to pin down the precise time when the virus was transmitted.
Late Symptoms Four to 10 days after the initial phase of illness, the late symptoms of HPS appear. These include coughing and shortness of breath, with the sensation of, as one survivor put it, a “..tight band around my chest and a pillow over my face” as the lungs fill with fluid.
Uncommon Symptoms Earache, sore throat and rash are very uncommon.
Summing Up: Symptoms of HPS ·
Early (universal): fever, fatigue, muscle aches
·
Early (about half): headaches, dizziness, chills, abdominal problems
·
Late (universal): coughing, shortness of breath
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How Do I Prevent HPS? Eliminate or Minimize Contact with Rodents Make your home, workplace, vacation home or campsite unattractive to them! Why is this so important? If rodents don’t find that where you are is a good place for them to be, too—that means lots of easy-to-get food and nesting material—then you’re less likely to come into contact with them. Recent research results show that many people who became ill with HPS got the disease after having been in frequent contact with rodents and/or their droppings around a home or a workplace. On the other hand, many people who became ill reported that they had not seen rodents or rodent droppings at all. Therefore, if you live in an area where the carrier rodents are known to live, it makes sense to try to keep your home, vacation place, workplace— and as far possible, campsite—clean. The following sections offer tips for preventing Hantavirus infection in all kinds of situations and explain in detail how to clean up areas where you have found rodents or their droppings.
Tips For Preventing HPS: Prevention Indoors and Outdoors Indoors ·
Keep a clean home, especially kitchen (wash dishes, clean counters and floor, keep food covered in rodent-proof containers).
·
Keep a tight-fitting lid on garbage, discard uneaten pet food at the end of the day.
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Set and keep spring-loaded rodent traps. Set traps near baseboards because rodents tend to run along walls and in tight spaces rather than out in the open.
·
Set Environmental Protection Agency-approved rodenticide with bait under plywood or plastic shelter along baseboards. These are sometimes known as “covered bait stations.” Remember to follow product use instructions carefully, since rodenticides are poisonous to pets and people, too.
26 Hantavirus Pulmonary Syndrome
·
If bubonic plague is a problem in your area, spray flea killer or spread flea powder in the area before setting traps. This is important. If you control rodents but do not control fleas as well, you may increase the risk of infection with bubonic plague, since fleas will leave rodents once the rodents die and will seek out other food sources, including humans.
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Seal all entry holes 1/4 inch wide or wider with lath screen or lath metal, cement, wire screening or other patching materials, inside and out. Outdoors
·
Clear brush, grass and junk from around house foundations to eliminate a source of nesting materials.
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Use metal flashing around the base of wooden, earthen or adobe homes to provide a strong metal barrier. Install so that the flashing reaches 12 inches above the ground and six inches down into the ground.
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Elevate hay, woodpiles and garbage cans to eliminate possible nesting sites. If possible, locate them 100 feet or more from your house.
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Trap rodents outside, too. Poisons or rodenticides may be used as well, but be sure to keep them out of the reach of children or pets.
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Encourage the presence of natural predators, such as non-poisonous snakes, owls and hawks.
·
Remember, getting rid of all rodents isn’t feasible, but with ongoing effort you can keep the population very low.
Common Signs of Rodent Infestation Do you think you have rodents infesting your home, barn or workplace, but aren’t sure? Here are some common signs that you may have a rodent problem.
You See Rodent Droppings This is one of the most reliable signs that you have a rodent problem. You may find droppings in places where you store your food or your pet/animal food, such as in cupboards and drawers or in bins. Because mice like to run in places that offer them some protection from predators, you may find droppings in cupboards or under the sink, along walls, or on top of wall
Guidelines 27
studs or beams. Mice will leave droppings near their nests as well. Storage rooms, sheds, barns, or cabins loaded with boxes, bags, old furniture, and other objects make an ideal home for rodents, so you may find droppings there, even inside boxes and other containers. Size of deer mouse and white-footed mouse droppings compared with the droppings of other household pests:
Workplaces can also make good rodent homes. Warehouses, restaurants, and the like are obvious places to look because food may be plentiful there. However, rodents can infest office buildings, too. Once again, look for droppings in protected places, such as closets, storage rooms, or inside boxes. You See Signs of Rodent Nests Rodents tend to build their nests from materials that are soft, fuzzy, or warm. Among common rodent nest materials are shredded paper, bunches of dry grass or small twigs, fabric, and furniture stuffing. Rodents will nest wherever safety from enemies can be found close enough to food and water, and they prefer places that are relatively quiet. Inside buildings, here are some places to look: ·
Inside cabinet
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Under or inside dressers
28 Hantavirus Pulmonary Syndrome
·
In and among boxes
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Behind and inside machinery and appliances (kitchen appliances such as stoves or refrigerator drip pans; water coolers; and electric motor cases or computer cases)
·
Inside upholstered furniture
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Inside double walls or the space between floors and ceilings.
You Find Food Boxes, Containers, or Food Itself That Appears to Be Nibbled Look for droppings nearby. Rodents can chew through plastic, so plastic bags do not make safe food storage containers.
You Find Signs of Rodent “Feeding Stations” These are semi-hidden spots where rodents eat food they have collected. At these stations, rodents may leave larger-than-normal amounts of droppings/urine, plus remnants of a variety of foods (such as nut shells), bits of plastic or paper, and cockroach carcasses.
You Find Evidence of Gnawing To get to food, rodents will gnaw on almost anything that is softer than the enamel of their teeth. This includes such things as wood, paperboard, cloth sacks, and materials even harder than these. Because rodents’ teeth grow continuously, they must gnaw to keep them short. That may help to explain why chair legs or similar surfaces show gnawed spots or tooth marks in rodent-infested places.
You Notice an Odd, Stale Smell In closed-up rooms infested by rodents, you will commonly smell an unusual, musky odor.
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You See a Mouse in Your House However, this doesn’t happen very frequently! Why? Rodents are normally active at night, and generally avoid humans. If you have rodents, unless the infestation is large, you may never see one. Remember that not all types of rodents carry Hantavirus. Neither common house mice nor common rats have been associated with HPS in humans, for example. Yet because it can be tough to tell just what kind of rodents you have, play it safe -- clean up the infestation and rodent-proof your home or workplace.
Safety Precautions for Cleaning Up Infested Areas ·
Put on latex rubber gloves before cleaning up.
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Don’t stir up dust by sweeping up or vacuuming up droppings, urine or nesting materials.
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Instead, thoroughly wet contaminated areas with detergent or liquid to deactivate the virus. Most general purpose disinfectants and household detergents are effective. However, a hypochlorite solution prepared by mixing 1 and 1/2 cups of household bleach in 1 gallon of water may be used in place of commercial disinfectant. When using the chlorine solution, avoid spilling the mixture on clothing or other items that may be damaged.
·
Once everything is wet, take up contaminated materials with a damp towel, then mop or sponge the area with disinfectant.
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Spray dead rodents with disinfectant, then double-bag along with all cleaning materials and bury or burn—or throw out in appropriate waste disposal system. If burning or burying isn’t feasible, contact your local or state health department about other disposal methods.
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Finally, disinfect gloves before taking them off with disinfectant or soap and water. After taking off the clean gloves, thoroughly wash hands with soap and warm water.
·
When going into cabins or outbuildings (or work areas) that have been closed for awhile, open them up and air out before cleaning.
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What If My House or Workplace Is Heavily Infested with Rodents? You should get help from a professional exterminator if you see lots of droppings or rodents—you may have a bad infestation problem. Or you can contact your local health authorities for advice. CDC has recommendations for how heavy infestations may most safely be handled.
Why Spray Disinfectant and Wash Traps with Bleach? These viruses are surrounded by a lipid (fatty) envelope, so they are somewhat fragile. The lipid envelope can be destroyed and the virus killed by fat solvents, such as alcohol, ordinary disinfectants and household bleach. That is why one of the most important ways to prevent transmitting the disease is to carefully wet down dead rodents and areas where rodents have been with disinfectant and/or bleach. When you do this, you are killing the virus itself and reducing the chance that the virus will get into the air.
Summing Up: How to Prevent HPS ·
Make your home, workplace, vacation home unattractive to rodents
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Clean up infested areas by using safety precautions
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Wet down infested areas with bleach/disinfectant to kill the virus before it aerosolizes
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In other words: air out, seal up, trap up, clean up.
Special Precautions for Homes of Persons with Confirmed Hantavirus Infection or Buildings with Heavy Rodent Infestations Special precautions should be used for cleaning homes or buildings with heavy rodent infestations in areas where HPS has been reported. If you are attempting to deal with such an infestation, it is recommended that you contact the responsible local, state, or federal public health agency for guidance. The special precautions may also apply to vacant dwellings that have attracted numbers of rodents while unoccupied and to dwellings and other
Guidelines 31
structures that have been occupied by persons with confirmed Hantavirus infection. Workers who are either hired specifically to perform the clean-up or asked to do so as part of their work activities should receive a thorough orientation from the responsible health agency about Hantavirus transmission and should be trained to perform the required activities safely. Precautions to be used: ·
A baseline serum sample, preferably drawn at the time these prevention activities are initiated, should be available for all persons conducting the clean-up of homes or buildings with heavy rodent infestation. The serum sample should be stored at -20 C.
·
Persons involved in the clean-up should wear coveralls (disposable, if possible), rubber boots or disposable shoe covers, rubber or plastic gloves, protective goggles, and an appropriate respiratory protection device, such as a half-mask air-purifying (or negative-pressure) respirator with a high-efficiency particulate air (HEPA) filter or a powered airpurifying respirator (PAPR) with HEPA filters.
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Personal protective gear should be decontaminated upon removal at the end of the day. If the coveralls are not disposable, they should be laundered on site. If no laundry facilities are available, the coveralls should be immersed in liquid disinfectant until they can be washed.
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All potentially infective waste material (including respirator filters) from clean-up operations that cannot be burned or deep buried on site should be double bagged in appropriate plastic bags. The bagged material should then be labeled as infectious (if it is to be transported) and disposed of in accordance with local requirements for infectious waste.
·
Workers who develop symptoms suggestive of HPS within 45 days of the last potential exposure should immediately seek medical attention. The physician should contact local health authorities promptly if Hantavirusassociated illness is suspected. A blood sample should be obtained and forwarded with the baseline serum through the state health department to CDC for Hantavirus antibody testing.
Precautions for Workers in Affected Areas Who are Regularly Exposed to Rodents Persons who frequently handle or are exposed to rodents (e.g., mammalogists, pest-control workers) in the affected area are probably at
32 Hantavirus Pulmonary Syndrome
higher risk for Hantavirus infection than the general public because of their frequency of exposure. Therefore, enhanced precautions are warranted to protect them against Hantavirus infection. Precautions to be used: ·
Workers in potentially high-risk settings should be informed about the symptoms of the disease and be given detailed guidance on prevention measures.
·
Workers who develop a febrile or respiratory illness within 45 days of the last potential exposure should immediately seek medical attention and inform the attending physician of the potential occupational risk of Hantavirus infection. The physician should contact local health authorities promptly if Hantavirus-associated illness is suspected. A blood sample should be obtained and forwarded through the state health department to CDC for Hantavirus antibody testing.
·
Workers should wear a half-face air-purifying (or negative-pressure) respirator or PAPR equipped with HEPA filters when removing rodents from traps or handling rodents in the affected area. (Please note: the HEPA classification recently has been discontinued. Under the new classification system, the N-100 filter type is recommended.
·
Respirators (including positive-pressure types) are not considered protective if facial hair interferes with the face seal, since proper fit cannot be assured. Respirator use practices should be in accord with a comprehensive user program and should be supervised by a knowledgeable person.
·
Workers should wear rubber or plastic gloves when handling rodents or handling traps containing rodents. Gloves should be washed and disinfected before removing them, as described above.
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Traps contaminated by rodent urine or feces or in which a rodent was captured should be disinfected with a commercial disinfectant or bleach solution. Dispose of dead rodents as described in the section on Eliminating Rodents inside the Home.
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Persons removing organs or obtaining blood from rodents in affected areas should contact the Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, [telephone (404) 639-1115] for detailed safety precautions.
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Precautions for Other Occupational Groups Who Have Potential Rodent Contact Insufficient information is available at this time to allow general recommendations regarding risks or precautions for persons in the affected areas who work in occupations with unpredictable or incidental contact with rodents or their habitations. Examples of such occupations include telephone installers, maintenance workers, plumbers, electricians, and certain construction workers. Workers in these jobs may have to enter various buildings, crawl spaces, or other sites that may be rodent infested. Recommendations for such circumstances must be made on a case-by-case basis after the specific working environment has been assessed and state or local health departments have been consulted.
Precautions for Campers and Hikers in the Affected Areas There is no evidence to suggest that travel into areas where HPS has been reported should be restricted. Most usual tourist activities pose little or no risk that travelers will be exposed to rodents or their urine and/or droppings. However, persons who do outdoor activities such as camping or hiking in areas where the disease has been reported should take precautions to reduce the likelihood of their exposure to potentially infectious materials. Useful precautions: ·
Avoid coming into contact with rodents and rodent burrows or disturbing dens (such as pack rat nests).
·
Air out, then disinfect cabins or shelters before using them. These places often shelter rodents.
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Do not pitch tents or place sleeping bags in areas in proximity to rodent droppings or burrows or near areas that may shelter rodents or provide food for them (e.g., garbage dumps or woodpiles).
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If possible, do not sleep on the bare ground. In shelters, use a cot with the sleeping surface at least 12 inches above the ground. Use tents with floors or a ground cloth if sleeping in the open air.
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Keep food in rodent-proof containers!
34 Hantavirus Pulmonary Syndrome
·
Promptly bury (or--preferably--burn followed by burying, when in accordance with local requirements) all garbage and trash, or discard in covered trash containers.
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Use only bottled water or water that has been disinfected by filtration, boiling, chlorination, or iodination for drinking, cooking, washing dishes, and brushing teeth.
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And last but not least, do not play with or handle any rodents that show up at the camping or hiking site, even if they appear friendly.
What Is the Treatment for HPS? At the present time, there is no specific treatment or “cure” for Hantavirus infection. However, we do know that if the infected individuals are recognized early and are taken to an intensive care unit, some patients may do better. In intensive care, patients are intubated and given oxygen therapy to help them through the period of severe respiratory distress. The earlier the patient is brought in to intensive care, the better. If a patient is experiencing full distress, it is less likely the treatment will be effective. Therefore, if you have been around rodents and have symptoms of fever, deep muscle aches and severe shortness of breath, see your doctor immediately. Be sure to tell your doctor that you have been around rodents—this will alert your physician to look closely for any rodent-carried disease such as HPS.
More Guideline Sources The guideline above on Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome. 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 35
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. From there you can either search using the alphabetical index or browse by broad topic areas. 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 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 “Hantavirus pulmonary syndrome” or synonyms. The following was recently posted: ·
Hemorrhagic fever viruses as biological weapons: medical and public health management. Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University.; 2002 May 8; 15 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2450&sSearch_string=hantavirus
·
Practice guidelines for the management of community-acquired pneumonia in adults. Source: Infectious Diseases Society of America.; 2000 February; 36 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1891&sSearch_string=hantavirus
36 Hantavirus Pulmonary Syndrome
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: ·
Diseases, Selected Prevention and Program Areas - National Center for Infectious Diseases Summary: Choose from a comprehensive alphabetical listing -- from a to z -- for information on any of a variety of infectious diseases and health topics, including Bacterial Diseases, Ebola, Foodborne Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=249
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 Hantavirus pulmonary syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
Guidelines 37
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
·
drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
·
Family Village: http://www.familyvillage.wisc.edu/specific.htm
·
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
·
Med Help International: http://www.medhelp.org/HealthTopics/A.html
·
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
·
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
·
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: 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] Camping: Living outdoors as a recreational activity. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used
38 Hantavirus Pulmonary Syndrome
on inanimate objects. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fleas: Parasitic, blood-sucking, wingless insects comprising the order Siphonaptera. [NIH] Grasses: A large family, gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Incidental: 1. small and relatively unimportant, minor; 2. accompanying, but not a major part of something; 3. (to something) liable to occur because of something or in connection with something (said of risks, responsibilities, ...) [EU]
Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU]
Guidelines 39
Owls: Members of the Strigiformes order of birds, with strongly hooked beaks, sharp talons, large heads, forward facing eyes, and facial disks. While considered nocturnal raptors, some owls do hunt by day. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [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]
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] Pneumonia: Inflammation of the lungs with consolidation. [EU] Pulmonary: Pertaining to the lungs. [EU] Respiratory: Pertaining to respiration. [EU] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [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] 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] Solvent: 1. dissolving; effecting a solution. 2. a liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Ventilation: 1. in respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually
40 Hantavirus Pulmonary Syndrome
measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. in psychiatry, verbalization of one's emotional problems. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU]
Seeking Guidance 41
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with Hantavirus pulmonary syndrome. 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.8 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 Hantavirus pulmonary syndrome. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Hantavirus Pulmonary Syndrome 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.9 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. 9 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 8
42 Hantavirus Pulmonary Syndrome
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. 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, 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 Hantavirus pulmonary syndrome. 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.
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 “Hantavirus pulmonary syndrome” (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 “Hantavirus pulmonary syndrome”. 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
Seeking Guidance 43
making these selections and typing in “Hantavirus pulmonary syndrome” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with Hantavirus pulmonary syndrome. 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 “Hantavirus pulmonary syndrome” (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: 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.
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 Hantavirus pulmonary syndrome 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:10 ·
If you are in a managed care plan, check the plan’s list of doctors first.
10
This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
44 Hantavirus Pulmonary Syndrome
·
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: ·
Check with the associations listed earlier in this chapter.
·
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 11 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.
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.
11
Seeking Guidance 45
Selecting Your Doctor12 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 Hantavirus pulmonary syndrome?
·
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 Hantavirus pulmonary syndrome?
·
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 Doctor13 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.
12 This
section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 13 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
46 Hantavirus Pulmonary Syndrome
·
It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.
·
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.
Seeking Guidance 47
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:14 ·
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
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
14
Clinical Trials 49
CHAPTER 3. CLINICAL PULMONARY SYNDROME
TRIALS
AND
HANTAVIRUS
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 Hantavirus pulmonary syndrome.
What Is a Clinical Trial?15 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 Hantavirus pulmonary syndrome 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.
15
50 Hantavirus Pulmonary Syndrome
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 Hantavirus pulmonary syndrome.
·
Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. In other clinical trials, where a new surgery or device
Clinical Trials 51
(not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. 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.
52 Hantavirus Pulmonary Syndrome
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 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 Hantavirus Pulmonary Syndrome 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 Hantavirus pulmonary syndrome.16 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. ·
A Collaborative Double-Blind Placebo-Controlled Trial of Intravenous Ribavirin As a Treatment for Presumed Hantavirus Pulmonary Syndrome. Condition(s): Hantavirus Pulmonary Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose is to test the safety and effectiveness of intravenous ribavirin therapy in persons with suspected and subsequently proven hantavirus infection. The hantavirus is spread through the air into the lungs when dry rodent feces are moved or disturbed. It is characterized by fever and bleeding. Study Type: Interventional
16
These are listed at www.ClinicalTrials.gov.
Clinical Trials 53
Contact(s): Alabama; NIAID/DMID/CASG Central Unit, Birmingham, Alabama, 35294, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001123;jsessionid=2392606 3B368238194604004F2F68389
Benefits and Risks17 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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome. 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.
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=9jmun6f291.
17
54 Hantavirus Pulmonary Syndrome
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 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.
·
Know any costs involved for you or your insurance provider.
·
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.
Clinical Trials 55
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.
·
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 Hantavirus pulmonary syndrome? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?
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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?
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How long will the treatment last? How often will I have to come back for follow-up exams?
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What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?
56 Hantavirus Pulmonary Syndrome
·
Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?
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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?
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Will taking part in the study affect my daily life? Do I have time to participate?
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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 “Hantavirus pulmonary syndrome” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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·
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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. 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
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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
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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
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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
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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
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·
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: Intravenous: Within a vein or veins. [EU] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH]
59
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome. In Part II, as in Part I, our objective is not to interpret the latest advances on Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome is suggested.
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CHAPTER 4. STUDIES ON HANTAVIRUS PULMONARY SYNDROME Overview Every year, academic studies are published on Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome and teach you how to keep current on new studies as they are published or undertaken by the scientific community.
Federally-Funded Syndrome
Research
on
Hantavirus
Pulmonary
The U.S. Government supports a variety of research studies relating to Hantavirus pulmonary syndrome and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of
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Health.18 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 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome: ·
Project Title: Ecology Factors Regulating Outbreaks of Hantavirus in Chile Principal Investigator & Institution: Yates, Terry; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000 Summary: This project will develop a spatially explicit model using Geographic Information System (GIS) technology to predict environmental correlates of high human hantaviral risk in Chile. A combination of descriptive and analytical techniques will be used in the study both in the field and the laboratory. The major hypotheses to be tested are that; 1) surges in rodent populations can be predicted using satellite-derived climate and environmental data from a GIS, 2) fluctuations in human hantavirus infection can be predicted from fluctuations in rodent populations derived from rodent surveillance and data from hypothesis one, 3) GIS data combined with generalized models can be developed to provide techniques to predict environmental change and many human infections transmitted by animals and, 4) virus titers in blood and excretions are higher during the spring breeding pulse of reservoir rodents when young of the year are dispersing. Results from these studies will provide information on the degree of human risk
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).
18
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associated with this virus and allow predictions regarding future outbreaks. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Ecology of Hantavirus Enzootics: Immune Interventions Principal Investigator & Institution: Hjelle, Brian L.; Assistant Professor; Pathology; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000; Project Start 1-AUG-1997; Project End 1-JUL2002 Summary: A 1993 outbreak of severe respiratory disease among rural residents of the southwestern US was caused by the emergence of a previously-unknown hantavirus, Sin Nombre virus (SNV). Well before SNV was isolated in culture and could be virologically characterized, large amounts of RNA sequence were available from the SNV genome, and used to characterize it antigenically and to develop diagnostic tests. SNV thus represents an excellent model organism for situations in which rapid development and deployment of empirically-designed DNA vaccines could be used to intervene in an outbreak caused by newlyemerged or poorly- characterized pathogens. Virtually nothing is known of how SNV is carried by its reservoir host, the deer mouse. We wish to investigate the mechanisms of transmission of SNV among deer mice in a field setting and to explore mechanisms of immune responses and protection from SNV challenge, using both deer mice and standard laboratory mice (C57/Bl). We will prepare large open-air outdoor enclosures on a patrolled, remote wildlife refuge in western New Mexico to explore transmission of SNV by directly introducing a defined number of infected and uninfected deer mice, which will be fitted with radiotransmitters. The demographics of input rodents will be carefully controlled to investigate the routes of transmission. Their nesting behavior within the enclosure will be monitored by radiotelemetry and correlated with efficiency of transmission of SNV. Studies to determine whether virus-contaminated nest bedding is associated with transmission will also be conducted. Both deer mice and C57/Bl mice will be used to determine the efficacy and immune reactivity to naked DNA immunization using the GI, G2, and N genes of SNV. Lab mice will be used to determine what portions of the SNV genome elicit strong B-cell and T-cell responses, and deer mice will be used to study protection against SNV challenge. Both experimental infection and field transmission challenges will be used. Our long-term goals are to establish the mechanisms by which deer mouse populations maintain SNV infection in natural settings, to identify genetic immunization strategies
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that may be used to protect at-risk human populations in an outbreak, and to identify ways to disrupt the transmission of SNV among deer mice, and thus to design prevention, control, and treatment strategies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Effects of Androgens On Hantavirus Infection Principal Investigator & Institution: Klein, Sabra L.; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2000; Project Start 6-FEB-2000 Summary: Males are more susceptible to many parasite infections than females. The goal of this research proposal is to determine whether males are more susceptible to viruses, specifically hantaviruses, because androgens suppress immune function or because males engage in more androgen- dependent behaviors (e.g., aggression) that influence susceptibility to hantavirus. These studies are based on field observations of many species that report a high proportion of males being infected with hantavirus. The goal of this proposal will be met by examining: the role of sex steroid hormones in sex differences in immune responses to hantavirus infection; 2) how androgen metabolites influence the course of hantavirus infection; 3) when during ontogeny hormones influence adult susceptibility to infection; 4) whether aggressive males are more susceptible to hantavirus infection than less aggressive males. These studies represent a thorough examination of potential mechanisms that underlie population variation in hantavirus infection and serve to expand our knowledge of disease processes in general and, specifically, factors that affect susceptibility to hantavirus. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Hantavirus Cell Interactions Principal Investigator & Institution: Mackow, Erich R.; Associate Professor; Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2000; Project Start 5-JUL-2000; Project End 0-JUN2004 Summary: (Adapted from the Investigator's abstract) Hantaviruses are the cause of 2 highly lethal human diseases: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). However, mehanisms of hantavirus pathogenesis have not been defined and currently there is no animal model of hantavirus disease. We have recently determined that alphanubeta3 and alphaIIbbeta3 integrins are
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cellular receptors for pathogenic, but not non-pathogenic, hantaviruses and this finding directly relates hantavirus disease to the use of key adhesive integrins on platelet and endotheial cells. Further, human but not murine beta3 subunits render cells susceptible to infection by pathogenic hantaviruses. This permits us to define elements of beta3 integrins required for hantavirus interaction and to propose the development of human-beta3 transgenic mice for use as models of hantavirus infectivity and pathogenesis. beta3 integrin deficient knockout mice have recently been shown to mimic a human bleeding disorder, Glanzmanns thrombasthenia, and have marked vascular hemorrhage and defects in platelet aggregation. We have shown that cellular susceptibility to HPS- and HFRS-causing hantaviruses is confered by human beta3 integrins. Interestingly, human but not murine beta3 integrins permit hantavirus infection and this is consistent with the fact that laboratory mice (MUS musculis) are not hantavirus hosts. Although there is little known about beta3 integrins from their natural hosts, the findings demonstrate that beta3 subunits are sufficient to determine cellular susceptibility to pathogenic hantaviruses. The role of beta3 integrins in platelet and endothelial cell function, the nature of hantavirus disease and the use of beta3 integrins by only pathogenic hantaviruses, suggests that hantavirus-receptor interactions play a central role in hantavirus pathogenesis. We will investigate the interaction of pathogenic hantavirus with beta3 integrin receptors, and develop human beta3 integrin transgenic mice as potential models of hantavirus infectivity and pathogenesis. This proposal will define integrin specific requirements for hantavirus attachment and inhibitors of hantavirus infectivity with therapeutic and prophylactic uses. Development of an animal model of hantavirus pathogenesis within this proposal is broadly applicable to studies of hantavirus disease, therapeutics and protective immunity. Specific Aims: 1) beta3 Integrin Requirements for Hantavirus Infectivity; 2) Blocking beta3 Integrin-Hantavirus Interactions; 3) Transgenic Model of Hantavirus Infection and Pathogenesis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Hantavirus Ecology and Disease in Chile Principal Investigator & Institution: Mertz, Gregory J.; Professor; Internal Medicine; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000; Project Start 5-SEP-1999; Project End 1-AUG2004 Summary: Hantavirus cardiopulmonary syndrome (HCPS) is an acute viral infection with a 50% case-fatality that was first recognized in 1993 in
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New Mexico. Wild rodents transmit it to man. Both North and South America have experienced outbreaks and sporadic cases of HCPS, with 500 cases now recognized. University of New Mexico (UNM) faculty are leaders in the study of HCPS and its ecology, diagnosis, molecular biology, vaccine development, treatment, and pathogenesis. They have traveled to 5 countries in South America, Europe, Israel and Australia to teach courses and conduct workshops, and several have served on NIH and CDC committees on HCPS. UNM currently holds more than $1 million/year in direct costs in federal grants that are directed solely in hantavirus research, as well as other large grants with a hantavirus component. This application describes an International Collaboration in Infectious Diseases Research (ICIDR) program for hantavirus research that matches UNM expertise and resources with similar impressive expertise and resources in Chile. Chilean collaborators are in Santiago at the federal Ministry of Health, including its laboratory branch, the Institute of Public Health (ISP); at Catholic University and University of Chile; and at regional hospitals in Coyhaique and Temuco, two of the primary sites at which HCPS patients are treated. Highly qualified and well-trained collaborators have been identified at all sites. The Ministry of Health rapidly developed resources and manpower to address the HCPS outbreaks, which were first recognized only in August 1997. They have constructed a new laboratory for biological containment work involving the very dangerous Andes hantavirus strain at the ISP and have secured a steady funding stream of $600,000/year from the federal government solely for hantavirus prevention and treatment. Most of these monies can be considered matching funds for the present application. The application involves 4 very strongly linked projects on the ecology of hantaviruses in wild rodents, the interpersonal transmission of HCPS, the genetic basis for severe HCPS and the treatment of HCPS. Two other US universities also provide specific research expertise. Each project pairs strong US technology and experience with highly motivated and experienced Chilean collaborators. Each project has clear and achievable specific aims that will advance the field considerably. A major goal of each project is the rapid and early transfer of technology to Chile to advance scientific knowledge about HCPS for the mutual benefit of both Chilean and US public health. The projects will foster Chilean science well beyond the hantavirus research arena. This ICIDR application is uniquely situated to produce a tremendous return in scientific knowledge because of the substantial cost-matching in Chile and the US and because there is currently relatively little knowledge regarding hantavirus ecology, transmission, disease causation, and treatment. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Pathogenesis of a Novel Hantavirus from Laboratory Rats Principal Investigator & Institution: Simmons, Joe H.; Laboratory Animal Medicine; University of Missouri Columbia 105 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2001; Project Start 1-APR-2001; Project End 1-MAR2006 Summary: (Adapted from the applicant's abstract): Dr. Simmons, the candidate for this SERCA, is a highly qualified young investigator who has achieved a MS in chemistry, a DVM and residency certification in laboratory animal medicine. He is a candidate for a PhD in veterinary pathobiology with an expected graduation date of summer semester 2001. During the course of the SERCA, Dr. Simmons will obtain additional training that will allow him to develop into an independently funded research investigator. To develop his scientific skills, Dr. Simmons will participate in a variety of research training opportunities, including an in-depth research project, scientific meetings, seminars and journal clubs relevant to his area of research, and specialized topical courses at the Cold Spring Harbor Laboratory. Further, Dr. Simmons will receive additional training via collaboration with Dr. Connie Schmaljohn of the US Army Medical Research Institute of Infectious Diseases. He will present his research findings at national scientific meetings, and he will publish his findings in peer reviewed journals. Preliminary results from this SERCA will be used to pursue additional extramural grant funding during year 5 of the granting period. The focus of Dr. Simmons' research project is a novel hantavirus that was recently isolated from laboratory rats with interstitial pneumonia. Preliminary serologic analysis indicates that this novel hantavirus is widespread in laboratory rodents in North America and Europe with approximately 8% of rats infected. Further study of this novel agent is warranted because hantaviruses are potentially zoonotic, subclinical viral infections of laboratory rodents can invalidate research data, and infected rats may represent a critically needed animal model of human hantavirus diseases. The short-term goals of this grant application are to characterize this novel rat hantavirus (RRV), to initiate studies to determine its pathogenesis in rats and to describe the rat's inflammatory cell and cytokine responses to RRV. The long term goal is to develop the RRV-infected rat into a rodent model of human hantavirus diseases. Dr. Riley's laboratory provides a unique environment for this project as it is the only laboratory that has isolated and cultured this novel hantavirus. Further, the UM Research Animal Diagnostic and Investigative Laboratory is an internationally respected rodent diagnostic laboratory with specialized handling facilities and
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expertise in the infectious diseases of rodents necessary to complete this project. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Pathogenesis of South American Hantaviruses Principal Investigator & Institution: St. Jeor, Stephen C.; Professor; Microbiology; University of Nevada Reno Reno, Nv 89557 Timing: Fiscal Year 2000; Project Start 8-SEP-1999; Project End 1-AUG2004 Summary: The University of Nevada, Reno and the Instituto Nacional de Enfermedades Virales Humanas (INEVH) have initiated a collaborative effort to investigate the pathogenesis, ecology and epidemiology of South American Hantaviruses. In our earlier studies we reported the presence of seven novel and phylogenetically distinct hantavirus linages in Argentina. These linages differ at the nucleotide level from 11-21 percent among themselves and 23-26 percent from North American hantaviruses. Three of the linages have been associated with hantavirus pulmonary syndrome and the other with a hemorrhagic fever with renal syndrome. One of the linages (Andes virus) is known to be transmitted directly from humans to humans and a second virus (Oran) is widespread in rodent populations in northern Argentina and is present in 25-40 percent of the native population, as compared to a greater than 1 percent exposure rate throughout Argentina. We propose to determine if the variation in clinical syndromes observed is caused by genetic differences in virus strains or genetic differences in the host. This hypothesis will be tested with the following specific aims: 1) Hantavirus strains associated with a spectrum of clinical syndromes will be examined to identify genetic differences using archived tissue samples, from patients with clinical manifestations varying from a hemorrhagic fever with renal syndrome to a disease resembling hantavirus pulmonary syndrome. 2) A comparison of the pathology of the disease in rodents infected with different hantavirus lineages will be done to determine if the epidemiologic and clinical differences associated with South American hantaviruses is caused by an altered pathogenesis of the viruses in rodents. 3. Identification of neutralizing epitopes in hantavirus glycoproteins: Human monoclonal antibody libraries will be used for the identification and mapping of neutralizing epitopes in both tissue culture and in the rodent reservoir. 4. The pattern of association and co-evolution of South American hantaviruses with their sigmodontine rodent hosts will be identified. 5. Differences in the susceptibility of different human haplotypes to infection with hantaviruses will be determined using archived tissue samples from INEVH. It is anticipated that a clearer
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understanding of the pathogenesis, ecology and epidemiology of South American hantaviruses will help in the prevention of outbreaks of disease caused by new world hantaviruses. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Search for Residual Disease in Hantavirus Survivors Principal Investigator & Institution: Goade, Diane; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000 Summary: This study is a 5 year longitudinal pilot study evaluating pulmonary, cardiac, renal and laboratory parameters in patients who have been confirmed as having had hantavirus disease. Patients will be followed on a yearly basis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Biochemical Principles in Encapsidation Pathways of Human Viral Pathogens Principal Investigator & Institution: Linial, Maxine L.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 2-JUN-2002; Project End 1-MAY2007 Summary: Specific Aims: Dr. Jonsson and Linial propose collaborative experiments to analyze the RNA: protein interactions leading to genomic RNA encapsidation for two different classes of viruses, hantaviruses and retroviruses. The Jonsson lab brings to the proposal expertise in hantavirology and biochemistry and chemistry of RNA-protein interactions. The Linial lab provides the expertise in retrovirology and molecular genetic analysis of RNA-protein interactions using yeast. For retroviruses, we have chosen the avail or alpharetroviruses, Rous sarcoma virus (RSV). Work on the packaging signal of these viruses has pin pointed a small, contiguous RNA sequence that interacts specifically with residues in the nucleocapsid (NC) domain of the viral structure protein precursor Gag. For the hantaviruses, we will use the Hantaan virus (HTNV). A putative packaging signal has been identified in the Ssegment of the HTNV to interact with the nucleoprotein (N). The two specific aims of this pilot project are: Aim 1). To identify the domain/amino acids in the HTNV N protein responsible for interaction with viral genomic and anti-genomic RNA using the yeast three-hybrid assay (YTHA), and Aim 2). To characterize the chemistry of the interaction of the RSV NC with its packaging signal, psi.
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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Syndrome
Immunogenetics
of
Hantaviral
Cardiopulmonary
Principal Investigator & Institution: Kester, Frederick; University of New Mexico Albuquerque Albuquerque, Nm 87131 Timing: Fiscal Year 2000 Summary: Hantavirus Cardio-Pulmonary Syndrome (HCPS) due to Sin Nombre Virus has a mortality rate of 45% while HCPS due to Andes virus is at least as severe, with death due to cardiogenic shock and noncardiogenic pulmonary edema. Current evidence indicates that the pathology of HCPS/SNV is mediated at least in part by an exuberant T cell-mediated immune response against HSV-infected endothelial cells. This notion is supported by recent evidence that patients with severe or fatal HCPS express a specific class I MHC allele, HLA-B*35. Since the GB35- restricted nucleocapsid protein epitope is conserved between SNV and Andes viruses, the same association between HCPS severity and B*35 allele may occur among hospitalized patients with HCPS in Chile. This proposal test the hypothesis that severe hantavirus disease (shock and pulmonary edema is directly related to one or more MHC alleles through their role regulating the intensity of the cytotoxic T cell response. One hundred fifty hospitalized patients with HCPS will be HLA-typed at class I (A, B and C loci) and class II will be compared. This study will also test the hypothesis that the intensity of cytokine gene transcription and subsequent organ damage is determined in lesser part by allelic polymorphisms in HLA-linked genes, particularly in the TNF complex linked to HLA-B loci. Finally, in contrast to susceptibility to severe disease, susceptibility to infection with Andes virus is not associated with allelic polymorphisms in the MHC complex, as tested in a field study of seropositive versus seronegative individuals. Detailed analysis will seek to identify individual contributions of one or multiple MHC alleles determining disease severity. Planned parallel studies in North and South America on the immunogenetics of hantavirus infection will enhance the insights from each syndrome. The strategy of 'reverse immunogenetics" of hantavirus infection will enhance the insights from each syndrome. The strategy of 'reverse immunogenetics' may identify specific cellular or cytokine targets for future therapeutic interventions. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Laboratory Animal Models Principal Investigator & Institution: Dewey, Michael J.; Biological Sciences; University of South Carolina at Columbia Columbia, Sc 29208
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Timing: Fiscal Year 2000; Project Start 1-JUL-1999; Project End 0-JUN2002 Summary: The deer mouse (Peromyscus maniculatus) and congeneric species are the most abundant and widely distributed native rodents in North America. As a consequence they impact on many aspects of human health as reservoirs for infectious disease organisms and as laboratory models useful in biomedical research. Deer mice have been maintained in captivity since early in the century and are widely used in physiological, environmental and other studies. The Peromyscus Genetic Stock Center at the University of South Carolina proposes to expand utilization of Peromyscus and improve these animals as a convenient model for health-related research. Six or more Peromyscus stocks will be developed specifically for the study of hantavirus, ehrlichiosis and other diseases for which these animals are hosts, as well as for a variety of other biomedical research projects. Utility of this animal model will be improved through in-house studies of reproduction, including cyropreservation of gametes, and further genetic characterization. The stocks developed will be available to the scientific community for research and educational purposes. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Pilot--Biochemical Principles in Encapsidation Pathways of Human Viral Pathogens Principal Investigator & Institution: Jonsson, Colleen B.; Associate Professor; New Mexico State University Las Cruces Box 3001, Dept 3Da Las Cruces, Nm 88003 Timing: Fiscal Year 2002; Project Start 2-JUN-2002; Project End 1-MAY2007 Summary: Specific Aims: Drs. Jonsson and Linial propose collaborative experiments to analyze the RNA: protein interactions leading to genomic RNA encapsidation for two different classes of viruses, hantaviruses and retroviruses. The Jonsson lab brings to this proposal expertise in hantavirology and biochemistry and chemistry of RNA-protein interactions. The Lineal lab provides the expertise in retrovirology and molecular genetic analysis of RNA-protein interactions using yeast. For retroviruses, we have chosen the avian or alpharetroviruses, Rous sarcoma virus (RSV). Work on the packaging signal of these viruses has pin pointed a small, contiguous RNA sequence that interacts specifically with residues in the nucleocapsid (NC ) domain of the viral structural protein precursor Gag. For the hantaviruses, we will use the Hantaan virus (HTNV). A putative packaging signal has been identified in the Ssegment of the HTNV to interact with the nucleoprotein (N). The two
72 Hantavirus Pulmonary Syndrome
specific aims of this pilot project are: Aim 1). To identify the domain/amino acids in the HTNV N protein responsible for interaction with viral genomic and anti-genomic RNA using the yeast three-hybrid assay (YTHA), and Aim 2). To characterize the chemistry of the interaction of the RSV NC with its packaging signal, psi. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Structural Investigation of the Hantaan Virus L Protein Principal Investigator & Institution: Niles, Edward G.; Professor; Biochemistry; State University of New York at Buffalo Capen Hall Buffalo, Ny 14260 Timing: Fiscal Year 2000; Project Start 0-SEP-1998; Project End 1-AUG2002 Summary: (adapted from applicant's abstract): Bunyaviruses represent the largest family of negative stranded RNA viruses. Each contains a genome consisting of three RNA segments wrapped in a nucleoprotein complex. Most Bunyaviruses are propagated in an insect vector with the notable exception of Hantaviruses which are carried in rodents. Hantaan virus, the initial Hantavirus, was first shown to be the causative agent of Korean Hemorraghic Fever, a disease endemic in the Orient. Viruses closely related to Hantaan virus, however, have a worldwide distribution and to be associated with hemorraghic fever. With the recent unexpected outbreak of acute pulmonary syndrome in the Southwest, also caused by a hantavirus referred to as Sin Nombre Virus (SNV), the identification of additional cases in other regions of the country, and the characterization of several new species of hantavirus in North America, it is important to obtain a detailed understanding of the hantavirus life cycle. The longterm goals of the application are to elucidate the mechanisms of hantavirus mRNA synthesis and RNA replication. In this proposal, the applicant will focus on developing a topological map of the viral L protein. Due to the anticipated difficulty in obtaining large amounts of pure L protein sufficient for structural studies, we propose a novel approach to generating, identifying and characterizing active subdomains of the L protein. The results of the proposed studies will serve as the groundwork for future studies on viral transcription and replication. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Workshops On Viral Pathogenesis and Oncogenesis Principal Investigator & Institution: Fan, Hung Y.; Professor; Cancer Research Institute; University of California Irvine Campus Dr Irvine, Ca 92697
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Timing: Fiscal Year 2002; Project Start 1-MAR-2002; Project End 8-FEB2005 Summary: A series of workshops on viral pathogenesis and oncogenesis will be organized. Viral infectious diseases continue to be major human health threats in both the developed and developing worlds. They can cause acute infections (both new [e.g. hantavirus] and established [e.g. influenza]) and also chronic diseases- notably cancers (e.g. cervical cancer, lymphomas and hepatocellular carcinoma) and neurodegenerative diseases. An important foundation for development of viral vaccines and anti-virals is establish the knowledge base for how a particular virus causes disease. Ultimately, experimentation in whole infected organisms must be carried out, and this often necessitates developing animal models. These workshops will temporally coincide with meetings of the NIH Virology and Experimental Virology study sections. The workshops will be 1 + days in length, featuring 12 plenary speakers. Approximately six speakers will be drawn from study section membership, and the other six will be invited on the basis of their recent groundbreaking discoveries. The workshops will be advertised through journals (e.g. ASM News, the Journal of Virology) as well as through relevant websites (NIH and otherwise). Attendance will be open to all interested investigators, and we anticipate an attendance of 75-150. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
E-Journals: PubMed Central19 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).20 Access to this growing archive of e-journals is free and unrestricted.21 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “Hantavirus pulmonary syndrome” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 20 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. 21 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. 19
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items found for Hantavirus pulmonary syndrome in the PubMed Central database: ·
[beta]3 integrins mediate the cellular entry of hantaviruses that cause respiratory failure by Irina N. Gavrilovskaya, Michael Shepley, Robert Shaw, Mark H. Ginsberg, and Erich R. Mackow; 1998 June 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=22743
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Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus) by Jason Botten, Katy Mirowsky, Donna Kusewitt, Mausumi Bharadwaj, Joyce Yee, Roy Ricci, Richard M. Feddersen, and Brian Hjelle; 2000 September 12 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27067
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Genetic Diversity, Distribution, and Serological Features of Hantavirus Infection in Five Countries in South America by P. J. Padula, S. B. Colavecchia, V. P. Martinez, M. O. Gonzalez Della Valle, A. Edelstein, S. D. L. Miguel, J. Russi, J. Mora Riquelme, N. Colucci, M. Almiron, and R. D. Rabinovich; 2000 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87178&ren dertype=external
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New York 1 and Sin Nombre Viruses Are Serotypically Distinct Viruses Associated with Hantavirus Pulmonary Syndrome by Irina Gavrilovskaya, Rachel LaMonica, Mary-Ellen Fay, Brian Hjelle, Connie Schmaljohn, Robert Shaw, and Erich R. Mackow; 1999 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84184&ren dertype=external
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Risk factors for human hantavirus infection: Franco-Belgian collaborative case-control study during 1995-6 epidemic by N S Crowcroft, A Infuso, D Ilef, B Le Guenno, J-C Desenclos, F Van Loock, and J Clement; 1999 June 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=31102
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Truncated Hantavirus Nucleocapsid Proteins for Serotyping Hantaan, Seoul, and Dobrava Hantavirus Infections by Koichi Araki, Kumiko Yoshimatsu, Michiko Ogino, Hideki Ebihara, Ake Lundkvist, Hiroaki Kariwa, Ikuo Takashima, and Jiro Arikawa; 2001 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88161&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
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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.22 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 Hantavirus pulmonary syndrome, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “Hantavirus pulmonary syndrome” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “Hantavirus pulmonary syndrome” (hyperlinks lead to article summaries): ·
Glomerular basement membrane antibodies in hantavirus disease (hemorrhagic fever with renal syndrome). Author(s): Billheden J, Boman J, Stegmayr B, Wieslander J, Settergren B. Source: Clinical Nephrology. 1997 September; 48(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9342483&dopt=Abstract
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Hantavirus in the southwestern United States: epidemiology of an emerging pathogen. Author(s): Sands L, Kioski C, Komatsu K. Source: J Am Osteopath Assoc. 1993 December; 93(12): 1279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8307808&dopt=Abstract
Vocabulary Builder Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical 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.
22
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and developmental process. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Cardiac: Pertaining to the heart. [EU] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Chronic: Persisting over a long period of time. [EU] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Glycoproteins:
Conjugated protein-carbohydrate compounds including
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mucins, mucoid, and amyloid glycoproteins. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lethal: Deadly, fatal. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Metabolite: process. [EU] Neonatology: infant. [NIH]
Any substance produced by metabolism or by a metabolic A subspecialty of Pediatrics concerned with the newborn
Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH]
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Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Papillomavirus: A genus of papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [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] 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
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s.) or the complete range of manifestations of a disease. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]
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CHAPTER 5. PATENTS ON HANTAVIRUS PULMONARY SYNDROME Overview You can learn about innovations relating to Hantavirus pulmonary syndrome 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.23 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 Hantavirus pulmonary syndrome 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 Hantavirus pulmonary syndrome. 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.
23Adapted
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 Hantavirus Pulmonary Syndrome By performing a patent search focusing on Hantavirus pulmonary syndrome, 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 Hantavirus pulmonary syndrome: ·
Rio Mamore hantavirus nucleocapsid protein and diagnostic methods employing said protein Inventor(s): Hjelle; Brian L. (Albuquerque, NM), Torrez-Martinez; Norah (Albuquerque, NM) Assignee(s): Science & Technology Corporation @UNM (Albuquerque, NM) Patent Number: 6,416,761 Date filed: June 8, 1999 Abstract: The Hantavirinae encompass a large number of species which are distributed worldwide. Although hantaviruses generally reside in murine hosts, they are also the causative agents of a number of human diseases including hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). Tissue samples were obtained from hantavirus-infected rodents (e.g., Oligoryzomys microtis) and subjected to reverse transcription-polymerase chain reaction (RTPCR) analysis to amplify hantaviral-specific nucleic acids. A molecular clone encoding the complete nucleocapsid (N) protein of the Rio Mamore Virus (RMV) was obtained and used to express high-levels of protein. The availability of the RMV N protein and its incorporation into immunodiagnostic assays will facilitate the detection of hantavirusspecific antibodies. Excerpt(s): Since there are so many distinct species of Hantaviruses, there is no single test or single reagent that allows the diagnosis of all hantavirus infection. In each case, the best reagents for detection of antibodies to a given hantavirus are those which are based upon the hantavirus species that actually caused the infection. The nucleocapsid (N) protein is the portion of each hantavirus that is most strongly
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immunogenic, and the standard for diagnosis of Hantaviruses has increasingly been to rely upon the expression of homologous N protein in bacteria or other microbial expression system to generate high concentrations of recombinant-expressed antigen. Classical methods of viral antibody detection have depended upon the growth of the virus in culture, with use of the viral antigens from infected cultures in immunologic detection, but these methods are increasingly falling out of favor for a variety of technical and practical reasons. ... Because none of the prototype Hantaviruses listed above occurs in rodents with distribution in South America, it is virtually certain that human Hantavirus disease in South America is due to novel virus(es) that will be detected in a less-than-optimal manner by tests that utilize antigens derived from prototype species. These virus(es) are almost certainly associated with indigenous rodents of the subfamily Sigmodontinae, family Muridae, because the clinical disease that has been noted in Brazilian, Argentinean, and Paraguayan patents is closely similar to those diseases caused by North American Hantaviruses of sigmodontine rodents. Detection of Hantavirus infection in South America has relied most heavily upon cross-reactivity between the prototypic sigmodontine rodent-borne Hantavirus Sin Nombre (Four Corners) virus (SNV) and the South American virus(es). ... The invention provides a molecular clone encoding and expressing the complete nucleotide protein of Rio Mamore virus. The RMV N protein includes antigenically active domains useful in immunoassays for detecting South American Hantavirus infection, and in vaccines. Web site: http://www.delphion.com/details?pn=US06416761__ ·
Strain of hantavirus nucleotide sequences thereof related probes, primers and vectors, and methods for detection Inventor(s): Nichol; Stuart T. (Atlanta, GA), Spiropoulou; Christina F. (Atlanta, GA), Ksiazek; Thomas G. (Lilburn, GA), Rollin; Pierre E. (Lilburn, GA) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,945,277 Date filed: May 30, 1996 Abstract: The present invention relates to the discovery of a novel Hantavirus. In particular, the present invention relates to nucleic acids of the newly discovered virus and to nucleic acid reagents and antibodies for use in methods of detection and prevention of infection by the virus.
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Excerpt(s): The present invention relates to discovery of a novel Hantavirus. In particular, the present invention relates to nucleic acids of the novel Hantavirus and to nucleic acid reagents and antibodies for use in methods of detection and prevention of infection by the new virus. ... The high mortality associated with ARDS and the unknown etiology of the pathogen created an urgent need to isolate and identify the pathogen and to provide reliable methods for diagnosis, treatment and prevention of the disease. The present invention satisfied that need by identifying a previously unreported strain of Hantavirus as the causative agent of the ARDS outbreak. The present invention also provides methods to diagnose and prevent infection. ... The present invention provides the discovery and isolation of a new virus. This virus is the etiologic agent responsible for the outbreak of the Adult Respiratory Distress Syndrome (ARDS) in the Four Corners Region of the United States. Based upon genetic characteristics, this new virus should be classified in the Hantavirus family. Web site: http://www.delphion.com/details?pn=US05945277__ ·
Bayou hantavirus and related methods Inventor(s): Nichol; Stuart T. (Atlanta, GA), Morzunov; Sergey (Atlanta, GA), Ksiazek; Thomas G. (Lilburn, GA), Rollin; Pierre E. (Lilburn, GA), Spiropoulou; Christina F. (Atlanta, GA) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,916,754 Date filed: February 17, 1995 Abstract: The present invention relates to the discovery and isolation of a novel hantavirus designated the Bayou hantavirus. In particular, the present invention relates to nucleic acids of the newly discovered virus and to nucleic acid reagents (primers and probes), purified polypeptides and antibodies for use in methods of detection and prevention of infection by the virus. A vaccine or purified immunogenic polypeptide of the Bayou hantavirus in a pharmaceutically acceptable carrier is provided. A vector comprising the nucleic acids of the invention is provided. A method of detecting the presence of a hantavirus in a subject comprising contacting an antibody-containing sample from the subject with a purified polypeptide of the invention and detecting the reaction of the polypeptide and the antibody is provided. A method of detecting the presence of the Bayou hantavirus is provided comprising reverse transcribing viral RNA to synthesize a complementary DNA sequence
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followed by amplifying the DNA using primers which are selective for the Bayou hantavirus and detecting the presence of amplification, thereby indicating presence of the Bayou hantavirus in the sample. Excerpt(s): The present invention relates to discovery of a new hantavirus species. In particular, the present invention relates to the isolated Bayou hantavirus, to attenuated or inactivated derivatives of the Bayou hantavirus, to nucleic acids of the new hantavirus, and to nucleic acid reagents and antibodies for use in methods of detection and prevention of infection by the new virus. ... In general, hantaviruses are spherical 28nm viruses that were initially identified from the feces of rodents. They have distinctive ultrastructural glycoprotein surfaces of 5-10 nm that are embedded in a lipid bi-layer envelope. The negative sense RNA of the viral genome consists of three segments, generally designated as S, M, and L for the small, medium, and large genome fragments, respectively. The S segment encodes a nucleocapsid protein (N) and the M segment encodes the surface qlycoproteins G1 and G2. (Schmaljohn, C. S. et al., Fund. Virol. 545:545 (1991)). The S segment may additionally encode a 6.times.10.sup.3 -dalton protein. (Bishop, D. H. L. Bunyaviridae and their replication. In, Virology, 2nd ed. B. N. Fields and D. M. Knipe, Eds. Raven Press, Ltd. (1990)). The L segment encodes the viral polymerase gene. (Elliott, M. Molecular biology of the Bunyaviridae. J. Gen. Virol. 71:501-522 (1990)). Seven species of hantavirus are currently recognized and are designated Hantaan (HTN) virus species, Seoul (SEO) virus species, Puumala (PUU) virus species, Dobrava-Belgrade (DOB) virus species, Prospect Hill virus species (PH), Harvest Mouse (HM) virus species, and the Sin Nombre (SN) virus species. Infection with these viral agents is usually contracted through contact with the feces and urine of infected rodents, the primary reservoir of hantaviruses in nature. ... Until recently, hantaviruses were thought to be responsible for causing human diseases collectively called hemorrhagic fever with renal syndrome (HFRS) in southeast Asia (HTN, SEO) and in western Europe (PUU), or not associated with human disease (PH). In May and June, 1993, an outbreak of an unknown disease presenting the abrupt onset of fever, myalgia, headache, cough and finally respiratory failure in the southwestern United States led to the description of the hantavirus pulmonary syndrome (HPS). A new hantavirus pathogenic for humans, the Sin Nombre (SN) virus was isolated and determined to be the causative agent of this disease. The primary reservoir for the Sin Nombre virus was found to be deer mice, Peromyscus maniculatus. Through Dec. 31, 1993, this disease was confirmed in 53 persons with a 60% fatality ratio. Web site: http://www.delphion.com/details?pn=US05916754__
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·
Black creek canal hantavirus and related methods Inventor(s): Rollin; Pierre E. (Lilburn, GA), Elliott; Luanne (Atlanta, GA), Ksiazek; Thomas G. (Lilburn, GA), Nichol; Stuart T. (Atlanta, GA), Morzunov; Sergey (Atlanta, GA), Ravkov; Eugeny (Atlanta, GA) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC), National Institutes of Health Office of Technology Transfer (Bethesda, MD) Patent Number: 5,853,980 Date filed: February 3, 1997 Abstract: The present invention relates to the discovery and isolation of a novel hantavirus designated the Black Creek Canal hantavirus. In particular, the present invention relates to nucleic acids of the newly discovered virus and to nucleic acid reagents (primers and probes), purified polypeptides and antibodies for use in methods of detection and prevention of infection by the virus. A vaccine or purified immunogenic polypeptide of the Black Creek Canal hantavirus in a pharmaceutically acceptable carrier is provided. A vector comprising the nucleic acids of the invention is provided. A method of detecting the presence of a hantavirus in a subject comprising contacting an antibody-containing sample from the subject with a purified polypeptide of the invention and detecting the reaction of the polypeptide and the antibody is provided. A method of detecting the presence of the Black Creek Canal hantavirus is provided comprising reverse transcribing viral RNA to synthesize a complementary DNA sequence followed by amplifying the DNA using primers which are selective for the Black Creek Canal hantavirus and detecting the presence of amplification, thereby indicating presence of the Black Creek Canal hantavirus in the sample. Excerpt(s): The present invention relates to discovery of a new hantavirus species. In particular, the present invention relates to the isolated Black Creek Canal hantavirus, to attenuated or inactivated derivatives of the Black Creek Canal hantavirus, to nucleic acids of the new hantavirus, and to nucleic acid reagents and antibodies for use in methods of detection and prevention of infection by the new virus. ... In general, hantaviruses are spherical 28-nm viruses that were initially identified from the feces of rodents. They have distinctive ultrastructural glycoprotein surfaces of 510 nm that are embedded in a lipid bi-layer envelope. The negative sense RNA of the viral genome consists of three segments, generally designated as S, M, and L for the small, medium, and large genome fragments, respectively. The S segment encodes a nucleocapsid protein (N) and the M segment encodes the surface glycoproteins G1 and G2. (Schmaljohn, C. S. et al., Fund. Virol. 545:545 (1991)). The S segment may additionally
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encode a 6.times.10.sup.3 -dalton protein. (Bishop, D. H. L. Bunyaviridae and their replication. In, Virology, 2nd ed. B. N. Fields and D. M. Knipe, Eds. Raven Press, Ltd. (1990)). The L segment encodes the viral polymerase gene. (Elliott, M. Molecular biology of the Bunyaviridae. J. Gen. Virol. 71:501-522 (1990)). Seven species of hantavirus are currently recognized and are designated Hantaan (HTN) virus species, Seoul (SEO) virus species, Puumala (PUU) virus species, Dobrava-Belgrade (DOB) virus species, Prospect Hill virus species (PH), Harvest Mouse (HM) virus species, and the Sin Nombre (SN) virus species. Infection with these viral agents is usually contracted through contact with the feces and urine of infected rodents, the primary reservoir of hantaviruses in nature. ... Until recently, hantaviruses were thought to be responsible for causing human diseases collectively called hemorrhagic fever with renal syndrome (HFRS) in southeast Asia (HTN, SEO) and in western Europe (PUU), or not associated with human disease (PH). In May and June, 1993, an outbreak of an unknown disease presenting the abrupt onset of fever, myalgia, headache, cough and finally respiratory failure in the southwestern United States led to the description of the hantavirus pulmonary syndrome (HPS). A new hantavirus pathogenic for humans, the Sin Nombre (SN) virus was isolated and determined to be the causative agent of this disease. The primary reservoir for the Sin Nombre virus was found to be deer mice, Peromyscus maniculatus. Through Dec. 31, 1993, this disease was confirmed in 53 persons with a 60% fatality ratio. Web site: http://www.delphion.com/details?pn=US05853980__ ·
Hantavirus-associated respiratory distress virus antigens Inventor(s): Hjelle; Brian (Albuquerque, NM), Jenison; Steve (Albuquerque, NM) Assignee(s): University of New Mexico (Albuquerque, NM) Patent Number: 5,837,441 Date filed: March 22, 1994 Abstract: The invention provides HARDS virus rDNA for expression in molecular clones. The expressed products are useful in immunodiagnostics, prophylactics, and therapeutics for the HARDS virus and related hantaviruses. Of particular interest are a type-specific epitope of the HARDS virus G1 protein, and dominant epitopes of the HARDS virus N protein cross-reactive with antibodies to the HARDS virus and the related hantavirus PHV, both expressed by cDNA clones according to the invention.
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Excerpt(s): The invention relates to the HARDS virus, the etiologic agent of Hantavirus-Associated Respiratory Distress Syndrome. ... An epidemic of unexplained adult respiratory distress syndrome, affecting primarily residents of the Four Corners region formed by the borders of New Mexico, Arizona, Utah, and Colorado, was recognized in May, 1993. The disease is characterized by a prodromal illness of fever, myalgias, and, in some cases, conjunctivitis, lasting 1-5 days, followed by a severe and acute illness characterized by pulmonary edema and shock. According to the federal Centers for Disease Control and Prevention (CDC), through Jul. 27, 1993, death from suffocation and/or shock had occurred in 14 (78%) of the 18 patients diagnosed with the illness since the epidemic was recognized. The syndrome was eventually determined to be caused by a viral infection of a newly-identified hantavirus virus subsequently named the HARDS virus (also referred to as Sin Nombre Virus and Four Corner Virus, or FCV). According to the CDC, the predominant vector for this virus is the deer mouse Peromyscus maniculatus, which ranges throughout the southwest U.S. with the potential for spreading HARDS infection within this area. ... By early June, it was recognized that the victims of the new syndrome were developing, during their illness, IgM antibodies that reacted with one or both of two members of the Hantavirus genus of Bunyaviruses. Those viruses are known as Puumala virus, a vole virus that causes the human disease nephropathia epidemica (Europe), and Seoul virus, a virus of Norwegian rats first identified in Korea. Scientists at the federal Centers for Disease Control and Prevention (CDC), in Atlanta, Ga., were able to obtain molecular clones and limited sequence information from the new virus. The sequence information supported the notion that the new virus is a hantavirus; and suggested that its closest relatives among the hantaviruses might be Puumala virus, and another rodent virus known as Prospect Hill virus (PHV). Web site: http://www.delphion.com/details?pn=US05837441__ ·
Hantavirus vaccine Inventor(s): Schmaljohn; Connie S. (Frederick, MD), McClain; David J. (Frederick, MD), Dalrymple, deceased; Joel (late of Myersville, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 5,614,193 Date filed: March 28, 1994
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Abstract: Vaccine formulations for inducing protective immune response to Hantaviruses in humans are disclosed. These formulations include an attenuated vaccinia virus vector containing cDNA's encoding Hantavirus nucleocapsid N protein, G1 and G2 glycoproteins. Methods for the use of these formulations also are disclosed. Excerpt(s): Subsequently, it was recognized that Korean hemorrhagic fever and clinically similar diseases, collectively termed hemorrhagic fever with renal syndrome (HFRS), pose a significant health threat in much of Asia and parts of Europe and Scandinavia. Non-pathogenic infection of rodent populations apparently provides a reservoir for the causative agent. Infection of humans occurs via aerosol of the agent, a Hantavirus of the family Bunyaviridae, from rodent urine, feces and saliva. Mortality rates have decreased from the 10 to 15% seen during the Korean conflict to 5% or less, if improved fluid and electrolyte management and/or renal dialysis are available. Currently, an estimated 50,000-100,00 case occur annually in the Peoples' Republic of China, with mortality rates ranging from 5 to 20%, in various provinces. ... A Hantavirus vaccine has been approved and is in use in South Korea. Lee and Ahn (1988). This vaccine was developed by serial passage of the virus in brains of suckling pigs, followed by inactivation with formalin. Initial claims reported that two doses of the vaccine, given via a subcutaneous route one month apart, resulted in 100% seroconversion as measured by immunofluorescence. The production of this vaccine, however, was not in compliance with current U.S. Food and Drug Administration guidelines on "Good Manufacturing Practices," and the protective efficacy has not yet been determined. Furthermore, adventitious agents in the product were not rigorously excluded and the animal colony used for the vaccine's development was not pathogen-free. Other vaccines are currently undergoing testing in Japan, North and South Korea and China. Both Korean vaccine trials involved the use of formalin-inactivated, Hantaan virus-infected mouse brain. Suh et al., Virus Information Exchg. Newsl. 6: 131 (1989); Lee and Ahn (1988). The Chinese and Japanese trials involve inactivated, tissue culture-derived Hantavirus preparations. Yu and Zhe, Virus Information Exchg. Newsl. 6: 131 (1989). ... A second Hantavirus, the "Seoul" serotype, has been isolated and sequenced. Antic et al., Virus Res. 19: 47-58 (1991): Antic et al., Virus Res. 19: 59-66 (1991). The Hantaan and Seoul serotypes show about 75% sequence homology at the RNA level. Antic et al., Virus Res. 24: 35-46 (1992). Patients with HFRS caused by the Seoul serotype appear to suffer a milder clinical form of the disease. Recent studies indicate that six other Hantaviruses exist: Puumala, Prospect Hill, Thailand, Dobrava, Thottapalayam and Four Corners. Arikawa et al., Virology 176: 114-125 (1990); Xiao et al., Virology 198: 205-217 (1994); Chu et al., Virology 198:
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196-204 (1994); Nichol et al., "Genetic Identification of a Novel Hantavirus Associated with an Outbreak of Acute Respiratory Illness in the Southwestern United States, " Science in press (1994). Only Hantaan, Seoul, Puumala , and Dobrava are known to cause HFRS. Four Corners was described recently and linked to an extremely deadly form of pulmonary distress in the southwest United States. Thottapalayam, Prospect Hill and Thailand are not known to cause human disease. Web site: http://www.delphion.com/details?pn=US05614193__
Patent Applications on Hantavirus Pulmonary Syndrome As of December 2000, U.S. patent applications are open to public viewing.24 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 Hantavirus pulmonary syndrome, 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 “Hantavirus pulmonary syndrome” (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 Hantavirus pulmonary syndrome. You can also use this procedure to view pending patent applications concerning Hantavirus pulmonary syndrome. 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 Antigens: Substances that are recognized by the immune system and induce an immune reaction. [NIH] 24
This has been a common practice outside the United States prior to December 2000.
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Bunyaviridae: A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: bunyavirus, hantavirus, nairovirus, phlebovirus, and tospovirus. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] 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] Immunogenic: Producing immunity; evoking an immune response. [EU] Myalgia: Pain in a muscle or muscles. [EU] 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] 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 found together in either parent; usually applied to linked genes. [EU] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU]
Books 93
CHAPTER 6. BOOKS ON HANTAVIRUS PULMONARY SYNDROME Overview This chapter provides bibliographic book references relating to Hantavirus pulmonary syndrome. You have many options to locate books on Hantavirus pulmonary syndrome. 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 Hantavirus pulmonary syndrome 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: 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 Hantavirus pulmonary syndrome (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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·
Hantavirus en las Américas: guía para el diagnóstico, el tratamiento, la prevención y el control by Pan American Health Organization; ISBN: 9275330476; http://www.amazon.com/exec/obidos/ASIN/9275330476/icongroupin terna
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Hantavirus in the Americas: Guidelines for Diagnosis, Treatment, Prevention, and Control (Series TP 47) ; ISBN: 9275130477; http://www.amazon.com/exec/obidos/ASIN/9275130477/icongroupin terna
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Of Mice, Men, and Microbes: Hantavirus by Andrea S. Meyer, et al; ISBN: 012326460X; http://www.amazon.com/exec/obidos/ASIN/012326460X/icongroupi nterna
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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
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 “Hantavirus pulmonary syndrome” (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:25 ·
Correspondence on the discovery and original investigations on hemorrhagic fever with renal syndrome and hantaviruses, 1970-1999 =
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.
25
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Hant`an pairosu palgyon mit sinjunghu ch`urhyolyol yon'gu e kwanhan sohanjip. Author: edited by H. W. Lee; Year: 2000; Seoul, Korea: The Hantaan Life Science Foundation, [2000] ·
Emergence and control of rodent-borne viral diseases: hantaviral and arenal diseases: emerging diseases: 28-31 October 1998, "Les Pensières", Veyrier-du-Lac, Annecy, France. Author: edited by Jean-François Saluzzo, Betty Dodet; Year: 1999; Amsterdam; New York: Elsevier, c1999; ISBN: 2842991141 http://www.amazon.com/exec/obidos/ASIN/2842991141/icongroupin terna
·
Hantavirus testing in small mammal populations of northcentral New Mexico [microform]. Author: James Biggs ... [et al.]; Year: 1995; Los Alamos, N.M.: Los Alamos National Laboratory; Springfield, VA: Available from National Technical Information Service, U.S. Dept. of Commerce, [1995]
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Hantaviruses. Author: edited by C.S. Schmaljohn and S.T. Nichol; Year: 2001; Berlin; New York: Springer, 2001; ISBN: 3540410457 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/3540410457/icongroupin terna
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Of mice, men, and microbes: hantavirus. Author: David R. Harper, Andrea S. Meyer; Year: 1999; San Diego: Academic Press, c1999; ISBN: 012326460X (alk. paper) http://www.amazon.com/exec/obidos/ASIN/012326460X/icongroupi nterna
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Report of a meeting on hantavirus vaccine development: Helsinki, Finland, 31 May 1995. Author: World Health Organization. Working Group on the Prevention and Control of Hantavirus Infections; Year: 1995; [Geneva?]: World Health Organization, Bacterial, Viral Diseases, and Immunology, [1995]
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Report. Author: Working Group on the Prevention and Control of Hantavirus Infections, convened by World Health Organization, Regional Office for the Western Pacific, Seoul, Republic of Korea, 5-6 November 1997; Year: 1998; Manila, Philippines: Printed and distributed by World Health Organization, Regional Office for the Western Pacific, [1998]
Chapters on Hantavirus Pulmonary Syndrome Frequently, Hantavirus pulmonary syndrome will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are
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specifically dealing with Hantavirus pulmonary syndrome, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Hantavirus pulmonary syndrome using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “Hantavirus pulmonary syndrome” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books.
General Home References In addition to references for Hantavirus pulmonary syndrome, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · The Invisible Enemy: A Natural History of Viruses by Dorothy H. Crawford; Hardcover - 208 pages (November 2000), Oxford University Press (Trade); ISBN: 0198503326; http://www.amazon.com/exec/obidos/ASIN/0198503326/icongroupinterna · Encyclopedia of Infectious Diseases (Encyclopedia of Infectious Diseases, 1998) by Carol Turkington, Bonnie Ashby; Library Binding - 384 pages (September 1998), Facts on File, Inc.; ISBN: 0816035121; http://www.amazon.com/exec/obidos/ASIN/0816035121/icongroupinterna · Epidemic! The World of Infectious Disease by Rob Desalle (Editor), American Museum of Natural History; Paperback - 246 pages, 1st edition (September 1999), New Press; ISBN: 1565845463; http://www.amazon.com/exec/obidos/ASIN/1565845463/icongroupinterna · Outbreak Alert: Responding to the Increasing Threat of Infectious Diseases by Jason, M.D Eberhart-Phillips; Paperback - 292 pages (July 2000), New Harbinger Pubns; ISBN: 1572242019; http://www.amazon.com/exec/obidos/ASIN/1572242019/icongroupinterna
Multimedia 97
CHAPTER 7. MULTIMEDIA ON HANTAVIRUS PULMONARY SYNDROME Overview Information on Hantavirus pulmonary syndrome can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on Hantavirus pulmonary syndrome. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.
Bibliography: Multimedia on Hantavirus Pulmonary Syndrome The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in Hantavirus pulmonary syndrome (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on Hantavirus pulmonary syndrome. For more information, follow the hyperlink indicated: ·
Engaging the enemy: invisible enemies: aerial enemies. Source: a presentation of Films for the Humanities & Sciences; a production of
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Discovery Channel; Year: 2001; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2001 ·
Hantavirus pulmonary syndrome clinical update 1999. Source: CDC, Centers for Disease Control and Prevention [and] Public Health Training Network; Year: 1999; Format: Videorecording; [Atlanta, Ga.: Centers for Disease Control and Prevention, 1999]
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Ounce of prevention: keeps the germs away. Source: Centers for Disease Control and Prevention; produced by Public Health Practice Program Office, Division of Media and Training Services; Year: 1998; Format: Videorecording; [Atlanta, Ga.]: The Centers, [1998]
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Preventing hantavirus disease. Source: CDC, Centers for Disease Control; produced by Division of Media and Training Services, Public Health Practice Program Office, Centers for Disease Control and Prevention; Year: 1994; Format: Videorecording; Atlanta, GA: Centers for Disease Control and Prevention, [1994]
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CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.
NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/health/diseases.htm
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.26 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:27 ·
Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 27 See http://www.nlm.nih.gov/databases/databases.html. 26
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Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
While all of the above references may be of interest to physicians who study and treat Hantavirus pulmonary syndrome, the following are particularly noteworthy. The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and Hantavirus pulmonary syndrome using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “Hantavirus pulmonary syndrome”
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(or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with Hantavirus pulmonary syndrome. The following is a sample result: The NLM Gateway28 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM’s information resources or databases.29 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.30 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Hantavirus pulmonary syndrome” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 30 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 28 29
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Results Summary Category Items Found Journal Articles 344613 Books / Periodicals / Audio Visual 2564 Consumer Health 292 Meeting Abstracts 3093 Other Collections 100 Total 350662
HSTAT31 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.32 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.33 Simply search by “Hantavirus pulmonary syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists34 Some patients may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 33 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 34 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 31 32
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may one day assist physicians in developing treatments. To this end, we recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.35 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.36 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
·
Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.
·
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.
·
Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 36 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 35
Physician Guidelines and Databases 105
generally used by caregivers into terms from formal, controlled vocabularies; see http://www.lexical.com/Metaphrase.html.
Specialized References The following books are specialized references written for professionals interested in Hantavirus pulmonary syndrome (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · 2002 Pocket Book of Infectious Disease Therapy by John G. Bartlett; Paperback - 348 pages, 11th edition (November 15, 2001), Lippincott, Williams & Wilkins Publishers; ISBN: 0781734320; http://www.amazon.com/exec/obidos/ASIN/0781734320/icongroupinterna · Clinical Virology by Douglas D. Richman (Editor), et al; Hardcover - 1355 pages, 1st edition (January 15, 1997), Churchill Livingstone; ISBN: 0443076537; http://www.amazon.com/exec/obidos/ASIN/0443076537/icongroupinterna · Current Diagnosis & Treatment in Infectious Diseases by Walter R. Wilson (Editor), et al; Paperback - 985 pages, 1st edition (June 22, 2001), McGraw-Hill Professional Publishing; ISBN: 0838514944; http://www.amazon.com/exec/obidos/ASIN/0838514944/icongroupinterna · Hunter’s Tropical Medicine and Emerging Infectious Diseases by George W. Hunter (Editor), et al; Hardcover - 1192 pages, 8th edition (January 15, 2000), W B Saunders Co; ISBN: 0721662234; http://www.amazon.com/exec/obidos/ASIN/0721662234/icongroupinterna · Infectious Disease by Barbara Bannister, et al; Paperback - 506 pages, 2nd edition (August 15, 2000), Blackwell Science Inc.; ISBN: 0632053194; http://www.amazon.com/exec/obidos/ASIN/0632053194/icongroupinterna · Infectious Disease Epidemiology : Theory and Practice by Kenrad E. Nelson, et al; Hardcover - 600 pages (May 2000), Aspen Publishers, Inc.; ISBN: 083421766X; http://www.amazon.com/exec/obidos/ASIN/083421766X/icongroupinterna · Mandell, Douglas, and Bennett’s Principles & Practice of Infectious Diseases (2 Vol. Set) by Gerald L. Mandell (Editor), et al; Hardcover - 3263 pages, 5th edition (June 15, 2000), Churchill Livingstone; ISBN: 044307593X; http://www.amazon.com/exec/obidos/ASIN/044307593X/icongroupinterna
· Molecular Epidemiology of Infectious Diseases by R. C. Andrew Thompson; Hardcover - 326 pages, 1st edition (October 15, 2000), Edward
106 Hantavirus Pulmonary Syndrome
Arnold; ISBN: 0340759097; http://www.amazon.com/exec/obidos/ASIN/0340759097/icongroupinterna · Pathology and Pathogenesis of Human Viral Disease by John E. Craighead; Hardcover - 447 pages, 1st edition (March 15, 2000), Academic Press; ISBN: 012195160X; http://www.amazon.com/exec/obidos/ASIN/012195160X/icongroupinterna
· Principles and Practice of Clinical Virology, 4th Edition by Arie J. Zuckerman (Editor), et al; Hardcover - 800 pages, 4th edition (December 13, 1999), John Wiley & Sons; ISBN: 0471973408; http://www.amazon.com/exec/obidos/ASIN/0471973408/icongroupinterna · Rickettsial Infection and Immunity (Infectious Agents and Pathogenesis) by Burt Anderson (Editor), et al; Hardcover (August 1997), Plenum Publishing Corp.; ISBN: 0306455285; http://www.amazon.com/exec/obidos/ASIN/0306455285/icongroupinterna · Viral Infections of Humans : Epidemiology and Control by Alfred S. Evans (Editor), Richard A. Kaslow (Editor); Hardcover - 1078 pages, 4th edition (January 15, 1997), Plenum Publishing Corp.; ISBN: 0306448556; http://www.amazon.com/exec/obidos/ASIN/0306448556/icongroupinterna
Dissertations 107
CHAPTER 9. DISSERTATIONS PULMONARY SYNDROME
ON
HANTAVIRUS
Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to Hantavirus pulmonary syndrome. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.
Dissertations on Hantavirus Pulmonary Syndrome ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to Hantavirus pulmonary syndrome. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with Hantavirus pulmonary syndrome: ·
Hantavirus in Alberta's Boreal Forest: Reducing the Occupational Health Risk of Exposure for Farmers and Forest Professionals by
108 Hantavirus Pulmonary Syndrome
Naidoo, Komali; Msc from University of Alberta (canada), 2001, 148 pages http://wwwlib.umi.com/dissertations/fullcit/MQ60478
Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to Hantavirus pulmonary syndrome is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.
109
PART III. APPENDICES
ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with Hantavirus pulmonary syndrome and related conditions.
Researching Your Medications 111
APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with Hantavirus pulmonary syndrome. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for Hantavirus pulmonary syndrome. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of Hantavirus pulmonary syndrome. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
112 Hantavirus Pulmonary Syndrome
Your Medications: The Basics37 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of Hantavirus pulmonary syndrome. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with Hantavirus pulmonary syndrome take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·
Ask about all parts of your treatment, including diet changes, exercise, and medicines.
·
Ask about the risks and benefits of each medicine or other treatment you might receive.
·
Ask how often you or your doctor will check for side effects from a given medication.
Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for Hantavirus pulmonary syndrome. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·
The name of the medicine and what it is supposed to do.
·
How and when to take the medicine, how much to take, and for how long.
·
What food, drinks, other medicines, or activities you should avoid while taking the medicine.
·
What side effects the medicine may have, and what to do if they occur.
37
This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.
Researching Your Medications 113
·
If you can get a refill, and how often.
·
About any terms or directions you do not understand.
·
What to do if you miss a dose.
·
If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).
Do not forget to tell your doctor about all the medicines you are currently taking (not just those for Hantavirus pulmonary syndrome). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·
Name of medicine
·
Reason taken
·
Dosage
·
Time(s) of day
Also include any over-the-counter medicines, such as: ·
Laxatives
·
Diet pills
·
Vitamins
·
Cold medicine
·
Aspirin or other pain, headache, or fever medicine
·
Cough medicine
·
Allergy relief medicine
·
Antacids
·
Sleeping pills
·
Others (include names)
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Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for Hantavirus pulmonary syndrome. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.38 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of Hantavirus pulmonary syndrome. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Hantavirus pulmonary syndrome:
Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.
38
Researching Your Medications 115
Epinephrine ·
Ophthalmic - U.S. Brands: Epifrin; Epinal; Eppy/N; Glaucon http://www.nlm.nih.gov/medlineplus/druginfo/epinephrineoph thalmic202213.html
Ribavirin ·
Systemic - U.S. Brands: Virazole http://www.nlm.nih.gov/medlineplus/druginfo/ribavirinsystemi c202509.html Ribavirin and Interferon Alfa-2B, Recombinant ·
Systemic - U.S. Brands: Rebetron http://www.nlm.nih.gov/medlineplus/druginfo/ribavirinandinte rferonalfa2bre500032.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor’s office.
Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html.
Mosby’s GenRx Mosby’s GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.
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Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.
Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.
Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with Hantavirus pulmonary syndrome--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat Hantavirus pulmonary syndrome or potentially create deleterious side effects in patients with Hantavirus pulmonary syndrome. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense.
Researching Your Medications 117
Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.
A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with Hantavirus pulmonary syndrome. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with Hantavirus pulmonary syndrome. The FDA warns patients to watch out for39: ·
Secret formulas (real scientists share what they know)
·
Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)
·
Quick, painless, or guaranteed cures
·
If it sounds too good to be true, it probably isn’t true.
If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
39
This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.
118 Hantavirus Pulmonary Syndrome
General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): · Antiviral Therapy by E. Blair (Editor), et al; Paperback - 161 pages, 1st edition (May 15, 1998), Springer Verlag; ISBN: 0387915109; http://www.amazon.com/exec/obidos/ASIN/0387915109/icongroupinterna · Drug Interactions in Infectious Diseases (Infectious Disease) by Stephen C. Piscitelli (Editor), et al; Hardcover - 372 pages (September 2000), Humana Press; ISBN: 0896037509; http://www.amazon.com/exec/obidos/ASIN/0896037509/icongroupinterna · Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance by Arch G. Mainous, Ph.D. (Editor), et al; Hardcover - 350 pages, 1st edition (January 15, 2001), Humana Press; ISBN: 0896038211; http://www.amazon.com/exec/obidos/ASIN/0896038211/icongroupinterna · Manual of Antibiotics and Infectious Diseases: Treatment and Prevention by John E. Conte; Paperback - 755 pages, 9th edition (December 15, 2001), Lippincott, Williams & Wilkins Publishers; ISBN: 0781723167; http://www.amazon.com/exec/obidos/ASIN/0781723167/icongroupinterna
Vocabulary Builder 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Ophthalmic: Pertaining to the eye. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU]
Researching Alternative Medicine 119
APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to Hantavirus pulmonary syndrome. Finally, at the conclusion of this chapter, we will provide a list of readings on Hantavirus pulmonary syndrome from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.
What Is CAM?40 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also 40
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.
120 Hantavirus Pulmonary Syndrome
known as “preventive,” which means that the practitioner educates and treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.
What Are the Domains of Alternative Medicine?41 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each.
Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are 41
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.
Researching Alternative Medicine 121
practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.
122 Hantavirus Pulmonary Syndrome
Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.
Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.
Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.
Researching Alternative Medicine 123
Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.
Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.42
42
Adapted from http://www.4woman.gov/faq/alternative.htm.
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Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.
Finding CAM References on Hantavirus Pulmonary Syndrome Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for Hantavirus pulmonary syndrome. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required. National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine’s databases to allow patients to search for articles that specifically relate to Hantavirus pulmonary syndrome and complementary medicine. To search the database, go to www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Hantavirus pulmonary syndrome” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to Hantavirus pulmonary syndrome: ·
Detection for anti-hantaviurs IgM in patient serum with silver enhanced dot immunogold filtration assay Author(s): Zhang TH, Liu L, He ZA, Yang XZ, Duan ZF.
Researching Alternative Medicine 125
Source: Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2000 September; 14(3): 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11498694&dopt=Abstract ·
Glomerular basement membrane antibodies in hantavirus disease (hemorrhagic fever with renal syndrome). Author(s): Billheden J, Boman J, Stegmayr B, Wieslander J, Settergren B. Source: Clinical Nephrology. 1997 September; 48(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9342483&dopt=Abstract
·
Hantavirus in the southwestern United States: epidemiology of an emerging pathogen. Author(s): Sands L, Kioski C, Komatsu K. Source: J Am Osteopath Assoc. 1993 December; 93(12): 1279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8307808&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
·
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
·
Chinese Medicine: http://www.newcenturynutrition.com/
·
drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html
·
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
·
Google: http://directory.google.com/Top/Health/Alternative/
·
Healthnotes: http://www.thedacare.org/healthnotes/
·
Open Directory Project: http://dmoz.org/Health/Alternative/
·
TPN.com: http://www.tnp.com/
·
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
·
WebMDÒHealth: http://my.webmd.com/drugs_and_herbs
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·
WellNet: http://www.wellnet.ca/herbsa-c.htm
·
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Alternative Medicine for Dummies by James Dillard (Author); Audio Cassette, Abridged edition (1998), Harper Audio; ISBN: 0694520659; http://www.amazon.com/exec/obidos/ASIN/0694520659/icongroupinterna ·
Complementary and Alternative Medicine Secrets by W. Kohatsu (Editor); Hardcover (2001), Hanley & Belfus; ISBN: 1560534400; http://www.amazon.com/exec/obidos/ASIN/1560534400/icongroupinterna
·
Dictionary of Alternative Medicine by J. C. Segen; Paperback-2nd edition (2001), Appleton & Lange; ISBN: 0838516211; http://www.amazon.com/exec/obidos/ASIN/0838516211/icongroupinterna
·
Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating by Walter C. Willett, MD, et al; Hardcover - 352 pages (2001), Simon & Schuster; ISBN: 0684863375; http://www.amazon.com/exec/obidos/ASIN/0684863375/icongroupinterna
· Encyclopedia of Natural Medicine, Revised 2nd Edition by Michael T. Murray, Joseph E. Pizzorno; Paperback - 960 pages, 2nd Rev edition (1997), Prima Publishing; ISBN: 0761511571; http://www.amazon.com/exec/obidos/ASIN/0761511571/icongroupinterna ·
Integrative Medicine: An Introduction to the Art & Science of Healing by Andrew Weil (Author); Audio Cassette, Unabridged edition (2001), Sounds True; ISBN: 1564558541; http://www.amazon.com/exec/obidos/ASIN/1564558541/icongroupinterna
Researching Alternative Medicine 127
·
Natural Alternatives to Antibiotics by John McKenna; Paperback - 176 pages (November 1998), Avery Penguin Putnam; ISBN: 0895298392; http://www.amazon.com/exec/obidos/ASIN/0895298392/icongroupinterna
·
New Encyclopedia of Herbs & Their Uses by Deni Bown; Hardcover - 448 pages, Revised edition (2001), DK Publishing; ISBN: 078948031X; http://www.amazon.com/exec/obidos/ASIN/078948031X/icongroupinterna
· Textbook of Complementary and Alternative Medicine by Wayne B. Jonas; Hardcover (2003), Lippincott, Williams & Wilkins; ISBN: 0683044370; http://www.amazon.com/exec/obidos/ASIN/0683044370/icongroupinterna For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218
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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with Hantavirus pulmonary syndrome. Any dietary recommendation is based on a patient’s age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with Hantavirus pulmonary syndrome may be given different recommendations. Some recommendations may be directly related to Hantavirus pulmonary syndrome, while others may be more related to the patient’s general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of Hantavirus pulmonary syndrome. We will then show you how to find studies dedicated specifically to nutrition and Hantavirus pulmonary syndrome.
Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and
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(6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·
Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.
·
Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.
·
Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.
·
Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.
Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·
Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.
·
Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.
·
Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs.
·
Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains
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·
Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.
·
Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.
·
Vitamin C allows the body’s immune system to fight various diseases, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.
·
Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.
·
Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.
·
Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.
·
Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.
It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·
Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.
·
Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.
·
Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.
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·
Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.
·
Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.
·
Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.
·
Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.
·
Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.
·
Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.
The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:43 ·
DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.
·
DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.
·
RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals
43
Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.
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and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.” ·
RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?44
Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”45 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.46 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 45 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail:
[email protected]. 46 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 44
134 Hantavirus Pulmonary Syndrome
To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail:
[email protected]
Finding Studies on Hantavirus Pulmonary Syndrome The NIH maintains an office dedicated to patient nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.47 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
47
Researching Nutrition 135
researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Hantavirus pulmonary syndrome” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “Hantavirus pulmonary syndrome” (or a synonym): ·
A minority of seropositive wild bank voles (Clethrionomys glareolus) show evidence of current Puumala virus infection. Author(s): Department of Virology, Umea University, S-90 185 Umea (Sweden) Source: Alexeyev, O.A. Ahlm, C. Elgh, F. Aava, B. Palo, T. Settergren, B. Tarnvik, A. Wadell, G. Juto, P. Epidemiology-and-Infection (United Kingdom). (1998). volume 121(2) page 419-425. rodentia hantavirus viruses viroses voles hosts zoonoses epidemiology mankind human diseases rodents wild animals antibodies lungs blood serum rna antigens pathogenesis Summary: rodentia hantavirus virus virose campagnol hote zoonose epidemiologie genre humain maladie de l' homme rongeur animal sauvage anticorps poumon serum sanguin arn antigene pathogenese
Additional physician-oriented references include: ·
Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine. Author(s): Institute of Immunological Science, School of Medicine, Hokkaido University, Sapporo, Japan. Source: Yoo, Y C Yoshimatsu, K Koike, Y Hatsuse, R Yamanishi, K Tanishita, O Arikawa, J Azuma, I Vaccine. 1998 Jan-February; 16(2-3): 216-24 0264-410X
·
Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus. Author(s): Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Source: Murphy, M E Kariwa, H Mizutani, T Tanabe, H Yoshimatsu, K Arikawa, J Takashima, I J-Vet-Med-Sci. 2001 June; 63(6): 637-45 0916-7250
136 Hantavirus Pulmonary Syndrome
·
Coding strategy of the S and M genomic segments of a hantavirus representing a new subtype of the Puumala serotype. Source: Reip, A. Haring, B. Sibold, C. Stohwasser, R. Bautz, E.K.F. Darai, G. Meisel, H. Kruger, D.H. Arch-virol. Wien, Austria : Springer-Verlag. 1995. volume 140 (11) page 2011-2026. 0304-8608
·
In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus. Author(s): Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Source: Murphy, M E Kariwa, H Mizutani, T Yoshimatsu, K Arikawa, J Takashima, I Arch-Virol. 2000; 145(8): 1571-82 0304-8608
·
Interaction between molecules of hantavirus nucleocapsid protein. Author(s): Department of Virology, Haartman Institute, PO Box 21, FIN00014 University of Helsinki, Finland.
[email protected] Source: Kaukinen, P Koistinen, V Vapalahti, O Vaheri, A Plyusnin, A JGen-Virol. 2001 August; 82(Pt 8): 1845-53 0022-1317
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
·
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
·
The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
Researching Nutrition 137
·
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
·
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
·
Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.thedacare.org/healthnotes/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDÒHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU]
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Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Rodentia: A mammalian order which consists of 29 families and many genera. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH]
Finding Medical Libraries 139
APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.48
48
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):49 ·
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
·
California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/
49
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 141
·
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: San José PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html
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California: University of California, Davis. Health Sciences Libraries
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html
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California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/
142 Hantavirus Pulmonary Syndrome
·
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm
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Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/
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Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml
Finding Medical Libraries 143
·
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
·
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
·
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html
·
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
·
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp
·
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital), http://www.southcoast.org/library/
·
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
·
Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/
·
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
·
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
·
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
·
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm
·
Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html
·
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41
144 Hantavirus Pulmonary Syndrome
·
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
·
National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
·
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
·
Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm
·
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
·
New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm
·
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm
·
New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/
·
New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
·
New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/
·
New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html
·
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
·
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
·
Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp
Finding Medical Libraries 145
·
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/
·
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/
·
Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml
·
Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html
·
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html
·
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
·
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp
·
Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm
·
Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/
·
South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm
·
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
·
Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html
·
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
·
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/
Your Rights and Insurance 147
APPENDIX E. YOUR RIGHTS AND INSURANCE Overview Any patient with Hantavirus pulmonary syndrome faces a series of issues related more to the healthcare industry than to the medical condition itself. This appendix covers two important topics in this regard: your rights and responsibilities as a patient, and how to get the most out of your medical insurance plan.
Your Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your rights as a patient.50
Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·
Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider
50Adapted
from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.
148 Hantavirus Pulmonary Syndrome
network composition, the procedures that govern access to specialists and emergency services, and care management information. ·
Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.
·
Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.
·
Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding. Choice of Providers and Plans
Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·
Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.
·
Women’s health services. Women should be able to choose a qualified provider offered by a plan -- such as gynecologists, certified nurse midwives, and other qualified healthcare providers -- for the provision of covered care necessary to provide routine and preventative women’s healthcare services.
·
Access to specialists. Consumers with complex or serious medical conditions who require frequent specialty care should have direct access to a qualified specialist of their choice within a plan’s network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan.
Your Rights and Insurance 149
·
Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition (or who are in the second or third trimester of a pregnancy) at the time they involuntarily change health plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days (or through completion of postpartum care) to allow for transition of care.
·
Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans.
Access to Emergency Services Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer’s health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part. Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·
Provide patients with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.
·
Discuss all treatment options with a patient in a culturally competent manner, including the option of no treatment at all.
·
Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.
·
Discuss all current treatments a consumer may be undergoing.
·
Discuss all risks, nontreatment.
benefits,
and
consequences
to
treatment
or
150 Hantavirus Pulmonary Syndrome
·
Give patients the opportunity to refuse treatment and to express preferences about future treatment decisions.
·
Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with patients and their designated family members.
·
Abide by the decisions made by their patients and/or their designated representatives consistent with the informed consent process.
Health plans, health providers, and healthcare facilities should: ·
Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.
·
Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers’ ability to communicate with and advise patients about medically necessary treatment options.
·
Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients.
Respect and Nondiscrimination Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·
Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.
·
Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.
Your Rights and Insurance 151
Confidentiality of Health Information Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records.
Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient’s Bill of Rights is available from the American Hospital Association.51
Patient Responsibilities Treatment is a two-way street between you and your healthcare providers. To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that patients understand the following “Consumer Responsibilities.”52 In a healthcare system that protects consumers’ rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater individual involvement by the consumer in his or her care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·
Take responsibility for maximizing healthy habits such as exercising, not smoking, and eating a healthy diet.
·
Work collaboratively with healthcare providers in developing and carrying out agreed-upon treatment plans.
·
Disclose relevant information and clearly communicate wants and needs.
To order your free copy of the Patient’s Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient’s Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 52 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1. 51
152 Hantavirus Pulmonary Syndrome
·
Use your health insurance plan’s internal complaint and appeal processes to address your concerns.
·
Avoid knowingly spreading disease.
·
Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.
·
Be aware of a healthcare provider’s obligation to be reasonably efficient and equitable in providing care to other patients and the community.
·
Become knowledgeable about your health plan’s coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.
·
Show respect for other patients and health workers.
·
Make a good-faith effort to meet financial obligations.
·
Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.
Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.53 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for you.54 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer’s human resource office, the health plan administrator, or your union can provide information to help you match your needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 54 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 53
Your Rights and Insurance 153
face. Matching your needs and those of your family members will result in the best possible benefits. Cheapest may not always be best. Your goal is high quality health benefits. 3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to you. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan’s summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse’s employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer’s plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and
154 Hantavirus Pulmonary Syndrome
requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan’s notice. Be sure to follow up with your plan sponsor if you don’t receive notice, and make sure you respond within the allotted time. 7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer’s human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits you will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if your health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan’s decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits you receive. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.
Your Rights and Insurance 155
Medicare and Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. The Health Care Financing Administration (HCFA) administers Medicare, the nation’s largest health insurance program, which covers 39 million Americans. In the following pages, you will learn the basics about Medicare insurance as well as useful contact information on how to find more in-depth information about Medicaid.55 Who is Eligible for Medicare? Generally, you are eligible for Medicare if you or your spouse worked for at least 10 years in Medicare-covered employment and you are 65 years old and a citizen or permanent resident of the United States. You might also qualify for coverage if you are under age 65 but have a disability or EndStage Renal disease (permanent kidney failure requiring dialysis or transplant). Here are some simple guidelines: You can get Part A at age 65 without having to pay premiums if: ·
You are already receiving retirement benefits from Social Security or the Railroad Retirement Board.
·
You are eligible to receive Social Security or Railroad benefits but have not yet filed for them.
·
You or your spouse had Medicare-covered government employment.
If you are under 65, you can get Part A without having to pay premiums if: ·
You have received Social Security or Railroad Retirement Board disability benefit for 24 months.
·
You are a kidney dialysis or kidney transplant patient.
Medicare has two parts: ·
Part A (Hospital Insurance). Most people do not have to pay for Part A.
·
Part B (Medical Insurance). Most people pay monthly for Part B.
This section has been adapted from the Official U.S. Site for Medicare Information: http://www.medicare.gov/Basics/Overview.asp.
55
156 Hantavirus Pulmonary Syndrome
Part A (Hospital Insurance) Helps Pay For: Inpatient hospital care, care in critical access hospitals (small facilities that give limited outpatient and inpatient services to people in rural areas) and skilled nursing facilities, hospice care, and some home healthcare. Cost: Most people get Part A automatically when they turn age 65. You do not have to pay a monthly payment called a premium for Part A because you or a spouse paid Medicare taxes while you were working. If you (or your spouse) did not pay Medicare taxes while you were working and you are age 65 or older, you still may be able to buy Part A. If you are not sure you have Part A, look on your red, white, and blue Medicare card. It will show “Hospital Part A” on the lower left corner of the card. You can also call the Social Security Administration toll free at 1-800-772-1213 or call your local Social Security office for more information about buying Part A. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Fiscal Intermediary about Part A bills and services. The phone number for the Fiscal Intermediary office in your area can be obtained from the following Web site: http://www.medicare.gov/Contacts/home.asp. Part B (Medical Insurance) Helps Pay For: Doctors, services, outpatient hospital care, and some other medical services that Part A does not cover, such as the services of physical and occupational therapists, and some home healthcare. Part B helps pay for covered services and supplies when they are medically necessary. Cost: As of 2001, you pay the Medicare Part B premium of $50.00 per month. In some cases this amount may be higher if you did not choose Part B when you first became eligible at age 65. The cost of Part B may go up 10% for each 12-month period that you were eligible for Part B but declined coverage, except in special cases. You will have to pay the extra 10% cost for the rest of your life. Enrolling in Part B is your choice. You can sign up for Part B anytime during a 7-month period that begins 3 months before you turn 65. Visit your local Social Security office, or call the Social Security Administration at 1-800-7721213 to sign up. If you choose to enroll in Part B, the premium is usually taken out of your monthly Social Security, Railroad Retirement, or Civil Service Retirement payment. If you do not receive any of the above
Your Rights and Insurance 157
payments, Medicare sends you a bill for your part B premium every 3 months. You should receive your Medicare premium bill in the mail by the 10th of the month. If you do not, call the Social Security Administration at 1800-772-1213, or your local Social Security office. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Medicare carrier about bills and services. The phone number for the Medicare carrier in your area can be found at the following Web site: http://www.medicare.gov/Contacts/home.asp. You may have choices in how you get your healthcare including the Original Medicare Plan, Medicare Managed Care Plans (like HMOs), and Medicare Private Fee-for-Service Plans. Medicaid Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. People on Medicaid may also get coverage for nursing home care and outpatient prescription drugs which are not covered by Medicare. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm. States also have programs that pay some or all of Medicare’s premiums and may also pay Medicare deductibles and coinsurance for certain people who have Medicare and a low income. To qualify, you must have: ·
Part A (Hospital Insurance),
·
Assets, such as bank accounts, stocks, and bonds that are not more than $4,000 for a single person, or $6,000 for a couple, and
·
A monthly income that is below certain limits.
For more information on these programs, look at the Medicare Savings Programs brochure, http://www.medicare.gov/Library/PDFNavigation/PDFInterim.asp?Langua ge=English&Type=Pub&PubID=10126. There are also Prescription Drug Assistance Programs available. Find information on these programs which offer discounts or free medications to individuals in need at http://www.medicare.gov/Prescription/Home.asp.
158 Hantavirus Pulmonary Syndrome
NORD’s Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.56 NORD programs ensure that certain vital drugs are available “to those individuals whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare diseases or disorders. For more information, visit www.rarediseases.org.
Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:57 ·
Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html
·
Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html
·
HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html
·
Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html
·
Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html
·
Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html
·
Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html
Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30. 57 You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html. 56
Your Rights and Insurance 159
·
Patient’s Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html
·
Veteran’s Health, Persian Gulf War, Gulf War Syndrome, Agent Orange: http://www.nlm.nih.gov/medlineplus/veteranshealth.html
More on Hantavirus: Technical Information 161
APPENDIX F. MORE ON HANTAVIRUS: INFORMATION
TECHNICAL
Overview58 In May 1993, a cluster of unexplained deaths occurred among young Native Americans living in a semi-arid region of the southwestern United States known as the Four Corners area. The illness was characterized by a febrile prodrome and acute pulmonary edema simulating acute respiratory distress syndrome (ARDS). A 6-month investigation of this cluster of cases concluded with the recognition of Hantavirus pulmonary syndrome (HPS), which is caused by a hitherto unknown virus, subsequently isolated and named Sin Nombre Virus (SNV). HPS is now recognized as a pan-American zoonosis, with an expanding clinical spectrum, caused by many novel New World Hantaviruses with distinct rodent hosts. Humans become infected by contact with infected rodents or their excretions. Infection is strongly associated with disturbing rodent urine, droppings or nests in closed-up spaces; once disturbed, viral particles become airborne and are inhaled. In North America there is no evidence of secondary, person-to-person transmission. In South America person-to-person transmission may be a factor in disease spread. The following material will help the clinician and other interested professionals understand: ·
Clinical manifestations, pathology and treatment of HPS;
·
Diagnostic assays developed to identify the syndrome;
Adapted from The Centers for Disease Control and Prevention (CDC): http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/technicalinfoindex.htm.
58
162 Hantavirus Pulmonary Syndrome
·
Epidemiology and ecology of the disease and its agent;
·
Virology of SNV and the other New World Hantaviruses;
·
HPS prevention guidelines;
·
Protocol for submission of specimens to CDC.
HPS Case Definition59 Hantavirus Pulmonary Syndrome Clinical Description60 Hantavirus pulmonary syndrome (HPS), commonly referred to as Hantavirus disease, is a febrile illness characterized by bilateral interstitial pulmonary infiltrates and respiratory compromise usually requiring supplemental oxygen and clinically resembling acute respiratory disease syndrome (ARDS). The typical prodrome consists of fever, chills, myalgia, headache, and gastrointestinal symptoms. Typical clinical laboratory findings include hemoconcentration, left shift in the white blood cell count, neutrophilic leukocytosis, thrombocytopenia, and circulating immunoblasts. Clinical Case Definition An illness characterized by one or more of the following clinical features: ·
A febrile illness (i.e., temperature greater than 101.0 F {greater than 38.3 C}) characterized by bilateral diffuse interstitial edema that may radiographically resemble ARDS, with respiratory compromise requiring supplemental oxygen, developing within 72 hours of hospitalization, and occurring in a previously healthy person.
·
An unexplained respiratory illness resulting in death, with an autopsy examination demonstrating noncardiogenic pulmonary edema without an identifiable cause.
Laboratory Criteria for Diagnosis ·
Detection of Hantavirus-specific immunoglobulin M or rising titers of Hantavirus-specific immunoglobulin G,
This case definition was published in: “Case Definitions for Infectious Conditions Under Public Health Surveillance” in Morbidiy and Mortality Weekly Report, May 02, 1997/Vol 46, No RR10;1: http://www.cdc.gov/mmwr/preview/mmwrhtml/00047449.htm. 60 Revised 9/96. 59
More on Hantavirus: Technical Information 163
·
Detection of Hantavirus-specific ribonucleic acid sequence by polymerase chain reaction in clinical specimens,
·
Detection of Hantavirus antigen by immunohistochemistry.
Case Classification Confirmed A clinically compatible case that is laboratory confirmed.
Comment Laboratory testing should be performed or confirmed at a reference laboratory. Because the clinical illness is nonspecific and ARDS is common, a screening case definition can be used to determine which patients to test. In general, a predisposing medical condition (e.g., chronic pulmonary disease, malignancy, trauma, burn, and surgery) is a more likely cause of ARDS than HPS, and patients who have these underlying conditions and ARDS need not be tested for Hantavirus.
Clinical Disease Manifestations Presentation and First Evaluation Patients with HPS typically present in a very nonspecific way with a relatively short febrile prodrome lasting 3-5 days. In addition to fever and myalgias, early symptoms include headache, chills, dizziness, nonproductive cough, nausea, vomiting, and other gastrointestinal symptoms. Malaise, diarrhea, and lightheadedness are reported by approximately half of all patients, with less frequent reports of arthralgias, back pain, and abdominal pain. Patients may report shortness of breath, (respiratory rate usually 26 - 30 times per minute). Typical findings on initial presentation include fever, tachypnea and tachycardia. The physical examination is usually otherwise normal.
HPS Clinical Presentation Most Frequent: ·
Fever
164 Hantavirus Pulmonary Syndrome
·
Chills
·
Myalgias
Frequent: ·
Headaches
·
Nausea
·
Vomiting
·
Abdominal pain
·
Diarrhea
·
Cough
·
Malaise
Other: ·
Shortness of breath
·
Dizziness
·
Arthralgia
·
Back or chest pain
·
Sweats
The diagnosis is seldom made at this stage, as cough and tachypnea generally do not develop until approximately day seven. Once the cardiopulmonary phase begins, however, the disease progresses rapidly, necessitating hospitalization and often ventilation within 24 hours. Signs that make a diagnosis of HPS unlikely include rashes, conjunctival or other hemorrhages, throat or conjunctival erythema, petechiae, and peripheral or periorbital edema.
Clinical Assessment If a Hantavirus infection is suspected, a CBC and blood chemistry should be repeated every 8 to 12 hours. A fall in the serum albumin and a rise in the hematocrit may indicate a fluid shift from the patient’s circulation into the lungs. The white blood cell count tends to be raised with a marked left shift. The percentage of white blood
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cells precursors may be as high as 50% and atypical lymphocytes are frequently present, usually at the time of onset of pulmonary edema. In about 80% of individuals with HPS, the platelet count is below 150,000 units. A dramatic fall in the platelet count may herald a transition from the prodrome to the pulmonary edema phase of the illness. The most severe cases of HPS develop disseminated intravenous coagulation (DIC), but, unlike the Hantavirus-related hemorrhagic fevers (HFRS) seen in Asia, this is uncommon.
Coagulation Abnormalities in HPS A Fatal Case
PT PTT Fibrinogen Fibrin Split Products
Day 1
Day 3
13.5 (NL) 32.8 (NL)
29.8 (up) >240 (up) 144 (down) >4000 (up)
Proteinuria, and mild elevations of transaminases, CPK, amylase, and creatinine have also been reported. When metabolic acidosis, prolongation of PT and PPT times and rising serum lactate levels develop, the prognosis is poor. Marked renal insufficiency has mainly been noted among cases from the southeastern United States although some degree of renal insufficiency, assessed by elevated serum creatinine levels, has been noted in 15% of all patients. The combination of atypical lymphocytes, a significant bandemia, and thrombocytopenia in the setting of pulmonary edema is strongly suggestive of a Hantavirus infection.
Disease Development Within 24 hours of initial evaluation, most patients develop some degree of hypotension and progressive evidence of pulmonary edema and hypoxia, usually requiring mechanical ventilation. The patients with fatal infections appear to have severe myocardial depression which can progress to sinus bradycardia with subsequent electromechanical dissociation, ventricular tachycardia or fibrillation.
166 Hantavirus Pulmonary Syndrome
Hemodynamic compromise occurs a median of 5 days after symptom onset-usually dramatically within the first day of hospitalization. In contrast to HFRS, overt hemorrhage occurs rarely in HPS, although hemorrhage is occasionally seen in association with disseminated intravascular coagulation. In contrast to septic shock, HPS patients have a low cardiac output with a raised systemic vascular resistance. Poor prognostic indicators include a plasma lactate of greater than 4.0 mmol/L or a cardiac index of less than 2.2 L/min/m2 Whilst pulmonary edema and pleural effusions are common, multiorgan dysfunction syndrome is rarely seen. However, HPS patients sometimes have mildly impaired renal function. Survivors frequently become polyuric during convalescence and improve almost as rapidly as they decompensated.
Differential Diagnosis The prodromal phase of HPS is indistinguishable clinically from numerous other viral infections. Often the only guide to the etiology of the patient’s illness is the blood picture, which may show circulating immunoblasts, which appear as large atypical lymphocytes, and thrombocytopenia. However, unlike other viral infections, HPS patients usually have concurrent left-shifted neutrophilia with circulating myelocytes. In the cardiopulmonary stage of the disease, the patients have a diffuse pulmonary edema. The most frequent cause for such a picture is silent myocardial infarction so it is important to obtain an ECG and echocardiogram early to aid in the assessment. Intensivists at the University of New Mexico, where many of the patients have been managed, have found that a echocardiogram also helps to distinguish these patients from patients with ARDS as cardiac function is depressed to a much greater degree in the HPS patients and cardiac output does not respond to fluid challenge as it tends to with ARDS. Infections in the immunocompetent which might present with a non-specific prodrome leading to acute cardiopulmonary deterioration as in HPS include leptospirosis, Legionnaire’s disease, mycoplasma, Q fever, chlamydia, and in regions where the organisms are present, septicemic plague, tularemia, coccidioidomycosis and histoplasmosis. Non-infectious conditions such as Goodpasture’s syndrome should also be considered. Lack of coryza aids the clinical distinction between HPS and Influenza A infection.
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It must be remembered that HPS is relatively uncommon and in the immunocompromised PCP, CMV, cryptococcus, aspergillus and graft vs. host disease are far more likely to be the cause of diffuse pulmonary infiltrates than a Hantaviral infection.
Atypical Presentations Atypical clinical presentations with prominent renal insufficiency have also been reported; therefore, HPS and infection due to Seoul virus, one of the Old World Hantaviruses that cause HFRS, should be considered for patients with unexplained febrile nephropathies and appropriate laboratory findings. Asymptomatic illness is rare. However, an increasing number of acutely infected patients who develop either no cardiopulmonary disease or extremely mild pulmonary disease with minimal hypotension have been identified; one such patient was managed successfully as an outpatient.
Radiologic Findings HPS has a characteristic radiological evolution, beginning with minimal changes of interstitial pulmonary edema, progressing to alveolar edema with severe bilateral involvement. Pleural effusions are common and are often large enough to be evident radiographically. Heart size is usually normal. Cardiac silhouette size on chest radiographs is usually normal.
Large Effusion Associated with HPS. Approximately one-third of patients show evidence of pulmonary edema in the initial radiograph. Forty-eight hours after the initial radiograph, virtually all patients demonstrate interstitial edema and two-thirds have developed extensive bibasilar or perihilar airspace disease. The lack of peripheral distribution of the initial airspace disease, the prominence of interstitial edema and the presence of pleural effusions early in the disease process help distinguish HPS from ARDS. There is, however, overlap in the radiographic appearance of the two diseases. Atypical pneumonias such as that caused by mycoplasm pneumonia can produce radiographic findings similar to early HPS, although the clinical illness tends to be much less severe.
168 Hantavirus Pulmonary Syndrome
Detail of Mycoplasm Pneumonia Hyperacute hypersensitivity reactions, mitral stenosis, acute myocardial infarctions, all can cause interstitial edema with a normal heart size, and are also in the radiologic differential diagnosis of early HPS. Mitral stenosis can also cause interstitial edema with a normal-sized cardiac silhouette.
Treatment Treatment of patients with HPS remains supportive in nature. All patients should receive broad spectrum antibiotic coverage until HPS is proven. Early intensive care management is important, with prompt correction of electrolyte, pulmonary, and hemodynamic abnormalities. Flow-directed catheterization of the pulmonary artery is helpful not only in intensively monitoring and clinically managing the patient but also in verifying the normal-to-low pulmonary wedge pressure, decreased cardiac index, and increased systemic vascular resistance in patients who progress to shock. The UNM approach is to administer fluids (usually crystalloid) to reach a PAOP of 12-15 mm, and then to rely on inotropic agents to augment myocardial contractility. PAOP levels higher than this have resulted in pulmonary edema that responded poorly to mechanical ventilation, and in some cases, was refractory. As systemic vascular resistance is actually high, vasopressors such as norepinephrine have poor efficacy but tend to be added as a last resort in the critically ill.
Vasopressor Dosage Dopamine Dobutamine
4 - 8 micrograms/kg/min 5 - 20 micrograms/kg/min
Given that patients who recover from this syndrome do so rapidly, cardiovascular support with extracorporeal membrane oxygenation (ECMO), has been tried. ECMO successfully provided cardiopulmonary support in two of three patients with HPS. From their clinical appearance, prior to instituting ECMO, and by criteria developed from previous
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experience with HPS patients, none of the three patients had been expected to survive. Intravenous Ribavirin has reduced case fatality in a controlled trial for hemorrhagic fever with renal syndrome (HFRS), another disease syndrome caused by Old World Hantaviruses. However, despite its in vitro activity against Sin Nombre virus, an open-label trial during the initial 1993 outbreak failed to document a dramatic reduction in case fatality. This may due to the fact that patients were enrolled too late in their disease course or that the symptoms may relate more to the immunological response to the virus rather than direct viral invasion. Either condition would render direct antiviral therapy ineffective. There is an NIH-sponsored double-blinded placebo-controlled trial of intravenous ribavirin for presumed HPS. Information about the trial and active enrollment sites may be obtained by calling 1-888-866-7257.
Histopathology No single pathognomonic lesion is found that would permit certain histopathologic diagnosis of HPS. In fact, the incipient stages of ARDS can create a picture of pulmonary edema similar to HPS. However, the total picture is rather distinctive. Pathology in HPS patients is characterized mainly by pulmonary findings, as well as findings in the spleen, liver, and lymph nodes. Grossly, the lungs are dense, rubbery and heavy, usually weighing twice as much as the average lung. They are often found floating in a pool of yellow serous fluid within the pleural cavity. The pathologic lesions are primarily vascular with variable degrees of generalized capillary dilation and edema. Morphologic changes of the endothelium are uncommon and, when present, consist of prominent and swollen endothelial cells. Histopathologic lesions are mainly seen in the lung and spleen. In most cases, the lungs reveal a mild to moderate interstitial pneumonitis with variable degrees of congestion, edema, and mononuclear cell infiltration. The cellular infiltrate is composed of small and enlarged mononuclear cells with the appearance of immunoblasts. Focal hyalin membranes are observed, as well as extensive intraalveolar edema and fibrin. Neutrophils are scanty, and the respiratory epithelium is intact in
170 Hantavirus Pulmonary Syndrome
typical cases, with no evidence of cellular debris, nuclear fragmentation, or type II pneumocyte hyperplasia. Among patients who die after a longer-than-average course of the disease, and in lung biopsy specimens from survivors, the histopathologic changes are more characteristic of exudative and proliferative stages of diffuse alveolar damage. In these cases, proliferation of reparative type II pneumocytes, severe edematous and fibroblastic thickening of the alveolar septa with severe airspace disorganization, and distortion of lung architecture can be seen. Other typical histopathologic findings are seen in lymphoid tissues of HPS patients. These include the presence of immunoblasts within the red pulp and periarteriolar sheaths of the spleen and paracortex, within sinuses of lymph nodes, and in the peripheral blood.
Pathology and Pathogenesis Immunohistochemistry analysis has shown that viral antigens are distributed primarily within the endothelium of capillaries throughout various tissues from patients with HPS. Marked accumulations of Hantaviral antigens are seen in the pulmonary microvasculature and in follicular dendritic cells within the lymphoid follicles of spleen and lymph nodes. Hantaviral nucleic acids can also be localized to endothelial and inflammatory cells in tissues from HPS cases by using in situ hybridization. Electron micrographic studies confirm the infection of endothelial cells and macrophages in the lungs of HPS patients. Typical Hantaviral inclusions are seen frequently in pulmonary endothelial cells, and their identity can be confirmed by immunolabeling. In the heart, endothelial staining is mainly in the capillaries of the myocardium and varies from focal immunostaining in some cases to diffuse and extensive staining in others. Occasionally, staining of endothelial cells lining the endocardium is observed. Functional impairment of vascular endothelium is central to the pathogenesis of HPS. However, the pathogenesis of HPS is complex, and a myocardial depressant may contribute significantly to the mortality of this disease. It is unclear how the shock syndrome relates to factors such as viral distribution and immunologic and pharmacological mediators of capillary permeability. There appears to be compartmentalization of a selective immune response in the lungs of HPS patients in combination with extremely high levels of viral antigens in the pulmonary vasculature. This
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feature suggests that the mechanism of inflammatory cell recruitment in the lungs of HPS patients may result from specific attraction and adherence of a selective population of inflammatory cells to an activated pulmonary microvascular endothelium.
Diagnostics A positive serological test result, evidence of viral antigen in tissue by immunohistochemistry, or the presence of amplifiable viral RNA sequences in blood or tissue, with compatible history of HPS, is considered diagnostic for HPS.
Serologic assays At the time of the 1993 outbreak in the Four Corners area, cross-reactive antibodies to the previously known Hantaviruses (e.g., Hantaan, Seoul, Puumala, and Prospect Hill viruses) were found in the acute- and convalescent-phase sera of some of the initial HPS patients. Tests based on specific viral antigens from SNV have since been developed and are now widely used for the routine diagnosis of HPS. CDC uses an enzyme-linked immunosorbent assay (ELISA) to detect IgM antibodies to SNV and to diagnose acute infections with other Hantaviruses. This assay is also available in some state health laboratories. An IgG test is used in conjunction with the IgM-capture test. Acute- and convalescent-phase sera should reflect a four-fold rise in IgG antibody titer or the presence of IgM in acute-phase sera to be diagnostic for hantaviral disease. Note that acute-phase serum sent as an initial diagnostic specimen may not yet have IgG. IgG antibody is long lasting, and sera of patients retrospectively identified appear to have retained antibody for many years. The SNV IgG ELISA has therefore been used in serologic investigations of the epidemiology of the disease and appears to be appropriate for this purpose. Investigations of selected populations using this assay have confirmed that infections with the virus are not common and that mild or inapparent infections are rare. A Western blot assay using recombinant antigens and isotype-specific conjugates for IgM-IgG differentiation has also been developed and its results are generally in agreement with those of the IgM-capture format.
172 Hantavirus Pulmonary Syndrome
Also in use is a rapid immunoblot strip assay (RIBA), an investigational prototype assay to identify serum antibody to recombinant proteins and peptides specific for SNV and other Hantaviruses. Serologic confirmation of hantaviral infections has traditionally been done with neutralizing plaque assays, which have been recently described for SNV. However, these specific assays are also not commercially available. Isolation Isolation of Hantaviruses from human sources is difficult, and the viruses causing HPS seem to be no exception to this rule. To date, no isolates of SNV-like viruses have been recovered from humans, and therefore virus isolation is not a consideration for diagnostic purposes.
Immunohistochemistry (IHC) IHC testing of formalin-fixed tissues with specific monoclonal and polyclonal antibodies can be used to detect Hantavirus antigens and has proven to be a sensitive method for laboratory confirmation of Hantaviral infections. IHC has an important role in the diagnosis of HPS in patients from whom serum samples and frozen tissues are unavailable for diagnostic testing and in the retrospective assessment of disease prevalence in a defined geographic region.
Polymerase Chain Reaction (PCR) Reverse transcriptase-PCR (RT-PCR) can be used to detect Hantaviral RNA in fresh frozen lung tissue, blood clots, or nucleated blood cells. However, RT-PCR is very prone to cross-contamination and should be considered an experimental technique. Differences in viruses in the United States complicate the use and sensitivity of RT-PCR for the routine diagnosis of Hantaviral infections.
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Epidemiology HPS an Old Disease, Newly Recognized Although the high-profile investigation of the HPS syndrome emphasized public health authorities’ warnings about new and emerging infectious diseases, HPS has turned out to be a newly identified, but not a “new,” disease. In fact, the earliest case of a serologically confirmed SNV infection was in a person who developed an HPS-compatible illness in July 1959 and was found to have IgG antibodies in September 1994. The earliest case of HPS to be confirmed by IHC with direct visualization of Hantaviral antigens in postmortem tissue involved a patient who died in 1978.
Risk Factors for Disease Little is known about activities that lead to a greater risk of infection. However, an early case-control study suggests that increased numbers of rodents in the household is the strongest risk factor for infection. Entering rarely opened or seasonally closed buildings may also contribute to infection. Among the confirmed cases of HPS for which exposure information is available, 70% of the patients in the case control study had exposures closely associated with peridomestic activities, such as cleaning, in homes that showed signs of rodent infestation. Four clusters of HPS cases involving 2-4 persons have been documented; for each cluster, exposure probably occurred within a shared, enclosed structure. Taken together, these observations suggest that disturbing or inhabiting closed, actively rodentinfested structures may constitute an important risk factor for contracting HPS Potentially occupationally acquired SNV infections have been recognized but are infrequent. Among documented U.S. cases of HPS, patients with potential occupational exposures have included grain farmers, an extension livestock specialist, field biologists, and agricultural, mill, construction, utility and feedlot workers. Many of these individuals had concurrent peridomestic exposures. Among U.S. mammalogists and rodent workers with varying degrees of rodent exposure, the seroprevalence of SNV antibodies was 1.14%. In contrast, a recent HPS seroprevalence study focused on selected occupational groups with frequent contact with rodents and their excreta (e.g., farm workers, laborers, professionals, home repairers, service industry and park service workers, heating and plumbing contractors, utility workers, and technicians) found no evidence of SNV infection.
174 Hantavirus Pulmonary Syndrome
Travel to and within all areas where Hantavirus infection has been reported is not considered a risk factor for infection with HPS. The possibility of exposure to Hantavirus for campers, hikers, and tourists is very small and is reduced further if steps are taken to reduce rodent contact.
Ecology The identification of the etiology of HPS has added another group of Hantaviruses and their associated sigmodontine rodent hosts to the annals of Hantavirus vector relationships.
Reservoir and Reservoir Distribution: United States The investigation of the original HPS outbreak in the Four Corners region implicated the deer mouse, Peromyscus maniculatus, (subfamily Sigmodontine, family: Murideae) as the primary rodent reservoir. However, cases of HPS have been identified in people who have not visited the regions populated by P. maniculatus, and three additional Hantaviruses with different rodent hosts have now been identified. The first of these three viruses, Black Creek Canal virus (BCCV), is associated with the cotton rat (Sigmodon hispidus); a single case of infection with this virus has been described in Dade County, Florida. Investigations of cases of HPS in Louisiana and Texas have yielded the unique viral sequence of a second, Bayou virus. This virus sequence has now been associated with the rice rat (Oryzomys palustris). Finally, cases of HPS in the northeastern United States have been caused by a virus (New York-1) that is similar to SNV, but distinct enough to suggest that it is a variant found in the eastern third of the United States. This virus is associated with both P. maniculatus and the white footed mouse, P. leucopus . To date, most of the human cases of HPS have been associated with the SNV. Recent studies have confirmed that infected rodents are present in every habitat type--from desert to alpine tundra--but that the prevalence of infection is higher among certain species of Peromyscus and in certain middle-altitude habitats. Surveys of rodents throughout the United States suggest that SNV is distributed in all locations where P. maniculatus occurs and that related viruses are found in P. leucopus throughout its range. Thus cases of HPS can be expected to occur throughout the range of rodent distribution. This probably reflects the fact that P. maniculatus and P. leucopus are found in a wider range of habitats, are more commonly found
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in the peridomestic setting; and typically have much higher population densities than other rodents. Other implicated species, such as S. hispidus and O. palustris, generally do not live in such close proximity to human habitats, and this factor may decrease the probability of human exposure to viruses shed by these rodents.
Idealized Profile of Biomes Sampled from the Southwestern United States Lower population density, a lesser propensity for peridomestic encroachment and a narrower geographic and ecologic distribution (and perhaps differing virulence) may explain the lack of human disease associated with Hantaviruses (or genetic sequences thought to represent additional Hantaviruses) from meadow and California voles (Microtus pennsylvanicus and californicus, respectively) and the western harvest mouse (Reithrodontomys megalotis).
Reservoir Distribution Outside the United States HPS clearly occurs in South America and these cases are caused by viruses distinct from those described in the United States. A genetically distinct Hantavirus (provisionally named Juquitaba virus) has been detected in autopsy tissues from a fatal case of HPS in Brazil. The virus is probably carried by a distinct rodent vector and efforts to identify the host species are in progress. Cases of HPS-like disease have also been described in Argentina and Paraguay and similar efforts to determine the rodent vector are proceeding in these countries. The hosts will also likely be sigmodontine rodents. A number of New World rodent species from which distinct hantaviral sequences or viral isolates have been derived exist in Central and South America, but these viruses remain unassociated with human disease. It is likely that HPS does not occur in the Old World. All of the rodent hosts identified thus far belong to a New World subfamily of the family Muridae and order Rodentia. Among rodents trapped as part of the initial investigation of the Four Corners outbreak in 1993, the overall prevalence rate of Hantavirus antibody in P. Maniculatus was 30.4%. Almost ninety-seven percent of the mice with detectable antibodies had amplifiable genetic sequences in their tissues, suggesting viral persistence in this host species. Body mass studies of the infected rodents show that there is a direct correlation between weight and
176 Hantavirus Pulmonary Syndrome
antibody reactivity, indicating that the virus is transmitted horizontally among rodents. Transmission from rodent to rodent is believed to occur primarily after weaning and through contact, perhaps aggressive contact with accompanying combat wounds. Although Hantaviruses infect their rodent hosts, there is minimal evidence to suggest that they cause illness in the rodents. Studies of the genomic sequences indicate that the virus is not the result of genomic rearrangement, but has probably evolved over a long period of time concurrently with its rodent host.
Transmission Aerosols are most likely to be the major route of transmission from rodents to humans. Humans, who are dead-end hosts, may contract the virus when saliva or excreta from infected rodents are inhaled as aerosols produced directly from the animal. Transmission may also occur when fresh or dried materials contaminated by rodent excreta are disturbed, directly introduced into broken skin, introduced into the eyes, or, possibly, ingested in contaminated food or water. Persons have also become infected after being bitten by rodents. Ticks, fleas, mosquitoes and other biting insects have not been implicated in the transmission of HPS. In fact, aside from the rodent vectors described above, no other animals are known to have a direct role in the transmission of the previously identified Hantaviruses or with any case of HPS. However, domestic cats and dogs may bring infected rodents into contact with humans. Person-to-person transmission of HFRS in Asia and HPS in the United States has not been reported. In addition, a study of 396 health care workers in the southwestern United States failed to show nosocomial transmission. Therefore, CDC guidelines for management of HPS patients in the U.S. recommend standard precautions. Information collected recently in Argentina, however, suggests that person-to-person transmission may have ocurred during a 1996 outbreak centered in the towns of El Bolson and Bariloche. Nosocomial transmission of HFRS has also never been reported, which is consistent with the difficulty of culturing virus from infected persons. Analogously, nosocomial transmission of HPS has not been reported. Furthermore, a serosurvey among health care workers who took care of the initial cluster of HPS patients failed to show any seropositive results.
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Therefore, no additional precaution besides universal precautions is indicated for HPS patients.
Virology Hantaviruses Hantaviruses belong to the bunyavirus family of viruses. There are 5 genera within the family: bunyavirus, phlebovirus, nairovirus, tospovirus, and Hantavirus. Each is made up of negative-sensed, single-stranded RNA viruses. All these genera include arthropod-borne viruses, with the exception of Hantavirus, which is rodent-borne. Like other members of the bunyavirus family, Hantaviruses are enveloped viruses with a genome that consists of three single-stranded RNA segments designated S (small), M (medium), and L (large). All hantaviral genes are encoded in the negative (genome complementary) sense. The S RNA encodes the nucleocapsid (N) protein. The M RNA encodes a polyprotein that is cotranslationally cleaved to yield the envelope glycoproteins G1 and G2. The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. Within virions, the genomic RNAs of Hantaviruses are thought to complex with the N protein to form helical nucleocapsids, which circularize due to sequence complementarity between the 5’ and 3’ terminal sequences of each genomic segment. Hantaviruses replicate exclusively in the host cell cytoplasm. Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. Transcription of viral genes is initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this “cap snatching,” the mRNAs of Hantaviruses are believed to be capped and contain nontemplated 5’ terminal extensions. The viral N and L mRNAs are thought to undergo translation at free ribosomes, whereas the M mRNA is translated in the endoplasmic reticulum. G1 and G2 glycoproteins form heterodimers and are then transported from the endoplasmic reticulum to the Golgi complex, where glycosylation is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirions are believed to form by association of
178 Hantavirus Pulmonary Syndrome
nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the Golgi cisternae. Nascent virions are then transported in secretory vesicles to the plasma membrane and released by exocytosis.
Hantaviruses Causing HPS Sin Nombre virus (SNV) was first isolated from rodents collected on the premises of one of the initial HPS patients in the Four Corners region. Isolation was achieved through blind passage in Peromyscus maniculatus and subsequent adaptation to growth in Vero E6 cells. Additional viral strains have also been isolated from P. maniculatus associated with a fatal case in California and P. leucopus from the vicinity of probable infection of a New York case. Black Creek Canal virus was isolated from S. hispidus collected near the residence of a human case in Dade County, Florida. Other Hantaviruses Several members of the Hantavirus genus cause different forms of hemorrhagic fever with renal syndrome (HFRS), an ancient disease first described in Russia in 1913. The four viruses that are associated with HFRS, each named for the region from where they were first isolated, have different primary rodent hosts: Apodemus agrarius (the striped field mouse) for Hantaan virus, Rattus norvegicus (the Norway rat) and Rattus rattus (the black rat) for Seoul virus, Clethrionomys glareolus (the bank vole) for Puumala virus, and Apodemus flavicollis (the yellow-necked field mouse) for Dobrava virus. Hantaan virus from Korea and Dobrava virus from Slovenia are associated with a severe form of HFRS characterized by renal failure that can precede pulmonary edema and disseminated intravascular coagulation (DIC), with estimated mortality rates of 5% to 15%. A moderate form of HFRS caused by Seoul virus (which, along with its host, is distributed worldwide) is responsible for thousands of Eurasian cases annually. Serologic evidence for infection with Seoul-like Hantaviruses has been found in rodents in major cities of the United States, and this virus was recently implicated in human cases of HFRS in Baltimore. One report has also associated Seoul virus with chronic renal disease. A mild form of HFRS, caused by Puumala virus, is responsible for nephropathia epidemica in Scandinavia, with an estimated mortality rate of 1% to 3%.
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Characteristics of Some Known Hantaviruses Geographic Region
Hantaan
Seoul
Puumala
Prospect Hill
Sin Nombre
Asia
Worldwide
Northern Europe
U.S.
North America
Reservoir
Field Mouse
Domestic Rat Bank Vole
Meadow Vole
Deer Mouse
Pathology
Renal
Renal
Renal
No known
Pulmonary
Mortality
5 - 15%
1%
1%
N/A
human disease 50%
Another Hantavirus, Prospect Hill, has been previously isolated in the United States, but has not been implicated as a cause of human disease. Prospect Hill virus was originally isolated from Microtus pennsylvanicus (meadow vole) in Frederick, MD.
Comparison of HFRS and HPS HFRS
HPS
Major Target Organ First Phase Second Phase Evolution
kidney febrile shock oliguria, diureses, convalescence
lung febrile “prodrome” shock, pulmonary edema diureses, convalescence
Mortality
1 - 15%
50%
Epidemiology in the Virology Laboratory During the outbreak in 1993, definitive proof that the agent causing HPS was a novel Hantavirus was obtained using a genetic detection assay. Oligonucleotide primers were designed on the basis of regions of the M segment (G2 coding region) conserved among Hantaviruses and were used in a nested RT-PCR assay to amplify Hantavirus-specific DNA fragments from RNA extracted from the tissues of patients. The amplified DNA fragments were then sequenced. Comparative and phylogenetic analyses of derived sequence data demonstrated that the Hantavirus associated with the HPS outbreak (SNV) was a novel virus most closely related to Prospect Hill virus (PHV). In addition, a direct genetic link was made between the human HPS cases and the virus harbored by peridomestic P. maniculatus rodents. Characterization of hantaviral genetic sequences recovered from human tissues demonstrated that these sequences were identical to those from rodents captured at the site of the patient’s presumed infection. This characterization has continued to facilitate identification of the site of infection when more than one such site exists and therefore focus the public
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health response. These techniques also allow implication of a specific rodent host in areas of overlapping hosts.
Sin Nombre Virus Sequencing The entire genomic sequence of SNV has subsequently been determined by using RNA extracted from autopsy material as well as RNA extracted from cell culture-adapted virus. The L RNA is 6562 nucleotides (nt) in length; the M RNA is 3696 nt long; and the S RNA is 2059 to 2060 nt long. Interestingly, when the prototype sequence (NMH10) of SNV detected in tissues from an HPS case was compared with the sequence of the SNV isolate (NMR11; isolated in Vero E6 cells from P. maniculatus trapped in the residence of the same case), only 16 nucleotide changes were found, and none of these changes resulted in alterations in amino acid sequences of viral proteins. It had been assumed that in the process of adaptation to cell culture, selection of SNV variants which grow optimally in cell culture would occur, and selected variants would differ genetically from the parental virus. Though NMH10 and NMR11 are identical in protein sequence, nucleotide substitutions in nontranslated regions of the genome could be responsible for altered viral phenotypes, as could changes in protein glycosylation or virus membrane components. The nested RT-PCR assay developed during the initial HPS outbreak provided a rapid method for the genetic characterization of novel Hantaviruses that did not require a virus isolate. Numerous new Hantaviruses have been detected by RT-PCR in rodent tissues but have yet to be associated with human disease. These include El Moro Canyon virus associated with the western harvest mouse (Reithrodontomys megalotis), Tula virus with Microtus arvalis and M. rossiaemeridionalis, Rio Segundo virus with the Mexican harvest mouse (R. mexicanus), Isla Vista virus with the California vole (M. californicus), and Prospect Hill-like viruses in Microtus species.
Phylogenetic Analysis Phylogenetic analysis of Old World and American Hantaviruses indicates that the relationship among Hantaviruses corresponds with the phylogeny of their rodent hosts. Viruses of rodents belonging to the subfamily Murinae are monophyletic as are Hantaviruses of arvicoline and sigmodontine rodents, suggesting that long-term virus-rodent coevolution is taking place. Hantavirus evolution is best understood as co-evolution within specific
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lineages in the rodent family Muridae. The apparent coupling between Hantaviruses and their rodent hosts suggests that viruses of sigmodontine rodents share a common ancestor, as do viruses of the subfamily Arvicolinae and Murinae. This coupling also has a geographic and clinical correlate: viruses found in Old World murine rodents, including Hantaan virus (HTNV), Seoul virus (SEOV) and Dobrava virus, are associated with HFRS in Eurasia. By contrast, viruses carried by New World sigmodontine rodents, including SNV Black Creek Canal virus (BCCV) and Bayou virus (BAYV), are associated with HPS in the Americas. This distinction can narrow the search for a rodent host for newly discovered HPS-like diseases and suggest disease implications for the various new viruses being genetically amplified from rodents.
Sequence Divergence Detection and characterization of Sin Nombre-like viruses in P. maniculatus and P. leucopus populations have shown that multiple phylogenetic lineages of SNV exist in North America, and in some cases similar viruses are detected in both Peromyscus species. Sequence divergence among SNV genes has been shown to be as high as 23% nucleotide dissimilarity and 7% amino acid dissimilarity. Comparison of SNV sequences with those of other Hantaviruses provides no obvious explanation as to why SNV and related viruses cause HPS while other Hantaviruses are associated with HFRS. The development of a reverse genetics system for manipulation of virus genomes and an animal model for studying pathogenesis will be necessary to define the molecular mechanism(s) of SNV pathogenicity. Genomic reassortment by RNA viruses with segmented genomes is well documented and has the potential to produce viruses with altered biological activity, host range, and disease potential. For example, segment reassortment among influenza virus strains (antigenic shift) is thought to be responsible for influenza pandemics. Genomic reassortment among SNV variants is known to occur in nature, but the precise role of genomic reassortment in the epidemiology of HPS and HFRS is unknown.
Prevention Information Special Pathogens Branch has several sources of information on HPS prevention issues.
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Prevention of HPS in the Laboratory ·
“Laboratory Management of Agents Associated with Hantavirus Pulmonary Syndrome: Interim Biosafety Guidelines”: This document provides interim biosafety guidelines for preventing laboratoryassociated infections with agents that cause Hantavirus pulmonary syndrome. It is also part of the supplement to “Hantavirus Infection-Southwestern United States: Interim Recommendations for Risk Reduction”, published in the Morbidity and Mortality Weekly Report, July 30, 1993, Volume 42, Number RR-11, Pages i-13. http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00031653.htm
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“Methods for Trapping and Sampling Small Mammals for Virologic Testing“: This manual is intended as a guide for those persons performing ecologic and epidemiologic studies involving populations of rodents which are potentially infected with Hantavirus. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/rodentmanual.htm Controlling Rodent Infestations
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How to handle small-scale infestations and how to prevent rodent infestations from occurring is covered in “How Do I Prevent HPS?”: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/prevent.htm
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Guidelines for dealing with particularly heavy rodent infestations may be found at: “Special Precautions for Homes of Persons with Confirmed Hantavirus Infection or Buildings with Heavy Rodent Infestations”: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/prevent4.htm
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“The Prevention of Hantavirus Disease” / “La Prevencion del Hantavirus” hand-out card. Downloadable direct from our web page! For use in HPS prevention efforts. This 3.3” x 11” card has simply written tips and pictures on rodent-proofing a home and cleaning up a rodent infestation. It’s available in English and Spanish. The card can be downloaded in two versions: as two full-size web images, and as two 300 dpi .tif images that can be sent to a quick printer for production as twosided handout cards. http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/prevcard.htm Updated Information on Respirator Use
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Read the “Update On the Nomenclature and Use of Respirators as a Precaution for Hantavirus Infection, February, 1999”: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/prevent7.htm
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Formal Risk Reduction Recommendations ·
See “Hantavirus Infection — Southwestern United States: Interim Recommendations for Risk Reduction” in the Morbidity and Mortality Weekly Report, May 13, 1994, Vol. 43, No. RR-7: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00030643.htm
Suspected HPS Specimen Submission Guidelines Special Pathogens Branch (SPB), Division of Viral and Rickettsial Diseases performs a variety of diagnostic techniques for Hantavirus pulmonary syndrome.
Who May Submit Specimens and How Should They Be Submitted? ·
State Health Departments: If you would like information on the protocol for specimen submission, visit here. http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/specime n/hlthdept.htm
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U.S. Physicians: Please contact your state health department (http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/statecon.htm) before sending specimens to CDC.
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Non U.S. Physicians: Because of the hazard associated with handling specimens and virus isolation, testing is only done with prior consultation. Without prior consultation the choice of tests and the availability of appropriate specimens may delay the initiation of testing. Consultation is available 24 hours a day by calling 404 639 2888. During normal business hours (8:00 - 4:30 EST) the SPB phone number is 404 639 1115; FAX 404 639 1118 or 404 639 1509.
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Individuals other than physicians or appropriate state health department employees: Private citizens may not submit specimens to CDC for testing. If you feel that diagnostic testing is necessary, consult your physician or state health department (http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/statecon.htm) .
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Health Departments: Specimens
Protocol
For
Submitting
Hantavirus
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Read the “Guidelines for Submitting Specimens to the Special Pathogens Branch”: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/specime n/specguide.htm. This document explains types of specimens that may be sent, packaging and shipping requirements.
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Fill out and include with your specimen(s) the “Hantavirus Pulmonary Syndrome Case Report” (http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/specim en/caseform.htm) and the “National Surveillance Laboratory Specimen Form” (http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/specim en/subform.htm). Forms are available online or by calling 404 639 1511.
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Call SPB at 404 639 1511 to obtain specific shipping information and to notify us that a specimen will arrive for testing.
Guidelines for Submitting Specimens to the Special Pathogens Branch Serology The following specimen types may be submitted: ·
Serum drawn near admission with clots retained from red top tube
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As late a serum as available
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Convalescent serum drawn approximately 21 days after first specimen
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Post-mortem heart blood
Specimen packaging requirements: ·
Minimum volume: 1ml serum (2.5 ml preferred)
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Serum samples must be shipped with a cold pack, or on dry ice in a plastic tube.
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Clots and acute blood for virus isolation must be sent on dry ice in a plastic tube.
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Immunohistochemistry (IHC) The following types of formalin-fixed or paraffin-embedded tissues may be submitted: ·
Lung, kidney, and spleen tissues are preferred.
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Other tissues that may be sent include lymph nodes, heart, pancreas, pituitary, brain, or liver.
Specimen packaging requirements: ·
Paraffin blocks are preferred, particularly if death was not recent.
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If paraffin blocks are not available, formalin-fixed tissues may be sent.
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Ship paraffin blocks or formalin-fixed tissue at room temperature--do not freeze.
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An autopsy or surgical report must accompany these results.
PCR/Virus Isolation The following types of samples may be submitted: ·
Ante-mortem: You may submit biopsy material of the lung or bone marrow aspirate or clot.
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Post-mortem: spleen, lung, kidney, liver, lymph nodes, heart, pancreas, pituitary, brain, or liver tissue, or heart blood.
Specimen packaging requirements: ·
Clots must be sent on dry ice in a plastic tube.
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Tissues should be at least 1cm3.
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Buffy coat and fresh tissues must be shipped on dry ice.
HPS Clinical Update, 1999 Satellite Conference In May 1999 CDC and the Public Health Training Network presented the satellite conference “Hantavirus Pulmonary Syndrome Clinical Update, 1999”. Experts in the field of HPS presented current information on HPS to a nationwide audience of clinicians, state and local public health epidemiologists and laboratorians, specialists in vector control and wildlife biology, and health educators. Topics covered included the following:
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Pathology and pathogenesis of HPS (presented by Dr. Sherif Zaki, CDC)
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Clinical update (presented by Dr. Fred Koster, University of New Mexico)
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Patient management (presented by Dr. Steven Simpson, University of Kansas)
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Diagnostic update (presented by Dr. James Olson, CDC)
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Epidemiology: HPS in the U.S. and South America (presented by Dr. C. J. Peters, CDC)
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Ecology (presented by Dr. Barbara Ellis, CDC)
During the question and answer period following the main presentation and via email afterwards, participants were able to ask the panel detailed questions. This page has been set up to make many of them available in print. References to useful articles are also offered where possible. ·
Clinicians and public health professionals in areas affected by HPS can order a videotape copy of the conference from Prevention and Information Materials Available Via Mail on the Special Pathogens Branch Web page. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/mailmatl.htm
The following continuing education credits are available: ·
Continuing Education Units (CEUs) -- 0.2
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Continuing Nursing Education (CNE) -- 2 contact hours
The Centers for Disease Control and Prevention (CDC) is an Authorized CEU Sponsor of the International Association for Continuing Education and Training and is accredited as a provider of continuing education in nursing by the American Nurses Credentialing Center’s Commission on Accreditation. ·
Is there any information on re-infection with Hantaviruses, for example, in areas of South America where there is high prevalence of antibodies indicating widespread exposure? Have any correlates of protective immunity been identified in epidemiologic studies? Answer: There are no known re-infections with the homologous Hantavirus; virus neutralizing antibodies are formed. Closely related Hantaviruses, such as Seoul and Hantaan viruses, seem to cross-protect against re-infection in experimental animals, and one might expect cross-
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protection among the Hantaviruses derived from sigmodontine rodents. Dr. C. J. Peters, Special Pathogens Branch, CDC . For discussion and references, see: Peters CJ. Hantavirus pulmonary syndrome in the Americas. In: Scheld WM, Craig WA, Hughes JM, editors. Emerging Infections II. Washington, D.C.: ASM Press; 1998. p. 1764.Note: It would be interesting to have observations from areas of the Balkans where Dobrava virus and Puumala virus co-circulate; these two viruses are more distantly related and thus cross-protection might not be seen. ·
Are the findings for HPS in South America the same as those in the United States? Is it the same disease? Answer: Most disease seen in the United States is caused by Sin Nombre virus. The other SNV-related viruses in the United States (New York and Monongahela) seem to cause a very similar disease. Two other viruses in North America, Bayou and Black Creek Canal, cause HPS that fits the surveillance case definition, and the cases were recognized by clinicians as HPS. The few cases that have been evaluated seem to have more renal failure and higher elevations of serum creatine phosphokinase than the typical SNV infection. In South America, all the recognized cases have been basically HPS, but there are some clusters that seem to have more renal failure, petechiae and bleeding manifestations, and/or involvement of children. In addition, some have had facial flushing, which is not seen with HPS but is seen with hemorrhagic fever with renal syndrome. It must be borne in mind that cases are usually recognized by HPS surveillance or by the dramatic manifestations of HPS, so there is a strong ascertainment bias. Until there is at least a common protocol for evaluating cases in South America, the different manifestations reported by various groups need to be interpreted cautiously.Dr. C. J. Peters, Special Pathogens Branch, CDC For a summary and references to South American publications, see: Peters CJ. Hantavirus pulmonary syndrome in the Americas. In: Scheld WM, Craig WA, Hughes JM, editors. Emerging Infections II. Washington, D.C.: ASM Press; 1998. p. 17-64. For a discussion of milder SNV infections, see: Kitsutani PT. Acute NonHPS Sin Nombre Hantavirus Infection in the U.S. Emerg Infect Dis 1999; (in press).
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If HPS occurs mostly in rural areas, why are the greatest number of cases affecting white males -- up to 76%? Answer: That is an interesting question and can best be answered by looking at the way we keep HPS records at CDC. As you noted, most (70%) of U.S. cases occur in rural areas. The most recent statistics show
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that 61% of cases are male and 75% are white, but only 45% of the cases are white males. While these data seem to show an increased risk for white males, this distribution of cases requires further clarification. In addition to gender, CDC classifies confirmed cases of HPS by race. The U.S. population west of the Mississippi River, where the majority of HPS cases has occurred, is predominantly white, with the following breakdown: white (77%), Asian (7%), black (5%), American Indian (2%), and other (10%). We also record Hispanic ethnicity. Individuals of Hispanic origin make up a large portion of the population of the Southwest, where Sin Nombre virus is endemic. To date, 10% of cases are Hispanic, 9% are white Hispanic, and 5.5% are white Hispanic males. Clearly, there is a statistically significant increased risk associated with being male. Males have a 1.5-fold higher risk for HPS than females. This small increased risk is possibly due to occupational exposure. Dr. James Olson, Special Pathogens Branch, CDC. ·
Why is HPS uncommon in children in the United States? Answer: As of June 1, 1999, 217 cases of HPS have been reported in the United States. Thirteen (6%) were 16 years of age or younger, although this age group represents 24.2% of the US population. The youngest reported patient was 10 years of age. Two or more factors may explain the relative scarcity of HPS cases among children. The first is that children may be less likely to get infected because they do not perform the activities that would put them at risk for infection, such as cleaning in enclosed spaces. Even if they perform these types of activities or have their noses closer to the ground, their total lung exposure to virus may be less than an adult’s; despite the fact that children breathe faster than adults, their minute volume is less. Alternatively, they may just be less likely to get infected due to nonspecific immune mechanisms. The second possibility is that children are as likely to get infected as adults, but less likely to develop HPS, the severest manifestation of infection. We would not generally know of these mild infections, but are aware of a 4-year-old boy who had a very mild illness and did not develop the severe cardiac and pulmonary syndrome. We know that HPS is a disease that reflects your immune response to the virus, so it is possible that children respond differently than adults. The total picture of HPS infection among children is further complicated by studies in South America. There appear to be proportionately more children infected, more children with asymptomatic or mild infections, and children with hemorrhagic manifestations after infections. Some data
More on Hantavirus: Technical Information 189
suggest Hantavirus transmission via breast-milk. Further research will help answer this question and provide us a clue to the immunology that underlines infection and disease development. Dr. Ali Khan, Special Pathogens Branch, CDC. For further information, see: Pini NC, Resa A, Laime GDJ, Lecot G, Ksiazek TG, Levis S, et al. Hantavirus Infection in Children in Argentina. Emerg Infect Dis 1998;4(1):85-7. ·
What types of respirators or masks can farmers and homeowners in rural areas use for protection against Hantavirus? Answer: For those who frequently handle or are frequently exposed to rodents in rural areas (such as mammalogists and pest control workers), CDC recommends wearing either a half-mask air-purifying (or negativepressure) respirator or a powered air-purifying respirator (PAPR) with N-100 filters. CDC does not recommend routine use of respirators by farmers and homeowners in rural areas. CDC guidelines (MMWR 1993; 42, RR-11) address specific risk-reduction measures for rural residents (rodentproofing, environmental management, and trapping) and precautions to be taken during activities that may pose increased risk of Hantavirus infection (cleanup of rodent infested areas). Cleanup of very heavy rodent infestations or of homes associated with known cases of HPS are special instances for which we do recommend respiratory protection, and these tasks are best left to pest control or public health professionals. There is no evidence that farmers operating farm machinery in open fields (even though rodents may be crushed in the machinery) are at increased risk. Under these conditions, the natural circulation of air and virucidal properties of natural UV light make inhalation of infectious aerosols less likely. The possibility of human exposure is greater in indoor closed spaces, such as barns and sheds, that may be infested with rodents. It is important that outbuildings be rodentproofed to the greatest extent possible. When effective rodentproofing is not possible, snap traps (and, if necessary, rodenticides) should be used continuously, and recommended precautions (concerning airing out and cleanup of infestations) should be followed when entering such buildings after periods of non-use.Dr. James Mills, Special Pathogens Branch, CDC.
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Is exposure to sunlight an effective means of disinfecting materials contaminated with Hantavirus? If so, how long of an exposure is recommended? Answer: Ultraviolet (UV) light is a very effective way to kill viruses under certain circumstances. Sunlight produces high intensities of UV and finely dispersed aerosols of the kind that infect humans are readily
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penetrated by the light. Virus inactivation has never been measured under those circumstances, but it must be very rapid. However, the UV light must penetrate to the virus particle. One reason why the interior of structures may be dangerous is that the reflected white light from outside will not contain sufficient UV. Similarly, solids or liquids provide a challenge to UV penetration. We also don’t recommend UV lights for disinfection because of the considerations above, the difficulties in assuring continued strength of the radiation at the site for disinfection, and possible health effects.Dr. C. J. Peters, Special Pathogens Branch, CDC. ·
If Sin Nombre is an enveloped virus, why is it not destroyed by desiccation? Also, do you have data on how long the virus is infective in dried feces, urine, and other excreta of rodents? Answer: Studies on Hantaan virus have shown that the virus infectivity cannot be recovered after 2 days upon desiccation. Studies with Sin Nombre virus are pending.Dr. C. J. Peters, Special Pathogens Branch, CDC.
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You discussed the platelet count and the blood smear in the diagnosis of HPS. What about the white blood cell count (WBC) count and hematocrit. Are they helpful? Answer: Thrombocytopenia, left shift of the myeloid series, and appearance of immunoblasts are consistent findings in almost all HPS patients. The total white cell count is quite variable, ranging from as low as 2,800 during prodrome, to over 100,000 /mm-3 in some severe HPS cases. The elevation of the WBC is not an accurate indicator of severity. The hematocrit is significantly elevated (>50 in men, >48 in women) in only approximately 50% of cases, and is a function of preceding existence of anemia, as well as severity of the capillary leak syndrome. Dr. Frederick Koster, University of New Mexico, School of Medicine.
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Is there evidence to correlate immunologic or immunogenetic characteristics (such as HLA type, immunosuppression) with the severity of the disease? Answer: A search for correlates to severity of HPS has not revealed any relationships to gender or ethnicity. Individuals under the age of 15 years appear to have milder disease. Preliminary data using HLA typing have suggested that individuals bearing one particular B-locus allele, B*35, appear to be at higher risk for severe disease than all other B alleles. No associations have yet been found for alleles in other HLA genes. Other than supporting the notion that T cells are critically involved in mediating the lung and/or cardiac injury in HPS, the significance of
More on Hantavirus: Technical Information 191
these immunogenetic data is not yet known. Dr. Frederick Koster, University of New Mexico, School of Medicine. ·
Are there specific cytokine-blocking agents or antibiotics that would be helpful in the treatment of acute HPS cases? Answer: The simple answer to this question is that there have been no studies of any cytokine blocking agents in HPS, so they should not be tried empirically. Such agents should only be used on an experimental protocol. However, the simple answer begs the question of whether an anti-cytokine protocol should be implemented. There is evidence that certain cytokines are involved in the pathogenesis of HPS. Tumor necrosis factor (TNF) alpha or beta and interleukin 2 (IL2) seem especially important. When direct measurements of these cytokines were made in acutely ill HPS patients, the serum levels were found to be not statistically different from those of normal volunteers or from critically ill control patients. However, evaluation of soluble receptors for TNF and IL-2 demonstrated that they were strikingly elevated in HPS patients, as compared with controls. Additionally, the levels of these soluble receptors were highest in severely ill patients, as compared with patients who had mild HPS. In patients who survived the acute illness, the levels of soluble cytokine receptors for TNF and IL-2 decreased during the convalescent period. Administration of TNF or IL-2 to animals causes syndromes that are quite similar to HPS. Both cytokines can cause myocardial depression, as is seen in HPS, via activation of intracellular nitric oxide in cardiac myocytes. IL-2 causes pulmonary edema and hypotension when it is given to humans as cancer chemotherapy. A plausible explanation for the cytokine findings in HPS is that TNF alpha or beta and IL-2 levels may have been strikingly increased in the period leading up to the acute illness, or that a surge of one or another or all of these cytokines led to rapid onset of pulmonary edema and shock. By the time of hospital admission and blood collection, the cytokine levels had either decreased to normal or were masked by binding to high levels of circulating soluble receptors. However, alternative explanations for the cytokine findings should not be ignored. For example, both forms of soluble TNF receptor (55 kd and 75 kd) and the soluble IL-2 receptor can be released from activated mononuclear cells, even in the absence of binding of the respective cytokine. Presumably, this release of soluble receptors represents a mechanism of slowing or modulating inflammation. So, a more circumspect answer to the question may be that there is as yet insufficient evidence to attempt a therapeutic trial that hinges on blocking the actions of one of these cytokines. There are currently no
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agents available for blocking the action of IL-2. However, several antiTNF agents have been developed, including a humanized murine monoclonal antibody to TNF alpha and a fusion protein of recombinant 75 kd receptor and the Fc portion of human IgG. These agents have failed to prove useful in sepsis resulting from microorganisms other than Hantaviruses. Other agents that are potentially useful include the antiinflammatory cytokines IL-10 and TGF-beta. Before trials with anticytokine agents are designed, a more definite association must be made between increased cytokine levels and the development of shock and pulmonary edema in patients with HPS. This will probably require earlier evaluation of cytokine profiles in patients who have not yet developed pulmonary edema. As to the use of antibiotics in HPS, it is clear that no antibacterial is likely to be an effective therapy. Nevertheless, patients should be placed on broad spectrum antibiotics until the diagnosis of HPS is well established, since bacterial shock is far more common than hantaviral shock. The antiviral agent ribavirin is effective in improving survival and shortening the length of illness in another hantaviral illness, hemorrhagic fever with renal syndrome caused by Hantaan virus. An open label trial of ribavirin in 1993-94 did not demonstrate the drug to be effective in HPS. However, most patients who received the drug were critically ill at the time, and it is difficult to postulate that inhibition of the virus reverses shock. An NIH-sponsored, double-blinded, placebo-controlled trial of ribavirin administered earlier in the syndrome is currently under way, but ribavirin should not be regarded as the standard of care. Steven Q. Simpson, University of Kansas Medical Center, School of Medicine. ·
What is known about virus attachment and entry into host cells? Can this information be used to design treatment strategies? Answer: The cellular receptor for pathogenic Hantaviruses has been recently identified as the b3 integrins. The b3 integrins have been characterized as the receptors for many other viruses, such as adenovirus, foot-and-mouth disease virus, coxsackievirus, and papillomavirus. Antibodies to the b3 integrins can partially inhibit Hantavirus entry into cells in tissue culture experiments. Based on these results, a therapeutic potential to anti-b3 antibodies has been suggested, but it is too early in the Hantavirus studies to know their real application. More information is needed on the cause of the vascular leakage and on Hantavirus pathogenesis in general. In addition, the above studies are hampered by the lack of any animal model for diseases caused by the Hantaviruses Dr. Christina Spiropoulou, Special Pathogens Branch, CDC . For more information on receptor studies, see:
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Gavrilovskaya IN, Brown EJ, Ginsberg MH, and Mackow ER. Cellular entry of Hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by b3 integrins. J Virol 1999; 73:3951-59. Gavrilovskaya IN, Shepley M, Shaw R, Ginsberg MH, and Mackow ER. B3 integrins mediate the cellular entry of Hantaviruses that cause respiratory failure. Proc Natl Acad Sci USA 1998;95:7074-79. Additional information on these outbreaks can be found in: Chapparo J, Vega J, Terry W, Barra B, Meyer R, Peters CJ, et al. Assessment of person-to-person transmission of Hantavirus pulmonary syndrome in a Chilean hospital setting. J Hosp Inf 1998;40:281-5. Padula PJ, Edelstein A, Miguel SD, Lopez NM Rossi CM, Rabinovich RD. Hantavirus pulmonary syndrome outbreak in Argentina: molecular evidence for person-to-person transmission of Andes virus. Virology 1998; 241(2):323-30. Parisi MDN, Enria DA, Pini NC, sabattini MS. Retrospective detection of clinical infections caused by Hantavirus in Argentina. Medicina (Buenos Aires) 1996; 56(1):113. Toro J, Vega JD, Khan AS, Mills JN, Padula P, Terry W, et al. An outbreak of Hantavirus pulmonary syndrome, Chile, 1997. Emerg Infect Dis, 1998;4:687-94. Wells RM, Sosa Estani S, Yadon ZE, et al. An unusual Hantavirus outbreak in southern Argentina: Person-to-person transmission? Emerg Infect Dis 1997;3:171-4. Wells RM, Sosa Estani S, Yadon ZE, Enria D, Padula P, Pini NC, et al. Seroprevalence of antibodies to Hantavirus in health care workers and other residents of southern Argentina. Clin Inf Dis 1998;27:895-6. Wells RM, Young J, Williams RJ, Armstrong LR, Busico K, Khan AS, et al. Hantavirus transmission in the United States. Emerg Infect Dis 1997;3:361-5. ·
HPS patients seem to recover quite promptly after their acute insult. Do they have residua, either from the time on the ventilator or from their disease process? Answer: Following recovery from HPS, patients often experience fatigue and exercise intolerance for several months. Almost all patients, including those not requiring mechanical ventilation, have evidence for a modest degree of small airways obstruction, which persists for more than one year after recovery. Evidence for decreased diffusion capacity in the lung resolves after 3 to 6 months. A few patients have mild proteinuria
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and mild pulmonary hypertension, but the number of patients studied is too small to draw conclusions on the significance of these findings. Dr. Frederick Koster, University of New Mexico, School of Medicine. ·
What percent of the population in disease-endemic areas have HPS antibody but have not presented with symptoms of disease? Answer: Studies in the United States suggest that most people who are infected with Sin Nombre virus (SNV) develop HPS. The prevalence of antibody to SNV among healthy people residing in the disease-endemic area is extremely low (0.3%). On the other hand, the prevalence of antibodies to South American Hantaviruses among health populations in disease-endemic areas of South America may be considerably higher, suggesting that there are inapparent infections or that the disease is mild and unrecognized following infection with some Hantaviruses. Dr. James Olson, Special Pathogens Branch, CDC. For further information, see: Williams RJ, Bryan RT, Mills JN, Palma E, Vera I, de Velasquez F, et al. An outbreak of Hantavirus pulmonary syndrome in western Paraguay. Am J Trop Med Hyg 1997;57:274-82.
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We recently had a Sin Nombre false-positive result with a laboratory report from a commercial laboratory. The patient was in ICU and ARDS was part of her clinical presentation: IgM was 1:80 and the IgG was 1:512 with > 1:80 being positive. When we tested the patient’s blood at our laboratory, it was negative, and another diagnosis was clinically relevant to the patient. The commercial laboratory is representing that they do Sin Nombre testing now -- not other related Hantaviruses. Most of our hospitals know to send all samples here, but the occasional mistake with a new employee may occur. Do you know what test they have developed and its sensitivity and specificity? There are at least three tests we are aware of that are being done for diagnosis. One, developed at the University of New Mexico, is a strip that is treated with serum and then the resulting bands are analyzed. This method has been compared to the ELISA and seems to give very similar results in testing human diagnostic sera. The other two have not been compared. One of these is an ELISA similar to the one in use at CDC, but does not use the same controls and we would not be surprised if it gave false-positives from time to time. None of the tests for SNV are licensed by the FDA for diagnostic use with human sera. Dr. James Olson, Special Pathogens Branch, CDC.
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For further information, see: Ksiazek TG, Peters CJ, Rollin PE, Zaki S, Nichol ST Spiropoulou CF, et al. Identification of a new North American Hantavirus that causes acute pulmonary insufficiency. Am J Trop Med Hyg 1995; 52(2):1017-23.
Online Glossaries 197
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
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Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html
Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to Hantavirus pulmonary syndrome and keep them on file.
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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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HANTAVIRUS PULMONARY SYNDROME GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] 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]
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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] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Showing or causing no symptoms. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autopsy: Postmortem examination of the body. [NIH] Bilateral: Having two sides, or pertaining to both sides. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bradycardia: Slowness of the heart beat, as evidenced by slowing of the pulse rate to less than 60. [EU] Bunyaviridae: A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: bunyavirus, hantavirus, nairovirus, phlebovirus, and tospovirus. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU]
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Cardiac: Pertaining to the heart. [EU] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiopulmonary: Pertaining to the heart and lungs. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Catheterization: The employment or passage of a catheter. [EU] Cervical: Pertaining to the neck, or to the neck of any organ or structure. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chlamydia: A genus of the family chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is chlamydia trachomatis. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Coagulation: 1. the process of clot formation. 2. in colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. in surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: stimulus. [EU]
Capacity for becoming short in response to a suitable
Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH] Cryptococcus: A mitosporic Tremellales fungal genus whose species usually
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have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium. [NIH] 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] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]
Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diffusion: The process of becoming diffused, or widely spread; the spontaneous movement of molecules or other particles in solution, owing to their random thermal motion, to reach a uniform concentration throughout the solvent, a process requiring no addition of energy to the system. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Earache: Pain in the ear. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Endemic: Present or usually prevalent in a population or geographical area
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at all times; said of a disease or agent. Called also endemial. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membranelimited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels, and the serous cavities of the body, originating from the mesoderm. [EU] 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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelium: The covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] 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] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [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] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria,
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cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fleas: Parasitic, blood-sucking, wingless insects comprising the order Siphonaptera. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Grasses: A large family, gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]
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Hepatocellular: Pertaining to or affecting liver cells. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] 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] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH] Hyalin: A clear, homogenous, structureless, eosinophilic substance occurring in pathological degeneration of tissues. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hyperplasia: The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue. [EU] Hypersensitivity: A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance. Hypersensitivity reactions are classified as immediate or delayed, types I and IV, respectively, in the Gell and Coombs classification (q.v.) of immune responses. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Hypotension: Abnormally low blood pressure; seen in shock but not necessarily indicative of it. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied
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serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Incidental: 1. small and relatively unimportant, minor; 2. accompanying, but not a major part of something; 3. (to something) liable to occur because of something or in connection with something (said of risks, responsibilities, ...) [EU] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Infarction: 1. the formation of an infarct. 2. an infarct. [EU] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Invalidate: To weaken or make valueless : to discredit. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a
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nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Leptospirosis: Infections with bacteria of the genus leptospira. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lethal: Deadly, fatal. [EU] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Lipid: Any of a heterogeneous group of flats and fatlike substances characterized by being water-insoluble and being extractable by nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major constituent aliphatic hydrocarbons. The lipids, which are easily stored in the body, serve as a source of fuel, are an important constituent of cell structure, and serve other biological functions. Lipids may be considered to include fatty acids, neutral fats, waxes, and steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Metabolite: process. [EU]
Any substance produced by metabolism or by a metabolic
Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microgram: A unit of mass (weight) of the metric system, being onemillionth of a gram (10-6 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microorganism: A microscopic organism; those of medical interest include bacteria, viruses, fungi and protozoa. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass
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of matter. [EU] Myalgia: Pain in a muscle or muscles. [EU] 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]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nairovirus: A genus of the family bunyaviridae named after nairobi sheep disease, an acute, hemorrhagic, tick-borne, gastroenteritis affecting sheep and goats. Some viruses in this genus are capable of causing severe and fatal disease in humans. [NIH] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Neonatology: infant. [NIH]
A subspecialty of Pediatrics concerned with the newborn
Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH]
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Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Oliguria: Secretion of a diminished amount of urine in relation to the fluid intake. Called also hypouresis and oligouresis. [EU] Ophthalmic: Pertaining to the eye. [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Owls: Members of the Strigiformes order of birds, with strongly hooked beaks, sharp talons, large heads, forward facing eyes, and facial disks. While considered nocturnal raptors, some owls do hunt by day. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 - oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the islets of langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papillomavirus: A genus of papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH]
Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical anti-inflammatory. It is also commonly used as an embedding material in histology. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periorbital: Situated around the orbit, or eye socket. [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]
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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] Phlebovirus: A genus of the family bunyaviridae comprising many viruses, most of which are transmitted by Phlebotomus flies and cause phlebotomus fever. The type species is Sandfly Fever Sicilian Virus, which is not part of the antigenic complex sandfly fever group viruses. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] 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] Pneumonia: Inflammation of the lungs with consolidation. [EU] 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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Pulmonary: Pertaining to the lungs. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various
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kinds. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Refractory: Not readily yielding to treatment. [EU] Respiratory: Pertaining to respiration. [EU] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Rodentia: A mammalian order which consists of 29 families and many genera. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [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] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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
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on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Solvent: 1. dissolving; effecting a solution. 2. a liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Tachycardia: Excessive rapidity in the action of the heart; the term is usually applied to a heart rate above 100 per minute and may be qualified as atrial, junctional (nodal), or ventricular, and as paroxysmal. [EU] Thermoregulation: Heat regulation. [EU] Thrombocytopenia: Decrease in the number of blood platelets. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Topical: Pertaining to a particular surface area, as a topical anti-infective applied to a certain area of the skin and affecting only the area to which it is applied. [EU] Tospovirus: A genus of plant viruses in the family bunyaviridae. Tomato
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spotted wilt virus is the type species and only confirmed member, but there are many other possible members. Transmission occurs by at least nine species of thrips. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasopressor: 1. stimulating contraction of the muscular tissue of the capillaries and arteries. 2. an agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU] Ventilation: 1. in respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. in psychiatry, verbalization of one's emotional problems. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [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] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH]
214 Hantavirus Pulmonary Syndrome
General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna
·
Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna
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A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna
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Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna
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Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna
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Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618
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Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna
·
Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna
Glossary 215
·
Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna
·
Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna
216 Hantavirus Pulmonary Syndrome
INDEX A Abdominal........................23, 24, 163, 209 Abrupt ..............................................85, 87 Acidosis ...............................................165 Alleles ............................................70, 190 Androgens .............................................64 Anemia ........................................190, 204 Antibacterial...................78, 192, 202, 212 Antibiotic ................................78, 168, 212 Antibody....31, 32, 68, 83, 84, 86, 91, 171, 172, 175, 192, 194, 202, 205, 206, 207, 211 Antigens....78, 83, 87, 135, 170, 171, 172, 173, 210 Aspergillus ...........................................167 Assay .......69, 72, 91, 124, 171, 172, 179, 180, 205 Asymptomatic ......................................188 Atypical ........................................165, 166 Autopsy........................162, 175, 180, 185 B Bilateral........................................162, 167 Biochemical ...........................75, 199, 204 Biopsy..........................................170, 185 Bradycardia .........................................165 C Camping ..........................................33, 34 Capillary...............................169, 170, 190 Capsules..............................................133 Carbohydrate.........................76, 132, 204 Carcinoma .............................................73 Cardiac ...69, 79, 118, 166, 168, 188, 190, 191, 202, 203, 208, 212 Cardiogenic ...........................................70 Cardiopulmonary ...65, 164, 166, 167, 168 Cardiovascular.....................................168 Catheterization ....................................168 Cervical..................................................73 Chemotherapy .....................................191 Chlorine .................................................29 Cholesterol ....................79, 130, 132, 212 Chronic ..........................73, 149, 163, 178 Coagulation .........................165, 166, 178 Congestion ..................................169, 203 Conjunctivitis .........................................88 Contamination .....................................172 Contractility..........................................168 Convalescence ............................166, 179 Creatine .......................................187, 201 Cryptococcus.......................................167 Cytokines .............................................191 Cytoplasm....................................177, 208
Cytotoxic ............................................... 70 D Dendritic.............................................. 170 Diarrhea ................................ 23, 130, 163 Diffusion ...................................... 193, 206 Disinfectant ................... 22, 29, 30, 31, 32 Disinfection ......................................... 190 Dizziness................................. 23, 24, 163 E Edema...... 37, 70, 88, 161, 162, 164, 165, 166, 167, 168, 169, 178, 179, 191, 192, 201 Ehrlichiosis............................................ 71 Electrolyte ..................... 89, 138, 168, 210 Endemic .................. 72, 79, 188, 194, 212 Endocardium....................................... 170 Endocytosis................................. 177, 203 Endothelium ................................ 169, 170 Enzyme ....................................... 171, 203 Epinephrine......................................... 208 Epithelium ............................. 78, 169, 209 Erythema............................................. 164 Exocytosis........................................... 178 Extracorporeal .................................... 168 F Facial .............................. 32, 39, 187, 209 Fatigue .................................... 23, 24, 193 Febrile ........... 32, 161, 162, 163, 167, 179 Feces .................... 32, 52, 85, 86, 89, 190 Fibrillation............................................ 165 Filtration ........................................ 34, 124 Fleas ............................................. 26, 176 Flushing .............................................. 187 G Gastrointestinal ... 118, 162, 163, 203, 204 Glucose........................... 76, 77, 204, 206 Glycoproteins ...... 68, 77, 86, 89, 177, 204 Glycosylation .............................. 177, 180 Grasses................................... 19, 38, 204 H Haplotypes ............................................ 68 Hematocrit........................... 164, 190, 204 Hemorrhage .................................. 65, 166 Hepatocellular ....................................... 73 Herpes .......................................... 77, 205 Homologous.................... 75, 83, 186, 199 Hormones .. 64, 76, 78, 79, 199, 202, 210, 212 Hyalin .................................................. 169 Hybridization ....................................... 170 Hyperplasia ........................... 78, 170, 211 Hypersensitivity................................... 168
Index 217
Hypertension .......................................194 Hypotension.........................165, 167, 191 Hypoxia................................................165 I Immunity ..........................65, 91, 186, 206 Immunization ......39, 63, 77, 91, 205, 211, 212 Immunogenetics ....................................70 Immunohistochemistry ................163, 171 Incidental ...............................................33 Incubation ..............................................23 Infarction......................................166, 202 Infiltration .............................................169 Inflammation ............38, 78, 191, 206, 211 Influenza ..................................12, 73, 181 Inhalation .............................................189 Inotropic ...............................................168 Insulin ..............................76, 77, 204, 206 Interstitial .67, 78, 162, 167, 168, 169, 211 Intestinal ..............................................130 Intravascular ................................166, 178 Intravenous............................52, 165, 169 Invalidate ...............................................67 L Leptospirosis .......................................166 Lesion ..........................................169, 203 Lethal .....................................................64 Leukocytosis........................................162 Lipid .............................30, 77, 85, 86, 206 Lymphoma.....................................77, 207 M Membrane ....75, 125, 168, 177, 180, 203, 208 Metabolite ............................................133 Microbiology ........................................200 Microorganism .......................39, 118, 199 Molecular ....12, 14, 66, 69, 71, 78, 82, 83, 87, 88, 100, 104, 181, 193, 210 Myalgia ......................38, 85, 87, 162, 206 Mycoplasma ........................................166 Myocardium .........................................170 N Nausea ..........................................23, 163 Necrosis...............................................191 Neural ..................................................131 Niacin...................................................130 Norepinephrine ....................................168 Nosocomial..................................176, 209 Nucleocapsid ....69, 70, 71, 78, 82, 85, 86, 89, 136, 177, 209 O Oliguria ................................................179 Overdose .............................................131 Owls.........................................26, 39, 209 Oxygenation ................................168, 209
P Pancreas............................... 77, 185, 206 Papillomavirus .................................... 192 Paraffin................................................ 185 Particle ................................................ 190 Pathogen............. 38, 75, 84, 89, 125, 206 Periorbital............................................ 164 Phenotype........................................... 210 Phlebovirus ......................................... 177 Phylogeny ........................................... 180 Plague............... 12, 26, 39, 166, 210, 213 Pneumonia.............................. 35, 67, 167 Polypeptide ............................. 84, 86, 205 Potassium ........................................... 132 Precursor ........................................ 69, 71 Prevalence .......... 172, 174, 175, 186, 194 Progressive ................................. 165, 208 Pulse ............................................. 62, 200 R Reagent .................................. 37, 82, 201 Receptor ............................... 65, 191, 192 Recombinant................. 83, 171, 172, 192 Refractory ........................................... 168 Respiratory..... 12, 15, 31, 32, 34, 38, 39, 63, 74, 85, 87, 88, 161, 162, 163, 169, 189, 193, 206, 213 Ribavirin ................ 52, 135, 136, 169, 192 Riboflavin ............................................ 130 Rodentia.............................................. 135 Rodenticides ........................... 25, 26, 189 S Saliva .......................... 17, 18, 21, 89, 176 Sarcoma.......................................... 69, 71 Selenium ............................................. 132 Septic .................................................. 166 Seroconversion ..................................... 89 Serum .... 31, 39, 124, 135, 164, 165, 171, 172, 184, 187, 191, 194, 211 Solvent ................................................ 202 Species ... 12, 18, 21, 39, 64, 71, 72, 82, 85, 86, 118, 174, 175, 177, 180, 181, 200, 201, 203, 209, 210, 212, 213 Spectrum....................... 68, 161, 168, 192 Sporadic................................................ 66 Stenosis .............................................. 168 Steroid..................................... 64, 78, 210 Subclinical............................................. 67 Surgical ............................................... 185 Systemic ....... 91, 118, 166, 168, 203, 213 T Tachycardia ........................ 163, 165, 202 Thermoregulation................................ 130 Thrombocytopenia .............. 162, 165, 166 Thyroxine ............................................ 132 Topical ............................ 67, 79, 209, 212 Tospovirus .......................................... 177
218 Hantavirus Pulmonary Syndrome
Tularemia.............................................166 V Vaccine .....66, 84, 86, 88, 89, 91, 95, 135, 137, 199, 213 Vaccinia .................................................89 Vascular.........65, 166, 168, 169, 170, 192 Ventilation 11, 39, 164, 165, 168, 193, 213 Ventricular ...................................165, 212
Viral.. 4, 38, 65, 67, 69, 71, 72, 73, 83, 84, 85, 86, 88, 95, 161, 166, 169, 170, 171, 174, 175, 177, 178, 180, 206, 213 Virion..................................... 78, 177, 209 Virulence ............................................. 175 Z Zoonoses ............................................ 135
Index 219
220 Hantavirus Pulmonary Syndrome
Index 221
222 Hantavirus Pulmonary Syndrome
