EMERGING INFECTIONS

Microbial Threats to Health in the United States

Joshua Lederberg, Robert E. Shope,
and Stanley C. Oaks, Jr., Editors

Committee on Emerging Microbial Threats to Health

Division of Health Sciences Policy

Division of International Health

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C. 1992



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Emerging Infections: Microbial Threats to Health in the United States EMERGING INFECTIONS Microbial Threats to Health in the United States Joshua Lederberg, Robert E. Shope, and Stanley C. Oaks, Jr., Editors Committee on Emerging Microbial Threats to Health Division of Health Sciences Policy Division of International Health INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1992

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Emerging Infections: Microbial Threats to Health in the United States NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy’s 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. Funding for this study was provided by the Centers for Disease Control, the Fogarty International Center, Lederle-Praxis Laboratories, the Lucille P. Markey Charitable Trust, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Rockefeller Foundation, and the U.S. Army Medical Research and Development Command. Library of Congress Cataloging-in-Publication Data Emerging infections: Microbial threats to health in the United States / Joshua Lederberg, Robert E. Shope, and Stanley C. Oaks, Jr., editors. p. cm. Includes bibliographical references and index. ISBN 0-309-04741-2 1. Communicable diseases—United States. I. Lederberg, Joshua. II. Shope, Robert E. III. Oaks, S. C. RA643.5.E43 1992 614.4'273—dc20 92-26480 CIP First Printing, October 1992 Second Printing, November 1992 Third Printing, December 1993 Copyright 1992 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin. COVER: The background for the cover of this report is a photograph of batik designed and printed specifically for the Malaysian Society of Parasitology and Tropical Medicine. The print contains drawings of various parasites and insects; it is used with the kind permission of the Society.

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Emerging Infections: Microbial Threats to Health in the United States COMMITTEE ON EMERGING MICROBIAL THREATS TO HEALTH JOSHUA LEDERBERG (Co-chair),* University Professor and Sackler Foundation Scholar, Rockefeller University, New York, New York ROBERT E. SHOPE (Co-chair), Professor of Epidemiology and Director, Yale Arbovirus Research Unit, Yale University School of Medicine, New Haven, Connecticut BARRY R. BLOOM,* Weinstock Professor and Chairman, Department of Microbiology and Immunology, and Investigator, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York ROBERT L. BUCHANAN, Research Leader, Microbial Food Safety Research Unit, Agricultural Research Service, Eastern Regional Research Center, U.S. Department of Agriculture, Philadelphia, Pennsylvania JOHN R. DAVID,† Richard Pearson Strong Professor and Chairman, Department of Tropical Public Health, Harvard School of Public Health, and Professor of Medicine, Harvard Medical School, Boston, Massachusetts CIRO A. DE QUADROS, Regional Advisor, Expanded Programme on Immunization, Pan American Health Organization, Washington, D.C. PATRICIA N. FULTZ, Associate Professor, Department of Microbiology, University of Alabama, Birmingham JOHN J. HOLLAND, Professor, Department of Biology and Institute for Molecular Biology, University of California, San Diego, La Jolla, California DEAN T. JAMISON, Professor, Department of Community Health Sciences and Department of Education, University of California, Los Angeles EDWIN D. KILBOURNE,§ Distinguished Service Professor, Department of Microbiology, Mount Sinai School of Medicine, New York, New York ADEL A. F. MAHMOUD,† John H. Hord Professor of Medicine and Chairman, Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio GERALD L. MANDELL, Professor of Medicine, Owen R. Cheatham Professor of Sciences, and Head, Division of Infectious Diseases, Department of Internal Medicine, University of Virginia, Charlottesville STEPHEN S. MORSE, Assistant Professor, Rockefeller University, New York, New York JUNE E. OSBORN,† Dean and Professor of Epidemiology, School of Public Health, and Professor of Pediatrics and Communicable Disease, Medical School, University of Michigan, Ann Arbor WILLIAM C. REEVES, Professor Emeritus of Epidemiology, School of Public Health, University of California, Berkeley

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Emerging Infections: Microbial Threats to Health in the United States PHILIP K. RUSSELL, Professor of International Health, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland ALEXIS SHELOKOV, Director of Medical Affairs, the Salk Institute-Government Services Division, San Antonio, Texas P. FREDERICK SPARLING, Chairman, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill ANDREW SPIELMAN, Professor of Tropical Public Health, Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts PROJECT STAFF RUTH ELLEN BULGER, Director, Division of Health Sciences Policy POLLY F. HARRISON, Director, Division of International Health STANLEY C. OAKS, JR., Study Director ELIZABETH E. MEYER, Research Associate NANCY DIENER, Budget Analyst GREG W. PEARSON, Consultant Writer/Editor *   Member, Institute of Medicine and National Academy of Sciences †   Member, Institute of Medicine §   Member, National Academy of Sciences

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Emerging Infections: Microbial Threats to Health in the United States Preface As the human immunodeficiency virus (HIV) disease pandemic surely should have taught us, in the context of infectious diseases, there is nowhere in the world from which we are remote and no one from whom we are disconnected. Consequently, some infectious diseases that now affect people in other parts of the world represent potential threats to the United States because of global interdependence, modern transportation, trade, and changing social and cultural patterns. The United States currently expends 14 percent of its gross national product on health; the vast majority of the money is spent on curative medicine to treat people who are already ill. The major premise of this report is that anticipation and prevention of infectious diseases are possible, necessary, and ultimately cost-effective. In the battle against infectious disease, drugs, vaccines, and pesticides are important weapons. Because of the evolutionary potential of many microbes, however, the use of these weapons may inadvertently contribute to the selection of certain mutations, adaptations, and migrations that enable pathogens to proliferate or nonpathogens to acquire virulence. In those circumstances in which humankind has been successful in the battle against specific diseases, complacency (i.e., the assumption that we have conquered a disease and can thus shift our concern to other pressing problems) can also constitute a major threat to health. Such complacency can extend beyond those infectious diseases that have been successfully suppressed to embrace the concept that all infectious diseases are readily suppressed because of the advances of modern medicine. Shifting priorities, therefore, can allow for the reemergence, as well as the emergence, of diseases.

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Emerging Infections: Microbial Threats to Health in the United States In May 1989, Rockefeller University, the National Institute of Allergy and Infectious Diseases, and the Fogarty International Center co-sponsored a conference on emerging viral agents. Although the conference focused on viruses, it spurred interest in the emergence and resurgence of all classes of infectious agents. At the conference and in other forums, concern was expressed about the apparent complacency of the scientific and medical communities, the public, and the political leadership of the United States toward the danger of emerging infectious diseases and the potential for devastating epidemics. Recognizing these concerns, the Board on Health Sciences Policy of the Institute of Medicine (IOM) determined that the IOM could play a unique role by reviewing the relevant science, developing a research agenda, considering the implications for policy, and making specific recommendations for minimizing the public health impact of future emerging microbial threats. In mid-1989, a study proposal was developed and approved, and sponsors were secured. Thus, the 1989 conference served as an excellent prelude to the IOM study. In February 1991, the IOM convened a 19-member multidisciplinary committee to conduct an 18-month study of emerging microbial threats to health. Committee expertise comprised the fields of epidemiology, virology, immunology, food safety microbiology, food toxicology, public health, molecular biology, cell biology, economics, microbial genetics, parasitology, infectious diseases, microbial pathogenesis, medical entomology and systematics, and bacterial physiology. The charge to the Committee on Emerging Microbial Threats to Health was to identify significant emerging infectious diseases, determine what might be done to deal with them, and recommend how similar future threats might be confronted to lessen their impact on public health. The committee did not address biological warfare because this issue is already under study by another panel within the National Academy of Sciences. The full committee held four meetings over the course of the study. At the first meeting, it was noted that a significant number of the members had ties to the biotechnology industry, which involved specific products such as diagnostic test kits and vaccines. Because the committee was not expected to make any disease-or product-specific recommendations, these ties were not considered to be conflicts of interest. Also at the first meeting, the committee determined that, owing to the breadth of the topic, it would confine its work to emerging microbial threats to U.S. public health; it recognized, however, that even that topic could not be adequately addressed without considering emerging threats globally. The committee's recommendations thus target U.S. public health concerns, although they may have some relevance for the global population. The IOM published two earlier reports that bear on microbial threats outside the

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Emerging Infections: Microbial Threats to Health in the United States United States: The U.S. Capacity to Address Tropical Infectious Disease Problems (1987) and Malaria: Obstacles and Opportunities (1991). In addition to the meetings of the full committee, four task forces and a subcommittee met over the course of the study. The task forces provided additional information in four areas: bacteria, chlamydiae, and rickettsiae; viruses; protozoans, helminths, and fungi; and policy options. The subcommittee met to refine the committee's conclusions and recommendations. For the purposes of this report, the committee makes an important distinction between infection and disease. Infection implies that an agent, such as a virus, has taken up residence in a host and is multiplying within it—perhaps with no outward signs or symptoms. In contrast, those who appear "sick" are said to have a "disease," and generally it is for these individuals that public concern is greatest. In fact, though, many more people usually are infected with the causative agent or exposed to the source of infection (such as an insect vector) than become ill. Controlling or limiting the disease depends in many cases on suppressing transmission. For example, although chronic carriers of hepatitis B virus or Salmonella bacteria may not be ill themselves, they are capable of transmitting infections to susceptible individuals and thus are a potential threat to public health. Rather than organize the report around specific diseases, the committee decided to focus on factors that are implicated in the emergence of infectious diseases within the United States. The report begins with an executive summary, which reviews the main points of the committee's deliberations and presents its recommendations from Chapter 3. Chapter 1 provides background material for the general reader, lays out some of the reasons for optimism about the future, tempers that with information on some diseases that have recently emerged or that are emerging, and outlines the fundamental problems that must be addressed if we are to be prepared for the future. Chapter 2 defines "emerging microbial threats to health," identifies and discusses major factors in the emergence of such threats, and gives specific examples of situations in which these factors have been important to the emergence or reemergence of disease. The factors discussed are (1) human demographics and behavior, (2) technology and industry, (3) economic development and land use, (4) international travel and commerce, (5) microbial adaptation and change, and (6) breakdown of public health measures. Chapter 3 considers past and current efforts to address emerging threats in the context of recognition and intervention; it includes the committee's recommendations for approaching current and future emerging microbial threats. The report is written in large part as background for the general reader because the committee believes that the public needs to understand the importance of these threats. It is this committee's considered opinion that the next major infectious agent to emerge as a threat to health in the United States may, like HIV, be

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Emerging Infections: Microbial Threats to Health in the United States a pathogen that has not been previously recognized. Therefore, rather than attempt to list and discuss all organisms that might pose a future threat, this report uses examples to illustrate principles involved in the emergence of contemporary infectious diseases and the resurgence of old diseases. It is the committee's hope that lessons from the past will illuminate possible approaches to prevention and control of these diseases in the future. Joshua Lederberg, Co-chair Robert E. Shope, Co-chair

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Emerging Infections: Microbial Threats to Health in the United States Acknowledgments In addition to the work of the committee and staff, the successful completion of a study such as this requires input from many people. The committee wishes to express its sincere gratitude to those who participated in the various task forces (see Appendix A) and prepared background papers: Scott Halstead of the Rockefeller Foundation, D. A. Henderson of the Office of Science and Technology Policy, Jonathan Kaplan and William Reeves, Jr. of the Centers for Disease Control, James LeDuc of the U.S. Army Medical Research Institute of Infectious Diseases, Llewellyn Legters of the Uniformed Services University of the Health Sciences, and Thomas Monath of OraVax, Incorporated. The contributions of these individuals, who gave generously of their time and expertise, were critical to the preparation of this report. The committee also thanks those who gave presentations to its members: Deborah Keimig of the Armed Forces Medical Intelligence Center; Mitchel Cohen, Joseph Davis, Samuel Dooley, Jr., Walter Dowdle, Robert Gaynes, James Hughes, Brian Mahy, Joseph McDade, C. J. Peters, William Reeves, Jr., William Roper, and Stephen Thacker of the Centers for Disease Control; John Gingrich of the Defense Pest Management Information Analysis Center; Anthony Fauci of the National Institutes of Health; D. A. Henderson of the Office of Science and Technology Policy; and Thomas Monath of OraVax, Incorporated. These presentations contributed useful information and insightful consideration of issues related to emerging microbes. The committee gratefully acknowledges the following who provided tables, graphs, funding data, and other information critical to the committee's deliberations: Marcia Lane of the American Association of Blood Banks; Brooke Whiting of the Association of American Medical Colleges; Janet Shoemaker

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Emerging Infections: Microbial Threats to Health in the United States of the American Society for Microbiology; Anthony Robbins of the Boston University Medical Center; Carmine Bozzi, Louisa Chapman, Nancy Cox, David Dennis, Robert Gaynes, Philip Horn, James Hughes, Robert Kaiser, Lauri Markowitz, Charles McCance, Peter Schantz, Carl Schieffelbein, and Dixie Snider, Jr. of the Centers for Disease Control; Jonathan Mann of the Harvard AIDS Institute; John Mekalanos of the Harvard Medical School; Gerald Meyers of Los Alamos National Laboratory; Marta Glass, Michael Gottlieb, James Meegan, Mona Rowe, Christine Stone, Tina Suhana, and Karl Western of the National Institutes of Health; Daniel Lahn of the National Vaccine Program Office; Lyman Roberts of the Office of the Surgeon General, U.S. Army; Jean-Marc Olivè of the Pan American Health Organization; Charles Clements of SatelLife; Francis Cole, Jr., and Stephen Speights of the U.S. Army Medical Research and Development Command; Roy Widdus of the U.S. Commission on AIDS; Maridette Schloe of the University of California, Los Angeles; Sam Joseph of the University of Maryland, College Park; Charles Hoke of the Walter Reed Army Institute of Research; and C. J. Clements, Marjorie Dam, and Akira Shirai of the World Health Organization. We owe special recognition and thanks to Stanley Oaks, study director, who helped organize the committee, guided us through the study process, and assumed major responsibility for the preparation of this report, and to Elizabeth Meyer, research associate, whose many contributions included preparing meeting summaries, collecting and cataloging references, and the drafting of case studies, charts, tables, appendices, and several of the boxes scattered throughout the report. We also thank April Powers, Linda Clark, Lisa Jager, and Mary Jane Ball, project assistants, who helped with meeting planning and logistics, prepared briefing materials, and provided general committee support. Special thanks are owed to Greg Pearson, consultant editor/writer, who worked to incorporate the many pieces of written material into a coherent draft and who prepared the executive summary. Others within the Institute of Medicine who were instrumental to the work of the committee are Ruth Ellen Bulger and Polly Harrison, directors of the Divisions of Health Sciences Policy and International Health, respectively. This study took place during a period of transition at the Institute of Medicine. Samuel Thier was president of the IOM at the initiation of the study. Following his move to Brandeis University in the fall of 1991, Stewart Bondurant became acting president. In January 1992, Kenneth Shine was designated president-elect; he assumed his full responsibilities in July 1992. The committee offers its sincere gratitude to these leaders and to Enriqueta Bond, the IOM executive officer, who provided guidance and advice during this critical period. Joshua Lederberg, Co-chair Robert E. Shope, Co-chair

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Emerging Infections: Microbial Threats to Health in the United States Contents     EXECUTIVE SUMMARY   1 1   BACKGROUND   16     Plague   16     Influenza   18     Optimism and Indifference   20     Trouble Ahead   26     Next Steps   32 2   FACTORS IN EMERGENCE   34     The Concept of Emergence   42     Human Demographics and Behavior   48     Technology and Industry   57     Economic Development and Land Use   71     International Travel and Commerce   77     Microbial Adaptation and Change   84     Breakdown of Public Health Measures   106 3   ADDRESSING THE THREATS   113     Recognition   113     Intervention   137     REFERENCES   170

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Emerging Infections: Microbial Threats to Health in the United States     APPENDIXES         A Task Forces   195     B Catalog of Emerging Infectious Disease Agents   199     C Global Resources for Infectious Disease Surveillance   261     D Committee and Staff Biographies   265     GLOSSARY   273     ACRONYMS AND ABBREVIATIONS   280     INDEX   283

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Emerging Infections: Microbial Threats to Health in the United States EMERGING INFECTIONS Microbial Threats to Health in the United States

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