MICROBIAL THREATS TO HEALTH

EMERGENCE, DETECTION, AND RESPONSE

Mark S. Smolinski, Margaret A. Hamburg, and Joshua Lederberg, Editors

Committee on Emerging Microbial Threats to Health in the 21st Century

Board on Global Health

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C. www.nap.edu



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Review of the Narsto Draft Report: Narsto Assessment of the Atmospheric Science on Particulate Matter MICROBIAL THREATS TO HEALTH EMERGENCE, DETECTION, AND RESPONSE Mark S. Smolinski, Margaret A. Hamburg, and Joshua Lederberg, Editors Committee on Emerging Microbial Threats to Health in the 21st Century Board on Global Health INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 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. Support for this project was provided by the Centers for Disease Control and Prevention’s National Center for Infectious Diseases (Contract No. H75/CCH311468, TO#8), the U.S. Department of Defense (Contract No. DAMD17-01-2-0040), the U.S. Agency for International Development (Contract No. HRN-A-00-00-00012-00), the U.S. Department of Agriculture’s Food Safety and Inspection Service (Contract No. 590-0790-1-188), the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, the National Institutes of Health’s Fogarty International Center, the Ellison Medical Foundation, the U.S. Food and Drug Administration, and the U.S. Joint Institute for Food Safety Research. The views presented in this report are those of the Institute of Medicine Committee on Emerging Microbial Threats to Health in the 21st Century and are not necessarily those of the funding agencies. Library of Congress Cataloging-in-Publication Data Microbial threats to health : emergence, detection, and response / Mark S. Smolinski, Margaret A. Hamburg, and Joshua Lederberg, editor(s) ; Committee on Emerging Microbial Threats to Health in the 21st Century, Board on Global Health. p. ; cm. Includes bibliographical references. ISBN 0-309-08864-X (hardcover) — ISBN 0-309-50730-8 (PDF) 1. Communicable diseases—United States. 2. Public health—United States. [DNLM: 1. Communicable Diseases, Emerging—epidemiology. 2. Communicable Diseases, Emerging—prevention & control. 3. Communicable Disease Control. WA 110 M626 2003] I. Smolinski, Mark S. II. Hamburg, Margaret A. III. Lederberg, Joshua. IV. Institute of Medicine (U.S.). Committe on Emerging Microbial Threats to Health in the 21st Century. RA643.5.M53 2003 614.5′7—dc21 2003008754 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2003 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 serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

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“Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Shaping the Future for Health

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THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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COMMITTEE ON MICROBIAL THREATS TO HEALTH IN THE 21ST CENTURY MARGARET A. HAMBURG (Co-chair), Vice President for Biological Programs, Nuclear Threat Initiative JOSHUA LEDERBERG (Co-chair), Professor Emeritus and Sackler Foundation Scholar, The Rockefeller University BARRY BEATY, Professor of Microbiology, Colorado State University RUTH BERKELMAN, Professor, Department of Epidemiology, Rollins School of Public Health, Emory University DONALD BURKE, Professor, Departments of International Health and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University GAIL CASSELL, Vice President of Scientific Affairs and Distinguished Research Scholar in Infectious Diseases, Eli Lilly and Company JIM YONG KIM, Co-director of program in Infectious Disease and Social Change, Department of Medicine, Harvard University KEITH KLUGMAN, Professor of International Health, Department of International Health, Rollins School of Public Health; Professor of Medicine, Division of Infectious Diseases, School of Medicine, Emory University ADEL MAHMOUD, President, Merck Vaccines, Merck and Co, Inc. LINDA MEARNS, Scientist and Deputy Director, Environmental and Societal Impacts Group, National Center for Atmospheric Research FREDERICK MURPHY, Professor, Schools of Veterinary Medicine and Medicine, University of California, Davis MICHAEL OSTERHOLM, Director, Center for Infectious Disease Research and Public Policy, Professor, School of Public Health, University of Minnesota CLARENCE PETERS, Professor, Departments of Microbiology and Immunology and Pathology, University of Texas Medical Branch PATRICIA QUINLISK, Iowa State Epidemiologist, Iowa Department of Public Health FREDERICK SPARLING, Professor of Medicine and Microbiology and Immunology, University of North Carolina, Chapel Hill ROBERT WEBSTER, Professor, Virology Division, Department of Infectious Diseases, Rose Marie Thomas Chair, St. Jude Children’s Research Hospital MARK WILSON, Director, Global Health Program, Associate Professor of Epidemiology, University of Michigan MARY WILSON, Associate Professor of Medicine, Harvard Medical School, Associate Professor of Population and International Health, Harvard School of Public Health

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Staff MARK S. SMOLINSKI, Study Director PATRICIA A. CUFF, Research Associate KATHERINE A. OBERHOLTZER, Project Assistant RICHARD MILLER, Director, Medical Follow-up Agency

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Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: John G. Bartlett, The Johns Hopkins University, Baltimore, Maryland Michael G. Groves, Louisiana State University, Baton Rouge, Louisiana Marcelle C. Layton, New York City Department of Health, New York, New York Lord Robert May, University of Oxford, Oxford, United Kingdom Mark Nichter, University of Arizona, Tucson, Arizona Jonathan Patz, The Johns Hopkins University, Baltimore, Maryland Regina Rabinovich, Malaria Vaccine Initiative, Rockville, Maryland Bill Roper, University of North Carolina, Chapel Hill, North Carolina Robert Shope, University of Texas, Galveston, Texas Andrew Spielman, Harvard University, Boston, Massachusetts Robert A. Weinstein, Cook County Hospital, Chicago, Illinois

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Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Ronald W. Estabrook, the University of Texas Southwestern, Dallas, Texas, and Samuel L. Katz, Duke University, Durham, North Carolina. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Cover Artwork INFLUENZA* The global nature of influenza and the aqueous environment needed for virus spread are depicted by the world viewed from space and its aqueous environs (blue globe). Gulls and wild ducks are the natural host of all known influenza A viruses. During evolution these viruses adapted to migratory birds that travel long distances and spread virus by transmission to mammals (lines of migration and interspecies spread). Pigs act as intermediate hosts with receptors for avian and mammalian influenza viruses and occasionally transmit the viruses to humans. There are 15 different subtypes of influenza A viruses (different shades of virus particles) that vary in shape and size. After transmission to mammalian hosts influenza viruses evolve rapidly. The segmented RNA genomes (8 segments per virion) permit related viruses to reassort (virus particle with 14 genes—should be 16—artistic license). In mammalian hosts *   A stained glass window 21 × 56” depicting the natural history of influenza viruses and zoonotic exchange in the emergence of new strains is shown in reduced size on the back cover of this report. A detailed section of the image was used to design the front cover. Based on the work done at St. Jude Children’s Research Hospital supported by American Lebanese Syrian Associated Charities (ALSAC) and the National Institute of Allergy and Infectious Diseases (NIAID). Artist: Jenny Hammond, Highgreenleycleugh, Northumberland, England Commissioned by Rob and Marjorie Webster.

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the ever-changing spike glycoproteins (spike-like fringe on particles) permit the virus to evade the immune response resulting in annual disease outbreaks. At irregular intervals the reassortment of viruses gives rise to pandemic strains with the potential of devastating disease. The yearly outbreaks of influenza and occasional pandemics cause high fever (red) and excess mortality.

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Preface As we enter the twenty-first century, infectious diseases continue to burden populations around the world. Both naturally occurring and intentionally introduced biological threats hold increasing potential to cause disease, disability, and death. And beyond disease itself, the ability of infectious agents to destabilize populations, economies, and governments is fast becoming a sad fact of life. The prevention and control of infectious diseases are fundamental to individual, national, and global health and security; failure to recognize—and act on—this essential truth will surely lead to disaster. Over the past decade, the United States has taken important steps to strengthen its capacity to address the threats posed by these diseases. However, we must do more to improve our ability to detect, prevent, and control emerging and resurging diseases if we are to be better prepared for future microbial threats to health. In 1992, the Institute of Medicine published a landmark report, Emerging Infections: Microbial Threats to Health in the United States, which pointed to major challenges for the public health and medical care communities in detecting and managing infectious disease outbreaks and monitoring the prevalence of endemic diseases. Completed just about a decade ago, it reflected the consensus of a wide-ranging group of specialists that America needed a wake-up call, that infectious diseases remained a tangible threat to our security, and that the comfort and complacency that overtook us in the 1960s with the advent of wonder drugs and vaccines might be short-lived. That report was a stimulus for numerous other studies and policy actions, many in response to the harsh realities of the spread of HIV/AIDS, the

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    Breakdown of Public Health Measures,   107     Poverty and Social Inequality,   121     War and Famine,   125     Lack of Political Will,   127     Intent to Harm,   130     A Case in Point: Influenza—We Are Unprepared,   136 4   ADDRESSING THE THREATS: CONCLUSIONS AND RECOMMENDATIONS   149     Enhancing Global Response Capacity,   149     Improving Global Infectious Disease Surveillance,   154     Rebuilding Domestic Public Health Capacity,   159     Improving Domestic Surveillance Through Better Disease Reporting,   163     Exploring Innovative Systems of Surveillance,   170     Developing and Using Diagnostics,   174     Educating and Training the Microbial Threat Workforce,   181     Vaccine Development and Production,   184     Need for New Antimicrobial Drugs,   190     Inappropriate Use of Antimicrobials,   204     Vector-borne and Zoonotic Disease Control,   209     Comprehensive Infectious Disease Research Agenda,   220     Interdisciplinary Infectious Disease Centers,   222     EPILOGUE   227     GLOSSARY   231     REFERENCES   241     APPENDIXES     A   Microbial Threats to Health Public Committee Meeting Agendas   277 B   Syndromic Surveillance   281 C   Pathogen Discovery, Detection, and Diagnostics   313 D   Forum on Emerging Infections Membership and Publications, Board on Global Health   331 E   Computational Modeling and Simulation of Epidemic Infectious Diseases   335 F   Committee and Staff Biographies   343     INDEX   353

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List of Figures, Tables, and Boxes FIGURES ES-1   The Convergence Model,   5 2-1   The first two decades of HIV/AIDS,   27 2-2   Examples of recent emerging and re-emerging infectious diseases,   33 2-3   Fluoroquinolone prescriptions per capita and frequency of pneumococci with reduced susceptibility to fluoroquinolones in Canada,   40 2-4   Percentage of fluoroquinolone-resistant Neisseria gonorrhoeae,   41 3-1   The Convergence Model,   55 3-2   New world hantaviruses and their rodent reservoirs,   75 3-3   The human population explosion,   80 3-4   The world’s populations by age and sex: 1950, 1990, and projections for the year 2030,   82 3-5   Estimated life expectancy at birth in years: 1900–2000, United States,   83 3-6   World urbanization trends, 1950–2030,   84 3-7   International tourist arrivals, 1950–2020,   102 3-8   International agriculture trade, 1961–2000,   103 3-9   Reported diptheria cases in the Soviet Union and the Newly Independent States,   116

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3-10   Diagram of influenza virus,   140 3-11   The reservoir of influenza A viruses,   141 3-12   Direct transmission of avian influenza viruses to humans,   142 4-1   Global surveillance of communicable diseases: a network of networks,   155 4-2   Three-year treatment with indinavir, zidovudine, and lamivudine,   200 B-1   EMS respiratory call syndrome 99 percent threshold precedes influenza sentinel physician surveillance by 2–3 weeks, 1999– 2001,   296 B-2   Gastroenteritis syndrome count, ESSENCE, San Diego, 2002,   306 E-1   Continuous wavelet transform decomposition of 1928–1964 Baltimore measles time series data,   337 E-2   Visual display of a two-dimensional agent-based model,   338 E-3   Internet routing map (80,000 nodes),   339 E-4   Representation of evolving bit strings in a fitness landscape,   340 TABLES 2-1   Leading Infectious Causes of Death Worldwide, 2001,   26 2-2   Examples of Recent Emerging and Re-Emerging Infectious Diseases,   34 2-3   Infections Associated with Chronic Conditions,   42 3-1   World Megacities, 1975, 2000, and (Projected) 2015: Population in Millions,   85 3-2   Organ Transplants Performed and Patients Awaiting Transplants in 2001,   96 4-1   Selected Sentinel Surveillance Systems for Monitoring Infectious Diseases,   168 4-2   Antibiotics and Antivirals in Development,   192 4-3   Stages of Virus Replication and Possible Targets of Action of Antiviral Agents,   199 4-4   Approved Antiretroviral Drugs,   201 B-1   Syndromic Surveillance: Characteristics, Advantages, and Disadvantages,   286 B-2   Selected Syndromic Surveillance Systems: Domestic,   302

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BOXES 2-1   The End of Infectious Diseases in the United States?,   24 2-2   Diseases/Agents of Biological Warfare,   47 3-1   Factors in Emergence,   54 3-2   The Microbiome,   58 3-3   Fungal Threats,   66 3-4   An Outbreak of Cryptosporidiosis,   67 3-5   Rift Valley Fever,   69 3-6   Nipah Virus,   72 3-7   The Changing Demographics of Child Care in the United States,   79 3-8   Sexually Transmitted Diseases,   89 3-9   A Behavior Paradox,   90 3-10   E. Coli O157:H7,   91 3-11   Neisseria meningitidis: A Sacred Peril,   98 3-12   West Nile Virus,   100 3-13   Shigella sonnei: A Garnish of Parsley?,   105 3-14   Transmissible Spongiform Encephalopathies: From Herd to Mortality,   108 3-15   Ebola Virus,   113 3-16   The Breakdown of Vector Control,   120 3-17   World Poverty Statistics,   123 3-18   Lost Windows of Opportunity,   128 3-19   Anthrax: Postmarked for Terror,   133 3-20   The 1918 Influenza Pandemic,   137 4-1   The World Health Organization Office in Lyon,   152 4-2   Global Outbreak Alert and Response Network,   157 4-3   Epidemic Information Exchange,   161 4-4   Emerging Infections Program,   166 4-5   Nationally Notifiable Infectious Diseases in the United States, 2003,   169 4-6   The Electronic Surveillance System for Early Notification of Community-Based Epidemics,   172 4-7   The Value of Autopsies,   178 4-8   Training in Foreign Animal Disease Control,   183 4-9   WHO Global Strategy for Antimicrobial Resistance,   210 4-10   Public Health Action Plan to Combat Antimicrobial Resistance,   212 B-1   Syndromic Surveillance Systems: Nomenclature,   284 B-2   Issues in Developing Syndromic Surveillance Systems,   290 B-3   Potential Data Sources for Syndromic Surveillance Systems,   294

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Acronyms ABCs: Active Bacterial Core Surveillance AFO: animal feeding operation AIDS: acquired immunodeficiency syndrome APHIS: Animal and Plant Health Inspection Service APUA: Alliance for the Prudent Use of Antibiotics ARS: Agricultural Research Service BSE: bovine spongiform encephalopathy BSI: blood stream infection CAFO: concentrated animal feeding operation CAREC: Caribbean Epidemiology Center CDC: Centers for Disease Control and Prevention CIN: cervical intraepithelial neoplasia CJD: Creutzfeldt-Jakob disease CLIA: Clinical Laboratory Improvement Amendments CMV: cytomegalovirus CSTE: Council of State and Territorial Epidemiologists CWD: chronic wasting disease DARPA: Defense Advanced Research Projects Agency DHF-SS: dengue hemorrhagic fever and shock syndrome DNA: deoxyribonucleic acid DOD: Department of Defense

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DOT: directly observed therapy DOTS: directly observed therapy, short course DTP: diptheria, tetanus, and pertussis vaccine EBV: Epstein-Barr virus EIP: Emerging Infections Program EIS: Epidemic Intelligence Service EMS: Emergency Medical System Epi-X: Epidemic Information Exchange ESSENCE: Electronic Surveillance System for Early Notification of Community-Based Epidemics EU: European Union EWORS: Early Warning Outbreak Recognition System FADDL: Foreign Animal Disease Diagnostic Laboratory FAO: Food and Agriculture Organization FDA: Food and Drug Administration FETP: Field Epidemiology Training Programs FIC: National Institutes of Health Fogarty International Center for Advanced Study in the Health Sciences FoodNet: Foodborne Disease Active Surveillance Network GAO: General Accounting Office GDP: gross domestic product GEIS: Global Emerging Infections Surveillance GIS: geographic information system GISP: Gonococcal Isolate Surveillance Project GOCO: government owned, contractor operated GPHIN: Global Public Health Intelligence Network HA: hemagglutinin HERV: human endogenous retrovirus HFRS: hemorrhagic fever with renal syndrome HHV-8: human herpesvirus-8 HIV: human immunodeficiency virus HLA: human leukocyte antigen HMO: health maintenance organization HPS: hantavirus pulmonary syndrome HPV: human papilloma virus HRSA: Health Resources and Services Administration HSV: herpes simplex virus HTLV: human T-cell lymphotropic viruses HUS: hemolytic uremic syndrome

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ICC: immunocytochemical ICD-9: International Classification of Diseases, 9th Revision ICIDR: International Collaborations in Infectious Disease Research ICU: intensive-care unit IOM: Institute of Medicine KSHV: kaposi’s sarcoma-associated herpesvirus MDR: multidrug-resistant MDR-TB: multidrug-resistant tuberculosis MRSA: methicillin-resistant Staphylococcus aureus NA: neuraminidase NCHS: National Center for Health Statistics NEDSS: National Electronic Disease Surveillance System NETSS: National Electronic Telecommunications System for Surveillance NIAID: National Institute of Allergy and Infectious Diseases NIH: National Institutes of Health NNDSS: National Notifiable Diseases Surveillance System NNIS: National Nosocomial Infections Surveillance System NRC: National Research Council NSF: National Science Foundation OIE: Office International des Epizooties PAHO: Pan American Health Organization PCR: polymerase chain reaction QRNG: fluoroquinolone-resistant Neisseria gonorrhoeae rDNA: ribosomal DNA RNA: ribonucleic acid RSVP: Rapid Syndrome Validation Program RVF: Rift Valley fever SIV: simian immunodeficiency viruses SNV: Sin Nombre virus STD: sexually transmitted disease STI: strategic treatment interruption SV: Simian virus

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TB: tuberculosis TLR: TOLL-like receptors TSE: transmissible spongiform encephalopathy TTV: TT virus UNAIDS: Joint United Nations Programme on HIV/AIDS UNICEF: United Nations Children’s Fund USAID: U.S. Agency for International Development USDA: U.S. Department of Agriculture UTI: urinary tract infection VA: Department of Veterans Affairs vCJD: variant Creutzfeldt-Jakob disease WHO: World Health Organization WTO: World Tourism Organization YF: yellow fever

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MICROBIAL THREATS TO HEALTH EMERGENCE, DETECTION, AND RESPONSE

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