LEARNING FROM SARS

Preparing for the Next Disease Outbreak

Workshop Summary

Stacey Knobler, Adel Mahmoud, Stanley Lemon, Alison Mack, Laura Sivitz, and Katherine Oberholtzer, Editors

Forum on Microbial Threats

Board on Global Health

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary LEARNING FROM SARS Preparing for the Next Disease Outbreak Workshop Summary Stacey Knobler, Adel Mahmoud, Stanley Lemon, Alison Mack, Laura Sivitz, and Katherine Oberholtzer, Editors Forum on Microbial Threats 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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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary 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. Support for this project was provided by the U.S. Department of Health and Human Services’ National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration; U.S. Agency for International Development; U.S. Department of Defense; U.S. Department of State; U.S. Department of Veterans Affairs; U.S. Department of Agriculture; American Society for Microbiology; Burroughs Wellcome Fund; Pfizer; GlaxoSmithKline; and The Merck Company Foundation. The views presented in this report are those of the editors and attributed authors and are not necessarily those of the funding agencies. This report is based on the proceedings of a workshop that was sponsored by the Forum on Microbial Threats. It is prepared in the form of a workshop summary by and in the name of the editors, with the assistance of staff and consultants, as an individually authored document. Sections of the workshop summary not specifically attributed to an individual reflect the views of the editors and not those of the Forum on Microbial Threats. The content of those sections is based on the presentations and the discussions that took place during the workshop. Library of Congress Cataloging-in-Publication Data Learning from SARS : preparing for the next disease outbreak : workshop summary / Stacey Knobler … [et al.], editors ; Forum on Microbial Threats, Board on Global Health. p. ; cm. Includes bibliographical references. ISBN 0-309-09154-3 (pbk.) ISBN 0-309-53034-2 (PDF) 1. SARS (Disease) [DNLM: 1. Severe Acute Respiratory Syndrome—prevention & control—Congresses. 2. Severe Acute Respiratory Syndrome—transmission—Congresses. 3. Disease Outbreaks—prevention & control—Congresses. 4. SARS Virus—isolation & purification—Congresses. 5. SARS Virus—pathogenicity—Congresses. 6. Socioeconomic Factors—Congresses. WC 505 L438 2004] I. Knobler, Stacey. II. Institute of Medicine (U.S.). Forum on Microbial Threats. III. Institute of Medicine (U.S.). Board on Global Health. IV. Title. RA644.S17L43 2004 614.5'92—dc22 2004007115 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 2004 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 Museum in Berlin. COVER: The background for the cover of this workshop summary is a photograph of a 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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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Adviser to the Nation to Improve Health

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary THE NATIONAL ACADAMIES 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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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary FORUM ON MICROBIAL THREATS ADEL MAHMOUD (Chair), President, Merck Vaccines, Whitehouse Station, New Jersey STANLEY LEMON (Vice-Chair), Dean, School of Medicine, University of Texas Medical Branch, Galveston, Texas DAVID ACHESON, Chief Medical Officer, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Rockville, Maryland STEVEN BRICKNER, Research Advisor, Pfizer Global Research and Development, Pfizer Inc., Groton, Connecticut DENNIS CARROLL, U.S. Agency for International Development, Washington, DC NANCY CARTER-FOSTER, Director, Program for Emerging Infections and HIV/AIDS, U.S. Department of State, Washington, DC GAIL CASSELL, Vice President, Scientific Affairs, Eli Lilly & Company, Indianapolis, Indiana JESSE GOODMAN, Director, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland EDUARDO GOTUZZO, Director, Instituto de Medicina Tropical “Alexander von Humbolt,” Universidad Peruana Cayetano Heredia, Lima, Peru MARGARET HAMBURG, Vice President for Biological Programs, Nuclear Threat Initiative, Washington, DC CAROLE HEILMAN, Director, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland DAVID HEYMANN, Director, Polio Eradication Program, World Health Organization, Geneva, Switzerland JAMES HUGHES, Assistant Surgeon General and Director, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia LONNIE KING, Dean, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan JOSHUA LEDERBERG, Raymond and Beverly Sackler Foundation Scholar, The Rockefeller University, New York, New York JOSEPH MALONE, Director, Department of Defense Global Emerging Infections System, Walter Reed Army Institute of Research, Silver Spring, Maryland LYNN MARKS, Global Head of Infectious Diseases, GlaxoSmithKline, Collegeville, Pennsylvania STEPHEN MORSE, Director, Center for Public Health Preparedness, Columbia University, New York, New York MICHAEL OSTERHOLM, Director, Center for Infectious Disease Research and Policy and Professor, School of Public Health, University of Minnesota, Minneapolis, Minnesota

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary GEORGE POSTE, Director, Arizona BioDesign Institute, Arizona State University, Tempe, Arizona GARY ROSELLE, Program Director for Infectious Diseases, VA Central Office, Veterans Health Administration, Department of Veterans Affairs, Washington, DC JANET SHOEMAKER, Director, Office of Public Affairs, American Society for Microbiology, Washington, DC P. FREDERICK SPARLING, J. Herbert Bate Professor Emeritus of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina Liaisons ENRIQUETA BOND, President, Burroughs Wellcome Fund, Research Triangle Park, North Carolina EDWARD McSWEEGAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Staff STACEY KNOBLER, Director, Forum on Microbial Threats KARL GALLE, Research Associate KATHERINE OBERHOLTZER, Research Assistant LAURA SIVITZ, Research Associate

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary BOARD ON GLOBAL HEALTH DEAN JAMISON (Chair), Senior Fellow, Fogarty International Center, National Institutes of Health, Bethesda, Maryland YVES BERGEVIN, Chief, Health Section, UNICEF, New York, New York JO IVEY BOUFFORD, Professor, Robert F. Wagner Graduate School of Public Service, New York University, New York, New York RICHARD FEACHEM, Executive Director, Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland MARGARET HAMBURG, Vice President for Biological Programs, Nuclear Threat Initiative, Washington, DC GERALD KEUSCH, Director, Fogarty International Center, National Institutes of Health, Bethesda, Maryland JEFFREY KOPLAN, Vice President for Academic Health Affairs, Emory University, Atlanta, Georgia ADEL MAHMOUD, President, Merck Vaccines, Whitehouse Station, New Jersey MAMPHELA RAMPHELE, Managing Director, The World Bank, Washington, DC MARK ROSENBERG, Executive Director, Task Force for Child Survival and Development, Emory University, Decatur, Georgia JAIME SEPULVEDA AMOR, Director, Instituto Nacional de Salud Publica, Cuernavaca, Mexico DONALD BERWICK (IOM Council Liaison), Clinical Professor of Pediatrics and Health Care Policy, Harvard Medical School, Boston, Massachusetts DAVID CHALLONER (IOM Foreign Secretary), Vice President for Health Affairs, University of Florida, Gainesville Staff PATRICK KELLEY, Director HARRIET BANDA, Senior Project Assistant ALLISON BERGER, Project Assistant STACEY KNOBLER, Senior Program Officer KATHERINE OBERHOLTZER, Research Assistant LAURA SIVITZ, Research Associate DIANNE STARE, Research Assistant/Administrative Assistant

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary Reviewers All presenters at the workshop have reviewed and approved their respective sections of this report for accuracy. In addition, this workshop summary has been reviewed in draft form by independent reviewers chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the Institute of Medicine (IOM) in making the published workshop summary as sound as possible and to ensure that the workshop summary meets institutional standards. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. The Forum and IOM thank the following individuals for their participation in the review process: Roy M. Anderson, Imperial College London, London, United Kingdom Ruth L. Berkelman, Emory University, Atlanta, Georgia David L. Heymann, World Health Organization, Geneva, Switzerland David Naylor, University of Toronto, Toronto, Ontario Jeffrey L. Platt, Mayo Clinic, Rochester, Minnesota Mary Wilson, Harvard University, Boston, Massachusetts The review of this report was overseen by Enriqueta C. Bond, President, Burroughs Wellcome Fund, Research Triangle Park, North Carolina. Appointed by the National Research Council she was 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 editors and the institution.

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary Preface The Forum on Emerging Infections was created in 1996 in response to a request from the Centers for Disease Control and Prevention and the National Institutes of Health. The goal of the Forum is to provide structured opportunities for representatives from academia, industry, professional and interest groups, and government1 to examine and discuss scientific and policy issues that are of shared interest and that are specifically related to research and prevention, detection, and management of infectious diseases. In accomplishing this task, the Forum provides the opportunity to foster the exchange of information and ideas, identify areas in need of greater attention, clarify policy issues by enhancing knowledge and identifying points of agreement, and inform decision makers about science and policy issues. The Forum seeks to illuminate issues rather than resolve them directly; hence, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its strengths are the diversity of its membership and the contributions of individual members expressed throughout the activities of the Forum. In September 2003 the Forum changed its name to the Forum on Microbial Threats. ABOUT THE WORKSHOP The global response to the recent severe acute respiratory syndrome (SARS) epidemic has demonstrated strengths and weaknesses in national and interna- 1   Representatives of federal agencies serve in an ex officio capacity. An ex officio member of a group is one who is a member automatically by virtue of holding a particular office or membership in another body.

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary tional capacities to address infectious disease challenges. The story of the emergence, spread, and control of SARS illustrates the considerable economic, political, and psychological effects—in addition to the impact on public health—of an unanticipated epidemic in a highly connected and interdependent world. At the same time, the rapid response to SARS reflects significant achievements in science, technology, and international collaboration. The future is likely to bring far greater challenges. Will SARS reemerge, and with greater virulence? Can we contain a more widely disseminated epidemic? Will we have preventive or therapeutic countermeasures? Can the necessary global cooperation and resources for containment be sustained? If not SARS, are we prepared for the next emerging infection? Are our public health and research investments (human, technical, and financial) flexible enough to respond to the ever-changing profile of microbial threats? These and other questions were explored during a September 30 and October 1 workshop of the Forum on Microbial Threats. The goals of the workshop were to: Discuss the origin, emergence, and spread of SARS and the ensuing global response to the epidemic. Evaluate measures employed to contain and control SARS, as well as its clinical management. Examine evidence of the economic impact of this and future epidemics. Look at the political repercussions of the international effort to address the threat posed by SARS. Explore the future of research and technological development related to SARS. Consider preparations for the next infectious disease outbreak. The issues pertaining to these goals were addressed through invited presentations and subsequent discussions, which highlighted ongoing programs and actions taken, and also identified the most vital needs in these areas. ORGANIZATION OF WORKSHOP SUMMARY This workshop summary was prepared for the Forum membership in the name of the editors, with the assistance of staff and consultants, as a collection of individually authored papers. The sections of this summary that are not specifically attributed to an individual reflect the views of the editors exclusively—they do not reflect the views of the Institute of Medicine (IOM) or of the organizations that sponsor the Forum on Microbial Threats. The contents of the unattributed sections are based on the presentations and discussions that took place during the workshop. The SARS workshop functioned as a venue for dialogue among representatives from many sectors about their beliefs on subjects that may merit further

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary attention. The reader should be aware that the material presented here reflects the views and opinions of those participating in the workshop and not the deliberations of a formally constituted IOM study committee. Moreover, these proceedings summarize only what participants stated in the workshop and are not intended to be an exhaustive exploration of the subject matter. This summary is organized as a topic-by-topic description of the presentations and discussions from the SARS workshop. The purpose is to present lessons from relevant experience, delineate a range of pivotal issues and their respective problems, and put forth some potential responses as described by the workshop participants. The Summary and Assessment chapter discusses the core messages that emerged from the speakers’ presentations and the ensuing discussions. Chapters 1 through 5 begin with overviews provided by the editors, followed by papers that reflect the contents of invited speaker presentations. The papers in Chapter 1 describe the emergence and detection of the SARS coronavirus and the global response to the epidemic. The papers in Chapter 2 describe the economic fall-out—known and projected—of the SARS epidemic and analyze political and governmental responses to it. Chapter 3 includes papers on the microbiology, ecology, and natural history of coronaviruses, the genus of viruses to which the SARS agent belongs. The articles in Chapter 4 describe the development of diagnostics, therapeutics, and other technologies to control SARS. Finally, the papers in Chapter 5 examine how SARS might reemerge and how the world could prepare for the next major outbreak of infectious disease. ACKNOWLEDGMENTS The Forum on Microbial Threats and IOM wish to express their warmest appreciation to the individuals and organizations who gave valuable time to provide information and advice to the Forum through participation in the workshop (see Appendix A for the workshop agenda and Appendix F for a list of forum, speaker, and staff biographies). The Forum is indebted to the IOM staff who contributed during the course of the workshop and the production of this workshop summary. On behalf of the Forum, we gratefully acknowledge the efforts led by Stacey Knobler, director of the Forum, and Alison Mack, technical consultant, who dedicated much effort and time to developing this workshop’s agenda, and for their thoughtful and insightful approach and skill in translating the workshop proceedings and discussion into this workshop summary. Particular recognition is given to Katherine Oberholtzer whose tireless research efforts and technical editing were essential to the framing of the workshop and its report. Considerable thanks is expressed to Laura Sivitz for her thoughtful guidance in preparing the report for review and her editing of the report. We also express our gratitude to Karl Galle who contributed greatly to the final editing and organization of the chapter overviews and technical papers. Initial drafts of the report benefited greatly from technical re-

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary views by James Hughes, Michael Osterholm, and David Relman. We would also like to thank the following IOM staff and consultants for their valuable contributions to this activity: Patrick Kelley, Bernadette Pryde Hackley, Marcia Lewis, Amy Giamis, Joe Esparza, Harriet Banda, Dianne Stare, Marjan Najafi, Jennifer Bitticks, Bronwyn Schrecker, Porter Coggeshall, Jennifer Otten, and Sally Stanfield. Finally, the Forum also thanks sponsors that supported this activity. Financial support for this project was provided by the U.S. Department of Health and Human Services’ National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration; U.S. Department of Defense; U.S. Department of State; U.S. Department of Veterans Affairs; U.S. Department of Agriculture; American Society for Microbiology; Burroughs Wellcome Fund; Pfizer; GlaxoSmithKline; and the Merck Company Foundation. The views presented in this workshop summary are those of the editors and workshop participants and are not necessarily those of the funding organizations. Adel Mahmoud, Chair Stanley Lemon, Vice-Chair Forum on Microbial Threats

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary Contents     SUMMARY AND ASSESSMENT   1 1   SARS: EMERGENCE, DETECTION, AND RESPONSE   41      The WHO Response to SARS and Preparations for the Future J.S. MacKenzie, P. Drury, A. Ellis et al.   42      The Centers for Disease Control and Prevention’s Role in International Coordination and Collaboration in Response to the SARS Outbreak James W. LeDuc and Anne Pflieger   50      Role of China in the Quest to Define and Control SARS Robert F. Breiman, Meirion R. Evans, Wolfgang Preiser et al.   56      SARS: Lessons from Toronto Donald E. Low   63      Isolation and Quarantine: Containment Strategies for SARS 2003 Martin Cetron, Susan Maloney, Ram Koppaka, and Patricia Simone   71      Impacts of SARS on Health Care Systems and Strategies for Combating Future Outbreaks of Emerging Infectious Diseases Abu Saleh M. Abdullah, Brian Tomlinson, G. Neil Thomas, and Clive S. Cockram   83 2   POLITICAL INFLUENCES ON THE RESPONSE TO SARS AND ECONOMIC IMPACTS OF THE DISEASE   91      Estimating the Global Economic Costs of SARS Jong-Wha Lee and Warwick J. McKibbin   92

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary      SARS: Political Pathology of the First Post-Westphalian Pathogen David P. Fidler   110      The SARS Epidemic and Its Aftermath in China: A Political Perspective Yanzhong Huang   116 3   MICROBIOLOGY, ECOLOGY, AND NATURAL HISTORY OF CORONAVIRUSES   137      Animal Coronaviruses: Lessons for SARS Linda J. Saif   138      Coronavirus Research: Keys to Diagnosis, Treatment, and Prevention of SARS Mark R. Denison   149      Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China Y. Guan, B.J. Zheng, Y.Q. He et al.   157 4   DIAGNOSTICS, THERAPEUTICS, AND OTHER TECHNOLOGIES TO CONTROL SARS   173      Evaluation of Reverse Transcription-PCR Assays for Rapid Diagnosis of Severe Acute Respiratory Syndrome Associated with a Novel Coronavirus W.C. Yam, K.H. Chan, L.L.M. Poon et al.   175      Novel Biosensor for Infectious Disease Daignostics Rangarajan Sampath and David J. Ecker   181      In Vitro Antiviral Activity of Human Rhinovirus 3C Protease Inhibitors Against the SARS Coronavirus David A. Matthews, Amy K. Patick, Robert O. Baker et al.   186      SARS: Clearing the Air Jerome J. Schentag, Charles Akers, Pamela Campagna, and Paul Chirayath   193 5   PREPARING FOR THE NEXT DISEASE OUTBREAK   206      Are We Ready for Pandemic Influenza? Richard J. Webby and Robert G. Webster   208      Modeling a Response Strategy Sam Amirfar, Mary Koshy, and Nathaniel Hupert   218      Reporting, Surveillance, and Information Exchange: The SARS Imperative for Innovation Ann Marie Kimball, Bill Lober, John Kobayashi et al.   222      Public Health Law Preparedness Gene Matthews   230

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Learning From Sars: Preparing for the Next Disease Outbreak - Workshop Summary      SARS: Lessons from a New Disease David L. Heymann and Guenael Rodier   234      SARS: Down But Still a Threat Karen J. Monaghan   246     APPENDIXES     A   Learning from SARS: Preparing for the Next Disease Outbreak   277 B   Clinical Guidance on the Identification and Evaluation of Possible SARS-CoV Disease Among Persons Presenting with Community-Acquired Illness   281 C   In the Absence of SARS-CoV Transmission Worldwide: Guidance for Surveillance, Clinical and Laboratory Evaluation, and Reporting   292 D   Selected Bibliography   303 E   Glossary and Acronyms   324 F   Forum Member, Speaker, and Staff Biographies   339

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