Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions

Workshop Summary

Rapporteurs: Stanley M. Lemon, Margaret A. Hamburg, P. Frederick Sparling, Eileen R. Choffnes, and Alison Mack

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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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions Workshop Summary Rapporteurs: Stanley M. Lemon, Margaret A. Hamburg, P. Frederick Sparling, Eileen R. Choffnes, and Alison Mack 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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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: 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. This project was supported by contracts between the National Academy of Sciences and the U.S. Department of Health and Human Services: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, and Food and Drug Administration; U.S. Department of Defense: Global Emerging Infections Surveillance and Response System, Walter Reed Army Institute of Research, and Defense Threat Reduction Agency; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; Lawrence Livermore National Laboratory; American Society for Microbiology; Sanofi Pasteur; Burroughs Wellcome Fund; Pfizer; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck Company Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number-13: 978-0-309-11114-0 International Standard Book Number-10: 0-309-11114-5 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 2007 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. COVER: A detailed section of a stained glass window 21" 56" depicting the natural history of influenza viruses and zoonotic exchange in the emergence of new strains 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. Suggested citation: Institute of Medicine. 2007. Global infectious disease surveillance and detection: Assessing the challenges—finding solutions. Workshop summary. Washington, DC: The National Academies Press.

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary “Knowing is not enough; we must apply. Willing is not enough; we must do.” —Goethe INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES Advising the Nation. Improving Health.

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary 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. Ralph J. Cicerone 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. Charles M. Vest 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. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary FORUM ON MICROBIAL THREATS STANLEY M. LEMON (Chair), School of Medicine, University of Texas Medical Branch, Galveston MARGARET A. HAMBURG (Vice-chair), Nuclear Threat Initiative/Global Health & Security Initiative, Washington, DC P. FREDERICK SPARLING (Vice-chair), University of North Carolina, Chapel Hill DAVID W. K. ACHESON, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Rockville, Maryland RUTH L. BERKELMAN, Emory University, Center for Public Health Preparedness and Research, Rollins School of Public Health, Atlanta, Georgia ENRIQUETA C. BOND, Burroughs Wellcome Fund, Research Triangle Park, North Carolina ROGER G. BREEZE, Centaur Science Group, Washington, DC STEVEN J. BRICKNER, Pfizer Global Research and Development, Pfizer Inc., Groton, Connecticut NANCY CARTER-FOSTER, Program for Emerging Infections and HIV/AIDS, U.S. Department of State, Washington, DC GAIL H. CASSELL, Eli Lilly & Company, Indianapolis, Indiana BILL COLSTON, Lawrence Livermore National Laboratory, Livermore, California RALPH L. ERICKSON, Global Emerging Infections Surveillance and Response System, Department of Defense, Silver Spring, Maryland MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., West Point, Pennsylvania J. PATRICK FITCH, National Biodefense Analysis and Countermeasures Center, Frederick, Maryland DARRELL R. GALLOWAY, Medical S&T Division, Defense Threat Reduction Agency, Fort Belvoir, Virginia S. ELIZABETH GEORGE, Biological and Chemical Countermeasures Program, Department of Homeland Security, Washington, DC JESSE L. GOODMAN, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von Humbolt, Universidad Peruana Cayetano Heredia, Lima, Peru JO HANDELSMAN, College of Agricultural and Life Sciences, University of Wisconsin, Madison CAROLE A. HEILMAN, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland DAVID L. HEYMANN, Polio Eradication, World Health Organization, Geneva, Switzerland PHIL HOSBACH, New Products and Immunization Policy, Sanofi Pasteur, Swiftwater, Pennsylvania

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary JAMES M. HUGHES, Global Infectious Diseases Program, Emory University, Atlanta, Georgia STEPHEN A. JOHNSTON, Arizona BioDesign Institute, Arizona State University, Tempe GERALD T. KEUSCH, Boston University School of Medicine and Boston University School of Public Health, Massachusetts RIMA F. KHABBAZ, National Center for Preparedness, Detection and Control of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia LONNIE J. KING, Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia GEORGE W. KORCH, U.S. Army Medical Research Institute for Infectious Diseases, Fort Detrick, Maryland JOSHUA LEDERBERG, The Rockefeller University, New York LYNN G. MARKS, Medicine Development Center, GlaxoSmithKline, Collegeville, Pennsylvania EDWARD McSWEEGAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland STEPHEN S. MORSE, Center for Public Health Preparedness, Columbia University, New York MICHAEL T. OSTERHOLM, Center for Infectious Disease Research and Policy, School of Public Health, University of Minnesota, Minneapolis GEORGE POSTE, Arizona BioDesign Institute, Arizona State University, Tempe DAVID A. RELMAN, Stanford University, Palo Alto, California GARY A. ROSELLE, Central Office, Veterans Health Administration, Department of Veterans Affairs, Washington, DC JANET SHOEMAKER, Office of Public Affairs, American Society for Microbiology, Washington, DC BRIAN J. STASKAWICZ, Department of Plant and Microbial Biology, University of California, Berkeley TERENCE TAYLOR, International Council for the Life Sciences, Washington, DC Staff EILEEN CHOFFNES, Forum Director ALLISON BRANTLEY, Senior Program Assistant* SARAH BRONKO, Senior Program Assistant† ALISON MACK, Science Writer KATE SKOCZDOPOLE, Research Associate * Ending June 2007. † Beginning June 2007.

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary BOARD ON GLOBAL HEALTH Margaret Hamburg (Chair), Consultant, Nuclear Threat Initiative, Washington, DC George Alleyne, Director Emeritus, Pan American Health Organization, Washington, DC Donald Berwick, Clinical Professor of Pediatrics and Health Care Policy, Harvard Medical School, and President and Chief Executive Officer, Institute of Healthcare Improvement, Boston, Massachusetts Jo Ivey Boufford (IOM Foreign Secretary), President, New York Academy of Medicine, New York David R. Challoner, Vice President for Health Affairs, Emeritus, University of Florida, Gainesville Ciro de Quadros, Albert B. Sabin Vaccine Institute, Washington, DC Sue Goldie, Associate Professor of Health Decision Science, Department of Health Policy and Management, Center for Risk Analysis, Harvard University School of Public Health, Boston, Massachusetts Richard Guerrant, Thomas H. Hunter Professor of International Medicine and Director, Center for Global Health, University of Virginia School of Medicine, Charlottesville Gerald T. Keusch, Assistant Provost for Global Health, Boston University School of Medicine, and Associate Dean for Global Health, Boston University School of Public Health, Massachusetts Jeffrey Koplan, Vice President for Academic Health Affairs, Emory University, Atlanta, Georgia Sheila Leatherman, Research Professor, University of North Carolina School of Public Health, Chapel Hill Michael Merson, Director, Duke Global Health Institute, Duke University, Durham, NC Mark L. Rosenberg, Executive Director, Task Force for Child Survival and Development, Emory University, Decatur, Georgia Philip Russell, Professor Emeritus, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland Staff Patrick Kelley, Director Allison Brantley, Senior Program Assistant IOM boards do not review or approve individual reports and are not asked to endorse conclusions and recommendations. The responsibility for the content of the reports rests with the authors and the institution.

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary 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 National Research Council’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 Besser, Public Health Laboratory, Minnesota Department of Health R. James Cook, Department of Plant Pathology, Washington State University Charlotte A Gaydos, Division of Infectious Diseases, The Johns Hopkins University and International STD Reference Laboratory Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the final draft of the report before its release. The review of this report was overseen by Melvin Worth, Scholar-in-Residence, Institute of Medicine. Appointed by the Institute of Medicine, he 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 authoring committee and the institution.

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary Preface The Forum on Emerging Infections was created by the Institute of Medicine (IOM) in 1996 in response to a request from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). The purpose of the Forum is to provide structured opportunities for leaders from government, academia, and industry to meet and examine issues of shared concern regarding research, prevention, detection, and management of emerging or reemerging infectious diseases. In pursuing this task, the Forum provides a venue 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; for this reason, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its value derives instead from the diversity of its membership and from the contributions that individual members make throughout the activities of the Forum. In September 2003, the Forum changed its name to the Forum on Microbial Threats. ABOUT THE WORKSHOP Early detection is essential to the control of emerging, reemerging, and novel infectious diseases, including agents of bioterrorism. Containing the spread of such a disease in a profoundly interconnected world requires active vigilance for signs of an outbreak, rapid recognition of its presence, and diagnosis of its microbial cause, as well as strategies and resources for an appropriate and efficient response. While often viewed in terms of public health, the challenges

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary of detecting natural and intentionally introduced disease outbreaks are equally shared by the plant and animal health communities. Currently, disease surveillance and detection relies heavily on the astute individual: the clinician, veterinarian, grower, livestock manager, or agricultural extension agent who notices atypical or suspicious symptoms and brings them to the attention of public health, veterinary medicine, or agricultural officials—including academicians and zoological parks. While most developed countries have a surveillance system in place and the ability to detect and diagnose human, animal, and plant diseases, many developing countries—where most of the global population resides—may not have the resources or infrastructure to support such activities. Under such circumstances, disease detection occurs on the local level and depends entirely on the early recognition of both known and novel infectious diseases. Technological advances in disease surveillance and detection such as regional syndromic surveillance, bioinformatics, and new rapid diagnostic methods have the potential to improve infectious disease control and prevention efforts. Further improvements are likely to result from ongoing innovations in infectious disease diagnostics, reporting, and surveillance. However, a number of challenges remain to be met before deployment of rapid, low-cost, sensitive, and specific point-of-care disease diagnostics become a reality. The Forum on Microbial Threats of the Institute of Medicine hosted a public workshop in Washington, DC, on December 12 and 13, 2006, to consider the scientific and policy issues—some of them long standing, others more recently arisen—relevant to the practice of disease surveillance and detection. Through invited presentations and discussions, participants examined current and emerging methods and strategies for the surveillance and detection of human, animal, and plant diseases, and assessed the resource needs and opportunities for improving and coordinating infectious disease surveillance, detection, and reporting. ACKNOWLEDGMENTS The Forum on Microbial Threats and the IOM wish to express their warmest appreciation to the individuals and organizations who gave their valuable time to provide information and advice to the Forum through their participation in this workshop. A full list of presenters can be found in Appendix A. 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 Eileen Choffnes, director of the Forum, and Kate Skoczdopole, research associate, for dedicating much effort and time to developing this workshop’s agenda and for their thoughtful and insightful approach and skill in translating the workshop’s proceedings and discussion into this workshop summary. We would also like to thank the following IOM staff and consultants for their valuable contributions to this activity: Patrick

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary Kelley, Alison Mack, Sarah Bronko, Bronwyn Schrecker, Allison Brantley, Lara Andersen, and Laura Penny. Finally, the Forum wishes to recognize the 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, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, and Food and Drug Administration; U.S. Department of Defense: Global Emerging Infections Surveillance and Response System, Walter Reed Army Institute of Research, and Defense Threat Reduction Agency; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; Lawrence Livermore National Laboratory; American Society for Microbiology; Sanofi Pasteur; Burroughs Wellcome Fund; Pfizer; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck Company Foundation. The views presented in this workshop summary report are those of the workshop participants and rapporteurs and are not necessarily those of the Forum on Microbial Threats or its sponsors. Stanley M. Lemon, Chair Margaret A. Hamburg, Vice-chair P. Frederick Sparling, Vice-chair Forum on Microbial Threats

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary Contents     Summary and Assessment   1 1   Surveillance Strategies   45      Overview,   45      Syndromic Surveillance: Moving from Theory to Practice, Patrick W. Kelley, M.D., Dr.P.H.   49      Syndromic Surveillance in Public Health Practice, Michael A. Stoto, Ph.D.   63      Implications of “Real Time” Versus “Batch Reporting” for Surveillance, Joseph Lombardo, M.S.   72      One World—One Health: Wildlife and Emerging Disease Surveillance, William B. Karesh, D.V.M.   77      Agricultural Biosecurity: Threats and Impacts for Plant Pathogens, Jacqueline Fletcher, Ph.D., and James P. Stack, Ph.D.   86      Plant Biosecurity Infrastructure for Disease Surveillance and Diagnostics, James P. Stack, Ph.D., and Jacqueline Fletcher, Ph.D.   95      References,   102 2   Surveillance Networks   107      Overview,   107      Global Infectious Disease Surveillance and Early Warning Systems: ProMED and ProMED-Mail, Stephen S. Morse, Ph.D.   109

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary      Global Public Health Surveillance: The Role of Nontraditional Surveillance Tools, Abla Mawudeku, M.P.H., M. Ruben, M.D., Ph.D., and R. Lemay, B.Sc., M.B.A.   116      HealthMap: Internet-Based Emerging Infectious Disease Intelligence, John S. Brownstein, Ph.D., Clark C. Freifeld, B.S., Ben Y. Reis, Ph.D., and Kenneth D. Mandl, M.D., M.P.H.   122      Using Cell Phone Technology for Infectious Disease Surveillance in Low-Resource Environments: A Case Study from Peru, Pamela R. Johnson, Ph.D., and David L. Blazes, M.D., M.P.H.Pamela R. Johnson, Ph.D., and David L. Blazes, M.D., M.P.H.   136      References,   153 3   Detection and Diagnostics   158      Overview,   158      Partnering for Better Microbial Diagnostics, Mark D. Perkins, M.D., and Peter M. Small, M.D.   160      Rapid Infectious Disease Diagnostic Assays, Mark J. Wolcott, Ph.D., Randal J. Schoepp, Ph.D., David A. Norwood, Ph.D., and David R. Shoemaker, Ph.D.   165      Emerging Tools for Microbial Diagnosis, Surveillance, and Discovery, W. Ian Lipkin, M.D., and Thomas Briese, Ph.D.   177      The Potential Importance of Presymptomatic, Host-Based Diagnosis in Biodefense and Standard Health Care, Stephen Albert Johnston, Ph.D.   193      References,   207 4   Resource Needs and Opportunities   213      Overview,   213      Coordination of Disease Surveillance, Detection, Diagnostics, and Reporting, William D. Hueston, D.V.M., Ph.D.   216      Improving Infectious Disease Surveillance and Detection: A Public Health Laboratory Perspective, Frances Pouch Downes, Dr.P.H.   224      References,   230     Appendixes     A   Agenda   233 B   Acronyms   238 C   Forum Member Biographies   243

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary Tables, Figures, and Boxes TABLES SA-1   Animal Diseases Associated with Direct and Indirect Human Impacts,   12 SA-2   Current Public Health Paradigm and Alternative World View,   34 1-1   Sources for Syndromic Surveillance, 2003 and 2006 Annual Meeting Abstracts,   62 1-2   Potential Sources of Data for Syndromic Surveillance,   62 1-3   U.S. Select Agent List for Plants,   91 2-1   Top Infectious Disease Alerts from the HealthMap System, October 1, 2006–February 16, 2007,   128 3-1   Department of Defense (DoD) Acquisition Program for Diagnostic Devices,   168 3-2   Criteria for Proof of Causation,   179 4-1   Current Public Health Paradigm and Alternative World View,   221 FIGURES SA-1   The economic impact of selected infectious diseases,   13 SA-2   Traditional public health reporting,   18 SA-3   The power of the ProMED surveillance network,   19

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary SA-4   Source of initial reporting of potential events of public health concern by WHO between January 1, 2001, and December 31, 2002,   21 SA-5   HealthMap alert volume by source,   23 SA-6   Telephone subscribers per 100 inhabitants, Africa 1995–2004,   24 SA-7   Star Trek medical tricorder,   30 1-1   Syndromic surveillance of U.S. marines for treated diarrheal syndromes during the lead-up to the Persian Gulf War, 1990–1991,   52 1-2   Conceptual steps in development and implementation of a syndromic surveillance system in a community,   53 1-3   The donut-hole effect,   55 1-4   Estimated sensitivity for West Nile virus by different surveillance methods,   57 1-5   E. coli O157:H7 spinach-associated outbreak, 2006,   58 1-6   Time associated with confirming spinach-related illness,   58 1-7   Locations of surveillance systems in abstracts for the 2006 International Society for Disease Surveillance (ISDS) meeting,   61 1-8   System requirements for public health surveillance,   63 1-9   Sensitivity of syndromic surveillance (probability of detection by day) for influenza-like illness at a typical urban hospital emergency room using four detection algorithms,   67 1-10   Electronic health monitoring components,   74 2-1   Epidemic intelligence framework,   117 2-2   Global Public Health Intelligence Network (GPHIN) flow of information,   119 2-3   Screenshot of the HealthMap system,   125 2-4   Framework for Internet-based surveillance,   126 2-5   HealthMap geographic coverage, October 1, 2006– February 16, 2007,   130 2-6   Distribution of the earth’s population,   138 2-7   Being able to enter and access data from any available communications channels can optimize the use of existing infrastructure,   141 2-8   Health-care personnel collect data,   146 2-9   Alerta network,   147 2-10   Data flow from the field,   148 2-11   Outbreak of diarrhea as reported by the system,   150 3-1   Product development path for microbial diagnostics,   164 3-2   Infection and response time course,   166 3-3   Orthogonal diagnostic testing,   167 3-4   Acquisition program—evolutionary strategy,   168 3-5   Diagnostic system architecture,   172

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Global Infectious Disease Surveillance and Detection: Assessing the Challenges—Finding Solutions: Workshop Summary 3-6   Comprehensive integrated diagnostic system,   176 3-7   A staged strategy for pathogen detection and discovery,   183 3-8   Schematic representation of MassTag PCR procedure,   183 3-9   Greene pathogen database,   186 3-10   The Bio-Maginot line,   195 3-11   Changing spectrum of biothreat risk,   196 3-12   Growth of GenBank, 1982–2005,   197 3-13   The combination of rapid knowledge and technological growth will create the potential to make new pathogens,   198 3-14   The threat space is becoming increasingly complex,   198 3-15   Biosignature pattern recognition in human diseases,   199 3-16   Personalized medicine based on biosignatures,   200 3-17   Biosignatures versus biomarkers,   201 3-18   Upper respiratory disease incubation periods,   202 3-19   Program to create DocInBox diagnosis,   203 3-20   Health-care spending projections,   204 3-21   In 2005, 18 percent of GDP was spent on health care,   205 3-22   Comparison of U.S. spending on energy and health care, 1970–2004,   206 3-23   Average annual health-care expenditures by age, 2005,   206 3-24   Human species needs to square life’s curve,   207 BOX 3-1   Example of Diagnostic Systems Validation Parameters,   173

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