Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary THE INFECTIOUS ETIOLOGY OF CHRONIC DISEASES Defining the Relationship, Enhancing the Research, and Mitigating the Effects Workshop Summary Stacey L. Knobler, Siobhán O’Connor, Stanley M. Lemon, Marjan Najafi, 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
OCR for page R2
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW 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; Ellison Medical Foundation; 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. International Standard Book Number 0-309-08994-8 (Book) International Standard Book Number 0-309-52673-6 (PDF) Library of Congress Control Number: 2004107939 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, 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 Museen 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.
OCR for page R3
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - 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
OCR for page R4
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - 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. 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
OCR for page R5
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - 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 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, Deputy 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, Executive Director, Communicable Diseases, World Health Organization, Geneva, Switzerland JAMES HUGHES, Assistant Surgeon General and Director, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta LONNIE KING, Dean, College of Veterinary Medicine, Michigan State University, East Lansing JOSHUA LEDERBERG, Raymond and Beverly Sackler Foundation Scholar, Rockefeller University, New York JOSEPH MALONE, Director, Department of Defense Global Emerging Infections System, Walter Reed Army Institute of Research, Silver Spring, Maryland LYNN MARKS, Senior Vice President of Infectious Diseases, Medicine Development Center, GlaxoSmithKline, Collegeville, Pennsylvania STEPHEN MORSE, Director, Center for Public Health Preparedness, Columbia University, New York
OCR for page R6
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary MICHAEL OSTERHOLM, Director, Center for Infectious Disease Research and Policy and Professor, School of Public Health, University of Minnesota, Minneapolis GEORGE POSTE, Director, Arizona BioDesign Institute, Arizona State University, Tempe 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. FREDRICK SPARLING, J. Herbert Bate Professor Emeritus of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill Liaisons YVES BERGEVIN, Department of Child and Adolescent Health and Development, World Health Organization, Geneva, Switzerland 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 MARJAN NAJAFI, Research Associate KATHERINE OBERHOLTZER, Research Assistant
OCR for page R7
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary BOARD ON GLOBAL HEALTH DEAN T. JAMISON, (Chair), Senior Fellow, Fogarty International Center, National Institutes of Health, Bethesda, Maryland JAIME SEPÚLVEDA AMOR, National Institute of Public Health, Mexico YVES BERGEVIN, Department of Child and Adolescent Health and Development, World Health Organization, Geneva, Switzerland JO IVEY BOUFFORD, Professor, Robert F. Wagner School of Public Service, New York University, 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 T. KEUSCH, Assistant Provost for Global Health, Medical Center, and Associate Dean for Global Health, Boston University School of Public Health, Boston JEFFREY KOPLAN, Vice President for Academic Health Affairs, Emory University, Atlanta ADEL A.F. MAHMOUD, President, Merck Vaccines, Whitehouse Station, New Jersey MAMPHELA A. RAMPHELE, Managing Director, The World Bank, Washington, DC MARK L. ROSENBERG, Executive Director, The Task Force for Child Survival and Development, Emory University, Atlanta DONALD M. BERWICK, (IOM Council Liaison), Clinical Professor of Pediatrics and Health Care Policy, Harvard Medical School; and President and CEO, Institute of Healthcare Improvement, Boston DAVID R. CHALLONER, (IOM Foreign Secretary), Vice President for Health Affairs, Emeritus, University of Florida, Gainesville Staff PATRICK KELLEY, Director MONISHA ARYA, Policy Intern HARRIET BANDA, Senior Project Assistant ALLISON BERGER, Senior Project Assistant STACEY KNOBLER, Senior Program Officer MARJAN NAJAFI, Research Associate (through November 2003) KATHERINE OBERHOLTZER, Research Assistant LAURA SIVITZ, Research Associate DIANNE STARE, Research Assistant/Administrative Assistant
OCR for page R8
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary This page intentionally left blank.
OCR for page R9
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - 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: Paul Eke, Centers for Disease Control and Prevention, Chamblee, Georgia Charlotte Gaydos, Johns Hopkins University School of Medicine, Baltimore, Maryland Julie Parsonnet, Stanford University School of Medicine, Palo Alto, California David Relman, Veterans Administration Palo Alto Health Care System, Palo Alto, California Donald Silberberg, University of Pennsylvania School of Medicine, Philadelphia
OCR for page R10
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary The review of this report was overseen by Melvin Worth, M.D., Scholar-in-Residence, National Academies, who 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 individual authors.
OCR for page R11
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary Preface The Forum on Microbial Threats 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 government 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 emerging 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. ABOUT THE WORKSHOP The belief that many long-recognized chronic diseases are infectious in origin goes back to the mid-nineteenth century, when cancer was studied as a possible infectious disease. In the 1950s and 1960s, much biomedical research was directed, unsuccessfully, at the identification of microorganisms purportedly causing a variety of chronic diseases. In recent years the picture has begun to change. One chronic disease after another has been linked, in some cases definitively, to
OCR for page R12
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary an infectious etiology (e.g., peptic ulcer disease with Helicobacter pylori, cervical cancer with several human papillomaviruses, Whipple’s disease with Tropheryma whippeli, Lyme arthritis and neuroborreliosis with Borrelia burgdorferi, AIDS with HIV). Evidence implicating microorganisms as etiologic agents of chronic diseases with substantial mortality and morbidity impact, including atherosclerosis and cardiovascular disease, diabetes mellitus, inflammatory bowel disease, and a variety of neurological and neuropsychiatric diseases, continues to mount. Emerging infectious diseases are conceptualized as either newly identified or appreciated illnesses, conditions, or well-recognized diseases that are newly attributed to infection. Now, scientists are beginning to believe that a substantial portion of chronic diseases may actually be associated with infection. In an effort to identify cross-disciplinary aspects of the challenge of infectious etiologies of chronic diseases, including inflammatory syndromes and cancer, the Institute of Medicine’s Forum on Microbial Threats hosted a two-day workshop on October 21–22, 2002. The workshop, Linking Infectious Agents and Chronic Diseases, explored the factors that drive infectious etiologies of chronic diseases to prominence, and sought to identify more broad-based strategies and research programs that need to be developed. The goals of the workshop were to: Review the range of pathogenic mechanisms and diversity of etiologic microbes and chronic diseases, including inflammatory syndromes and cancer; Explore trends, advances, and gaps in collaborative research on diagnostic technologies, and their integration into epidemiologic studies and surveillance; Identify chronic diseases and syndromes that warrant further investigation; Identify research needed to clarify the etiologic agents and pathogenic mechanisms involved in chronic diseases, screening for multiple potential agents of the same outcome, and considering that one microbe might induce multiple syndromes; Identify the principal bottlenecks and opportunities to detect, prevent, and mitigate the impact of chronic diseases on human health against the overall backdrop of emerging infections; Consider the benefits and risks of early detection and prevention of chronic diseases caused by infectious agents. 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 this important area.
OCR for page R13
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary ORGANIZATION OF WORKSHOP SUMMARY This workshop summary report is 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. 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’ sponsors or the Institute of Medicine (IOM). The contents of the unattributed sections are based on the presentations and discussions that took place during the workshop. The workshop summary is organized within chapters as a topic-by-topic description of the presentations and discussions. Its 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 4 begin with overviews provided by the editors, followed by authored papers that reflect the topics and findings of the authors’ workshop presentations. Chapter 1 presents case studies of infectious agents that have been shown to be associated with chronic diseases. Chapter 2 illustrates implications for developing countries where many infectious diseases remain endemic. Chapter 3 describes methodologies currently used in this area of research. Chapter 4 presents strategies to prevent and mitigate the impact of chronic diseases caused by infectious agents. Appendix A presents the workshop agenda. Appendix B is a list of information resources that review the relationship between infections and chronic diseases. Appendix C presents Forum member and speaker biographies. Although this workshop summary provides an account of the individual presentations, it also reflects an important aspect of the Forum philosophy. The workshop functions as a dialogue among representatives from different sectors and presents their beliefs on which areas may merit further attention. However, the reader should be aware that the material presented here expresses the views and opinions of those participating in the workshop and not the deliberations of a formally constituted IOM study committee. These proceedings summarize only what participants stated in the workshop and are not intended to be an exhaustive exploration of the subject matter. ACKNOWLEDGMENTS The Forum on Microbial Threats and the 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 their participation in the workshop. The Forum is indebted to the IOM staff who contributed their time and efforts in planning and executing the workshop and the production of this workshop
OCR for page R14
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary summary. On behalf of the Forum, we gratefully acknowledge the efforts led by Stacey Knobler, director of the Forum, and Marjan Najafi, research associate, coeditors of this report, 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. We would also like to thank the following Academies staff and consultants for their valuable contributions to this activity: Rob Coppock, Tom Burroughs, Carlos Orr, Jennifer Bitticks, Bronwyn Schrecker, Sally Stanfield, Rachel Marcus, Beth Gyorgy, Patricia Cuff, Katherine Oberholtzer, and Laura Sivitz. 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. 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; Ellison Medical Foundation; 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 A.F. Mahmoud, Chair Stanley M. Lemon, Vice-Chair Forum on Microbial Threats
OCR for page R15
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary Contents SUMMARY AND ASSESSMENT Stanley M. Lemon and Siobhán O’Connor 1 1 DEFINING THE RELATIONSHIP: AN EXAMINATION OF INFECTIOUS AGENTS ASSOCIATED WITH CHRONIC DISEASES 13 Overview, 13 The Role of Viruses in Oncogenesis: Human Papillomaviruses and Cervical Cancer as a Paradigm, Eduardo L. Franco 17 Chronic Hepatitis B Virus Infections, William Mason 28 Infectious Agents and Cardiovascular Disease, Michael Dunne 36 Demyelinating Diseases, Richard T. Johnson 45 Common Infections and Uncommon Disease: Elusive Associations of Enteroviruses and Type I Diabetes Mellitus, Mark A. Pallansch and M. Steven Oberste 52 Infectious Agents and Schizophrenia, Robert H. Yolken and E. Fuller Torrey 59 Ovine Pulmonary Adenocarcinoma: Identifying the Causative Agent for a Neoplastic Disease and Implications for Human Lung Cancer, Hung Fan 66 Propionibacterium acnes and Chronic Diseases, Ajay Bhatia, Jean-Francoise Maisonneuve, and David H. Persing 74
OCR for page R16
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary 2 ENDEMIC INFECTIOUS DISEASES LINKED TO CHRONIC DISEASES: IMPLICATIONS FOR DEVELOPING COUNTRIES 81 Overview, 81 Potential Long-Term Consequences of Early Childhood Enteric and Parasitic Infections, Richard L. Guerrant, Aldo A.M. Lima, Sean R. Moore, Breyette Lorntz, and Peter Patrick 83 Infectious Agents and Epilepsy, Josemir W. Sander 93 Control of Infectious Causes of Childhood Disability in Developing Countries, Maureen Durkin 99 HTLV-1: Clinical Impact of a Chronic Infection, Eduardo Gotuzzo and Kristien Verdonck 110 Progression of Hepatitis C Virus Infection with and Without Schistosomiasis, Sanaa Kamal 120 Interactions of Multiple Infectious Agents in Malaria-Endemic Areas: Concurrent HIV/AIDS and Malaria, Altaf A. Lal 126 3 OBSTACLES AND OPPORTUNITIES FOR FRAMING FUTURE RESEARCH 135 Overview, 135 Pathogens and Disease: Issues in Determining Causality, Patrick S. Moore 140 Exploring the Genetic Background–Environment Interplay in an Animal Model of Neurodevelopmental Disorders: A Multidisciplinary Approach, Mikhail V. Pletnikov 150 Infection, Cancer, and the Immune Response, David H. Persing and Franklyn G. Prendergast 154 4 OPPORTUNITIES TO PREVENT AND MITIGATE THE IMPACT OF CHRONIC DISEASES CAUSED BY INFECTIOUS AGENTS 174 Overview, 174 Developing Vaccines for Prevention of Chronic Disease, P. Helena Mäkelä 175 Toward a Strategic Approach: Integrating Epidemiology, Laboratory Research, and Surveillance; Setting Priorities, Siobhán O’Connor 183
OCR for page R17
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary APPENDIXES A Workshop Agenda 187 B Information Resources 192 C Biosketches 194 Members of the Forum on Microbial Threats, 194 Speakers, 205 Forum Staff, 215
OCR for page R18
The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects - Workshop Summary This page intentionally left blank.