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Gulf War and Health: Volume 5. Infectious Diseases
GULF WAR and HEALTH
Volume 5
INFECTIOUS DISEASES
Abigail E. Mitchell, Laura B. Sivitz, Robert E. Black, Editors
Committee on Gulf War and Health: Infectious Diseases
Board on Population Health and Public Health Practice
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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Gulf War and Health: Volume 5. Infectious Diseases
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. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract V101(93)P-2155 between the National Academy of Sciences and the Department of Veterans Affairs. 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-10: 0-309-10106-9 (Book)
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Library of Congress Control Number: 2006934962
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 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.
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Gulf War and Health: Volume 5. Infectious Diseases
“Knowing is not enough; we must apply.
Willing is not enough; we must do”
—Gothe
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
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Gulf War and Health: Volume 5. Infectious Diseases
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. 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. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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Gulf War and Health: Volume 5. Infectious Diseases
COMMITTEE ON GULF WAR AND HEALTH: INFECTIOUS DISEASES
ROBERT E. BLACK, MD, MPH, Edgar Berman Professor and Chair,
Department of International Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD
MARTIN J. BLASER, MD, Frederick H. King Professor of Internal Medicine, Chair of the Department of Medicine, and Professor of Microbiology,
New York University School of Medicine, New York
RICHARD D. CLOVER, MD, Dean and Professor,
School of Public Health and Information Sciences, University of Louisville, KY
MYRON S. COHEN, MD, J. Herbert Bate Distinguished Professor of Medicine and Microbiology,
Immunology and Public Health, University of North Carolina School of Medicine, Chapel Hill
JERROLD J. ELLNER, MD, Professor and Chair of the New Jersey Medical School at the University of Medicine and Dentistry of New Jersey,
Newark
JEANNE MARRAZZO, MD, MPH, Associate Professor,
Department of Medicine, University of Washington School of Medicine, Seattle
MEGAN MURRAY, MD, ScD, MPH, Assistant Professor of Epidemiology,
Harvard University, School of Public Health, Boston, MA
EDWARD C. OLDFIELD III, MD, Director,
Division of Infectious Diseases, Eastern Virginia Medical School, Norfolk
RANDALL R. REVES, MD, MSc, Professor,
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver
EDWARD T. RYAN, MD, Director,
Tropical and Geographic Medicine Center, Massachusetts General Hospital, and Associate Professor of Medicine, Harvard Medical School, Boston, MA
STEN H. VERMUND, MD, PhD, Amos Christie Chair and Director,
Vanderbilt University Institute for Global Health, and Professor of Pediatrics, Medicine, Preventive Medicine, and Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN
DAWN M. WESSON, PhD, Associate Professor,
Tulane School of Public Health and Tropical Medicine, New Orleans, LA
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Gulf War and Health: Volume 5. Infectious Diseases
STAFF
ABIGAIL E. MITCHELL, PhD, Senior Program Officer
LAURA B. SIVITZ, MSJ, Senior Program Associate
DEEPALI M. PATEL, Senior Program Associate
MICHAEL J. SCHNEIDER, MPH, Senior Program Associate
PETER JAMES, Research Associate
DAMIKA WEBB, Research Assistant
DAVID J. TOLLERUD, Program Assistant
RENEE WLODARCZYK, Program Assistant
NORMAN GROSSBLATT, Senior Editor
ROSE MARIE MARTINEZ, ScD, Director, Board on Population Health and Public Health Practice
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Gulf War and Health: Volume 5. Infectious Diseases
REVIEWERS
This report has been reviewed in draft form by persons 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 of 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 for their review of this report:
Lawrence R. Ash, Professor Emeritus, Department of Epidemiology, University of California, Los Angeles School of Public Health
Michele Barry, Tropical Medicine and International Health Programs, Yale University School of Medicine
Herbert DuPont, School of Public Health, University of Texas Health Science Center at Houston and St. Luke’s Episcopal Hospital
Robert Edelman, Travelers’ Health Clinic, University of Maryland
David Hill, National Travel Health Network and Centre, Hospital for Tropical Diseases, London
Richard T. Johnson, Department of Neurology, The Johns Hopkins Hospital
Arthur Reingold, Division of Epidemiology, University of California, Berkeley
Philip K. Russell, Professor Emeritus, Johns Hopkins School of Public Health
Mark Wallace, Independent Infectious Diseases Consultant and United States Navy, Retired
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 George Rutherford, Institute of Global Health, University of California, San Francisco, and Elaine L. Larson, School of Nursing, Columbia University. Appointed by the National Research Council, 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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Gulf War and Health: Volume 5. Infectious Diseases
PREFACE
Infectious diseases have been a problem for military personnel throughout history. The consequences in previous conflicts have ranged from frequent illnesses disrupting daily activities and readiness to widespread deaths. Preventive measures, early diagnosis, and treatment greatly limit the exposures and acute illnesses of troops today in comparison with those in armies of the past, but infections and consequent acute illnesses still occur. In addition, long-term adverse health outcomes of some pathogens are increasingly recognized.
The deployment of about 700,000 US troops to the Persian Gulf region in the Gulf War of 1991 potentially exposed them to pathogens that they had not encountered at home. After returning from that short campaign, some veterans reported symptoms and expressed the concern that they may have been exposed to biologic, chemical, or physical agents during their service in the Persian Gulf. In response to those concerns, the US Department of Veterans Affairs (VA) commissioned the Institute of Medicine (IOM) to review the scientific evidence on possible long-term adverse health outcomes of exposure to specific biologic, chemical, and physical agents and to draw conclusions on the strength of that evidence with regard to delayed and chronic illnesses of the veterans.
The authorizing legislation for the work of IOM included several infectious diseases endemic in the Persian Gulf region. In the charge to our committee, VA asked that we not limit consideration to those diseases but rather include all infectious exposures that had been documented in troops and consider their possible long-term adverse health outcomes. It further requested that the time and geographic dimensions of the committee’s work be widened to include military personnel deployed as part of Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF) in the Persian Gulf region. OEF began in 2001, and OIF in 2003; they continued as this report went to press. The number of military personnel involved in the more recent conflicts now exceeds that in the 1991 Gulf War. Furthermore, they have remained for much longer periods on the average than in the Gulf War, and many have been deployed for more than one tour in this region. Thus, the potential for exposure to endemic pathogens is greater in these troops than in those deployed to the Gulf War. Because the possible exposures are relatively recent, there has been only a short time to observe long-term adverse health outcomes. The committee needed to rely on observations from the Gulf War, information on infectious diseases in OEF and OIF, and evidence in the scientific literature to allow conclusions to be drawn on possible long-term adverse health outcomes. With further time to observe the possible consequences of infectious exposures, the knowledge base will increase. Given the continuing presence of troops in the areas and the variable nature of infectious diseases, the exposures may change.
Valuable contributions were made to this study by a number of people who shared their expertise on infectious diseases. On behalf of the committee, I thank several of them—K. Craig Hyams, MD, MPH, chief consultant, Occupational and Environmental Health Strategic Healthcare Group, VA; Michael Kilpatrick, MD, deputy director, Deployment Health Support, Department of Defense (DOD); and Alan Magill, MD, science director, Walter Reed Army Institute of Research, for presenting information on infectious diseases that have been diagnosed in military personnel during the Gulf War, OIF, and OEF and Richard Reithinger, PhD,
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Gulf War and Health: Volume 5. Infectious Diseases
infectious diseases consultant, for presenting information on infectious diseases that are endemic in southwest and south-central Asia to the committee at its May 26, 2005 meeting. I also thank William Winkenwerder, Jr., MD, MBA, assistant secretary for defense for health affairs, and his staff at DOD’s Deployment Health Support for expeditiously providing information to the committee on DOD health-related policies. Finally, the committee is grateful for the insight provided by representatives of veteran service organizations, veterans, and others who spoke with the committee or sent in written testimony.
I am grateful for the great expertise the committee members brought to bear on this subject. Furthermore, the report would not have been successfully completed without the diligent and expert contributions of the IOM staff, led by Abigail Mitchell and including Laura Sivitz, Deepali Patel, Michael Schneider, Peter James, Damika Webb, David Tollerud, and Renee Wlodarczyk.
Robert E. Black, MD, MPH, Chair
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Gulf War and Health: Volume 5. Infectious Diseases
CONTENTS
Summary
1
Methodology
1
Identifying the Pathogens to Study
2
Development of Conclusions
3
Summary of Conclusions
4
Sufficient Evidence of a Causal Relationship
4
Sufficient Evidence of an Association
5
Limited or Suggestive Evidence of an Association
6
Inadequate or Insufficient Evidence to Determine Whether an Association Exists
6
Limited or Suggestive Evidence of No Association
7
Department of Defense Policies on Tuberculin Skin Testing and Predeployment and Postdeployment Serum Collection
7
1
Introduction
9
Identifying the Infectious Diseases to Study
13
The Committee’s Approach to Its Charge
15
Organization of the Report
16
References
16
2
Methodology
19
Identifying the Infectious Diseases to Study
19
Geographic Boundaries
19
Infectious Diseases Endemic to Southwest and South-Central Asia That Have Long-Term Adverse Health Outcomes
20
Direct Attribution to Military Service in Southwest and South-Central Asia
24
Timing of Appearance of Long-Term Adverse Health Outcomes
27
The Infectious Diseases to Be Studied for Strength of Association with Long-Term Adverse Health Outcomes
27
Comments on Diseases and Agents of Special Interest to Gulf War, OEF, and OIF Veterans
28
Review and Evaluation of the Literature
29
Selection of the Literature
29
Amassing the Literature
29
Reviewing the Literature
29
Categories of Strength of Association
30
Origin and Evolution of the Categories
30
Sufficient Evidence of a Causal Relationship
30
Sufficient Evidence of an Association
31
Limited or Suggestive Evidence of an Association
31
Inadequate or Insufficient Evidence to Determine Whether an Association Exists
31
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Limited or Suggestive Evidence of No Association
31
References
31
3
Infectious Diseases Endemic to Southwest and South-Central Asia That Have Long-Term Adverse Health Outcomes
35
References
60
4
Infectious Diseases Diagnosed in US Troops Who Served in the Persian Gulf War, Operation Enduring Freedom, or Operation Iraqi Freedom
61
Diarrheal Disease
62
Enteric Infections in the Gulf War
62
Gastroenteritis in Operation Enduring Freedom and Operation Iraqi Freedom
69
Respiratory Disease
74
Mild Acute Respiratory Disease in the Gulf War
74
Severe Acute Respiratory Disease in the Gulf War
76
Respiratory Disease in Operation Enduring Freedom and Operation Iraqi Freedom
76
Insect-Borne Diseases
78
Leishmaniasis
78
Malaria
82
West Nile Fever
84
Brucellosis
84
Chicken Pox (Varicella)
85
Meningococcal Disease
85
Nosocomial Infections
85
Gulf War
85
Operation Enduring Freedom and Operation Iraqi Freedom
86
Q Fever
88
Q Fever Contracted During the Gulf War
89
Q Fever Contracted During Operation Enduring Freedom and Operation Iraqi Freedom
89
Viral Hepatitis
90
Tuberculosis
90
Department of Defense Medical Databases
91
Department of Defense Policy Regarding Predeployment and Postdeployment Serum Collection
93
References
94
5
Levels of Association Between Select Diseases and Long-Term Adverse Health Outcomes
101
Diarrheal Diseases: Campylobacter, Non-typhoid Salmonella, and Shigella Infections
103
Campylobacter Infection
103
Nontyphoidal Salmonella Infection
108
Shigella Infection
110
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Brucellosis
112
Transmission and Endemicity of Brucellosis
113
Acute Brucellosis
114
Treatments for Brucellosis and Related Long-Term Toxicity
115
Coinfection
115
Long-Term Adverse Health Outcomes of Brucellosis
115
Leishmaniasis
118
Transmission of Leishmaniasis
119
Endemicity in Southwest and South-Central Asia
120
Acute Leishmaniasis
120
Diagnosis of Leishmaniasis
121
Treatments for Leishmaniasis and Related Long-Term Toxicity
121
Coinfection by Leishmania Parasite and Human Immunodeficiency Virus
122
Long-Term Adverse Health Outcomes of Leishmaniasis
122
Malaria
123
Transmission of Malaria
124
Endemicity in Southwest and South-Central Asia
124
Acute Malaria
125
Treatments for Malaria and Related Long-Term Toxicity
125
Coinfection with Plasmodium Spp. and Human Immunodeficiency Virus
126
Long-Term Adverse Health Outcomes of Infection with Plasmodium Spp
126
Q Fever (Infection by Coxiella burnetii)
129
Transmission of Coxiella burnetii
129
Endemicity in Southwest and South-Central Asia
130
Acute Q Fever
130
Diagnosing Q Fever
131
Coinfection with Coxiella burnetii and Human Immunodeficiency Virus
131
Long-Term Adverse Health Outcomes of Q Fever
132
Tuberculosis
135
Transmission of Tuberculosis
135
Endemicity in Southwest and South-Central Asia
137
Risk of Progression from Latent Tuberculosis Infection to Active Tuberculosis
137
Treatment for Latent Tuberculosis Infection to Prevent Active Tuberculosis
140
Active Tuberculosis
140
Late Manifestations of Active Tuberculosis
142
Potential Relationships Between Tuberculosis and Military Service
144
West Nile Virus Infection
149
Transmission of West Nile Virus Infection
150
Endemicity in Southwest and South-Central Asia
150
Acute West Nile Fever
151
Diagnosis of West Nile Fever
151
Treatment of West Nile Virus Infection
152
Long-Term Adverse Health Outcomes of Infection with West Nile Virus
152
Recommendation
155
References
155
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6
Diseases and Agents of Special Concern to Veterans of the Gulf War, Operation Iraqi Freedom, and Operation Enduring Freedom
181
Al Eskan Disease
181
Description of Acute Illness
182
Long-Term Adverse Health Outcomes
182
Pathogenesis
182
Treatment
183
Summary
183
Idiopathic Acute Eosinophilic Pneumonia
183
Description of Acute Illness
183
Long-Term Adverse Health Outcomes
183
Pathogenesis
184
Treatment
184
Summary
184
Wound and Nosocomial Infections (Including Infections with Acinetobacter Spp.)
184
Concerns Regarding Acinetobacter baumannii
185
Other Wound Infections
186
Other Nosocomial Infections
187
Regional Experiences in Non-Americans
188
Summary
190
Mycoplasmas
190
Mycoplasmas and “Gulf War Illness”
191
Summary
193
Biologic-Warfare Agents
193
Summary
194
References
194
Appendix Biographical Sketches for Members of the Committee
201
Index
205
