Health Effects of
When Used for
David A. Savitz and Anne N. Styka, Editors
Committee to Review Long-Term Health Effects of Antimalarial Drugs
Board on Population Health and Public Health Practice
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by Contract Order No. VA 36C24E18C0067 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-67210-8
International Standard Book Number-10: 0-309-67210-4
Digital Object Identifier: https://doi.org/10.17226/25688
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Copyright 2020 by the National Academy of Sciences. All rights reserved.
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Assessment of long-term health effects of antimalarial drugs when used for prophylaxis. Washington, DC: The National Academies Press. https://doi.org/10.17226/25688.
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COMMITTEE TO REVIEW LONG-TERM HEALTH EFFECTS OF ANTIMALARIAL DRUGS
David A. Savitz (Chair), Professor, Brown University
Sara L. Dolan, Associate Professor of Psychology and Neuroscience and Graduate Program Director, Clinical Psychology Program, Baylor University
Marie R. Griffin, Professor, Health Policy and Medicine, Director, Vanderbilt Master of Public Health Program, Vanderbilt University
James P. Herman, Flor van Maanen Professor and Chair Department of Pharmacology and Systems Physiology, Director, University of Cincinnati Neurobiology Research Center; Director, Stress Neurobiology Laboratory, College of Medicine, University of Cincinnati
Yuval Neria, Professor of Medical Psychology, Director of PTSD Treatment and Research Program, Director of Columbia–NewYork Presbyterian Military Family Wellness Center, Columbia University Medical Center
Andy Stergachis, Professor of Pharmacy and Global Health, Associate Dean, School of Pharmacy, Director, Global Medicines Program, University of Washington
Elizabeth A. Stuart, Professor of Mental Health, Biostatistics, and Health Policy and Management, Associate Dean for Education, Bloomberg School of Public Health, Johns Hopkins University
Carol Tamminga, Professor, University of Texas Southwestern Medical Center
Jonathan L. Vennerstrom, Professor, Department of Pharmaceutical Sciences, University of Nebraska Medical Center
Christina M. Wolfson, Director of the Neuroepidemiology Research Unit and Professor, McGill University
Anne N. Styka, Study Director
Kristin E. White, Associate Program Officer
Stephanie J. Hanson, Research Associate
Rebecca F. Chevat, Senior Program Assistant
Rose Marie Martinez, Senior Board Director, Board on Population Health and Public Health
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This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, 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 thank the following individuals for their review of this report:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or
recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by Tracy Lieu, Kaiser Permanente, Northern California, and Brian L. Strom, Rutgers, The State University of New Jersey. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
The men and women who serve in the U.S. Armed Forces and who are deployed to distant locations around the world encounter myriad health threats. In addition to those associated with the potential for combat, exposure to harmful agents, and disruption of their family life, they may face disease threats that are specific to the locations to which they are sent. Prominent among these is malaria, a parasitic disease that is endemic to several locations where U.S. forces have been posted over the years, including in parts of Afghanistan and Iraq. The threat of malaria—a debilitating and potentially deadly illness—can be significantly mitigated through the use of antimalarial drugs for prevention. Such drugs have known side effects, however, and concerns over whether adverse events related to taking the drugs persist after administration is stopped are well justified. This is a challenging issue, given the diversity of antimalarial drugs used, the wide range of potential adverse events, and the numerous other health concerns that service members encounter following deployment.
While there are many questions that could be asked regarding the use of antimalarial drugs for deployed personnel, the committee’s charge was very specific: assemble, examine, and assess the research that contributes to an understanding of whether the use of antimalarial drugs may cause persistent or latent health problems. The committee was not asked to review patient reports or to make recommendations regarding the use of such drugs (as the Food and Drug Administration does) nor to provide guidelines for those traveling to malaria-endemic areas (as the Centers for Disease Control and Prevention does). Instead, the committee was charged with evaluating the available scientific and medical information, and it did not speculate or conjecture beyond that body of knowledge. It is thus important to note that a determination that the evidence was not sufficient to draw a conclusion
regarding a particular drug–outcome association should not be interpreted as a determination that the drug does not cause adverse health effects: the lack of evidence of adverse effects is not evidence of a lack of adverse effects. The committee looked carefully and exhaustively at the evidence and in this report describes the process by which the information it considered was gathered and presents its summary and assessment of what that research can tell us.
The committee hopes that its work will help the Department of Veterans Affairs, the Department of Defense, and other agencies, such as the Peace Corps and the Department of State, that send teams and workers to serve in malaria-endemic areas to provide guidance to its health care providers—in particular, regarding specific questions and symptoms in persons who have used the drugs of interest for prophylaxis and who may have concerns about their long-term health.
It is clear that some proportion of those who were deployed and prescribed antimalarial drugs became ill. The committee received accounts from a number of those who had experienced such illnesses, some quite severe, and there can be no doubt that their health problems are real and that they followed their use of antimalarial drugs. We very much appreciate the courage and commitment of those who took the time to educate the committee based on their personal experience.
The committee also wishes to acknowledge the Department of Veterans Affairs, Department of Defense, Food and Drug Administration, Peace Corps, Centers for Disease Control and Prevention, and Department of State who made presentations to the committee and responded to follow-up questions. We are extremely appreciative of the outstanding efforts of the staff of the National Academies of Sciences, Engineering, and Medicine’s Health and Medicine Division; Anne Styka, who served as study director; Stephanie Hanson and Kristin White, who had a daunting task of identifying and culling the large and complex literature and more generally guiding and assisting the committee in its mission. We also are grateful to Rebecca Chevat who generously and capably provided logistical support to the committee. Finally, the committee would like to acknowledge a number of other individuals who helped make this work possible: Daniel Bearss, a senior research librarian who helped design and perform the initial literature searches and who sadly passed away during the course of this work; Jorge Mendoza, a senior research librarian who conducted the second set of literature searches; Audrey Thevenon, a program officer on the Board on Life Sciences, who provided expertise in malaria; Andy Koltun, a summer intern through Georgetown University School of Medicine’s Population Health Scholars Track, who helped screen several thousand abstracts; Robert Pool for his editorial assistance; and Misrak Dabi, finance business partner who managed and led the financial and budgeting activities for the project.
David A. Savitz, Chair
Committee to Review Long-Term Health Effects of Antimalarial Drugs
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|AFP||Australian Federal Police Association|
|AIDS||acquired immunodeficiency syndrome|
|BMI||body mass index|
|CAS||Chemical Abstract Service|
|CDC||Centers for Disease Control and Prevention|
|CNS||central nervous system|
|DoD||Department of Defense|
|DSM||Diagnostic and Statistical Manual of Mental Disorders|
|DSM-5||Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition|
|FAERS||FDA Adverse Event Reporting System|
|FDA||Food and Drug Administration|
|FST||fluorescent spot test|
|GFR||glomerular filtration rate|
|GPRD||General Practice Research Database|
|HIV||human immunodeficiency virus|
|IBD||irritable bowel disease|
|IBS||irritable bowel syndrome|
|ICD||International Classification of Diseases|
|ICD-9-CM||International Classification of Diseases, Ninth Revision, Clinical Modification|
|IPTp||intermittent preventive treatment in pregnancy|
|IRR||incidence rate ratio|
|NewGen Study||National Health Study for a New Generation of U.S. Veterans|
|OEF||Operation Enduring Freedom|
|OIF||Operation Iraqi Freedom|
|OND||Operation New Dawn|
|PART||presumptive anti-relapse therapy|
|PCL-C||PTSD Checklist–Civilian version|
|PHQ||Patient Health Questionnaire|
|PICO||Participants, Inventions, Comparisons and Outcomes|
|PTSD||posttraumatic stress disorder|
|QTc||corrected QT interval (on an ECG)|
|SCID||Structured Clinical Interview for DSM-5|
|SD-OCT||spectral domain optical coherence tomography|
|SF-12||Medical Outcomes Study 12-item Short Form|
|SNP||single nucleotide polymorphism|
|VA||Department of Veterans Affairs|
|WHO||World Health Organization|
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