MALARIA

Obstacles and Opportunities

Stanley C. Oaks, Jr., Violaine S. Mitchell, Greg W. Pearson, andCharles C. J. Carpenter, Editors

A Report of the

Committee for the Study on Malaria Prevention and Control: Status Review and Alternative Strategies

Division of International Health

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C. 1991



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MALARIA: Obstacles and Opportunities MALARIA Obstacles and Opportunities Stanley C. Oaks, Jr., Violaine S. Mitchell, Greg W. Pearson, andCharles C. J. Carpenter, Editors A Report of the Committee for the Study on Malaria Prevention and Control: Status Review and Alternative Strategies Division of International Health INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1991

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MALARIA: Obstacles and Opportunities National Academy Press 2101 Constitution Avenue, N.W. Washington, D.C. 20418 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 report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. 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. Samuel O. Thier is president of the Institute of Medicine. Funding for this study was provided by the Agency for International Development, the U.S. Army Medical Research and Development Command, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Library of Congress Cataloging-in-Publication Data Institute of Medicine (U.S.). Committee for the Study on Malaria Prevention and Control: Status Review and Alternative Strategies. Malaria : obstacles and opportunities : a report of the Committee for the Study on Malaria Prevention and Control: Status Review and Alternative Strategies, Division of International Health, Institute of Medicine / Stanley C. Oaks, Jr. [et al.], editors. p. cm. Includes bibliographical references and index. ISBN 0-309-04527-4 1. Malaria. 2. Malaria—Prevention. 3. Malaria—Research.. I. Oaks, S. C. II. Title. [DNLM: 1. Malaria—prevention & control. WC 765 I59m] RA644.M2I56 1991 614.5'32—dc20 DNLM/DLC for Library of Congress 91-31312 CIP Copyright © 1991 by the National Academy of Sciences No part of this book may be reproduced by any mechanical, photographic or electronic procedure, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purpose of official use by the United States government. 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. Ths image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.

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MALARIA: Obstacles and Opportunities COMMITTEE FOR THE STUDY ON MALARIA PREVENTION AND CONTROL: STATUS REVIEW AND ALTERNATIVE STRATEGIES CHARLES C. J. CARPENTER (Chair), Professor of Medicine, Brown University, and Physician-in-Chief, The Miriam Hospital, Providence, Rhode Island JOHN C. BEIER, Associate Professor, Department of Immunology and Infectious Diseases, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland JACQUELINE A. CATTANI, Secretary, Steering Committee of the Scientific Working Group on Applied Field Research in Malaria (FIELDMAL), UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland JEFFREY D. CHULAY, Research Investigator, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland MARIO COLUZZI, Professor and Director, Institute of Parasitology, University of Rome “La Sapienza,” Rome, Italy ROSS L. COPPEL, Senior Research Fellow, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Melbourne, Victoria, Australia E. BRIAN DOBERSTYN, Chief, Malaria Unit, Control of Tropical Diseases, World Health Organization, Geneva, Switzerland TIMOTHY G. GEARY, Senior Research Scientist, Parasitology Research, The Upjohn Company, Kalamazoo, Michigan JEFFREY S. HAMMER, Senior Economist, Population and Human Resources Department, The World Bank, Washington, D.C. STEPHEN L. HOFFMAN, Director, Malaria Program, Naval Medical Research Institute, Rockville, Maryland JAMES B. JENSEN, Director, Benson Institute, and Dean, International Agriculture and Public Health, Brigham Young University, Provo, Utah CARL KENDALL, Associate Professor and Director, Center for International Community-Based Health Research, Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland WILBUR K. MILHOUS, Group Leader, Antimalarials, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. DAVID PIMENTEL, Professor of Insect Ecology and Agricultural Sciences, Department of Entomology and Limnology, Cornell University, Ithaca, New York

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MALARIA: Obstacles and Opportunities PEDRO L. TAUIL, Assistant Professor, Faculty of Medicine, University of Brasilia, and Health Advisor to the Federal Senate, Brasilia, Brazil TERRIE E. TAYLOR, Assistant Professor, Department of Community Health Science, Michigan State University, College of Osteopathic Medicine, East Lansing, Michigan AWASH TEKLEHAIMANOT, Malaria Unit, Control of Tropical Diseases, World Health Organization, Geneva, Switzerland McWILSON WARREN, Director, Office of Scientific Services, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia THEODORE F. WOODWARD, Professor of Medicine Emeritus, University of Maryland School of Medicine, Baltimore, Maryland Institute of Medicine Staff STANLEY C. OAKS, JR., Study Director VIOLAINE S. MITCHELL, Program Officer SHARON SCOTT-BROWN, Senior Secretary POLLY F. HARRISON, Director, Division of International Health STEPHANIE R. SAGEBIEL, Senior Program Officer, Division of International Health KATHERINE B. EDSALL, Administrative Assistant, Division of International Health

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MALARIA: Obstacles and Opportunities Preface Despite heroic efforts to eradicate malaria in the 1950s and 1960s, this disease not only has prevailed but has made a dramatic resurgence within the past two decades. Morbidity and mortality from malaria are at almost unprecedented levels, particularly in Africa south of the Sahara, where the disease claims more than 1 million lives per year. To address this dilemma, the Institute of Medicine (IOM) was asked by the U.S. Agency for International Development (USAID) to conduct a study and present recommendations that relevant U.S. government funding agencies could use to focus their efforts in malaria research, prevention, and control. Funding for the study came from USAID, from the U.S. Army Medical Research and Development Command, and from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. In response to the request, IOM formed the 19-member Committee for the Study on Malaria Prevention and Control. Its membership included international expertise in infectious diseases, epidemiology, economics, parasite biology, vector biology and control, clinical tropical medicine, drug and vaccine development and evaluation, molecular biology, immunology, control program management, anthropology, and ecology. The committee 's recommendations evolved from its deliberations and the analysis of information from a wide range of sources, including articles from peer-reviewed journals, material published in book form, commissioned background papers, academic dissertations, unpublished case studies, presentations by

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MALARIA: Obstacles and Opportunities and interviews with experts, and relevant conferences and workshops. The full committee met three times during the 18-month study; the final meeting was held in January 1991. To supplement its efforts, the committee sponsored a symposium on ethical issues in malaria research, prevention, and control at the 1990 annual meeting of the American Society for Tropical Medicine and Hygiene. In addition, several working groups were formed. The epidemiologic paradigms described in Chapter 10 were drafted by a working group composed of several committee members, IOM staff, and representatives of the World Health Organization (WHO). Another working group was convened to address more fully some of the issues related to host immunology and vaccine development. Finally, nine-and six-member subcommittees were constituted and tasked to refine the conclusions and recommendations developed at the third committee meeting and to respond to the comments of the National Research Council's Report Review Committee. The committee sees its report as a source of information and guidance that can be used in several ways, depending on the reader's perspective and interests. Readers who seek only the committee's conclusions and recommendations are directed to Chapter 1. Chapter 2 and Chapter 3 will be of particular interest to readers who are unfamiliar with malaria. Those who wish to delve still deeper into the biomedical aspects of the disease can read Chapter 4, Chapter 5, Chapter 6, Chapter 7, Chapter 8, Chapter 9, Chapter 10, Chapter 11 through Chapter 12, which provide state-of-the-science information as well as research agendas that offer more precise avenues for advancing knowledge in specific areas. As an appendix to this report, the reader will find a statement of dissent by committee member Awash Teklehaimanot. Overall, the committee believes that most of the concerns expressed by Dr. Teklehaimanot are, in fact, addressed in the report. The committee's charge was to assess the status of malaria research and control and make recommendations as to how the United States, as the largest single supporter of malaria research and control activities worldwide, could best contribute to global efforts to control the disease. Writing a “how-to” manual on malaria research and control was not a part of that charge. Rather, over the course of 18 months, the committee identified major challenges and obstacles in the science base and in the implementation of the current armamentarium of interventions for prevention and control. It then formulated specific recommendations on how U.S. support could be most effective in stemming the world's growing malaria problem. The committee calls for sustained U.S. and international support for malaria control activities; a renewed commitment by donor agencies to support national programs; and extensive support for training of individuals from malaria-endemic countries in research, prevention, and control. The committee firmly believes that the United States ' most effective contribu-

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MALARIA: Obstacles and Opportunities tion will come from support of a balanced agenda for both research and control: to develop the new tools that are desperately needed, to test and apply those tools appropriately and economically, and to utilize more contextually specific and rigorous approaches to U.S.-supported malaria control activities in countries where the disease is endemic. The committee is hopeful that the conclusions and recommendations it offers will provide the impetus for critical decisions and for needed research, which will allow progress to be made in the global fight against malaria. Charles C. J. Carpenter, Chair Committee on Malaria Prevention and Control

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MALARIA: Obstacles and Opportunities Acknowledgments This is perhaps the most difficult portion of the report to write, for fear of failing to acknowledge an individual or organization. Many people outside of the committee contributed to this study in various ways. Some prepared commissioned papers or provided relevant funding information; others participated in the symposium, the joint World Health Organization/Institute of Medicine effort to draft the paradigms, or the Immunology and Vaccine Development Working Group. Still others provided organizational information as members of the Liaison Panel. All of these contributors and others who provided the committee and staff with material for use in the study are listed on the following pages. To all of you, we offer our sincere appreciation. The committee is particularly grateful to the following individuals, who took time from their busy schedules (and, in some cases, traveled great distances) to express their viewpoints and answer the many questions posed by the committee: Carlos C. Campbell of the Centers for Disease Control; Udom Chitprarop of the Malaria Center in Chiangmai, Thailand; Deberati Guha-Sapir of the University of Louvain, Brussels; Bernhard Liese of the World Bank; and Milton Tam of DiaTech, Program for Appropriate Technology in Health. Thanks are also due to the staff of the American Association for the Advancement of Science 's project on malaria in Africa, directed by the Sub-Saharan Africa Program, for their cooperation and coordination with the Institute of Medicine study staff.

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MALARIA: Obstacles and Opportunities LIAISON PANEL WILLIAM H. BANCROFT, Military Disease Hazards Research Program, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, Maryland CARLOS C. CAMPBELL, Malaria Branch, Centers for Disease Control, Atlanta, Georgia TORE GODAL, United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland SCOTT B. HALSTEAD, Health Sciences Division, The Rockefeller Foundation, New York, New York STEPHANIE L. JAMES, Parasitic and Tropical Diseases Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland BERNHARD LIESE, Health Services Department, The World Bank, Washington, D.C. FRANCISCO LOPEZ-ANTUNANO, Tropical Disease Program, Pan American Health Organization, Washington, D.C. NANCY PIELEMEIER, Office of Science and Technology/Health, Agency for International Development, Washington, D.C. JAMES D. SHEPPERD, Bureau for Africa, Agency for International Development, Washington, D.C. CONTRIBUTORS TO THE STUDY ANDREW ARATA, Vector Biology and Control Project, Medical Service Corporation International, Arlington, Virginia JOHN H. AUSTIN, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C. MICHELE BARRY, Tropical Medicine and International Traveler's Clinic, Yale University School of Medicine, New Haven, Connecticut C. A. W. BATE, Department of Immunology, University College and Middlesex School of Medicine, London, United Kingdom FREDERICK BATZOLD, Clinical Research Management Branch, National Institutes of Health, Bethesda, Maryland JAY BERZOFSKY, Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland GRAHAM BROWN, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Melbourne, Victoria, Australia CARLOS C. CAMPBELL, Malaria Branch, Centers for Disease Control, Atlanta, Georgia

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MALARIA: Obstacles and Opportunities VICENTE I. CANO, Malaria Program, World Health Organization, Geneva, Switzerland DENNIS CARROLL, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C. UDOM CHITPRAROP, Malaria Center, Chiangmai, Thailand JANE COOLEY, International Health Programs, Centers for Disease Control, Atlanta, Georgia CARTER DIGGS, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C. MARY ETTLING, Department of Population Sciences, Harvard School of Public Health, Boston, Massachusetts RONALD GERMAINE, Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland DEBERATI GUHA-SAPIR, Department of Epidemiology, School of Public Health, University of Louvain, Brussels, Belgium ROBERT W. GWADZ, Medical Entomology Unit, Malaria Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland FABIENNE HARIGA, Department of Epidemiology, School of Public Health, University of Louvain, Brussels, Belgium BRUCE HARRISON, Office of International Affairs, National Academy of Sciences, Washington, D.C. J. DAVID HAYNES, Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. STEPHEN HEMBREE, Headquarters, U.S. Army Biomedical Research and Development Laboratory, Fort Detrick, Frederick, Maryland PUSHPA HERATH, Malaria Program, World Health Organization, Geneva, Switzerland DAVID KASLOW, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland URIEL D. KITRON, Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois JOHN LAMONTAGNE, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland ELLI LEONTSINI, Center for International Community-Based Health Research, Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland CAROL LEVINE, Citizens Commission on AIDS, New York, New York

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MALARIA: Obstacles and Opportunities TAMARA LEWIN, Center for International Health Information, USAID Health Information System, Arlington, Virginia BERNHARD LIESE, Health Services Department, The World Bank, Washington, D.C. A. DENNIS LONG, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C. WILLIAM H. LYERLY, JR., Bureau for Africa, Agency for International Development, Washington, D.C. AJOY MATHEW, National Coalition of Hispanic Health and Human Services Organizations, Washington, D.C. LAURA MEAGHER, Agricultural Molecular Biology Center, Rutgers University, New Brunswick, New Jersey KIRK D. MILLER, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C. LOUIS H. MILLER, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland BEVERLY MIXON, Parasitic Diseases Division, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia LOUIS MOLINEAUX, Malaria Program, World Health Organization, Geneva, Switzerland MALCOLM E. MOLYNEUX, Department of Tropical Medicine and Infectious Diseases, Liverpool School of Tropical Medicine, Liverpool, United Kingdom JONATHAN MOSLEY, Center for International Health Information, USAID Health Information System, Arlington, Virginia J. A. NAJERA, Division of Control of Tropical Diseases, World Health Organization, Geneva, Switzerland RUTH S. NUSSENZWEIG, Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York VICTOR NUSSENZWEIG, Department of Pathology, Division of Immunology, New York University School of Medicine, New York, New York RICHARD OBERST, Military Disease Hazards Research Program, U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, Maryland LORRIN PANG, Malaria Program, World Health Organization, Geneva, Switzerland JOHN H. L. PLAYFAIR, Department of Immunology, University College and Middlesex School of Medicine, London, United Kingdom LYMAN ROBERTS, Department of Entomology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C.

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MALARIA: Obstacles and Opportunities JERALD SADOFF, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. ALAN SHAPIRA, Malaria Program, World Health Organization, Geneva, Switzerland EDGAR SMITH, Entomology Consultant, Alexandria, Virginia ANDREW SPIELMAN, Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts MILTON TAM, DiaTech, Program for Appropriate Technology in Health, Seattle, Washington J. TAVERNE, Department of Immunology, University College and Middlesex School of Medicine, London, United Kingdom KARL WESTERN, Office of Tropical Medicine and International Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland PETER WINCH, Center for International Community-Based Health Research, Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland ROBERT WRIN, Bureau of Science and Technology, Office of Health, Agency for International Development, Washington, D.C.

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MALARIA: Obstacles and Opportunities Contents  1   Conclusions and Recommendations   1  2   Background   22  3   Overview   37  4   Clinical Medicine and the Disease Process   56  5   Diagnostic Tests   73  6   Parasite Biology   90  7   Vector Biology, Ecology, and Control   118  8   Drug Discovery and Development   144  9   Vaccines   169  10   Epidemiologic Approaches to Malaria Control   211  11   Economics of Malaria Control   237  12   Social and Behavioral Aspects of Malaria   257     Appendixes    A   Paradigms   279  B   Dissenting Opinion   283     Glossary   289     Index   297

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MALARIA: Obstacles and Opportunities MALARIA Obstacles and Opportunities

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