THE CAUSES AND IMPACTS OF NEGLECTED TROPICAL AND ZOONOTIC DISEASES

Opportunities for Integrated Intervention Strategies

Eileen R. Choffnes and David A. Relman, Rapporteurs

Forum on Microbial Threats

Board on Global Health

INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

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THE CAUSES AND IMPACTS OF NEGLECTED TROPICAL AND ZOONOTIC DISEASES Opportunities for Integrated Intervention Strategies Eileen R. Choffnes and David A. Relman, Rapporteurs Forum on Microbial Threats Board on Global Health

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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, Food and Drug Administration, and the Fogarty International Center; U.S. Department of Defense, Department of the Army: Global Emerging Infections Surveil - lance and Response System, Medical Research and Materiel Command, and the Defense Threat Reduction Agency; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; U.S. Agency for International Development; American Society for Microbiology; Sanofi Pasteur; Burroughs Wellcome Fund; Pfizer, Inc.; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck Company Foundation. Any opin - ions, 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: 978-0-309-18634-6 International Standard Book Number-10: 0-309-18634-X 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 2011 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 image: The life cycles of hookworms and schistosomes. Reprinted with the permis - sion of Nature Reviews: Microbiology. Suggested citation: IOM (Institute of Medicine). 2011. The Causes and Impacts of Ne- glected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strate - gies. Washington, DC: The National Academies Press.

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“Knowing is not enough; we must apply. Willing is not enough; we must do.” — Goethe Advising the Nation. Improving Health.

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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 examina - tion 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 Na - tional 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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FORUM ON MICROBIAL THREATS1 DAVID A. RELMAN (Chair), Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, California JAMES M. HUGHES (Vice-Chair), Global Infectious Diseases Program, Emory University, Atlanta, Georgia LONNIE J. KING (Vice-Chair), Ohio State University, Columbus, Ohio KEVIN ANDERSON, Department of Homeland Security, Washington, DC RUTH L. BERKELMAN, Emory University, Center for Public Health Preparedness and Research, Rollins School of Public Health, Atlanta, Georgia ENRIQUETA C. BOND, Consultant, Marshall, Virginia ROGER G. BREEZE, Centaur Science Group, Washington, DC STEVEN J. BRICKNER,2 SJ Brickner Consulting, LLC, Ledyard, Connecticut PAULA R. BRYANT, Medical S&T Division, Defense Threat Reduction Agency, Fort Belvoir, Virginia JOHN E. BURRIS, Burroughs Wellcome Fund, Research Triangle Park, North Carolina PETER DASZAK, EcoHealth Alliance, New York, New York JEFFREY DUCHIN, Public Health–Seattle and King County, Seattle, Washington JONATHAN EISEN, Genome Center, University of California, Davis, California MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., West Point, Pennsylvania JACQUELINE FLETCHER, Oklahoma State University, Stillwater, Oklahoma S. ELIZABETH GEORGE,2 Biological and Chemical Countermeasures Program, Department of Homeland Security, Washington, DC JESSE L. GOODMAN, Chief Scientist and Deputy Commissioner, Food and Drug Administration, Rockville, Maryland EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von Humbolt, Universidad Peruana Cayetano Heredia, Lima, Peru CAROLE A. HEILMAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland DAVID L. HEYMANN, Health Protection Agency, London, United Kingdom PHILIP HOSBACH, Sanofi Pasteur, Swiftwater, Pennsylvania STEPHEN A. JOHNSTON, Arizona BioDesign Institute, Arizona State University, Tempe, Arizona 1 Institute of Medicine forums and roundtables do not issue, review, or approve individual docu - ments. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution. 2 Forum member until December 31, 2010. v

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KENT KESTER, Walter Reed Army Institute of Research, Silver Spring, Maryland GERALD T. KEUSCH, Boston University School of Medicine and Boston University School of Public Health, Boston, Massachusetts RIMA F. KHABBAZ, Centers for Disease Control and Prevention, Atlanta, Georgia STANLEY M. LEMON, School of Medicine, University of North Carolina, Chapel Hill, North Carolina EDWARD McSWEEGAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland MARK A. MILLER, Fogarty International Center, Bethesda, Maryland PAUL F. MILLER, Pfizer, Inc., Groton, Connecticut STEPHEN S. MORSE,2 Center for Public Health Preparedness, Columbia University, New York, New York GEORGE POSTE, Complex Adaptive Systems Initiative, Arizona State University, Tempe, Arizona JOHN C. POTTAGE, JR., ViiV Healthcare, Collegeville, Pennsylvania GARY A. ROSELLE, Veterans Health Administration, Department of Veterans Affairs, Washington, DC ALAN S. RUDOLPH, Defense Threat Reduction Agency, Fort Belvoir, Virginia KEVIN RUSSELL, Global Emerging Infections Surveillance and Response System, Department of Defense, Silver Spring, Maryland JANET SHOEMAKER, American Society for Microbiology, Washington, DC P. FREDERICK SPARLING, University of North Carolina, Chapel Hill, North Carolina TERENCE TAYLOR, International Council for the Life Sciences, Arlington, Virginia MURRAY TROSTLE, U.S. Agency for International Development, Washington, DC MARY E. WILSON, Harvard School of Public Health, Harvard University, Boston, Massachusetts Staff EILEEN CHOFFNES, Director LEIGHANNE OLSEN, Program Officer KATHERINE McCLURE, Senior Program Associate COLLIN WEINBERGER, Research Associate3 ROBERT GASIOR, Senior Program Assistant4 3 Forum staff member until May 2011. 4 Forum staff member until February 2011. vi

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BOARD ON GLOBAL HEALTH1 Richard Guerrant (Chair), Thomas H. Hunter Professor of International Medicine and Director, Center for Global Health, University of Virginia School of Medicine, Charlottesville Jo Ivey Boufford (IOM Foreign Secretary), President, New York Academy of Medicine, New York Claire V. Broome, Adjunct Professor, Division of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia Jacquelyn C. Campbell, Anna D. Wolf Chair and Professor, Johns Hopkins University School of Nursing, Baltimore, Maryland Thomas J. Coates, Professor, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California Gary Darmstadt,2 Director, Family Health Division, Global Health Program, Bill & Melinda Gates Foundation, Seattle, Washington Valentin Fuster, Director, Wiener Cardiovascular Institute and Kravis Cardiovascular Health Center, and Professor, Cardiology, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York James Hospedales,3 Coordinator, Chronic Disease Project, Health Surveillance and Disease Management Area, Pan American Health Organization/World Health Organization, Washington, DC Peter J. Hotez, Professor and Chair, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC Clarion Johnson,3 Global Medical Director, Medicine and Occupational Medicine Department, Exxon Mobil, Fairfax, Virginia Fitzhugh Mullan, Professor, Department of Health Policy, George Washington University, Washington, DC Guy H. Palmer,3 Regents Professor of Pathology and Infectious Diseases and Director of the School for Global Animal Health, Washington State University, Pullman Jennifer Prah Ruger,3 Associate Professor, Division of Health Policy and Administration, Yale University School of Public Health and Yale University School of Medicine, New Haven, Connecticut Staff Patrick Kelley, Director Angela Mensah, Program Associate 1 Institute of Medicine boards do not review or approve individual workshop summaries and are not asked to endorse conclusions and recommendations. The responsibility for the content of the workshop summary rests with the authors and the institution. 2 Board member since December 2010. 3 Board member since September 2010. vii

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Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures ap - proved by the National Research Council’s Report Review Committee. The pur- pose 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 manu - script remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this report: Enriqueta Bond, Consultant Richard L. Guerrant, Division of Infectious Diseases and International Health, School of Medicine, University of Virginia Carole A. Heilman, National Institute of Allergy and Infectious Diseases, National Institutes of Health David Heymann, Health Protection Agency Regina Rabinovich, Infectious Disease and Global Health Program, Bill & Melinda Gates Foundation Although the reviewers listed above have provided many constructive com- ments 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 Dr. Melvin Worth. 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. ix

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Acknowledgments 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 govern- ment, academia, and industry to regularly meet and examine issues of shared concern regarding research, prevention, detection, and management of emerg - ing, reemerging, and novel infectious diseases in humans, plants, and animals. 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. 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 the planning and execution of this workshop. A full list of presenters, and their biographical information, may be found in Appendixes B and F, respectively. We would also like to express our deepest appreciation and gratitude to those that helped to identify or provided images illustrating the diseases of interest found in Text Box WO-6, including Doris Bravo (National Veterinary Services xi

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Tables, Figures, and Boxes TABLES WO-1 High-Prevalence and Other Vector-Borne Neglected Tropical Diseases, 8 WO-2 Environmental Classification of Water- and Excreta-related Infections,10 WO-3 Four NTDs Slated for Eradication or “Elimination,” 28 WO-4 Laboratory-Confirmed Dengue Fever in Study Sites Compared to Reported National Incidence, 42 A1-1 Evolution of Change in Epidemiological Parameters of Chagas Disease in LAC, 118 A1-2 Diseases, Foci, Population at Risk, and Treatment Coverage in Group 1 Countries, 124 A1-3 Diseases, Foci, Population at Risk, and Treatment Coverage in Group 2 Countries, 125 A1-4 Pre-SAC and SAC Population at Risk for Soil-Transmitted Helminths (STHs) in LAC, 2009, 126 A2-1 Studies in Conflict and Neglected Tropical Diseases Since 2007, 136 A2-2 Summary of Six Space-Time Clusters of Sleeping Sickness Incidence, Africa 1976–2004, 143 xvii

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xviii TABLES, FIGURES, AND BOXES A3-1 Zero-order correlations among average national IQ (LVE), log DALY owing to infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education, and GDP, 162 A3-2 Zero-order correlations between average national intelligence and log DALY owing to infectious disease within each of Murdock’s (1949) six world regions, 162 A3-3 Multiple regression analyses predicting average national intelligence using LVE and WEAM (in parentheses where different) by log DALY owing to infectious disease, log distance from EEA, average winter high temperature, average years of education (AVED), and log GDP, 163 A3-S-1 Zero-order correlations among average National IQ (LVCD), log DALY infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education, and GDP, 170 A3-S-2 Zero-order correlations among average National (WEAM), log DALY infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education, and GDP, 171 A3-S-3 Multiple regression analyses predicting average national intelligence using LVE and WEAM (in parentheses when different) by log DALY infectious disease, log distance from EEA, average winter high temperature, and average years of education (AVED), 172 A5-1 Disease-Specific Guidelines, 187 A5-2 Principal Drug Distribution Strategy in Endemic Districts, 190 A5-3 WHO Guidelines for Disease-Specific Mapping, 193 A5-4 Mapping of Districts in NTD Control Program Countries, 194 A5-5 NTD Control Program-Supported Treatments, 197 A5-6 Number of Tablets of Donated Drugs Provided to National NTD Programs in Year 3 of the NTD Control Program, 198 A5-7 Programmatic Coverage in NTD Control Program Countries, 199 A6-1 Current Situation of Ocular Morbidity and Transmission of Onchocerciasis Within the Americas Region, 2010, 213 A6-2 Four NTDs Slated for Eradication or “Elimination,” 219

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xix TABLES, FIGURES, AND BOXES A7-1 The Neglected Tropical Diseases, 223 A7-2 On the Outside Looking In: NTDs of Global Importance Not Typically Found on Lists of Diseases, 225 A7-3 Neglected Infections Amid Wealth: Major Neglected Infections of Poverty in the United States and Europe, 226 A7-4 The Seven Major NTDs Targeted for Integrated Control and Elimination with “Rapid Impact Packages,” 230 A8-1 Selected U.S. Census Bureau 2006 Poverty Data, 239 A8-2 Estimated Prevalence of Neglected Infections of Poverty in the US, 242 A8-3 Priority Needs for Enhanced Surveillance, Treatment, and Prevention Efforts for the High Priority Neglected Infections of Poverty, 256 A9-1 Impact of hookworm, schistosomiasis, HIV/AIDS, and malaria, 266 A9-2 Successful vaccines against helminth infections, 275 A9-3 Ranking of Lead Candidate Necator americanus Vaccine Antigens, 277 A9-4 Ranking of Lead Candidate Schistosoma mansoni Vaccine Antigens, 282 A10-1 Summary of the Bill & Melinda Gates Foundation Strategy Refresh Process, 298 A10-2 Summary of Bill & Melinda Gates Foundation Investments in NOIDs Through 2010, 304 A14-1 Tests Commonly Used by NTD Programs, 349 A15-1 MDA and Pregnancy, 372 A15-2 Selected NTDs and Children’s Health and Development, 373 A16-1 Neglected Disease R&D Funding 2008, 391 A16-2 NTD R&D Funding 2008, 392 A16-3 Top 12 Funders of R&D for NTDs, 2008, 392 A17-1 Population at Risk, 417 A17-2 Projected Health Impact-LF Related, 418 A17-3 Projected Health Impact-Beyond LF, 419 A18-1 Sub Populations of the “Benefit Cohort Population,” 444 A18-2 Benefit Cohort Population: Individuals and Person Years, 450

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xx TABLES, FIGURES, AND BOXES A18-3 Epidemiological and Cost Estimates Used in the Economic Benefit Model, 452 A18-4 GPELF MDA Treatments (2000–2007), 458 A18-5 Total Costs Prevented Over Lifetime of Benefit Cohort Population, 460 A18-6 Total Costs Prevented per Individual in the Benefit Cohort Population, 461 A18-7 Lifetime Economic Benefits per Region, 463 A18-8 Health System Economic Benefits, 463 A18-9 Sensitivity Analysis for Chronic Disease Reversal Following MDA, 465 A18-10 Country-Specific Benefit-Cost Ratios, 468 A19-1 Main Steps for the Development of Scientific Knowledge for NTD Control, 483 A19-2 Steps for the Promotion of Implementation of NTD Control, 484 A19-3 Steps for the Building of Consensus Among Partners and Donors, 485 A20-1 Trends in Journal Articles Incorporating Terms Related to “Neglected Disease,” 1998–2009, 492 A20-2 Trends in Journal Articles Incorporating Terms Related to “Determinants of Health,” 1998–2009, 494 A20-3 Journal Articles Using Terms from Both Paradigms, 1998–2009, 495 A20-4 Inclusion of Drug or Vaccine Mention in Literature on Neglected Diseases, 1998–2009, 496 A20-5 Inclusion of Terms in Journal Articles on Trachoma, 1998–2009, 497 FIGURES WO-1 Geographical overlap and distribution of the seven most common neglected tropical diseases, 5 WO-2 Depiction of the classical model of the Triangular trade, 7 WO-3 The convergence model, 12 WO-4 WHO list of neglected tropical diseases, 18 WO-5 Life cycle for dracunculiasis, 20 WO-6 Geographic distribution and transmission status of the 13 onchocerciasis foci of the Americas (2010), 23 WO-7 Onchocerciasis control programs in Africa, 24 WO-8 Life cycle of schistosomiasis, 32 WO-9 Dengue virus infection, 41

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xxi TABLES, FIGURES, AND BOXES WO-10 Distribution of NTDs in Africa and countries with integrated NTD control programs in sub-Saharan Africa, 51 WO-11 Endemic zoonotic diseases by district in Mali, 55 WO-12 Classification of NIDs and other poverty-related infections, 57 WO-13 Group I: elimination targets, 58 WO-14 Diseases targeted for drastic disease burden reductions, 59 WO-15 Global funding for NTDs by disease, 78 WO-16 Top 12 funders of NTD research, 2008 (US$), 79 WO-17 Opportunities for “vaccine diplomacy,” 85 WO-6-1 Anthrax, 86 WO-6-2 Ascariasis, 87 WO-6-3 Bovine tuberculosis, 88 WO-6-4 Brucellosis, 89 WO-6-5 Buruli ulcer (Mycobacterium ulcerans), 90 WO-6-6 Chagas disease, 91 WO-6-7 Hydatid disease, 92 WO-6-8 Cysticercosis, 93 WO-6-9 Dengue, 94 WO-6-10 Guinea worm (Dracunculus medinensis), 95 WO-6-11 Hookworm (Nematode Ancylostoma caninum), 96 WO-6-12 Leishmaniasis (Leishmania), 97 WO-6-13 Leprosy (Mycobacterium leprae), 98 WO-6-14 Lymphatic filariasis, 99 WO-6-15 Onchocerciasis, 10 WO-6-16 Rabies, 101 WO-6-17 Schistosomiasis, 102 WO-6-18 Parasitic roundworm associated with Toxocariasis (larvae), 103 WO-6-19 Trachoma, 104 WO-6-20 Trichuriasis (Whipworm), 105 WO-6-21 Human African Trypanosomiasis (Trypanosoma brucei), 106 WO-6-22 Yaws infection (Treponema pertenue), 107 A1-1 Overlapping of six neglected infectious diseases, 127 A1-2 Elimination and control of NIDs in LAC: Putting the pieces together, 129 A2-1 Search protocol and results, 134 A2-2 Conceptual framework for effect of conflict on NTDs, 142 A2-3 Map of the distribution of sleeping sickness incidence, Africa 1976–2004, 143 A2-4 Malaria in Timor Leste, 2004–2007, 149

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xxii TABLES, FIGURES, AND BOXES A3-1 Log DALY owing to infectious disease and average national IQ correlate (a) at r = -0.82 (LVE) and (b) at r = -0.76 (WEAM; n = 184, p < 0.0001), 161 A5-1 A. Persons reached (dark bars) and treatments provided (light bars) during each of the first three years of the Neglected Tropical Disease (NTD) Control Program. B. Cumulative totals of persons reached (dark line) and treatments provided (light line) over the first three years of the NTD Control Program, 196 A5-2 Number of districts covered by mass drug administration (MDA) treatment during the first three years of the Neglected Tropical Disease (NTD) Control Program in the seven implementing countries (an aggregated total of 526 districts in these countries), 200 A5-3 Number of workers in training programs supported by the Neglected Tropical Disease Control Program, 201 A5-4 Distribution of expenditures by the Neglected Tropical Disease Control Program during its first three years, 202 A6-1 Number of reported cases of dracunculiasis by year: 1989–2009, 211 A6-2 Geographic distribution of malaria and lymphatic filariasis on the island of Hispaniola in 2006, 216 A6-3 Prevalence of Trachomatus inflammation-follicular (TF) in children 1–9 years of age in Ghana and Ethiopia, 2007–2008, 218 A8-1 Location of counties that represent spatial clusters in which poverty rates are at least two standard deviations higher than the national mean, 240 A9-1 Global distributions and life cycles of hookworms and schistosomes, 268 A9-2 Necator americanus degradation of host blood components and potential vaccine targets, 276 A9-3 Schistosoma mansoni tegument, 283 A10-1 BMGF NOIDs investment by disease through 2010 with payments through 2014, 295 A10-2 BMGF NOIDs commitments by tool and strategic approach through 2010, 296 A10-3 Overview of drug donation for the NTDs, 299 A10-4 Research and development investments for NOIDs globally, 2009, 301

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xxiii TABLES, FIGURES, AND BOXES A11-1 Drug rate use for the treatment of second-stage T.b. gambiense: eflornithine versus melarsoprol (2003–2009), 314 A11-2 Institutional rate use of eflornithine: National Sleeping Sickness Control Programs versus nongovernmental organizations (2003–2009), 314 A11-3 Classification of human African trypanosomiasis-endemic countries according to cases reported in 2009, 317 A11-4 Evolution of reported cases of both forms of human African trypanosomiasis (1998–2009), 318 A11-5 Atlas of human African trypanosomiasis, 319 A12-1 Life cycle of Schistosoma spp. parasites, 324 A12-2 Disability-related health outcomes included in meta-analysis of schistosomiasis-related health impact, 330 A12-3 Reduced protective antibody response to anti-Haemophilus influenza b vaccination among children of mothers with schistosomiasis and/or filariasis during pregnancy, 332 A12-4 New estimates of schistosomiasis cases in 1995 and in 2005 according to the Global Burden of Disease Program’s world regions, 334 A12-5 Projected impact of different antischistosomal treatment strategies for S. haematobium, in which dipstick screening for hematuria may be used (as a proxy) to detect active infection, 337 A12-6 How long to treat: Without some modification of the local ecological factors that favor Schistosoma transmission (sewage contamination, snail habitat, and local surface water use) there is a tendency for local levels of schistosomiasis to recur within 10 to 15 years of stopping a drug treatment campaign, 338 A14-1 A generalized NTD program life cycle is presented schematically in this figure, 349 A14-2 Age-specific prevalence of Wuchereria bancrofti microfilaremia, antigenemia, and antifilarial antibody reactivity, 351 A15-1 Young woman with infant daughter in Papau Province, Indonesia, seeks medical care, 357 A15-2 The Eight Millennium Development Goals (MDGs), 358 A15-3 The convergence model, 360 A15-4 Global distribution of NTDs, 365 A15-5 Child swarmed with flies, which cause infection leading to trachoma, 367 A15-6 Women walking in river, South Asia, 368

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xxiv TABLES, FIGURES, AND BOXES A15-7 To address NTDs, the cycle of poverty must be broken, 377 A15-8 Women are key to NTD prevention efforts, 378 A16-1 Top country funders of NTD R&D, 2008, 393 A16-2 Share of NTD funding by disease, 2008, 394 A16-3 Top 12 funders of kinetoplastid R&D, 2008, 395 A16-4 Kinetoplastid investment by research area for each disease, 2008, 398 A16-5 Top 12 funders of dengue R&D, 2008, 400 A16-6 Dengue funding by product area, 2008, 402 A16-7 Top 12 funders of helminth R&D, 2008, 403 A16-8 Helminth funding by product area, 2008, 405 A16-9 Top 12 funders of leprosy R&D, 2008, 407 A16-10 Leprosy funding by product area, 2008, 409 A16-11 Top 12 funders of trachoma R&D, 2008, 410 A16-12 Trachoma funding by product area, 2008, 411 A16-13 Buruli ulcer funding by product area, 2008, 411 A16-14 Top 12 funders of Buruli ulcer R&D, 2008, 412 A16-15 Assessing health return on investment, 413 A17-1 Cumulative treatments in GPELF, 424 A17-2 Cumulative totals of donated drugs (Panel A), albendazole and invermectin (Mectizan), and purchased drug (Panel B) DEC, used in GPELF between 2000 and 2007, 425 A17-3 Effect of MDA on microfilaremia prevalence, 426 A17-4 Clearance of microfilaremia from each sentinel site (approximately 500 persons per site) reporting to the Global Programme after 5 rounds of MDA treatment (n = 68), 427 A18-1 General formula for calculating economic benefits, 448 A18-2 Duration of economic benefits, 449 A18-3 Total economic benefits by category, 461 A18-4 Cumulative economic benefits resulting from the first 8 years of the GPELF, 464 A18-5 Potential economic impact of the GPELF, 476 A20-1 Concurrent growth in “neglected disease” and “determinants of health” discourse 1998–2009, 495 A20-2 Overview of points of intervention to address disease and improve health security, 498

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xxv TABLES, FIGURES, AND BOXES A21-1 Amastigotes of T. cruzi within host cells, 513 A21-2 A setting of active transmission in the Gran Chaco region and the pyrethroid-resistant Triatoma infestans collected from the structure, 516 BOXES WO-1 Ancient Scourges, New Names, 6 WO-2 Definitions of Elimination, Eradication, and Control, 19 WO-3 NTDs Targeted by WHO for Elimination or Eradication, 20 WO-4 Cumulative Burdens of the NZDs, 50 WO-5 Common Features of Integrated Control Programs for Overlapping NTDs and NZDs, Malaria, and Other Infectious Diseases of Poverty, 52 WO-6 Key Neglected Diseases of Poverty, 86 A2-1 The Impact of Conflict on Neglected Diseases, 141 A9-1 Immune Evasion and Regulation of Helminth Infections, 267 A14-1 World Health Assembly Resolutions Targeting NTDs, 347 A17-1 The Global Programme to Eliminate LF—Its First 8 Years, 430 A19-1 NTDs and Their Common Features, 482

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