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Tropical Diseases Research in Panama: Historical Perspectives and Current Opportunities

Tropical Diseases Research in Panama: Historical Perspectives and Current Opportunities. Joel G. Breman, M.D., D.T.P.H. Fogarty International Center National Institutes of Health Bethesda, Maryland, USA

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Tropical Diseases Research in Panama: Historical Perspectives and Current Opportunities

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  1. Tropical Diseases Research in Panama:Historical Perspectives and Current Opportunities Joel G. Breman, M.D., D.T.P.H. Fogarty International Center National Institutes of Health Bethesda, Maryland, USA Workshop to Establish the Santiago Center for Geographic Medicine and Emerging Tropical Disease Santiago, Panama 6–7 December 2002

  2. 40 Years of Tropical Medicine Research A History of the Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc. and the Gorgas Memorial Laboratory Willard H. Wright, D.V.M., M.S., Ph.D. Washington, 1970 Reese Press, Baltimore, Maryland

  3. The Gorgas Memorial Laboratory, 1928-1968 Six Epochs 1928 – 1934 (political will) • Founded by Dr. Belisario Porras, President, Republic of Panama - Land - Building - U.S. Congress support 1934 – 1943 (scientific expertise) • Staffing - Protozologist (C.M. Johnson) - Helminthologist (A.O. Foster) - Entomologist (C.E. Rozeboom) 1943 – 1949 (scientific priorities) • Insect repellents, insecticides - U.S. Army Corps of Engineers

  4. The Gorgas Memorial Laboratory, 1928-1968 (2) 1949 – 1956 (public health priorities) • Yellow Fever (Santo Tomás, Hospital) • Yellow Fever Service of Panama 1956 – 1960 (resource increase) • $150,000 from U.S. Congress (tripled budget) • NIAID grant, leishmanasis 1960 – 1968 (resource increase) • $500,000 from U.S. Congress for infrastructure • Insectary • Grants and gifts

  5. The Gorgas Memorial Laboratory, 1928-1968Types of Research • Core activities - Epidemiology - Treatment - Control - Laboratory work in support of field activities

  6. The Gorgas Memorial Laboratory, 1928-1968Types of Research (2) • Major themes - Malaria - Yellow fever - Other arboviral infections - Chagas disease - Leishmaniasis - Equine trypanasomiasis - Residual insecticides

  7. The Gorgas Memorial Laboratory, 1928-1968Types of Research (3) - Helminithic and protozoal infections - Diarrheal diseases - Reservoir hosts - Immunology - Other: herpetology, insect genetics (Drosophila)

  8. Short- and Long-Term Research Trends • Short-term - Equine trypanosomiasis, 1930-1946 (H.S. Eakins), retirement; horses used less • Equine helminthiasis, 1934-1939 (A.O. Foster) • Cattle trypanasomiasis, 1940-1943 (war priorities) • Intestinal helminths, 1930 (intermittent, E.C. Faust) • Tropical climatology, 1941 - Tuberculosis, BCG vaccination, 1949-1951 (taken over by Servicio Cooperativo Interamericano de Salud Publica)

  9. Long Term Projects • Malaria, 1929 (H.C. Clark, C.M. Johnson) • Chagas disease, 1931 (C.M. Johnson) • Leishmaniasis, 1944 (M. Hertig, A. Herrer) • Insect taxonomy, 1929 (D.P. Curry) • Santa Rosa Field Station, 1931 and Chagres River Villages (DDT use)

  10. How Research Projects Chosen Incidence, prevalence, epidemics Available staff Outside scientific collaboration Resources Serendipity

  11. Major Achievements Malaria, began in 1929 • Drug treatment - Quinine studies, 1931 - Atebrin/plasmochin, 1935 - Quinine/plasmochin, 1935 - DDT house spraying, 1945 (continued to 1977) - Chloroquine/paludrine weekly, 1947 Parasite rates dropped 26.5 %  0.7 % (CQ) 34.8 %  1.5% (P) - Pyrimethamine/primaquine + DDT, 1960 (La Repressa and Mendoza villages) eliminated disease after 2 months! Maintained 2 years But 53 cases detected from 1962 - 1964

  12. Malaria (con’t) • Primate malaria - P. brasilianum, attempt transmission to human volunteers, 1930 - Immunity and P. falciparum, 1931 - Human malaria to monkeys, 1966 Aotus trivirgatus and P. vivax, 1967 Aotus (night monkey) Ateles (spider monkey) Saquinus (marmoset) Cebus • Transmission with Anopheles albimanus • DDT resistance detected after 8 years of use, late 1960s

  13. American Trypanasomiasis (T. cruzi)Chagas Disease, began 1931 • Diagnosis • Prevalence • Manifestations • Treatment • Epidemiology • Hosts • Vectors and ecology 3.8 % positive of 1,251 tested by CF test, 1963 40,000 cases, 1966

  14. Chagas Disease (2) • Studies in Santo Tomás Hospital • Arrythmias (RBBB, LBBB, A/V block) • Ventricular and atrial enlargement • Ventricular aneurysms • Treatment • 8 aminoquinolines

  15. Chagas Disease (3) • Parasitology and Ecology - T.cruzi found in 33 animal species; dogs, rats, positive - T. rangeli found to cross-react • Entomology and Ecology - Rhodnius pallescens efficient, but R. prolixus (not native) could not be infected with local isolates. - Other triatomes identified, but R. pallescens found in native houses of 3,203. 32.1% infected with T. cruzi and 4.1% - 8.1% with T. rangeli (non-pathogenic, 1960s)

  16. Leishmaniasis, 1944 • Epidemiology • Treatment • Vectors and ecology • Findings - Forest disease, disappears when forests cleared - Pyrimethamine, 90% cure - Geographic strain differences - Natural infection in wild caught Phlebotomines, infection rate 8.1% - Animal model studies; tried rats, mice, hamsters, kinkajou, olingo, porcupine, marmoset Succeeded with spiny rat

  17. Helminths, 1930 • Ascaris lumbricoides, “common”, 80% prevalence • Necator americanus, “common”, 80% prevalence • Trichuris trichiura, 1.0% - 21.0%, pos. • Strongyloides stercoralis, 20% pos. of 1,663 in Santa Tomás Hospital with 10.5% of those positive having symptoms • Mansonella ozzardi, 9.9% of 244 • Capillaria hepatica in 8% of 194 stools • First report of Echinococcus oligarthrus from fatal case; seen in puma, jaguar, jaguarundi, agouti • Trichinella spiralis; EEE, Ilhéus virus, Jap B encephelitis, ended fatally in animals

  18. Rickettsial and Viral Diseases • Rickettsial • Q fever, first report in Panama, 1946 • Murine typhus, first report, 1947 • RMSF, first report, 1951 • Viruses • Mosquito vectors of yellow fever, first description in Panama and Central America, 1949 • Vector ecology and transmission studies, 1949 • SLE, first recovery and identification of human patients, 1957 • Ilhéus virus, first isolation, 1958 • Changuinola, first isolation, 1960 • New arboviruses discovered, Madrid, Ossa, Patois, Zegla, 1961 • Wyeomia subgroup, first isolated from human, 1963 • Bussuquara, first isolation from human, 1964 • Ilhéus virus, first case of encephalitis, 1964 • SLE found Deinocerites (crab-hole mosquitoes) as host, 1964 • Vesicular Stomatitis Virus, isolation from humans, sentinel monkeys, 1968

  19. Entomology - Dermatobia hominis (human botfly), lifecycle in man, 1929 - An. albimanus, first laboratory colony in Central America, 1935 - DDT for Phlebotomine control, 1944 - DDT for Simulium control, 1945 - DDT for Culicoides sandflies, 1945 - Trombiculidae (chigger mites), habits and ecology, 1945 - Inventory of ticks and biting insects, 1966 • Miscellaneous - Inventory of poisonous snakes and incidence of snake bites, 1930-1954

  20. Papers Published by the Gorgas Memorial Laboratory, 1930-1969 * 1943-1945 = 12 papers

  21. Malaria, 60 papers Birds, 54 Culicidae, 51 Phlebotomus, 49 Tabanidae, 47 Animals, wild, 40 Monkey diseases, 36 Anopheles, 35 Laboratory infection, 35 Yellow fever, 26 Laboratory techniques, 23 Major Topics in Publications by the Gorgas Memorial Laboratory, 1930-1969

  22. Middle America Research Unit, National Institute of Allergy and Infectious Diseases, Canal Zone (1958-1972)* Focus on arthropod virology • Discovery of Machupo virus (Bolivian hemorrhagic fever) - Uncovered biology and ecology of virus, and rodent reservoir leading to building arenavirus family • Venezuelan Equine Encephalitis virus, discovery of antigenic and equine virulence variants; live virus vaccine (TC-83) for lab workers • Vesicular stomatitus virus; first clear demonstration of transovarial transmission of an arbovirus * Provided by Karl M. Johnson, MD, Director, MARU, 1964-1972

  23. “Every advantage in the past is judged in the light of the future issue”Demosthenes

  24. Recent National Institutes of Health and Government of Panama Collaborations • National Cancer Institute, 1993-2001 - Human retroviruses: epidemiological survey at Hospital Santo Tomás and Research Triangle Park Institute - Establishment of cancer information center at Instituto de Nacionale de Oncologie, Managua • National Institute on Drug Abuse, 1997-1999 - Drug involvement among Latin Americans, Departamento de Farmacodependencias and Johns Hopkins University

  25. Recent National Institutes of Health and Government of Panama Collaborations (2) • National Institute on Deafness and Other Communicable Disorders, 1997-2002 - Neural basis of complex-sound processing - National de Recursos Naturales Renovables and Washington University • Pan American Fellowship - PAHO/WHO partners with NIH - One year postdoctoral training in the NIH intramural laboratories - Focus on Caribbean, Central America and Andean countries - Regional public health issues are priority

  26. Recent National Institutes of Health and Government of Panama Collaborations (3) • Fogarty International Center - International Cooperative Biodiversity Group, 1995-1998: Bioprospecting to discover new drugs for malaria and other infectious diseases. Smithsonian Tropical Research Institute, University of Panama, Gorgas Memorial Institute for Health Research, G.W. Hansen’s Disease Center (Louisiana), Walter Reed Army Institute of Research, Nature Foundation of Panama, Novartis, Conservation International - Fogarty International Research Collaborative Awards Bioprospecting in the Panamanian rainforest, 1995-1998 Fundacion Para La Conservacion de Los Recursos and the University of Utah - Studies of Toxoplasma bradyzoite (1999-2002) Gorgas Memorial Institute for Health Research and Stanford University

  27. Fogarty International CenterScience for Global Health Mission:To promote and support research and training internationally to reduce disparities in global health

  28. FogartyInternational Center Research-Policy Interfaces Other ChronicDiseases Nutrition Responsible Medical Reporting International Research Scientist Career Development Maternal & Child Health Tobacco Prevention & Control Strategic Alliances Environment and Ecology Health & Economic Development Biodiversity Environmental & Occupational Health Medical Informatics HIV & Emerging Infectious Diseases Population & Demography Genetics Bioethics Medical Informatics Clinical/Operational Research Build International Research Capacity Create Collaborative International Research Networks Promote FIC In-house Research FUTURE NEW INITIATIVES CURRENT PROGRAMS FOUNDATION PLATFORM — MISSION

  29. Fogarty International CenterDivision of International Training and Research • Extramural Training Grants — 12 Programs • Research Grants — 5 Programs • International Training Grants for U.S. citizens* Minority International Research Training Grant (MIRT)* Scientist Development fellowship (post-doc)* Foreign-funded fellowship (Japan)

  30. Fogarty International CenterTraining Grants for Developing Countries • HIV/AIDS • Building Capacity in Support of ICIDR sites • Emerging Infectious Diseases • Environmental and Occupational Health • FIC-NLM Medical Informatics • Maternal and Child Health • Population and Health • Tuberculosis • Research Bioethics • Malaria • Clinical, Operational, and Health Services Research • Tobacco and Health Research

  31. Fogarty International CenterSupport Available Through Training Grants • Masters and Doctoral Degrees * Tuition, Stipends, Travel, Related Expenses • Post-doctoral Fellowships* Tuition, Stipends, Travel, Related Expenses • Short Courses (in U.S. or In-country)* Tuition, Travel, Per diem • Training-related In-country research grants, Re-entry grants • Limited salary, Administrative support for U.S. university

  32. Fogarty International CenterResearch Grants — 7 Programs • Ecology of Infectious Diseases • Fogarty International Research Collaboration Award • (FIRCA) • HIV-AIDS and Related Illnesses Collaboration Award • (AIDS-FIRCA) • International Cooperative Biodiversity Groups (ICBG) • International Studies on Health and Economic • Development • Proposed Global Health Research Initiative Program • (GRIP) for New Foreign Investigators • International Tobacco and Health Research and Capacity Building Program

  33. Fogarty International CenterProgram Characteristics • Individual and Institutional Partnerships • Long-term mentoring • Advanced In-country Research (re-entry grants) • Empowerment and mutual respect • Networking • Flexibility • Leverage • A systematic approach • Stability and Long-term Commitment • Response to Local Needs and Priorities • Mutual Reinforcement of Investments in Training and Research

  34. Fogarty International CenterExtramural Training Grants • Generally institutional training grant to U.S. universities and non-profit research institutions in response to a specific request for applications (RFA) • Awardees are generally current NIH grant recipients with demonstrated research collaboration with foreign research institutions • Purpose — support training for research-capacity building for scientists from developing nations

  35. Fogarty InternationalCenter Sustainability in FIC Programs Principles • Commitment * National * Institutional * Trainee • Re-entry grants for trainees • Diversified program themes • Contribution of resources from all partners

  36. Fogarty InternationalCenter Sustainability in FIC Programs Principles (continued) • Sustained linkages • Leveraged resources • Dual appointments for faculty • Connectivity via modern IT systems • Centers of excellence in home countries • Mutual benefits known to all

  37. Fogarty International CenterOn the Horizon • Brain Disorders in the Developing World • Trauma and Injury • Health, Environment, and Economic Development

  38. Navigating Your Way

  39. FIC Website: http://www.nih.gov/fic

  40. Fogarty International CenterScience for Global Health Priorities: Emerging infectious diseases, HIV/AIDS, malaria, tuberculosis, arboviral diseases, population, environment, tobacco-related illness, mental health, economics, ecology, genetics, ethics, stigma… Priority areas are driven by disease burden and scientific opportunity. Priorities are set through background work, consultations internally and externally (especially Third World), international conferences, coalition formation, national and international organizations.

  41. Research, Training and Support Needs According to Understanding of Diseases andEfficacy of Interventions High High Training Efficacy of Control Methods Research Needs Low Low Some Moderate High Research Support Needs

  42. Research, Training and Support Needs According to Understanding of Diseases andEfficacy of Interventions High High Training Efficacy of Control Methods DengueMalaria HIV/AIDSTuberculosisEbola/Marburg InfluenzaCancersAlzheimer’s SmallpoxGuinea wormPoliomyelitisH. influenzae type BMeaslesTetanus Research Needs Low Low Some Moderate High Research Support Needs

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