Tropical Diseases Research in Panama Historical Perspectives and

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

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

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

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

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

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

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

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)

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

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

Major Achievements n 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

Malaria (con’t) n n n 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 1960 s

American Trypanasomiasis (T. cruzi) Chagas Disease, began 1931 n n n n Diagnosis Prevalence Manifestations Treatment Epidemiology Hosts Vectors and ecology 3. 8 % positive of 1, 251 tested by CF test, 1963 40, 000 cases, 1966

Chagas Disease (2) Surveys, 1967 Number % Pos Blood bank 6, 253 2. 0 Outpatients 1, 294 11. 4 399 12. 5 Surveys • Studies in Santo Tomás Hospital Arrythmias (RBBB, LBBB, A/V block) Ventricular and atrial enlargement Ventricular aneurysms • Treatment 8 aminoquinolines

Chagas Disease (3) n n 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 (nonpathogenic, 1960 s)

Leishmaniasis, 1944 n n 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

Helminths, 1930 n n n n 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, jaguarundi, agouti Trichinella spiralis; EEE, Ilhéus virus, Jap B encephelitis, ended fatally in animals

n n Rickettsial u u u Rickettsial and Viral Diseases Q fever, first report in Panama, 1946 Murine typhus, first report, 1947 RMSF, first report, 1951 Viruses u u u 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

n n 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

Papers Published by the Gorgas Memorial Laboratory, 1930 -1969 1930 -1934 1935 -1939 1940 -1944* Papers 69 1945 -1949* 1950 -1954 -1959 1960 -1964 1965 -1969 1930 -1969 * 1943 -1945 = 12 papers 114 58 61 69 53 77 130 630 Mean 14 23 12 12 14 11 15 26 16

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

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

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

Recent National Institutes of Health and Government of Panama Collaborations n 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 n National Institute on Drug Abuse, 1997 -1999 - Drug involvement among Latin Americans, Departamento de Farmacodependencias and Johns Hopkins University

Recent National Institutes of Health and Government of Panama Collaborations (2) n National Institute on Deafness and Other Communicable Disorders, 1997 -2002 - Neural basis of complex-sound processing - National de Recursos Naturales Renovables and Washington University n 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

n 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

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

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

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

Fogarty International Center Training Grants for Developing Countries l l l 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

Fogarty International Center Support 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

Fogarty International Center Research 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

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

Fogarty International Center Extramural 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

Sustainability in FIC Programs Principles n Commitment * National * Institutional * Trainee n Re-entry grants for trainees n Diversified program themes n Contribution of resources from all partners Fogarty International Center

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

Fogarty International Center On the Horizon n Brain Disorders in the Developing World Trauma and Injury Health, Environment, and Economic Development

Navigating Your Way

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

Fogarty International Center Science 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.

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

Research, Training and Support Needs According to Understanding of Diseases and Efficacy of Interventions High Efficacy of Control Methods Low High Training Dengue Malaria Research HIV/AIDS Needs Tuberculosis Ebola/Marbur g Influenza Cancers Alzheimer’s Smallpox Guinea worm Poliomyelitis H. influenzae type B Measles Tetanus Some Moderate Research Support Needs High Low