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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 l.jpg

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


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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


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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


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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


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The Gorgas Memorial Laboratory, 1928-1968Types of Research

  • Core activities

    - Epidemiology

    - Treatment

    - Control

    - Laboratory work in support of field activities


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The Gorgas Memorial Laboratory, 1928-1968Types of Research (2)

  • Major themes

    - Malaria

    - Yellow fever

    - Other arboviral infections

    - Chagas disease

    - Leishmaniasis

    - Equine trypanasomiasis

    - Residual insecticides


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The Gorgas Memorial Laboratory, 1928-1968Types of Research (3)

- Helminithic and protozoal infections

- Diarrheal diseases

- Reservoir hosts

- Immunology

- Other: herpetology, insect genetics (Drosophila)


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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)


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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)


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How Research Projects Chosen

Incidence, prevalence, epidemics

Available staff

Outside scientific collaboration

Resources

Serendipity


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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


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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


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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


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Chagas Disease (2)

  • Studies in Santo Tomás Hospital

  • Arrythmias (RBBB, LBBB, A/V block)

  • Ventricular and atrial enlargement

  • Ventricular aneurysms

  • Treatment

  • 8 aminoquinolines


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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)


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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


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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


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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


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  • 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


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Papers Published by the Gorgas Memorial Laboratory, 1930-1969

* 1943-1945 = 12 papers


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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


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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


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


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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


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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


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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


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Fogarty International CenterScience for Global Health

Mission:To promote and support research and training internationally to reduce disparities in global health


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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


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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)


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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


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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


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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


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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


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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


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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


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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


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Fogarty International CenterOn the Horizon

  • Brain Disorders in the Developing World

  • Trauma and Injury

  • Health, Environment, and Economic Development


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Navigating Your Way


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


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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.


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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


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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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