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Title: Tropical Diseases Research in Panama: Historical Perspectives and Current Opportunities


1
Tropical Diseases Research in PanamaHistorical
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
  • 67 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, 1928-1968
Types 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, 1928-1968
Types 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 (cont)
  • 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)
Surveys, 1967 Number Pos
Blood bank 6,253 2.0
Outpatients 1,294 11.4
Surveys 399 12.5
  • 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
Papers Mean
1930-1934 69 14
1935-1939 114 23
1940-1944 58 12
1945-1949 61 12
1950-1954 69 14
1954-1959 53 11
1960-1964 77 15
1965-1969 130 26
1930-1969 630 16
1943-1945 12 papers
21
Major Topics in Publications by the Gorgas
Memorial Laboratory, 1930-1969
  • 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

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. Hansens 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
MissionTo promote and support research and
training internationally to reduce disparities in
global health
28
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
Sustainability in FIC Programs
Principles
  • Commitment National Institutional
    Trainee
  • Re-entry grants for trainees
  • Diversified program themes
  • Contribution of resources from all partners

36
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 and Efficacy of
Interventions
High
High
Training
Efficacy of Control Methods
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
42
Research, Training and Support Needs According
to Understanding of Diseases and Efficacy of
Interventions
High
High
Training
Efficacy of Control Methods
DengueMalaria HIV/AIDSTuberculosisEbola/Marburg
InfluenzaCancersAlzheimers
SmallpoxGuinea wormPoliomyelitisH. influenzae
type BMeaslesTetanus
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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