Transcript Tropical Disease 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)
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Founded by Dr. Belisario Porras, President, Republic of
Panama
- Land
- Building
- U.S. Congress support
1934 – 1943 (scientific expertise)
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Staffing
- Protozologist (C.M. Johnson)
- Helminthologist (A.O. Foster)
- Entomologist (C.E. Rozeboom)
1943 – 1949 (scientific priorities)
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Insect repellents, insecticides
- U.S. Army Corps of Engineers
The Gorgas Memorial Laboratory,
1928-1968 (2)
1949 – 1956 (public health priorities)
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Yellow Fever (Santo Tomás, Hospital)
Yellow Fever Service of Panama
1956 – 1960 (resource increase)
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$150,000 from U.S. Congress (tripled budget)
NIAID grant, leishmanasis
1960 – 1968 (resource increase)
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$500,000 from U.S. Congress for infrastructure
Insectary
Grants and gifts
The Gorgas Memorial Laboratory, 1928-1968
Types of Research
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Core activities
- Epidemiology
- Treatment
- Control
- Laboratory work in support of field
activities
The Gorgas Memorial Laboratory, 1928-1968
Types of Research (2)
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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
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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)
 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,
-Available
-Outside
prevalence, epidemics
staff
scientific collaboration
-Resources
-Serendipity
Major Achievements
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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)
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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
American Trypanasomiasis (T. cruzi)
Chagas Disease, began 1931
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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)
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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, 1960s)
Leishmaniasis, 1944
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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
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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
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Q fever, first report in Panama, 1946
Murine typhus, first report, 1947
RMSF, first report, 1951
Viruses
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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
Papers Published by the Gorgas Memorial
Laboratory, 1930-1969
1930-1934
1935-1939
1940-1944*
1945-1949*
Papers
69
Mean
114
58
61
14
23
12
12
1950-1954
1954-1959
1960-1964
69
53
77
14
11
15
1965-1969
130
26
1930-1969
630
16
* 1943-1945 = 12 papers
Major Topics in Publications by the Gorgas
Memorial Laboratory, 1930-1969
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Malaria, 60 papers 
Birds, 54
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Culicidae, 51
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Phlebotomus, 49
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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
 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
“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
 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
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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)
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National Institute on Deafness and Other
Communicable Disorders, 1997-2002
- Neural basis of complex-sound processing
- National de Recursos Naturales Renovables
and Washington University
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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
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

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)
Fogarty International Center
Training Grants for Developing Countries
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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

A systematic approach

Individual and Institutional
Partnerships

Stability and Long-term
Commitment

Long-term mentoring

Advanced In-country
Research (re-entry grants)
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Empowerment and mutual
respect

Networking

Flexibility

Leverage

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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 researchcapacity building for scientists from
developing nations
Sustainability in FIC Programs
Principles
Commitment
* National
* Institutional
* Trainee
 Re-entry grants for trainees
 Diversified program themes
 Contribution of resources from all
partners
Fogarty

International
Center
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

Fogarty
International
Center
Fogarty International Center
On the Horizon
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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
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