Tropical Diseases Research in Panama: Historical Perspectives and Current Opportunities

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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

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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, 1928-1968
Types 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, 1928-1968
Types 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 (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

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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)
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

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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
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
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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

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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. 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

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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
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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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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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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 and Efficacy of
Interventions
High
High
Training
Efficacy of Control Methods
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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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