We propose to develop further our present studies with scientists in Brazil on leishmaniasis, schistosomias, malaria and Chagas' disease. These are approached by a number of disciplines including immunology, molecular biology, biochemistry, pathology, entomology, malacology, epidemiology, and clinical medicine. Our long-term goal is to develop effective vaccines or to delineate other avenues to control these diseases. Studies on LEISHMANIASIS in Manaus, Belem, and Bahia include: the evaluation of a new diagnostic test we have developed using kinetoplast DNA hybridization for rapid identification of Leishmania species on a touch blot of cutaneous lesions; developing a rapid test for identifying Leishmania in lesions using species and subspecies specific monoclonal antibodies; obtaining purified species specific antigens with those antibodies to develop serologic and skin tests; evaluating the use of monoclonal antibodies to detect Leishmania in sandflies; and studying possible defects in the immune regulation of diffuse and mucocutaneous leishmaniasis. Studies on SCHISTOSOMIASIS in Bahia include: extending our previous studies on a factor produced by normal monocytes which enhances the killing of schistosomula by eosinophils, but which is not produced by cells from patients with schistosomiasis; evaluate the IgE-basophil system in these patients; produce human monoclonal antibodies to S. mansoni with peripheral lymphocytes from patients; analyze the S. mansoni antigens in kidney lesions with these antibodies, and, in Sergipe, evaluate the role of B. straminea in transmission of S. mansoni and analyze snail lectins that may play a part in the defense mechanisms of the snail. Studies on MALARIA in Manaus include: studies to determine the extent of the diversity of P. falciparum by surface immunofluorescence of infected rbc; developing a rapid diagnostic assay for the field using ELISA and monoclonal antibodies; applying methods of molecular biology to the rapid diagnosis of malaria and the cloning of enzymes which may be important in drug resistance, studying immunosuppression in patients with malaria and investigating the tropical splenomegaly syndrome. Studies on CHAGAS' disease are concerned with developing the model of chronic Chagasic myocarditis in dogs designed in part as a model to evaluate chemotherapy and the safety and efficacy of potential vaccine preparations of T. cruzi.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI016305-09
Application #
3091488
Study Section
Microbiology and Infectious Diseases Research Committee (MID)
Project Start
1979-09-30
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Rogers, W O; Wirth, D F (1988) Generation of sequence diversity in the kinetoplast DNA minicircles of Leishmania mexicana amazonensis. Mol Biochem Parasitol 30:1-8
Rogers, W O; Burnheim, P F; Wirth, D F (1988) Detection of Leishmania within sand flies by kinetoplast DNA hybridization. Am J Trop Med Hyg 39:434-9
Rogers, W O; Wirth, D F (1987) Kinetoplast DNA minicircles: regions of extensive sequence divergence. Proc Natl Acad Sci U S A 84:565-9
Barker Jr, R H; Suebsaeng, L; Rooney, W et al. (1986) Specific DNA probe for the diagnosis of Plasmodium falciparum malaria. Science 231:1434-6