This project will examine the pathogenesis of L. braziliensis infection in affected patients and the hamster experimental model. The experiments are based on observations on disease expression in previous longitudinal studies in humans and experimentally infected hamsters. The potential role of immunologically mediated responses to outcome of L. braziliensis infection in patients whose clinical phenotype is analogous to the healer and non-healer phenotypes defined in experimental systems using inbred mice infected with L. major and L. donovani will be analyzed by three approaches: 1. the lymphocytes expanded and antibodies produced in individuals who have experienced inapparent or rapidly self-healing infection and those who have had chronic, or recurrent disease will be utilized to, a) identify the corresponding antigens in two dimensional (2- D) molecular profiles, and b) to determine the lymphokine mediator repertoires elicited in vitro; 2. biopsies of Montenegro reaction sites and in some cases active lesions of these same patient groups will be characterized with respect to the in situ response to L. braziliensis antigen, and lymphocytes will be cultured and expanded from these tissues to probe 2-D molecular profiles; 3. IgE and atopy will be evaluated in patients with mucosal and cutaneous disease and matched controls as a possible marker or risk factor for mucosal involvement. In parallel with the studies in humans, the effects of distinctive hypersensitivity responses and biological and chemical modulators of these responses will be tested in the hamster model of L. braziliensis infection. Metastasis has been found to be a reproducible behavior and will be exploited as a biological index of pathogenesis. Latent persistence of Leishmania after healing of lesions has been achieved either spontaneously of chemotherapeutically, will also be evaluated in this model. Quantitative methods will be utilized to assess the dissemination of parasites within lesions, lymphoid organs and apparently unaffected skin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center (P50)
Project #
1P50AI030603-01
Application #
3804048
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Valle
Department
Type
DUNS #
City
Cali
State
Country
Colombia
Zip Code
Guarin, Nora; Palma, Gloria I; Pirmez, Claude et al. (2006) Comparative immunohistological analysis of the Montenegro skin test reaction in asymptomatic infection and in acute and chronic cutaneous leishmaniasis. Biomedica 26 Suppl 1:38-48
Travi, Bruno L; Tabares, Carlos Javier; Cadena, Horacio (2006) Leishmania (Viannia) braziliensis infection in two Colombian dogs: a note on infectivity for sand flies and response to treatment. Biomedica 26 Suppl 1:249-53
Rojas, Carlos A; Weigle, Kristen A; Barrera, Lena et al. (2002) Surveillance and screening of American cutaneous leishmaniasis by Colombian primary health care workers using a clinical prediction rule. Trans R Soc Trop Med Hyg 96:405-10
Weigle, Kristen A; Labrada, Luz Angela; Lozano, Caterin et al. (2002) PCR-based diagnosis of acute and chronic cutaneous leishmaniasis caused by Leishmania (Viannia). J Clin Microbiol 40:601-6
Saravia, Nancy Gore; Weigle, Kristen; Navas, Claudia et al. (2002) Heterogeneity, geographic distribution, and pathogenicity of serodemes of Leishmania viannia in Colombia. Am J Trop Med Hyg 66:738-44
Martinez, J E; Valderrama, L; Gama, V et al. (2000) Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster. J Parasitol 86:792-9
Montoya-Lerma, J; Cadena, H; Segura, I et al. (1999) Association of Lutzomyia columbiana (Diptera: Psychodidae) with a leishmaniasis focus in Colombia due to species of the Leishmania mexicana complex. Mem Inst Oswaldo Cruz 94:277-83
Fernandes, O; Catanho, M P; Segura, I et al. (1999) Minicircle variable region probes for characterization of Leishmania (Viannia) species. J Parasitol 85:563-8
Travi, B; Osorio, Y (1998) Failure of albendazole as an alternative treatment of cutaneous leishmaniasis in the hamster model. Mem Inst Oswaldo Cruz 93:515
Bosque, F; Milon, G; Valderrama, L et al. (1998) Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis. J Parasitol 84:1250-6

Showing the most recent 10 out of 34 publications