Immune responses, and in particular the cytokine response of CD4+ and CD8+ T cells, to T. cruzi correlates inversely with the presence of severe disease during chronic T. cruzi infection. This hypothesis is supported by numerous studies in experimental animals and by our previous work showing that individuals in the G0 and G1 clinical groups have range of T. cruzi-specific T cell responses while those in the G3 group are almost very low responders. We propose a longitudinal study that will follow individuals who initially exhibit no signs of disease and evaluate the progression of the disease symptoms in correlation with their anti-parasite cellular immune responses over the 5-year project period. In addition, we will observe both untreatedand drug-treated patients for evidence of cure. These patients will be evaluated to determine if cure associates with the qualitative and quantitative characteristics of the anti T. cruzi T cell response prior to cure and if the success of treatment to induce cure is associated with the anti-parasite response prior to or after treatment. Collection of these data will provide insights into the strength of the association between cellular immuninty, parasite load and disease development, determine the changes, if any, in cellular immune responses and parasite load over a five year follow-up period, and significantly expand our knowledge of cellular immune responses in chronic chagasic patients. Completion of these studies will also provide valuable information on the relationship between cellular immune responses and cure in human patients and on the immunological consequences of drug treatment. These data will be useful for assessing what constitutes an effective immune response in T. cruzi infection, therebyguiding our vaccine development program and providing insight into how to most effectively treatchronically infected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI044979-06
Application #
6834820
Study Section
Special Emphasis Panel (ZAI1-AWA-M (M1))
Project Start
2004-09-01
Project End
2009-02-28
Budget Start
2004-09-01
Budget End
2005-02-28
Support Year
6
Fiscal Year
2004
Total Cost
$154,677
Indirect Cost
Name
University of Georgia
Department
Type
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
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Bustamante, Juan M; Tarleton, Rick L (2014) Potential new clinical therapies for Chagas disease. Expert Rev Clin Pharmacol 7:317-25
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Perez-Mazliah, D E; Alvarez, M G; Cooley, G et al. (2013) Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study. J Antimicrob Chemother 68:424-37
Argüello, Rafael J; Albareda, María C; Alvarez, María G et al. (2012) Inhibitory receptors are expressed by Trypanosoma cruzi-specific effector T cells and in hearts of subjects with chronic Chagas disease. PLoS One 7:e35966
Minning, Todd A; Weatherly, D Brent; Flibotte, Stephane et al. (2011) Widespread, focal copy number variations (CNV) and whole chromosome aneuploidies in Trypanosoma cruzi strains revealed by array comparative genomic hybridization. BMC Genomics 12:139

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