Evaluation of memory T cell responses specific for Trypanosoma cruzi during treatment with benznidazole in chronic Chagas disease patients.

LAUCELLA S; BERTOCCHI G; PEREZ D; COOLEY G; ALVAREZ MG; ARMENTI A; VIOTTI R; ALBAREDA MC; LOCOCO B; POSTAN M; TARLETON RL

Bethesda, USA

Congreso; International research in infectious diseases. Annual Meeting National Institute of Allergy and Infectious Diseases/National Institutes of Health; 2007

The aim of this study was to determine the effect of treatment with benznidazole on memory T cell responses specific for Trypanosoma cruzi. Thirty three, 30-50 year-old subjects with chronic T. cruzi infections with no or mild clinical signs of cardiac disease were recruited for this study. Signed informed consent was obtained from all individuals before inclusion in this protocol. Chemotherapeutic treatment consisted of 5mg benznidazole/kg/day for 30 days. All participants were submitted to serological, clinical and immunological evaluation before treatment (time 0) and at 2, 6, 12 months post-treatment. IFN-g production in response to a T. cruzi amastigote lysate preparation was evaluated in peripheral blood mononuclear cells by ELISPOT analysis.   The frequency of IFN-g-producing T cells specific for T.  cruzi significantly decreased in the treated subject group (n=24) compared to non-treated (n=9) (Mann-Whitney U test on post-treatment/pre-treatment differences in treated vs. non-treated groups; P= 0,031), 12 months after follow-up. IFN-gamma ELISPOT responses became negative in 8 out of the 24 (33%) patients receiving benznidazole whereas these responses remained unmodified in all non-treated patients (Fisher exact test P=0,035).  In contrast, in only 4 out of the 24 treated patients was the decrease in ELISPOT responses associated with a significant decrease in the levels of antibodies specific for T. cruzi, based upon conventional serologic tests. None of the subjects showed changes in clinical status in the post-treatment follow-up period. These findings suggest a higher sensitivity for T cell cytokine production for the early detection of parasite clearance during chemotherapy and might be useful to assess the success of therapy.