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Cure assessment in chronic Trypanosoma cruzi infection is controversial, mainly because of the lack of reliable tests to ensure parasite elimination. Here, we assess the impact of benznidazole therapy on the conventional serology and parasitaemia in chronic Chagas disease. A total of 455 patients with long-term Trypanosoma cruzi infection underwent specific chemotherapy with benznidazole. Their parasitological status was assessed by polymerase chain reaction (PCR) detection of T. cruzi DNA. Drops in the titres of antibody levels were serially measured by indirect immunofluorescence assay (IFI) and chemiluminescent microparticle immunoassay (CMIA). Patients were monitored during the treatment period and for a further 90, 150 and 240 days. Controls were repeated yearly during the 7-year follow-up. The PCR result was negative in all patients between 60-day ( n = 22) and 90-day ( n = 294) controls. Treatment failure was detected in 45 patients and was significantly more frequent in those who did not complete the therapy [12 out of 13 (92 %) vs. 33 out of 442 (7 %)] ( p = 0.0001). A significant drop in serum titres was detected after the first follow-up year in patients with sustained negative PCR results: 2nd year ( p = 0.029 by IFI; p = 0.002 by CMIA), 5th year ( p = 0.036 by IFI; p = 0.039 by CMIA) and 6th year ( p = 0.028 by IFI; p = 0.019 by CMIA). The results point to a beneficial effect of benznidazole and may be the cure of chronic patients who had a consistently negative PCR result throughout the follow-up period. [ABSTRACT FROM AUTHOR]

The enzyme indoleamine 2,3-dioxigenase ( IDO) is critical for the regulation of immune responses in pro-tolerogenic antigen-presenting cell. To address the profile of immune responses associated with Chagas disease, we measured IDO activity of peripheral blood mononuclear cells from 168 chronic patients and 13 healthy donors. We found that IDO activity was increased in patients with Chagas disease when compared with controls. Moreover, the IDO activity of patients with Chagas disease in the symptomatic chronic phase, involving cardiac or digestive alterations, was higher than that detected in asymptomatic patients and correlated with the severity of the symptoms. Furthermore, benznidazole treatment induced a long-lasting decrease in IDO activity in symptomatic patients, reaching levels comparable with those of healthy donors. These results suggest that a pro-tolerogenic state is associated with the severity of Chagas disease and that benznidazole treatment is a valuable tool for breaking the parasite-driven immune tolerance in the symptomatic chronic phase of Chagas disease. [ABSTRACT FROM AUTHOR]