IMPACT OF COMBINED TREATMENT OF ALLOPURINOL AND BENZNIDAZOLE ON TOTAL AND TRYPANOSOMA CRUZI-SPECIFIC T CELLS IN HUMAN CHRONIC CHAGAS DISEASE

PEREZ-MAZLIAH D ; VIOTTI R; COLLEY G; ALVAREZ MG; ALBAREDA MC; LOCOCO B; BERTOCCHI G; VIGLIANO CA; ARMENTI A; TARLETON RL; LAUCELLA S

Washington

Congreso; 58th Annual Meeting.American Society of Tropical Medicine and Hygiene; 2009

American Society of Tropical Medicine and Hygiene

Chagas disease affects 24 million people from Southern California to Central and South America. Etiological treatment in long term T. cruzi infection is controversial, despite the fact that BZ treatment showed significant protection from progression of heart pathology. We have previously found that a significant proportion of BZ-treated subjects exhibit an initial increase in IFN-γ producing T cells specific for T. cruzi between 2-6 months post-treatment followed by a decrease to undetectable levels 12-36 months after treatment in association with decreased levels of antibodies specific for T. cruzi recombinant proteins. An improvement in early differentiated antigen-experienced total CD8+ T cells at 24 months post-treatment was also observed in these subjects. Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment in human Chagas disease has not been performed. This study was aimed to evaluate the effect of sequential treatment with two drugs allopurinol (AL) and BZ on T cell responses in subjects chronically infected with T. cruzi. AL was administered for 3 months (600 mg/day) followed by 1 month of BZ (5 mg/kg/day) in 11 T. cruzi-infected subjects. The frequency of T. cruzi-specific IFN-γ-producing T cells significantly increased after AL treatment and decreased thereafter in a substantial proportion of subjects evaluated. Total naïve (CD45RA+ CCR7+ CD62L+) and central memory (CD45RA+ CCR7+ CD62L+) CD4+ and CD8+ T cells significantly increased after AL along with the raise in T. cruzi-specific T cells and maintained at 24 months post-treatment. These findings support that treatment with AL and BZ during chronic Chagas disease has a substantial impact on parasite-specific immune responses and also induced an earlier effect on the total T cell compartment compared with treatment with BZ alone. It remains to be elucidated whether the improved in naïve and central memory T cells is due to a direct effect of AL on the host immune system.