RANDOMIZED TRIAL OF EFFICACY OF BENZNIDAZOLE IN TREATMENT OF EARLY TRYPANOSOMA-CRUZI INFECTION

Background Benznidazole, a nitroimidazole derivative, has been recomme nded for the treatment of acute and congenital Trypanosoma cruzi infec tion (Chagas' disease). We have examined the safety and efficacy of th is drug in the treatment of the early chronic phase of T cruzi infecti on. Methods Between 1991 and 1995, we carried out a randomised, double -blind, placebo-controlled trial in a rural area of Brazil with endemi c Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identi fied in a census were screened for antibodies to T cruzi by indirect i mmunofluorescence, indirect haemagglutination, and ELISA. 130 were pos itive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for effic acy was the disappearance of specific antibodies (negative seroconvers ion) by the end of 3-year follow-up. The secondary endpoint was the re duction of antibody titres on repeated serological tests. One child mo ved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection. Findings Minor side-effects requiring no specific medication were recorded in a small proportion of individ uals. On a chemiluminescent ELISA with purified trypomastigote glycoco njugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-tr eated participants and 3 (5%) of those who received placebo were negat ive for T cruzi antibodies. The efficacy of benznidazole treatment est imated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower g eometric mean titres by indirect immunofluorescence than placebo-treat ed children (196 [147-256] vs 1068 [809-1408], p<0.00001). Interpretat ion The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in produ cing negative seroconversion of specific antibodies. The results are v ery encouraging and justify the recommendation of treatment for seropo sitive children as public health policy.