Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children.

As part of a major epidemiologic study on Chagas' disease, we compared the prevalence of electrocardiographic (ECG) abnormalities among 141 school children 7-12 years of age and seropositive for Trypanosoma cruzi, and 282 age-, sex-, and school-matched seronegative children in an endemic area in Brazil. The prevalence of ECG abnormalities was 11.3% among seropositive children and 3.5% among seronegative children (odds ratio = 3.5, 95% confidence interval [CI] = 1.5-8.4). The prevalence rate of ECG alterations was 10.7% for seropositive males versus 8.9% for seropositive females. Complete right bundle branch block (CRBBB), which is highly suggestive of Chagas' disease cardiopathy, was diagnosed in nine (6.4%) seropositive children and in only one (0.3%) seronegative child (odds ratio = 18.5, 95% CI = 2.3-146.5, attributable fraction = 58.3%). Five incident new cases of CRBBB were diagnosed after a 36-month follow-up of seropositive children who were enrolled in an independent clinical field trial. No case of frequent and/or multifocal ventricular premature beats was found in the cohort of children. The surprisingly high frequency of early ECG abnormalities, which indicates a rapid evolution from infection to disease, suggests the existence of endemic areas with a particular accelerated disease progression that was not described before. Under such conditions, a public health chemotherapy program focusing on the treatment of young seropositive children would be recommended.

Evaluation of risk factors for house infestation by Triatoma infestans in Brazil.

An active entomologic survey was conducted by a team of trained health workers in a rural area endemic for Chagas' disease in central Brazil. They used pyrethrum as a flushing agent and 4,232 houses were inspected for triatomine bugs both inside and in the immediate environs. Houses with Triatoma infestans or evidence of an established colony were identified and defined as infested houses (cases). The building and environmental characteristics of 161 randomly selected infested houses were compared with 161 matched, noninfested houses (controls) that were the shortest distance from the infested house. Domestic and peridomestic potential risk factors associated with house infestation by Triatoma infestans were assessed by logistic regression analysis. Incomplete house construction (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.5-4.1) was confirmed as a risk factor related to the presence or evidence of Triatoma infestans in the dwellings. The study also disclosed a statistically significant association between the presence of rats (OR = 1.6, 95% CI = 1.1-2.6) and indoor crop storage (OR = 2.3, 95% CI = 1.1-5.2) and house infestation. Further experimental field studies using tagged rodents should be conducted to assess their epidemiologic role in the domestic chain of Trypanosoma cruzi transmission.

Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection.

BACKGROUND: Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection. METHODS: Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved 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 individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated 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 geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001). INTERPRETATION: The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.