de Andrade A L, Zicker F, de Oliveira R M, Almeida Silva S, Luquetti A, Travassos L R, Almeida I C, de Andrade S S, de Andrade J G, Martelli C M
Department of Community Health, Universidade Federal de Golás, Goiânia, Brazil.
Lancet. 1996 Nov 23;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.
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.
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.
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).
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.
苯硝唑是一种硝基咪唑衍生物，已被推荐用于治疗急性和先天性克氏锥虫感染（恰加斯病）。我们研究了该药物治疗克氏锥虫感染早期慢性阶段的安全性和疗效。
1991年至1995年期间，我们在巴西一个恰加斯病流行的农村地区进行了一项随机、双盲、安慰剂对照试验。在一次普查中确定的2434名学童（7至12岁）中，82%通过间接免疫荧光、间接血凝和酶联免疫吸附测定法筛查了克氏锥虫抗体。130名在所有检测中呈阳性的儿童被随机分配接受苯硝唑（每日7.5毫克/千克，口服60天）或安慰剂。疗效的主要终点是在3年随访结束时特异性抗体消失（血清学转阴）。次要终点是重复血清学检测时抗体滴度的降低。一名儿童在随机分组后不久搬离该地区，被排除在分析之外。在整个试验过程中采取了杀虫措施以降低再次感染的风险。
一小部分个体出现了无需特殊药物治疗的轻微副作用。在使用纯化的锥鞭毛体糖缀合物进行的化学发光酶联免疫吸附测定中，所有参与者的血清在试验开始时均呈阳性。随访结束时，64名接受苯硝唑治疗的参与者中有37名（58%）克氏锥虫抗体呈阴性，而接受安慰剂治疗的参与者中有3名（%）呈阴性。按意向性治疗估计，苯硝唑治疗的疗效为55.8%（95%可信区间40.8 - 67.0）。随访结束时，接受苯硝唑治疗的儿童通过间接免疫荧光法测得的几何平均滴度比接受安慰剂治疗的儿童低五倍（196[147 - 256]对1068[809 - 1408]，p < 0.00001）。
该试验表明，苯硝唑治疗克氏锥虫感染早期慢性阶段60天疗程是安全的，在使特异性抗体血清学转阴方面有55.8%的疗效。结果非常令人鼓舞，为将血清学阳性儿童的治疗作为公共卫生政策推荐提供了依据。
