Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil.
Instituto Federal do Sul de Minas Gerais, Pouso Alegre, Minas Gerais, Brazil.
Parasitology. 2022 Nov;149(13):1679-1694. doi: 10.1017/S0031182022001081. Epub 2022 Aug 12.
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
从系统评价框架的角度，我们分析了单药和联合化疗治疗恰加斯病（Chagas 病）的临床疗效和安全性的临床证据。研究方案基于系统评价和荟萃分析的首选报告项目以及患者、干预、比较和结局策略。仅从 Embase、Medline、Scopus 和 Web of Science 数据库中检索到随机对照试验（RCT）。调查了诊断工具、治疗方案、血清转化率和不良事件。确定了 15 项主要集中在流行地区的 RCT。恰加斯病的诊断主要基于红细胞凝集、免疫荧光、酶联免疫吸附试验和聚合酶链反应。苯硝唑（BNZ）、硝呋莫司、福沙韦康唑、泊沙康唑、别嘌醇和硫辛酸是已确定的药物。分别基于 BNZ（5mg/kg/天，200mg/天，150mg/天和 2.5mg/kg）治疗 60 天，可获得最佳的阴性血清转化率（100%、96%、94%和 91.3%）。别嘌醇（300mg/天，治疗 60 天）不能实现阴性血清转化率。接受抗寄生虫化疗的患者不良反应发生率为 5%至 73%。治疗中断（1.5%至 57%）主要与胃肠道、皮肤和神经系统表现有关。目前基于 RCT 的证据表明，BNZ 是治疗 Chagas 病的最可行选择。然而，需要开发新的方案来减轻副作用并提高患者对驱虫化疗的依从性。因此，较短的方案、较低的浓度以及将 BNZ 与泊沙康唑、福沙韦康唑或拉夫康唑联合治疗可能是可行的，以确保与基于 BZN 的单药治疗相当的疗效，有助于减少剂量和时间依赖性毒性反应。
