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洪都拉斯、危地马拉和玻利维亚恰加斯病病因学治疗方案的可行性、药物安全性和有效性:无国界医生组织 10 年经验。

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières.

机构信息

Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America.

出版信息

PLoS Negl Trop Dis. 2009 Jul 7;3(7):e488. doi: 10.1371/journal.pntd.0000488.

Abstract

BACKGROUND

Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness.

METHODOLOGY

From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs.

RESULTS

Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population.

CONCLUSIONS

These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.

摘要

背景

恰加斯病(美洲锥虫病)是一种由寄生虫克氏锥虫引起的人畜共患或人兽共患病。主要影响拉丁美洲贫困地区的人群,这种被忽视的疾病的医疗保健往往缺乏。无国界医生组织/无国界医生(MSF)自 1999 年以来一直为恰加斯病提供诊断和治疗服务。本报告描述了无国界医生组织在洪都拉斯、危地马拉和玻利维亚的四个项目中 10 年的现场经验,重点介绍了可行性方案、药物治疗安全性和治疗效果。

方法

1999 年至 2008 年,无国界医生组织在洪都拉斯的约罗(1999-2002 年)、危地马拉的奥拉帕(2003-2006 年)、玻利维亚的恩特雷里奥斯(2002-2006 年)和苏克雷(2005-2008 年)为 18 岁以下的 T. cruzi 血清阳性患者提供免费诊断、病因治疗和随访护理。实施的基本项目组成部分确保了可行性,包括在社区和家庭层面进行信息、教育和宣传(IEC);病媒控制;卫生工作人员培训;筛查和诊断;治疗和依从性,包括基于家庭的策略,以早期发现不良事件;以及后勤保障。恰加斯病诊断通过使用两种不同的诊断测试检测血液样本来确认。对 T. cruzi 阳性患者使用苯并咪唑作为一线治疗,同时进行适当的咨询、同意,并由父母或监护人每天为患者服用药物,以积极参与,早期发现不良事件,并在必要时停止治疗。每周进行随访,记录不良事件以评估药物安全性。进行血清学转换评估,以衡量治疗效果。所有项目均开展病媒控制、昆虫学监测和健康教育活动,并与国家和地区项目密切互动。

结果

在约罗、奥拉帕、恩特雷里奥斯和苏克雷,分别有 24471、8927、7613 和 19400 名儿童和青少年接受了 T. cruzi 检测。其中,分别有 232(0.9%)、124(1.4%)、1475(19.4%)和 1145(5.9%)名患者被诊断为血清阳性。患者接受苯并咪唑治疗,中南美项目的早期血清转换结果差异很大:约罗和奥拉帕分别为 18 个月后 87.1%和 58.1%;恩特雷里奥斯为 5.4%,最长可达 60 个月;苏克雷为 18 个月平均为 0%。在约罗和奥拉帕接受治疗的所有患者中,分别有 50.2%和 50.8%观察到苯并咪唑相关不良事件,而在恩特雷里奥斯和苏克雷接受治疗的患者中,分别有 25.6%和 37.9%观察到苯并咪唑相关不良事件。大多数不良事件是轻微的,易于管理。治疗人群中没有死亡病例。

结论

这些结果表明,在资源有限的环境中,包括偏远农村地区,实施恰加斯病诊断和治疗方案是可行的,同时解决了与药物相关不良事件相关的限制。明显治疗效果的差异可能反映了患者和寄生虫群体的差异,并说明了当前治疗方法和疗效衡量方法的局限性。急需新的治疗方法,具有更好的安全性,现有的和新的药物的儿科制剂,以及更快、更可靠的治愈检测。

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