Munoz-Calderon Arturo, Díaz-Bello Zoraida, Ramírez José Luis, Noya Oscar, de Noya Belkisyolé Alarcón
Sección de Inmunología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela (IMT-FM-UCV), Caracas, Venezuela.
Centro de Biotecnología, Fundación Instituto de Estudios Avanzados, Caracas, Venezuela.
J Vector Borne Dis. 2019 Jul-Sep;56(3):237-243. doi: 10.4103/0972-9062.289397.
BACKGROUND & OBJECTIVES: In Venezuela, Chagas disease (ChD) is considered a serious health problem, with about 6 million people at risk; and acute outbreaks due to oral transmission of Chagas Disease (OChD) are becoming increasingly important. In 2007 there was a major outbreak of OChD and although patients from this episode were treated with nifurtimox (Lampit®-Bayer), about 70% therapeutic failure was registered. These results led us to examine whether parasite's drug susceptibility was related to this therapeutic failure.
The Trypanosoma cruzi parasites were isolated by haemoculture of the peripheral blood drawn from the pre- and post-nifurtimox treated patients infected in the 2007 OChD outbreak at Caracas, Venezuela. The in vitro assays for drug testing were performed by the MTT methodology followed by calculation of inhibitory concentration-50 (IC) values.
Parasite isolates obtained from the infected patients prior and after nifurtimox treatment when subjected to variable concentrations of the drug showed great heterogeneity in susceptibility with IC values ranging from 4.07 ± 1.82 to 94.92 ± 7.24 μM.
INTERPRETATION & CONCLUSION: The high heterogeneity in nifurtimox IC values in the isolates and clones from the OChD patients, suggests that the therapeutic failure to nifurtimox could be due in part to a phenotypic variability that existed in the wild parasite population at the original source of contamination. Though, further pharmacological studies are needed to confirm the existence of natural nifurtimox resistance in the parasite.
在委内瑞拉，恰加斯病（ChD）被视为一个严重的健康问题，约600万人面临风险；且由恰加斯病经口传播（OChD）导致的急性疫情正变得日益重要。2007年发生了一次重大的OChD疫情，尽管该疫情中的患者接受了硝呋莫司（Lampit® - 拜耳公司）治疗，但记录显示约有70%的治疗失败率。这些结果促使我们研究寄生虫的药物敏感性是否与这种治疗失败有关。
通过对从委内瑞拉加拉加斯2007年OChD疫情中感染且接受硝呋莫司治疗前后的患者采集的外周血进行血细胞培养，分离出克氏锥虫寄生虫。采用MTT法进行药物测试的体外试验，随后计算半数抑制浓度（IC）值。
从接受硝呋莫司治疗前后的感染患者中获得的寄生虫分离株，在接受不同浓度药物处理时，显示出极大的敏感性异质性，IC值范围为4.07±1.82至94.92±7.24μM。
OChD患者的分离株和克隆中硝呋莫司IC值的高度异质性表明，硝呋莫司治疗失败可能部分归因于原始污染源处野生寄生虫群体中存在的表型变异性。不过，需要进一步的药理学研究来证实寄生虫中天然存在对硝呋莫司的耐药性。
