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十年大型口源性恰加斯病爆发的随访。感染的实验室生物标志物作为治疗失败的指标。

Ten-year follow-up of the largest oral Chagas disease outbreak. Laboratory biomarkers of infection as indicators of therapeutic failure.

机构信息

Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Venezuela.

Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Venezuela.

出版信息

Acta Trop. 2021 Oct;222:106034. doi: 10.1016/j.actatropica.2021.106034. Epub 2021 Jul 2.

DOI:10.1016/j.actatropica.2021.106034
PMID:34224715
Abstract

Trypanosoma cruzi uses various mechanisms of infection to access humans. Since 1967, food contaminated with metacyclic trypomastigotes has triggered several outbreaks of acute infection of Chagas disease by oral transmission. Follow-up studies to assess the effectiveness of anti-parasitic treatment of oral outbreaks are rather scarce. Here, we report a 10-year laboratory follow-up using parasitological, serological, and molecular tests of 106 individuals infected in 2007 of the largest known outbreak of orally transmitted Chagas disease, which occurred in Caracas city, Venezuela. Before treatment (2007), specific IgA, IgM and IgG, were found in 71% (75/106), 90% (95/106) and 100% (106/106), respectively, in addition to 21% (9/43) parasitemia, Complement Mediated Lysis (CML) in 98% (104/106) and 79% (34/43) parasitic DNA for PCR. Blood culture detected parasitemia up to 18 months post-treatment in 6% (6/106) of the patients. In 2017, the original number of cases in the follow-up decreased by 46% and due to the country's economic situation, not all the trials could be carried out in the entire population. During follow-up, IgA and IgM disappeared promptly, with IgM persisting in 19% (20/104) of the patients three years after treatment. The anti-T. cruzi IgG remained positive 10 years later in 41% (20/49) of the individuals evaluated. CML remained positive seven years later in 79% (65/82) of the cases. PCR positive cases decreased after treatment but progressively recovered, being positive in 69% (32/46) of the individuals evaluated in 2017. The group of children (under 18 years of age) showed the highest PCR positivity with 76% (26/34) of the cases, but their parasitic load tended to diminish, while in adults the parasitic load regained their initial values. The simultaneous evaluation of serological tests and PCR of the patients allowed us to separate patients among responders and non-responders to the anti-parasitic treatment, and this information prompted us to apply a second anti-parasitic treatment in the group of non-responders. In this population not subjected to the like lihood of re-infection, adult patients were more likely to be non-responders when compared to children. These results suggest that rigorous laboratory follow-up with T. cruzi infectious biomarkers is essential to detect cases of parasite persistence.

摘要

克氏锥虫通过多种感染机制进入人体。自 1967 年以来,食物中被污染的循环型锥鞭毛体已引发了几起因口服途径传播的恰加斯病急性感染的爆发。对于口服爆发的寄生虫治疗效果的后续研究相当稀缺。在这里,我们报告了一项为期 10 年的实验室随访,使用寄生虫学、血清学和分子检测,对 2007 年在委内瑞拉加拉加斯市发生的最大规模的已知经口传播恰加斯病爆发中感染的 106 名个体进行了检测。在治疗前(2007 年),71%(75/106)、90%(95/106)和 100%(106/106)的个体分别检测到特异性 IgA、IgM 和 IgG,此外还有 21%(9/43)的个体检测到寄生虫血症,98%(104/106)和 79%(34/43)的个体检测到 PCR 寄生虫 DNA 的补体介导的溶解(CML)。在治疗后 6%(6/106)的患者中,血液培养可检测到长达 18 个月的寄生虫血症。2017 年,随访中的原始病例数量减少了 46%,并且由于该国的经济状况,并非所有试验都能在整个人群中进行。在随访期间,IgA 和 IgM 迅速消失,IgM 在治疗后三年仍持续存在于 19%(20/104)的患者中。10 年后,在 41%(20/49)的个体中仍可检测到抗 T. cruzi IgG 呈阳性。CML 在 79%(65/82)的病例中仍为阳性,七年后。治疗后,PCR 阳性病例减少,但逐渐恢复,在 2017 年评估的 46%(32/46)个体中呈阳性。儿童组(18 岁以下)的 PCR 阳性率最高,为 76%(26/34),但寄生虫负荷趋于减少,而成年人的寄生虫负荷则恢复到初始值。对患者进行血清学检测和 PCR 的同时评估,使我们能够将对寄生虫治疗有反应和无反应的患者分开,这些信息促使我们在无反应组中应用第二种寄生虫治疗。在这群未再次感染的人群中,与儿童相比,成年患者更有可能对寄生虫治疗无反应。这些结果表明,使用克氏锥虫感染性生物标志物进行严格的实验室随访对于检测寄生虫持续存在至关重要。

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