Parasitemia and antibody response to benznidazole treatment in a cohort of patients with chronic Chagas disease

C. H. V. Moreira, A. Bierrenbach, C. Taconeli, Léa Campos de Oliveira-da Silva, Lewis F. Buss, Sheila M. Keating, E. Manuli, Noemia Barbosa Carvalho, C. Guastini, Sonia Bakkour Coco, J. Lindoso, Lucas Augusto Moyses Franco, Fabio Ghilardi, Flavia Cristina da Silva Sales, P. Contestable, C. Di Germanio, Michael P. Busch, E. Sabino
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Abstract

Evaluating the effectiveness of Chagas disease treatment poses challenges due to the lack of biomarkers for disease progression and therapeutic response. In this study, we aimed to assess the clearance of Trypanosoma cruzi (T. cruzi) parasites in a group of benznidazole (BNZ)-treated chronic Chagas disease patients using high-sensitivity quantitative PCR (qPCR) and track T. cruzi antibody levels through a semiquantitative chemiluminescent assay.A total of 102 T. cruzi seropositive patients with previous PCR-positive results were enrolled in the study. We collected samples 30 days before treatment (T-30d), on the day before initiating BNZ treatment (T0d), and at follow-up visits 60 days (T60d), 6 months (T6M), 12 months (T12M), and 36 months (T36M) after treatment initiation. Treatment efficacy was assessed by testing of serial samples using a target-capture qPCR assay specific to satellite T. cruzi DNA and the ORTHO T. cruzi ELISA Test System for antibody quantitation.Of the enrolled individuals, 87 completed at least 50% of the treatment course, and 86 had PCR results at follow-up visits T6M, T12M, and T36M. PCR results exhibited fluctuations before and after treatment, but levels were significantly lower post-treatment. Only 15 cases consistently tested PCR-negative across all post-treatment visits. Notably, nearly all participants demonstrated a declining antibody trajectory, with patients who tested PCR-negative at T36M exhibiting an earlier and more pronounced decline compared to PCR-positive cases at the same visit.Our study suggests that serial PCR results pose challenges in interpretation. In contrast, serial antibody levels may serve as an ancillary, or even a more reliable indicator of parasite decline following BNZ treatment. Monitoring antibody levels can provide valuable insights into the efficacy of treatment and the persistence of parasites in Chagas disease patients.
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慢性恰加斯病患者的寄生虫血症和对苯并硝唑治疗的抗体反应
由于缺乏疾病进展和治疗反应的生物标志物,评估恰加斯病治疗的有效性面临挑战。在这项研究中,我们旨在利用高灵敏度定量PCR (qPCR)评估一组苯并硝唑(BNZ)治疗的慢性恰加斯病患者对克氏锥虫(T. cruzi)寄生虫的清除,并通过半定量化学发光法追踪克氏锥虫抗体水平。共有102例既往pcr阳性的克氏锥虫血清阳性患者被纳入研究。我们在治疗前30天(T-30d)、BNZ治疗开始前一天(T0d)以及治疗开始后60天(T60d)、6个月(T6M)、12个月(T12M)和36个月(T36M)随访时采集样本。采用针对卫星克氏t型病毒DNA的靶向捕获qPCR检测和用于抗体定量的ORTHO克氏t型病毒ELISA检测系统对一系列样品进行检测,以评估治疗效果。在纳入的个体中,87例完成了至少50%的疗程,86例在随访T6M、T12M和T36M时有PCR结果。PCR结果在治疗前后出现波动,但治疗后水平显著降低。在所有治疗后访问中,只有15例始终检测为pcr阴性。值得注意的是,几乎所有参与者都表现出抗体下降的轨迹,在T36M时检测pcr阴性的患者与同一次就诊时pcr阳性的患者相比,表现出更早、更明显的下降。我们的研究表明,序列PCR结果在解释上存在挑战。相比之下,序列抗体水平可以作为辅助指标,甚至是BNZ治疗后寄生虫下降的更可靠指标。监测抗体水平可以对治疗效果和恰加斯病患者体内寄生虫的持久性提供有价值的见解。
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