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

Author:

Moreira Carlos Henrique Valente,Bierrenbach Ana Luiza,Taconeli Cesar Augusto,de Oliveira-da Silva Léa Campos,Buss Lewis F.,Keating Sheila M.,Manuli Erika Regina,Carvalho Noemia Barbosa,Guastini Cristina,Coco Sonia Bakkour,Lindoso José Ângelo Lauletta,Franco Lucas Augusto Moyses,Ghilardi Fabio,Sales Flavia Cristina da Silva,Contestable Paul,Di Germanio Clara,Busch Michael P.,Sabino Ester Cerdeira

Abstract

BackgroundEvaluating 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.MethodsA 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.ResultsOf 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.ConclusionOur 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.

Funder

Bill and Melinda Gates Foundation

Conselho Nacional de Desenvolvimento Científico e Tecnológico

National Institutes of Health

Publisher

Frontiers Media SA

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