A serological method's ability to distinguish treatment regimens by assessing early antibody decline in Chagas patients: insights from E1224 data.

Abstract

No reliable markers exist for parasitological cure in adult patients with chronic Chagas disease. We assessed whether a serological multiplex immunoassay for Trypanosoma cruzi, MultiCruzi, could differentiate the outcomes of treatment regimens. This analysis included adults with indeterminate Chagas disease from a randomized trial of E1224. Serum samples at baseline, 6, and 12 months post-treatment with Benznidazole, E1224 regimens, or placebo were tested at three dilutions using MultiCruzi. We calculated the dilution factor at which 50% of reactivity remained (DF50) and used mixed-effects models to assess antibody decline. Log2DF50 slopes compared Benznidazole and E1224 regimens, and pooled data from the BENDITA trials helped define a cut-off for treatment response. Within six months after treatment, participants exhibited a significantly greater rate of decline in antibody levels compared to the placebo group, contrasting with results from T. cruzi conventional ELISA tests. Our analysis showed a difference in response to benznidazole and to E1224 regimens after twelve months' follow-up, confirming results for benznidazole from BENDITA. Combining data from both trials allowed discrimination of benznidazole and E1224 treatment regimens after six months' follow-up. MultiCruzi enables the early assessment of treatment-associated biological responses in adults with Chagas disease, with antibody decline serving as an exploratory pharmacodynamic marker.