A serological method’s ability to distinguish treatment regimens by assessing early antibody decline in Chagas patients: insights from E1224 data
Ursula Saade, Juan Carlos Ramirez, Jasper de Boer, Noelia Anahi Bazan, Franco Mauricio Mangone, Thomas Ramadier, Ivan Scandale, Hans Pottel, Jaime Altcheh, Eric Chatelain, Maan ZreinAbstract
Background
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.
Methods
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.
Findings
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.
Conclusion
MultiCruzi enables the early assessment of treatment-associated biological responses in adults with Chagas disease, with antibody decline serving as an exploratory pharmacodynamic marker.