Small molecule biomarkers predictive of Chagas disease progression

Abstract

Chagas disease (CD) is a neglected tropical disease caused by the parasitic protozoan Trypanosoma cruzi. However, only 20% to 30% of infected individuals will progress to severe symptomatic cardiac manifestations. Current treatments are benznidazole and nifurtimox, which are poorly tolerated regimens. Developing a biomarker to determine the likelihood of patient progression would be helpful for doctors to optimize patient treatment strategies. Such a biomarker would also benefit drug discovery efforts and clinical trials. In this study, we combined untargeted and targeted metabolomics to compare serum samples from T. cruzi-infected individuals who progressed to severe cardiac disease, versus infected individuals who remained at the same disease stage (non-progressors). We identified four unannotated biomarker candidates, which were validated in an independent cohort using both untargeted and targeted analysis techniques. Overall, our findings demonstrate that serum small molecules can predict CD progression, offering potential for clinical monitoring.