Small molecule biomarkers predictive of Chagas disease progression

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, affects an estimated 10.5 million people worldwide and remains a leading cause of infectious cardiomyopathy in Latin America. Although infection is lifelong without treatment, only 20–30% of chronically infected individuals progress from an asymptomatic stage to clinically significant cardiac disease, and current antiparasitic therapies are limited by toxicity and variable efficacy. Reliable biomarkers capable of predicting disease progression would improve clinical risk stratification and support therapeutic development. Here, we performed a metabolomics study to identify serum biomarkers predictive of progression from asymptomatic infection to cardiac CD. Untargeted liquid chromatography–mass spectrometry profiling using complementary chromatographic platforms and univariate statistics, machine learning feature selection, and receiver operating characteristic (ROC) analysis were performed to identify candidate biomarkers. These biomarkers were validated by targeted analysis. We identified eight individual metabolite biomarkers and 45 combinatorial panels predictive of progression status, including 10 panels that met sensitivity and specificity criteria defined in the target product profile for CD treatment-response biomarkers. These findings demonstrate that circulating metabolites measured at baseline can predict future cardiac disease progression and provide a foundation for clinically deployable prognostic tools in chronic Chagas disease. In this study, authors show that serum metabolites measured before symptoms appear can predict which people with chronic Chagas disease will later develop heart damage, offering a way to identify patients at risk years in advance.