Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease

Abstract

Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of thera-peutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accu-racy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre-and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilis-tically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.