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

PLoS Negl Trop Dis. 2022 Nov 21;16(11):e0010828. doi: 10.1371/journal.pntd.0010828. eCollection 2022 Nov.

Abstract

Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic 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 accuracy. 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 probabilistically 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chagas Disease* / parasitology
  • Clinical Trials as Topic
  • Humans
  • Parasitemia / parasitology
  • Persistent Infection
  • Real-Time Polymerase Chain Reaction
  • Trypanosoma cruzi* / genetics

Associated data

  • ClinicalTrials.gov/NCT01489228

Grant support

PMD was partly supported by the Ramón Areces Foundation, postdoctoral grant, www.fundacionareces.es. PMD and COB were supported by the Burroughs Wellcome Fund, www.bwfund.org. ASM was supported by the Spanish Ministry of Health through the Program for Consolidated Researchers, Instituto de Salud Carlos II|, www.isciii.es (Juan Rodés; JR18/00022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.