Five-year serological and clinical evolution of chronic Chagas disease patients in Cochabamba, Bolivia

PLoS Negl Trop Dis. 2023 Dec 29;17(12):e0011498. doi: 10.1371/journal.pntd.0011498. eCollection 2023 Dec.

Abstract

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment-benznidazole and nifurtimox-but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up.

Methodology/principal findings: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year.

Conclusions/significance: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols.

Publication types

  • Observational Study

MeSH terms

  • Bolivia
  • Chagas Disease* / parasitology
  • Chronic Disease
  • Humans
  • Nitroimidazoles* / therapeutic use
  • Trypanocidal Agents* / therapeutic use
  • Trypanosoma cruzi*

Substances

  • benzonidazole
  • Nitroimidazoles
  • Trypanocidal Agents

Grants and funding

We thank the support by Agencia Española de Cooperación Internacional para el Desarrollo (AECID; grants 10-COI-039 and 14-CO1-558). JAP, MJP and JG research is supported by Departament d'Universitats, Recerca i Societat de la Informació (grant number AGAUR 2017SGR00924), the Instituto de Salud Carlos III (ES) RICET Network for Cooperative Research in Tropical Diseases (grant number ISCIII RD12/0018/0010, FEDER) and Centro de Investigación Biotecnológica en Red de Enfermedades Infecciosas (CIBERINFEC; grant number CB21/13/00112). CIBERINFEC is co-funded with FEDER funds. MJP research was also supported by the Conselleria de Sanitat Universal i Salut Pública (grant number PERIS 2016-2010 SLT008/18/00132). We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. The Drugs for Neglected Diseases initiative (DNDi) is grateful to its donors, public and private, who have provided funding to DNDi since its inception in 2003. A full list of DNDi’s donors can be found at http://www.dndi.org/donate/donors/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.