ELISA F29 -A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment

PLoS Negl Trop Dis. 2023 Jun 23;17(6):e0011440. doi: 10.1371/journal.pntd.0011440. eCollection 2023 Jun.

Abstract

Background: Measurement of the success of antitrypanosomal treatment for Chagas disease is difficult, particularly in the chronic phase of the disease, because anti-Trypanosoma cruzi antibodies persist in serum for prolonged periods. We studied the effects of nifurtimox administered by two different treatment regimens on the T. cruzi calcium-binding flagellar protein F29 in children diagnosed with Chagas disease measured using an enzyme-linked immunosorbent assay (ELISA) technique (ELISA F29).

Methods and principal findings: In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease and treated with nifurtimox for either 60 days or 30 days were analyzed using an ELISA with an F29 recombinant protein as the antigen, as well as conventional serological tests (recombinant ELISA and indirect hemagglutination assay). In an exploratory approach, serological response to nifurtimox treatment was evaluated for 4 years post-treatment. In both treatment groups, the number of patients with negative ELISA F29 values increased over the period of observation. The incidence rate of negative seroconversion using ELISA F29 was 22.94% (95% CI: 19.65%, 26.63%) in the 60-day treatment group and 21.64% (95% CI: 17.21%, 26.86%) in the 30-day treatment group. In the subpopulation of patients who tested seropositive for F29 before nifurtimox treatment, 88 patients (67.7%) in the 60-day regimen and 39 patients (59.1%) in the 30-day regimen were F29 seronegative at 4 years post-treatment. All patients who had a positive ELISA F29 test at baseline and seroconverted to negative measured by conventional serology reached seronegativity in ELISA F29 earlier than in conventional serology.

Conclusions: The results demonstrate a serological response to treatment with nifurtimox measured by the ELISA F29 test in children diagnosed with Chagas disease. The F29-based ELISA can be considered a potential early marker of response to antitrypanosomal therapy for Chagas disease.

Trial registration: ClinicalTrials.gov NCT02625974.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan
  • Biomarkers
  • Chagas Disease* / diagnosis
  • Chagas Disease* / drug therapy
  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Nifurtimox / therapeutic use
  • Trypanocidal Agents* / therapeutic use

Substances

  • Nifurtimox
  • Trypanocidal Agents
  • Antibodies, Protozoan
  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT02625974

Grants and funding

The CHICO and CHICO SECURE study was sponsored and funded by Bayer AG (https://www.bayer.com/en/); no funding number is available. Data analysis was undertaken by the sponsor and other aspects of the study – design, data collection, data interpretation and writing of this report – were done in close collaboration between the investigators and the sponsor. The funder had no additional role. All authors had full access to all study data and had final responsibility for the decision to submit for publication.