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

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.

An α-Gal antigenic surrogate as a biomarker of treatment evaluation in Trypanosoma cruzi-infected children. A retrospective cohort study

“…cruzi (mothers) were considered, α-Gal seroprevalence increased up to ∼70–80%, well in the range of other T . cruzi antigens proposed as post-therapeutic biomarkers for Chagas disease [ 18 , 44 ].…”

“…Most remarkably, of 24 patients belonging to Group 3 (3 to 16 years-old children), 14 (58.3%) achieved negative seroconversion for α-Gal-ELISA whereas none of them negativized for conventional serology. The difficulty in achieving post-treatment negativization using conventional serological methods in children aging >3 years (and also in chronically infected adults) constitutes a major issue in the clinical management of Chagas disease, and stresses the urgent need of surrogate drug efficacy indicators [7,31,44,45]. In addition to providing a novel tool to shorten follow-up periods after chemotherapy, the α-Gal-ELISA developed here may also assist T. cruzi infection diagnosis in certain clinical situations.…”

“…Importantly, α-Gal seroprevalence in babies born to T. cruzi-infected mothers seems irrespective of their infection status, as it was observed both in Group 1 (congenitally infected) and Group 4 (non-infected) patients. When only children >7 months (Groups 2 and 3) and/or patients chronically infected with T. cruzi (mothers) were considered, α-Gal seroprevalence increased up to *70-80%, well in the range of other T. cruzi antigens proposed as post-therapeutic biomarkers for Chagas disease [18,44].…”

Trypanosoma cruzi Secreted Cyclophilin TcCyP19 as an Early Marker for Trypanocidal Treatment Efficiency

“…In particular, the T. cruzi Ca 2+ -binding flagellar protein F29 has been extensively studied as an early marker of response to treatment with parasiticidal drugs in samples from treated patients. A significant decrease in antibodies against the anti-F29 antigen in an in-house ELISA was noted when monitoring the response to drug treatments [45], and although a low specificity has been detected [46], recent results have shown that 77.2% of T. cruzi-infected children treated with a 60-day regimen with Nifurtimox seroconvert for ELISA-F29 [47].…”