Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults

Abstract

Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF. Treatment response was evaluated by clinical, parasitological, and serological after-treatment evaluation. A total of 289 patients were enrolled, of which 199 were children and 90 adults. At diagnosis, 89.6% of patients were asymptomatic. Overall, all symptomatic patients showed clinical improvement. At baseline, parasitemia was positive in 130 of 260 (50%) patients. All but one adult patient had cleared their parasitemia by the end of treatment. That patient was considered a treatment failure. Median follow-up time for children was 37.7 months, with an interquartile range of (IQR25-75 12.2 to 85.3), and for adults was 14.2 months (IQR25-75, 1.9 to 33.8). After treatment, a decrease of T. cruzi antibodies and seroconversion were observed in 34.6% of patients. The seroconversion profile showed that, the younger the patient, the higher the rate of seroconversion (log rank test; P value, <0.01). At least 20% seroreduction at 1 year follow-up was observed in 33.2% of patients. Nifurtimox was highly effective for ChD treatment. Patients had excellent treatment responses with fully resolved symptoms related to acute T. cruzi infection. Clearance of parasitemia and a decrease in T. cruzi antibodies were observed as markers of treatment response. This study reinforces the importance of treating patients during childhood since the treatment response was more marked in younger subjects. (This protocol was registered at ClinicalTrials.gov under registration number NCT04274101).

Keywords: Trypanosoma cruzi; adults; children; efficacy; follow-up; nifurtimox; treatment; treatment effectiveness.

Conflict of interest statement

The authors declare a conflict of interest. J.A. is a consultant of Bayer. All other authors report no potential conflicts.

Figures

FIG 1

Flow diagram.

FIG 2

(A to C) Kaplan-Meier survival curves for seroconversion profile (A) and seroreduction profile (C) analysis stratified by age group. Ordinates depict the proportion of patients (P.P.) lacking seroconversion (A) or seroreduction (C). Only patients with positive serology at baseline 277/289 (95.8%) were included in the analysis. Of note, patients in the 0 to 8 months group have the fastest seroconversion rate. (B to D) Cox regression models for seroconversion (B) and seroreduction (D) analysis. In both cases, the infant age groups (0 to 8 months) were considered as reference for hazard ratio computing. Significance P values resulting from comparing HR among the considered reference are depicted according to the following: *, <0.05; **, <0.01; ***, <0.001. The whole analysis was performed by using the “survival” R package version 3.2-7 (29).

FIG 3

Kaplan-Meier curves of seroconversion (A) and seroreduction (B) stratified by parasitological results at baseline. Ordinates depict the proportion of patients (P.P.) lacking seroconversion (A) or seroreduction (B). Only patients with positive serology at baseline and a performed parasitological test were included in the analysis. Patients in the infant group (0 to 8 months) were excluded from this analysis in order to avoid a bias caused by the diagnosis criteria (see main text). Patients presenting a negative parasitological result at baseline (n = 130) were plotted in green (Parasit = N) and patients presenting a positive parasitological result (n = 76) at baseline were plotted in red (Parasit = P).