Trypanocidal therapy among children infected by Trypanosoma cruzi. Serological and electrocardiographic changes over a mean twenty-five-years follow-up period

Suasnábar, Santiago; Olivera, Verónica; Arias, Evelyn; Bizai, María Laura; Arias, Enrique; Fabbro, Diana Lucrecia

doi:10.1016/j.actatropica.2021.106050

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Indeed, it can take 10 to 20 years for chronically infected adults to become seronegative following treatment. In a recent study in children aged 2-14 years at the time of antitrypanosomal treatment initiation, the average (SD) time to negative seroconversion by conventional serology was 15.7 (8.7) years post-treatment (18). Thus, the lack of any direct relationship between efficacy endpoints and nifurtimox exposure in our analysis may be attributable to the limited duration of follow-up post-treatment in CHICO (12 months).…”

Section: Discussionmentioning

confidence: 80%

Nifurtimox for Treatment of Chagas Disease in Pediatric Patients: the Challenges of Applying Pharmacokinetic-Pharmacodynamic Principles to Dose Finding

Staß

Ince

Grossmann

et al. 2022

AAPS J

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The antiparasitic drug nifurtimox was approved in the USA in 2020 for the treatment of patients with Chagas disease aged less than 18 years and weighing at least 2.5 kg, based on outcomes from the phase 3 CHICO study. Accordingly, pediatric patients with Chagas disease take nifurtimox thrice daily with food at one of two body weight–adjusted dose ranges. We investigated possible relationships between pharmacokinetic (PK) data, and pharmacodynamic efficacy and safety data collected in an analysis population of 111 participants in CHICO, using a published population PK model to estimate nifurtimox exposure at the patient level. Pediatric exposure to nifurtimox was benchmarked against levels of nifurtimox exposure known to be effective in adults with Chagas disease. Given the complex dosing regimen for nifurtimox, we also modeled nifurtimox exposure associated with simpler dosing strategies. We found no relationship between exposure to nifurtimox and efficacy measures (e.g., serological response to treatment), or between exposure and safety outcomes (including typical adverse events, e.g., headache, decreased appetite, nausea/vomiting). The analysis population appeared to represent the overall CHICO population based on the similarity of their baseline characteristics and the profiles of adverse events in the two groups. Modeled exposure based on the dosing regimen in CHICO was within the reference range derived from phase 1 data in adults. The relationship between nifurtimox exposure and cure is complex; a simplified pediatric dosing regimen is unlikely to be beneficial. Graphical abstract

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Section: Discussionmentioning

confidence: 80%

Nifurtimox for Treatment of Chagas Disease in Pediatric Patients: the Challenges of Applying Pharmacokinetic-Pharmacodynamic Principles to Dose Finding

Staß

Ince

Grossmann

et al. 2022

AAPS J

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“…An inverse relationship between age and seronegative conversion has similarly been shown for children treated with nifurtimox, with younger patients, particularly those up to 2 years of age, showing an earlier response and a higher probability of seroconversion after treatment ( 16 ). A recently reported retrospective cohort study of children treated with nifurtimox or benznidazole during childhood also demonstrated a significantly higher probability of seroconversion with younger age during a subsequent mean follow-up of 25 years ( 28 ). The results of these studies and the present study reinforce the importance of early diagnosis and prompt effective treatment of children who have acquired T. cruzi infection.…”

Section: Discussionmentioning

confidence: 97%

Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE)

Altcheh

Sierra

Ramirez³

et al. 2023

Antimicrob Agents Chemother

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“…Recently a retrospective evaluation of treated children showed differences in ECG alterations between treated and non-treated (4/41 (9.75%) vs 9/41 (21.95%)) patients [ 36 ]. However, in contrast to our study, only very few patients were evaluated by 2D echocardiogram or Holter.…”

Section: Discussionmentioning

confidence: 99%

Long-term cardiology outcomes in children after early treatment for Chagas disease, an observational study

et al. 2022

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Background Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult’s ECG may be normal, age-related findings in a pediatric ECG trace. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment. Methodology A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children’s Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2–7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients. Conclusions A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children. Trial registration ClinicalTrials.gov NCT04090489.

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Trypanocidal therapy among children infected by Trypanosoma cruzi. Serological and electrocardiographic changes over a mean twenty-five-years follow-up period

Cited by 4 publications

References 26 publications

Nifurtimox for Treatment of Chagas Disease in Pediatric Patients: the Challenges of Applying Pharmacokinetic-Pharmacodynamic Principles to Dose Finding

Nifurtimox for Treatment of Chagas Disease in Pediatric Patients: the Challenges of Applying Pharmacokinetic-Pharmacodynamic Principles to Dose Finding

Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE)

Long-term cardiology outcomes in children after early treatment for Chagas disease, an observational study

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