Electrocardiographic Abnormalities and Treatment with Benznidazole among Children with Chronic Infection by Trypanosoma cruzi: A Retrospective Cohort Study

PLoS Negl Trop Dis. 2016 May 9;10(5):e0004651. doi: 10.1371/journal.pntd.0004651. eCollection 2016 May.

Abstract

Background: Chronic infection by Trypanosoma cruzi could cause heart conduction disturbances. We sought to analyze electrocardiographic abnormalities among children with chronic T. cruzi infection with and without trypanocidal treatment with benznidazole.

Methodology/principal findings: We studied 111 children 6-16 years of age with asymptomatic chronic T. cruzi infection who were recruited in 1991-1992 in Salta, Argentina. Most children were randomly assigned to benznidazole 5 mg/Kg/day (n = 47) or matching placebo (n = 48) for 60 days. Remaining children (n = 16) received treatment with benznidazole 5 mg/Kg/day open-label. Electrocardiograms were obtained at baseline and in 1995-1996, 1998, 2000 and 2005, and were analyzed using the Buenos Aires method. Among the 94 children with an electrocardiogram at baseline, 8 (8.5%) had electrocardiographic abnormalities, including 4 (4.7%) children with right bundle branch block. Proportion of abnormal electrocardiograms in the full population (n = 111) remained constant over time (media follow-up 8.6 years). Multivariable adjusted prevalence ratios (95% confidence interval [95%CI]) for electrocardiographic abnormalities in 1995-1996, 1998, 2000 and 2005 comparing children treated with benznidazole versus those not treated were 2.76 (0.66, 11.60), 2.33 (0.44, 12.31), 3.06 (0.48, 19.56), and 1.94 (0.33, 11.25), respectively. Among the 86 children with a normal electrocardiogram at baseline, 16 (18.6%) developed electrocardiographic abnormalities during follow-up. The multivariable adjusted hazard ratio for incident electrocardiographic abnormalities comparing children treated with benznidazole versus those not treated was 0.68 (95%CI: 0.25, 1.88).

Conclusions/significance: Electrocardiographic abnormalities are frequent among children with chronic T. cruzi infection. Treatment with benznidazole for 60 days may not be associated with less electrocardiographic abnormalities.

Publication types

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

MeSH terms

  • Adolescent
  • Argentina / epidemiology
  • Chagas Cardiomyopathy / drug therapy*
  • Chagas Cardiomyopathy / epidemiology
  • Chagas Cardiomyopathy / parasitology
  • Child
  • Cohort Studies
  • Double-Blind Method
  • Electrocardiography*
  • Female
  • Humans
  • Male
  • Nitroimidazoles / therapeutic use*
  • Retrospective Studies
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma cruzi*

Substances

  • Nitroimidazoles
  • Trypanocidal Agents
  • benzonidazole

Grants and funding

This study was supported by the Training and Research on Tropical Disease (TDR) UPND/WB/WHO/TDR Program, the National Ministry of Health of Argentina, and the Ministry of Health of the Province of Salta, Argentina. LDC was supported by a Fulbright scholarship to complete the PhD program in Epidemiology from the University of Alabama at Birmingham. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.