Safety of Escalating Doses of Tribendimidine in Children With Hookworm

Tribendimidine 400 mg has demonstrated efficacy and tolerability in children with mild hookworm infections, according to a study recently published in Clinical Infectious Diseases. 

This single-blind, randomized controlled trial included 148 children (18 of whom were lost to follow-up) in Côte d’Ivoire, who were between ages 6 and 12 years with confirmed hookworm infection, and had no major comorbid illnesses. The children were randomly assigned 1:1:1:1 to tribendimidine 100 mg (n=36), 200 mg (n=37), 400 mg (n=37), or placebo (n=38). The primary outcome was the cure rate for hookworm infection, which was measured along with egg reduction rate 2 to 3 weeks post-treatment. Secondary outcomes included Ascaris lumbricoides and Trichuris trichiura cure and egg reduction rates, as well as tolerability profiles. Clinical symptoms were assessed before the administration of treatment.

Higher doses of tribendimidine were associated with higher cure rates (placebo, 20.6%; 100 mg, 21.2%; 200 mg, 38.7%; 400 mg, 53.1%), as were egg reduction rates (placebo, 30.6%; 100 mg, 65.4%; 200 mg, 82.1%; 400 mg, 92.2%). A positive net effect of 34.3% (95% CI, 13.3-54.4) was predicted by the Emax model for a 400 mg dose, while a 95% egg reduction rate was predicted at treatment with a 500 mg dose. Adverse events were mostly mild, affecting 33% before treatment, 33% at 3 hours after treatment, and 8% at 1 day after treatment.

Limitations to this study included the absence of medium or heavy hookworm infection burden for comparison, as well as an insufficient number of participants with Ascaris lumbricoides and Trichuris trichiura coinfections for examination. In addition, the efficacy of tribendimidine is hookworm species dependent and this study did not rigorously assess the species of hookworm responsible for infection in study participants; researchers noted however, that it has been previously documented that Nector americanus is exclusively present in the study region

The study researchers concluded that “a 400 mg tribendimidine dose showed the highest efficacy in children and was well tolerated. Moreover, using the same dose in adults and school-aged children would simplify treatment programs. We advise that further investigation should be launched in moderate to heavy hookworm infection settings in order to assess the efficacy and safety of tribendimidine in these epidemiological contexts.”

Reference

Coulibaly JT, Hiroshige N, N’Gbesso YK, Hattendorf J, Keiser J. Efficacy and safety of ascending dosages of tribendimidine against hookworm infections in children: a randomized controlled trial [published online November 29, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy999