title: Efficacy and safety of oxantel pamoate in school-aged children infected with Trichuris trichiura on Pemba Island, Tanzania: a parallel, randomised, controlled, dose-ranging study.
abstract: BACKGROUND
  Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura. Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura. We aimed to assess the nature of the dose-response relation to determine the optimum dose.
  
  
  METHODS
  We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6-14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5-30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura, both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231.
  
  
  RESULTS
  Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11-36]; egg-reduction rate 85·0%, 64·5-92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44-65) with an egg-reduction rate of 97·5% (94·4-98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43-73) with an egg-reduction rate of 98·8% (96·8-99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment.
  
  
  CONCLUSIONS
  Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes.
  
  
  BACKGROUND
  Swiss National Science Foundation.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Wendelin
authors.initials: W
authors.lastname: Moser
authors.affiliation: Laboratory Division, Public Health Laboratory-Ivo de Carneri, Chake Chake, Tanzania.
authors.forename: Said M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Laboratory Division, Public Health Laboratory-Ivo de Carneri, Chake Chake, Tanzania.
authors.forename: Shaali M
authors.initials: SM
authors.lastname: Ame
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Speich
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
authors.forename: Maxim
authors.initials: M
authors.lastname: Puchkov
authors.affiliation: Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
authors.affiliation: Ivo de Carneri Foundation, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Albonico
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Hattendorf
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland. Electronic address: jennifer.keiser@unibas.ch.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
mesh_terms: D000293:Adolescent; D000818:Animals; D000969:Antinematodal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D008297:Male; D011716:Pyrantel Pamoate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016037:Single-Blind Method; D013636:Tanzania / Q000453:epidemiology; D014257:Trichuriasis / Q000188:drug therapy*; D014258:Trichuris
chemical_list: D000969:Antinematodal Agents; D011716:Pyrantel Pamoate; C037225:oxantel pamoate