Randomized placebo-controlled trial of the efficacy of mebendazole polymorphs in the treatment of hookworm infections

Abstract

INTRODUCTION: Mebendazole has three polymorphic forms, identified as A, B and C. Animal studies and one previous study in humans have suggested that unlike polymorph C, polymorph A is ineffective in the treatment of hookworm and whipworm infections. OBJECTIVES: A randomized double-blind, placebo-controlled trial was carried out to compare the efficacy of single dose 500 mg tablets of pure mebendazole polymorph C with those containing a 1:1 mixture of polymorphs Aand C, for the treatment of hookworm infections. . DESIGN, SETTING AND METHODS: All eligible individuals living in 219 households in 8 estate divisions in Ratnapura District known to have a high prevalence of hookworm, were recruited after obtaining written, informed consent. A single faecal sample was obtained and examined the same day, using the Kato-Katz technique for quantification of intestinal nematode infections. Those who were found infected with hook¬worms were randomized to one of three treatment arms and requested to provide a second faecal sample 10-14 days after treatment. This was examined in the same manner as the first. RESULTS: A total of 892 individuals were recruited; 601 provided faecal samples; 214 were found positive for hookworm infection; 70, 74 and 70 individuals were randomized to treatment arms A (mixture of polymorphs A and C), B (pure polymorph C) and C (placebo) respectively. Follow-up faeca! samples were provided by 53,48 and 49 persons respectively in each treatment arm. The cure rates in the three treatment arms were 28.3%, 18.8% and 16.3% respectively; they were not significantly different from one another. Comparison of faecal egg count reductions (FECR) in the 3 treatment arms (86.1%, 84.5% and -6.6% in arms A, B and C respectively) showed that both mebendazole formulations performed significantly better than placebo, but there was no statistically significant difference between FECR with the two drug formulations. CONCLUSIONS: A single SOOmg dose of mebendazole, either as Polymorph C alone, or as a mixture of Polymorphs A and C, has little efficacy in curing hookworm infections. However, both formulations are significantly better than placebo in reducing the intensity of infection, with no statistically significant difference between the two formulations.