Monitoring the Efficacy of Anthelmintics for the Treatment of Soil Transmitted Helminths P2
Condition: Ascaris Lumbricoides; Ascaris Suum; Trichuris Trichiura; Trichuris Vulpis; Ancylostoma Duodenal; Ancylostoma Caninum; Ancylostoma Ceylanicum; Necator Americanus
Study type: Interventional
Phase: Phase 4

Summary: 
      Objectives:

      The overall objective is to monitor efficacy of mebendazole (MBZ) against Soil-Transmitted
      Helminths (STH).

      The primary objective is:

      (1) to monitor the efficacy a single dose 500 mg of mebendazole (MBZ) against
      Soil-Transmitted Helminths (STH) infections by means of Faecal Egg Count Reduction (FECR) and
      Cure Rate (CR).

      The secondary objectives are:

        1. to assess the occurrence of Necator americanus and Ancylostoma duodenal.

        2. to assess the occurrence of β-tubulin mutations related to resistance before and after
           drug administration.

        3. to evaluate the role of dogs and pigs as reservoir for zoonotic transmission.
    

Detailed description: 
      Primary objective:

      Following obtaining informed consent, schoolchildren in the target age range group will be
      recruited and asked to provide a recent stool sample (an interval of less than 4 hours) that
      will be processed to determine the Faecal Egg Count (FEC) for each Soil-Transmitted Helminths
      (STH) present. For the initial sampling the aim is to enroll at least 250 infected children
      for at least one of the Soil-Transmitted Helminths (STH). This sample size was selected based
      on statistical analysis of study power, using random simulations of correlated over-dispersed
      Faecal Egg Count data reflecting the variance-covariance structure in a selection of real
      Faecal Egg Count (FEC) data sets. This analysis suggested that a sample size of up to 200
      individuals (α = 0.05, power = 80%) was required to detect a 10 percentage point drop from a
      null efficacy of ~ 80% (mean percentage FEC ∆ per individual) over a wide range of infection
      scenarios. Standard power analyses for proportions also indicated that the detection of a ~10
      percentage point drop from a null cure rate required sample sizes up to 200 (the largest
      samples being required to detect departures from null efficacies of around 50%). Given an
      anticipated non-compliance rate of 25%, a sample of 250 infected subjects was therefore
      considered necessary at each study site.

      All children providing stool samples will be treated with mebendazole (MBZ) single table of
      500mg under supervision (chewing + water). The mebendazole (MBZ) will be provided (free) by
      the coordinating group. Seven up to fourteen days (maximum interval) after treatment a second
      faecal sample will be collected from the children to determine again FEC. Subjects who are
      unable to provide a stool sample at follow-up, or who are experiencing a severe concurrent
      medical condition or have diarrhea at time of the first sampling, will be excluded from the
      study.

      Secondary objectives:

      In 5 study sites, faecal samples of 100 infected subjects should be preserved before
      treatment with mebendazole (MBZ) in one tube (1 gram in 10 ml 70% ethanol). Samples of the
      same children should be also preserved again in one tube (1 gram in 10 ml 70% ethanol) after
      treatment. Samples have be send to the Laboratory of Parasitology, Ghent University.

      The samples, collected before and after treatment will be subsequently examined by molecular
      assays the occurrence Necator americanus/Ancylostoma duodenal and the occurrence of β-tubulin
      mutations related to resistance.

      The samples collected before treatment will be subsequently examined by molecular assays to
      assess the role of animals as a reservoir for human Soil-Transmitted Helminths (STH).

      Parasitological techniques, determination of Faecal Egg Count of Soil-Transmitted Helminths
      (STH). All fecal samples were processed using the McMaster egg counting technique for the
      detection and the enumeration of infections with A. lumbricoides, T. trichiura and hookworms.
      All study sites are familiar with the technique and McMaster slides were provided previously.

      Molecular assays (Laboratory of Parasitology, Ghent University)and Deoxyribonucleic acid
      (DNA) extraction.

      DNA of Soil-Transmitted Helminths (STH) will be extracted from the samples preserved in
      ethanol 70% using the Qiagen mini stool kit.

      Molecular identification of Soil-Transmitted Helminths (STH). The presence of the
      Soil-Transmitted Helminths species: Ascaris (n= 2), Trichuris (n = 2) and hookworms (n = 4)
      will be assessed using different molecular assays. For the differentiation of Trichuris
      species, species-specific polymerase chain reaction (PCR) will be applied. For the
      differentiation of Ascaris and the canine hookworms a PCR-Restriction Fragment Length
      Polymorphism (PCR-RFLP) will be used. For the human hookworms, a quantitative PCR will be
      applied.

      Presence of mutations in β-tubulin related to mebendazole (MBZ) resistance This specific
      objective will be performed in collaboration with McGill University (Canada).

      Statistical analysis. Both Cure Rate (CR) and Faecal Egg Count Reduction (FECR) will be
      considered to monitor to efficacy of mebendazole (MBZ) against Soil-Transmitted Helminths.
      The statistical analysis will be assessed as described by Vercruysse et al., 2011.
    

Intervention name(s): Mebendazole
Intervention type(s): Drug
Intervention description(s): All children providing stool samples will be treated with mebendazole single table of 500mg under supervision (chewing + water).
Intervention MeSH terms: Mebendazole; Piperazine; Piperazine citrate; DMP 777
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment