Study to Test Whether Shoes Protect Children Against Hookworm Infection on Pemba Island, Zanzibar
Condition: Hookworm
MeSH terms: Hookworm Infections; Ancylostomiasis
Study type: Interventional

Summary: 
      Small association studies have hypothesised that shoes protect against hookworm infection.
      The purpose of this pragmatic study was determine, under field conditions, whether school-age
      children on Pemba Island, Zanzibar, would wear shoes and if shoes protected them against
      hookworm infection.
    

Detailed description: 
      Aim: To carry out a cluster randomised controlled trial (non-blinded) to test under field
      conditions whether the provision of shoes to school-aged children on Pemba Island, Zanzibar,
      an area of high hookworm prevalence and anaemia, could reduce the transmission, incidence and
      disease burden of hookworm infection among this susceptible population.

      Methods:

      Setting: Pemba Island is the northern of the two main islands that make up the Zanzibar
      archipelago, situated in the Indian Ocean and close to the coast of East Africa, just below
      the equator. The climate is tropical and humid and the island has two rainy seasons, from
      March-June (Masika) and October-December (Vuli). Humidity is high, up to 1000mm during the
      Masika rains. Economic activities are mainly agriculture and fishing and considerable
      improvements to infrastructure - roads and electricity - have been made in recent years. The
      island's population totalled 460,196 in 2008, of whom 50 percent were children aged <15
      years. Zanzibar is an autonomous part of the United Republic of Tanzania and on the mainland,
      the under 5 mortality rate (U5MR) is 81 per 1,000 live births but is substantially higher on
      Zanzibar at 116 per 1,000 live births. The area is highly endemic for soil transmitted
      helminths - a recent study on neighbouring Unguja Island found three-quarters of rural
      inhabitants and half of urban inhabitants to be infected with parasitic worms, despite 15
      years of mass drug treatment. Other risk factors for concomitant anaemia are poor nutrition,
      focal areas of Schistosoma haematobium transmission and malaria, although recent control
      efforts have made impressive reductions in malaria transmission (reduced to 0.8% prevalence
      in 2007).

      Study schools (clusters): 12 government primary schools from across the entire island were
      identified for the trial, where hookworm prevalence in a previous survey totalled >50%:
      Mizingani, Ng'ombeni, Chambani, Uwandani, Bagamoyo, Shumba Viamboni, Mkanyageni, Ziwani,
      Wesha, Tumbe, Wingwi, and Ngwachani.

      Study design: Pragmatic, cluster (non-blinded) randomised controlled trial with school-aged
      children randomized to either the intervention (a pair of shoes alongside standard care) or
      standard care (periodic de-worming with antihelminthics and health education). Children
      already wearing shoes were advised to continue to do so in the control arm.

      Sample size: The study aimed for 80% power and 5% significance, adjusted for cluster design,
      to look for a 25% reduction in hookworm prevalence, a 25% reduction in hookworm incidence and
      a 40% reduction in the geometric mean of residual hookworm infection intensity in the
      intervention arm, based on survey data at selected schools which showed >50% prevalence of
      hookworm infection in 2010. Using a sample size calculation in Stata 11.2 (StataCorp, 2009),
      adjusted for cluster design, the study needed to enrol an average 77 children in each of the
      12 clusters (n=924, 462 in each arm), using a correlation coefficient of 0.01. A greater
      number of clusters would have been preferable but available resources limited the study
      design to 12 schools.

      Inclusion criteria: Healthy school children were randomly selected (but stratified by class
      and sex) from 12 schools selected for enrolment into the trial. Stratification took place as
      follows: Class 1 at each school was called in and boys and girls divided into two groups. The
      children were then asked to count off '1', '2' along the line they had formed up in and then
      either the 1s or the 2s were asked to file out. The first 10 children in each group remaining
      (10 girls and 10 boys so 20 children in each class) were given a sample pot and a consent
      form to take home to their parents. This was repeated for all 5 primary school classes at
      each of the 12 schools.

      Exclusions: children whose parents did not consent to the participation of their child in the
      trial or children who have had a life-threatening allergic reaction to Albendazole.

      Baseline characteristics: were collected from enrolled children attending schools in both
      arms. A short questionnaire was used to collect information on age, sex, housing
      characteristics and other measures of wealth, sanitation at home and at school, footwear use
      (both observed and subjective), history of recent illness, when the child last had an
      antihelminthic drug (for Schistosomiasis or STHs) and bed net use.

      Parasitology: 1 stool sample from each child at baseline (July 2011) and six months after
      shoe distribution (October 2012) was examined at the Public Health Laboratory (PHL), Pemba
      Island, using the Kato-Katz method, to measure both prevalence of soild transmitted helminths
      (STH) and STH infection intensity in eggs/gram of stool. To minimise hookworm egg loss, the
      stool was collected at the beginning of the school day and placed in a coolbox while waiting
      for transfer to Pemba's Public Health Laboratory and then processed on arrival. An average 10
      percent of sample slides were re-checked for quality control by the most experienced
      microscopist.

      Randomisation of clusters: Simple randomisation was used where schools were entered into an
      Excel (Microsoft, 2010) spreadsheet and the "RAND" function was used to assign random numbers
      between 0 and 1. The six lowest numbers were assigned to the intervention arm and the six
      highest were assigned to the control arm before baseline data was gathered. Given the nature
      of the intervention, the trial is non-blinded.

      Data handling: Baseline data was analysed using Stata 11.2 (StataCorp, 2009). Subsequent data
      was analysed using SOFA Statistics Version 1.3.2 (Paton-Simpson and Associatiates Ltd, 2012).
      Data containing identity numbers but no names was stored on password-protected computers and
      available only to the prinicipal investigator, the co-principal investigator and the study's
      supervisor. Study registration details (to identify children with heavy hookworm load and for
      subsequent follow-up) are stored at the Public Health Laboratory, Pemba island.

      Shoe distribution: Shoes were distributed to all schools' pupils in the intervention arm (ie
      not only those being monitored in the trial, with approximately 6,500 pupils receiving a pair
      of shoes) to ensure trial subjects did not stand out from their peers; government sponsored
      de-worming and healthcare education (one stat dose Albendazole 400mg) continued for all
      schools' pupils in both intervention and control arms.

      Ethics approval: The study protocol was approved by both the Zanzibar Medical Research and
      Ethics Committee (ZAMREC) and the MSc Ethics Committee of the London School of Hygiene and
      Tropical Medicine. Approval was also sought and granted from Zanzibar's Ministry of Education
      at a presentation and meeting of ministry officials and school head teachers at the Public
      Health laboratory, Pemba Island.

      Consent: Consent forms, providing a detailed description of the trial in plain language and
      translated into Swahili, were distributed to children eligible for the study (see enrolment
      below) to take home to their parents or primary carers. It was explained to parents that they
      were free to remove their children from the study at any time. A telephone number to the
      research team was made available to parents (and was used on several occasions) in case
      parents had any questions or concerns. A child was enrolled in the study only if they brought
      a signed consent form with their stool sample.

      Safety monitoring and treatment: All children in both the intervention and control arms of
      the trial were treated for soil transmitted helminths as part of the Zanzibar government's
      ongoing mass drug treatment programme. Both shoes and Albendazole (de-worming drug) have
      established safety profiles and therefore monitoring between each phases of the trial was not
      considered necessary. Children in the study found to have heavy hookworm infection (>4,000
      eggs per gram of stool) were treated by a paediatrician with stat Mebendazole (Vermox 100mg
      twice daily for 3 days) and 10 days of Ferrous gluconate syrup (10mls twice daily - dosing
      for 6-18 year-olds) directly following diagnosis.
    

Intervention name(s): Shoes
Intervention type(s): Device
Intervention description(s): A unisex canvas slip-on with a sturdy sole.
Other intervention name(s): 'Giving Shoe' produced by TOMS Shoes, Los Angeles, California, USA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: hookworm; necator americanus; ancyclostoma duodenale; shoes; anaemia; children