title: Assessing the interruption of the transmission of human helminths with mass drug administration alone: optimizing the design of cluster randomized trials.
abstract: A method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant).
  
  
  
  The methodological approach first uses an age-structured deterministic model to predict the MDA coverage required for treating pre-school aged children (Pre-SAC), school aged children (SAC) and adults (Adults) to eliminate transmission (crossing the breakpoint in transmission created by sexual mating in dioecious helminths) with 3 rounds of annual MDA. Stochastic individual-based models are then used to calculate the positive and negative predictive values (PPV and NPV, respectively, for observing elimination or the bounce back of infection) for a defined prevalence of infection 2 years post the cessation of MDA. For the arm only involving the treatment of Pre-SAC and SAC, the failure rate is predicted to be very high (particularly for hookworm-infected villages) unless transmission intensity is very low (R0, or the effective reproductive number R, just above unity in value).
  
  
  
  The calculations are designed to consider various trial arms and stratifications; namely, community-based treatment and Pre-SAC and SAC only treatment (the two arms of the trial), different STH transmission settings of low, medium and high, and different STH species mixes. Results are considered in the light of the complications introduced by the choice of statistic to define success or failure, varying adherence to treatment, migration and parameter uncertainty.
authors.affiliation: Department of Infectious Disease Epidemiology, London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK. roy.anderson@imperial.ac.uk.
authors.forename: Roy
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Infectious Disease Epidemiology, London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Farrell
authors.affiliation: Department of Infectious Disease Epidemiology, London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
authors.forename: Hugo
authors.initials: H
authors.lastname: Turner
authors.affiliation: DeWorm3, Natural History Museum London, London, UK.|Departments of Global Health, Medicine, Pediatrics and Epidemiology, University of Washington, Seattle, USA.
authors.forename: Judd
authors.initials: J
authors.lastname: Walson
authors.affiliation: Department of Infectious Disease Epidemiology, London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: Department of Infectious Disease Epidemiology, London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
authors.forename: James
authors.initials: J
authors.lastname: Truscott
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003153:Community Health Services / Q000379:methods; D003695:Delivery of Health Care; D060740:Disease Eradication / Q000379:methods*; D005260:Female; D006373:Helminthiasis / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission*; D006376:Helminths / Q000302:isolation & purification; D006725:Hookworm Infections / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D012987:Soil / Q000469:parasitology; D013269:Stochastic Processes
chemical_list: D000871:Anthelmintics; D012987:Soil
keywords: Cluster randomized trial design; Interrupting transmission; Mass drug administration impact; Soil-transmitted helminths; Stochastic models of transmission