title: Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration.
abstract: Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane.
  
  
  
  We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6-12 years before and 25-27 days after treatment with praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds.
  
  
  
  The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%-93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%-99.08%) or 1 round (95% BCI, 95.51%-98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8-9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal praziquantel efficacy set by the World Health Organization.
  
  
  
  The reduced efficacy of praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored.
authors.affiliation: Department of Infectious Disease Epidemiology and the London Centre for Neglected Tropical Disease Research, Imperial College London, St Mary's Campus Wellcome Trust Sanger Institute, Hinxton Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Hertfordshire.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crellen
authors.affiliation: Department of Infectious Disease Epidemiology and the London Centre for Neglected Tropical Disease Research, Imperial College London, St Mary's Campus.
authors.forename: Martin
authors.initials: M
authors.lastname: Walker
authors.affiliation: Department of Infectious Disease Epidemiology and the London Centre for Neglected Tropical Disease Research, Imperial College London, St Mary's Campus Institute of Biodiversity, Animal Health & Comparative Medicine and Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, United Kingdom.
authors.forename: Poppy H L
authors.initials: PH
authors.lastname: Lamberton
authors.affiliation: Division of Vector Bourne Diseases, Ministry of Health, Kampala, Uganda.
authors.forename: Narcis B
authors.initials: NB
authors.lastname: Kabatereine
authors.affiliation: Division of Vector Bourne Diseases, Ministry of Health, Kampala, Uganda.
authors.forename: Edridah M
authors.initials: EM
authors.lastname: Tukahebwa
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton.
authors.forename: James A
authors.initials: JA
authors.lastname: Cotton
authors.affiliation: Department of Infectious Disease Epidemiology and the London Centre for Neglected Tropical Disease Research, Imperial College London, St Mary's Campus Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Hertfordshire.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Webster
mesh_terms: D000818:Animals; D002648:Child; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D000074381:Mass Drug Administration; D015233:Models, Statistical; D010270:Parasite Egg Count; D011223:Praziquantel / Q000008:administration & dosage / Q000627:therapeutic use*; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D012556:Schistosomicides / Q000008:administration & dosage / Q000627:therapeutic use*; D014454:Uganda
chemical_list: D012556:Schistosomicides; D011223:Praziquantel
keywords: anthelmintic efficacy; generalized linear mixed model; parasite; praziquantel; schistosomiasis