title: New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel.
abstract: BACKGROUND
  By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.
  
  
  METHODS
  We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.
  
  
  RESULTS
  We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90% threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.
  
  
  CONCLUSIONS
  Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals.
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine (St Mary's Campus), Imperial College London, London, W2 1PG, UK. m.walker06@imperial.ac.uk.|London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK. m.walker06@imperial.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Walker
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine (St Mary's Campus), Imperial College London, London, W2 1PG, UK. tarub.mabud@gmail.com.|Present address: Stanford School of Medicine, 291 Campus Drive, Stanford, CA, 94305, USA. tarub.mabud@gmail.com.
authors.forename: Tarub S
authors.initials: TS
authors.lastname: Mabud
authors.affiliation: UNICEF/UNDP/World Bank/WHO Special Programme on Research and Training in Tropical Diseases (TDR), World Health Organization, Av. Appia 20, CH-1211, Geneva 27, Switzerland. olliarop@who.int.|Centre for Tropical Medicine and Global Health Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. olliarop@who.int.
authors.forename: Piero L
authors.initials: PL
authors.lastname: Olliaro
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002, Basel, Switzerland. couljeanvae@yahoo.fr.|University of Basel, P.O. Box, CH-4003, Basel, Switzerland. couljeanvae@yahoo.fr.|Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, 22 BP 770, Abidjan 22, Côte d'Ivoire. couljeanvae@yahoo.fr.|Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, 01 BP 1303, Abidjan 01, Côte d'Ivoire. couljeanvae@yahoo.fr.
authors.forename: Jean T
authors.initials: JT
authors.lastname: Coulibaly
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, 44106, USA. chk@case.edu.|Schistosomiasis Consortium for Operational Research and Evaluation, University of Georgia, 500 D W Brooks Drive, Athens, GA, 30602, USA. chk@case.edu.
authors.forename: Charles H
authors.initials: CH
authors.lastname: King
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002, Basel, Switzerland. giovanna.raso@unibas.ch.|University of Basel, P.O. Box, CH-4003, Basel, Switzerland. giovanna.raso@unibas.ch.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Raso
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. alexandra.scherrer@usz.ch.
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.affiliation: Department of Parasitology, London School of Tropical Medicine, Liverpool, L3 5QA, UK. russell.stothard@lstmed.ac.uk.
authors.forename: J Russell
authors.initials: JR
authors.lastname: Stothard
authors.affiliation: Centro de Investigação em Saúde de Angola (Health Research Center in Angola), Rua direita do Caxito, Hospital Provincial, Bengo, Angola. josecarlos.figueiredo@gmail.com.|Department of Life Sciences, Natural History Museum, Wolfson Wellcome Biomedical Laboratories, Cromwell Road, London, SW7 5BD, UK. josecarlos.figueiredo@gmail.com.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Sousa-Figueiredo
authors.affiliation: Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany. kata.stete@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Stete
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002, Basel, Switzerland. juerg.utzinger@unibas.ch.|University of Basel, P.O. Box, CH-4003, Basel, Switzerland. juerg.utzinger@unibas.ch.
authors.forename: Jürg
authors.initials: J
authors.lastname: Utzinger
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine (St Mary's Campus), Imperial College London, London, W2 1PG, UK. m.basanez@imperial.ac.uk.|London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK. m.basanez@imperial.ac.uk.
authors.forename: Maria-Gloria
authors.initials: MG
authors.lastname: Basáñez
mesh_terms: D000293:Adolescent; D000349:Africa / Q000453:epidemiology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005243:Feces / Q000469:parasitology; D005260:Female; D006373:Helminthiasis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010063:Ovum; D011223:Praziquantel / Q000494:pharmacology*; D012551:Schistosomatidae / Q000187:drug effects*; D012552:Schistosomiasis / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000871:Anthelmintics; D011223:Praziquantel
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