title: Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation.
abstract: BACKGROUND
  Progress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper.
  
  
  METHODS
  Malaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively.
  
  
  RESULTS
  Cohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016.
  
  
  CONCLUSIONS
  The paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design.
authors.affiliation: MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Immo.Kleinschmidt@lshtm.ac.uk.|School of Public Health, University of the Witwatersrand, Johannesburg, South Africa. Immo.Kleinschmidt@lshtm.ac.uk.
authors.forename: Immo
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authors.lastname: Kleinschmidt
authors.affiliation: Global Malaria Programme, World Health Organization, Avenue Appia, Geneva, Switzerland. mnzavaa@who.int.
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authors.initials: AP
authors.lastname: Mnzava
authors.affiliation: Federal Ministry of Health, PO Box 1204, Khartoum, Sudan. hmoodatuok@gmail.com.
authors.forename: Hmooda Toto
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authors.affiliation: KEMRI Centre for Geographic Medicine Research Coast, P.O. Box 230, Kilifi, 80108, Kenya. CMbogo@kemri-wellcome.org.
authors.forename: Charles
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authors.lastname: Mbogo
authors.affiliation: Khartoum State Malaria Control Programme, VBDC, P.O. Box 1517, Khartoum, Sudan. bashiradam69@yahoo.co.uk.|School of Biological Sciences, Universiti Sains Malaysia (USM), 11800, Pulau Pinang, Malaysia. bashiradam69@yahoo.co.uk.
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authors.affiliation: National Reference Unit (NRU) for Vector Control, The Biotechnology Center, University of Yaoundé I, Messa, P.O. Box 3851, Yaoundé, Cameroon. jbigoga@gmail.com.
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authors.affiliation: Ministry of Health, Wad Madani, Gezera State, Sudan. fatihmmalik@gmail.com.
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authors.affiliation: Global Malaria Programme, World Health Organization, Avenue Appia, Geneva, Switzerland. nkuni50@yahoo.com.
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authors.affiliation: Organisation de Coordination pour la Lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroon. josyet2@gmail.com.|Faculty of Medicine and Pharmaceutical Sciences, University of Douala, PO Box 2701, Douala, Cameroon. josyet2@gmail.com.
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authors.forename: John
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authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. martin.donnelly@lstmed.ac.uk.|Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. martin.donnelly@lstmed.ac.uk.
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mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D002675:Child, Preschool; D009033:Culicidae / Q000187:drug effects*; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D007303:Insect Vectors / Q000187:drug effects*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology; D008288:Malaria / Q000453:epidemiology* / Q000517:prevention & control* / Q000635:transmission; D009032:Mosquito Control / Q000379:methods; D015995:Prevalence
chemical_list: D007306:Insecticides