title: Emerging knock-down resistance in Anopheles arabiensis populations of Dakar, Senegal: first evidence of a high prevalence of kdr-e mutation in West African urban area.
abstract: BACKGROUND
  Urban malaria is now considered a major emerging health problem in Africa and urban insecticide resistance may represent a serious threat to the ambitious programme of further scaling-up coverage with long-lasting insecticide-treated bed nets and indoor residual spray. This study evaluates the levels and mechanisms of insecticide resistance in Anopheles gambiae populations in 44 urban areas of Dakar in a longitudinal entomological surveillance study.
  
  
  METHODS
  Adult mosquitoes sampled by night-landing catches at 44 sites across Dakar from 2007 to 2010 were genotyped to assess the frequency and distribution of resistance alleles. In addition World Health Organization susceptibility tests to six insecticides were performed on F0 adults issuing from immature stages of An. gambiae s.l. sampled in August 2010, 2011 and 2012 in three sites of Dakar: Pikine, Thiaroye and Almadies and repeated in 2012 with three of the insecticides after PBO exposure to test for mechanisms of oxydase resistance. Species, molecular forms and the presence of kdr and ace-1 mutations were assessed by polymerase chain reaction.
  
  
  RESULTS
  High frequencies of the kdr-e allele, ranging from 35 to 100 %, were found in Anopheles arabiensis at all 44 sites. The insecticide susceptibility tests indicated sensitivity to bendiocarb in Almadies in 2010 and 2011 and in Yarakh between 2010 and 2012 and sensitivity to fenitrothion in Almadies in 2010. The mortality rate of EE genotype mosquitoes was lower and that of SS mosquitoes was higher than that of SE mosquitoes, while the mortality rate of the SW genotype was slightly higher than that of the SE genotype. Pyperonyl butoxide (PBO) had a significant effect on mortality in Pikine (OR = 1.4, 95 % CI = 1.3-1.5, with mortality of 42-55 % after exposure and 11-17 % without PBO) and Yarakh (OR = 1.6, 95 % CI = 1.4-1.7, with mortality of 68-81 % after exposure and 23-37 % without), but not in Almadies (OR = 1.0, 95 % CI = 0.9-1.1).
  
  
  CONCLUSIONS
  A high prevalence of kdr-e in West Africa was demonstrated, and knock-down resistance mechanisms predominate although some oxidases mechanisms (cytochrome P450 monooxygenases) also occur. In view of the increased use of insecticides and the proposed role of the kdr gene in the susceptibility of Anopheles to Plasmodium, this finding will significantly affect the success of vector control programmes.
authors.affiliation: Groupe G4 Institut Pasteur International Network, Institut Pasteur de Bangui, BP 237, Bangui, Central African Republic. ousmane.ndiath@gmail.com.|Laboratoire de Paludologie et de Zoologie, Campus UCAD-IRD, BP 1386, CP 18524, Dakar, Senegal. ousmane.ndiath@gmail.com.
authors.forename: Mamadou Ousmane
authors.initials: MO
authors.lastname: Ndiath
authors.affiliation: Afrique One, Centre Suisse de Recherches Scientifiques, 01 BP 1303, Abidjan, Côte d'Ivoire. aurelie.cailleau@gmail.com.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cailleau
authors.affiliation: UMR 6236, Unité d'entomologie médicale, IRBA antenne Marseille, GSBDD Marseille Aubagne, 111 avenue de la Corse, BP 40026, 13568, Marseille Cedex 2, France. eve.pradines@yahoo.fr.
authors.forename: Eve
authors.initials: E
authors.lastname: Orlandi-Pradines
authors.affiliation: The Roslin Institute, The University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK. paul.bessell@roslin.ed.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Bessell
authors.affiliation: UMR 6236, Unité d'entomologie médicale, IRBA antenne Marseille, GSBDD Marseille Aubagne, 111 avenue de la Corse, BP 40026, 13568, Marseille Cedex 2, France. frederic.pages@yahoo.com.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Pagès
authors.affiliation: Laboratoire de Paludologie et de Zoologie, Campus UCAD-IRD, BP 1386, CP 18524, Dakar, Senegal. jean-francois.trape@ird.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.affiliation: UMR 6236, Unité d'entomologie médicale, IRBA antenne Marseille, GSBDD Marseille Aubagne, 111 avenue de la Corse, BP 40026, 13568, Marseille Cedex 2, France. crogier@pasteur.mg.|Institut Pasteur de Madagascar, BP 1274, Ambohitrakely, 101, Antananarivo, Madagascar. crogier@pasteur.mg.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics; D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000235:genetics*; D002947:Cities; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D007305:Insecticide Resistance; D008137:Longitudinal Studies; D009154:Mutation; D016133:Polymerase Chain Reaction; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D015995:Prevalence; D012675:Senegal
chemical_list: D024642:Potassium Channels, Voltage-Gated; D003577:Cytochrome P-450 Enzyme System; D000110:Acetylcholinesterase