title: Dynamics of pyrethroid resistance in malaria vectors in southern Benin following a large scale implementation of vector control interventions.
abstract: Large-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014. The purpose of this study was to monitor the frequency and mechanisms of pyrethroid resistance in malaria vectors following the implementation of vector control tools for malaria prevention.
  
  
  
  Anopheles larvae were collected in 13 villages twice a year from 2012 to 2014. WHO tube tests were used to assess the phenotypic resistance of each population to 0.05 % deltamethrin. Sibling species within Anopheles gambiae complex were identified by PCR techniques. Taqman and biochemical assays were performed to identify the presence of kdr mutations in individual mosquitoes and to detect any increase in the activity of enzymes putatively involved in insecticide metabolism (oxidases, esterase and glutathione-S-transferases). Quantitative real time PCR was used to measure the expression of three metabolic genes involved in pyrethroid resistance (CYP6P3, CYP6M2 and GSTD3).
  
  
  
  Anopheles populations showed < 90 % mortality to deltamethrin in all villages and at all time points. The 1014 F kdr allele frequency was close to fixation (> 0.9) over the sampling periods in both An. gambiae and An. coluzzii. Biochemical assays showed higher activities of alpha esterase and GST in field malaria vector populations compared to susceptible mosquitoes. qPCR assays showed a significant increase of CYP6P3, CYP6M2 GSTD3 expression in An. gambiae after a three-year implementation of LLINs.
  
  
  
  The study confirmed that deltamethrin resistance is widespread in malaria vectors in Southern Benin. We suspect that the increase in deltamethrin resistance between 2012 and 2014 resulted from an increased expression of metabolic detoxification genes (CYP6M2 and CYP6P3) rather than from kdr mutations. It is urgent to evaluate further the impact of metabolic resistance on the efficacy of vector control interventions using pyrethroid insecticides.
authors.affiliation: Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), UMR UM1-UM2 - CNRS 5290 - IRD 224, Montpellier, France. gildas.yahouedo@ird.fr.|Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin. gildas.yahouedo@ird.fr.
authors.forename: Gildas A
authors.initials: GA
authors.lastname: Yahouédo
authors.affiliation: Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), UMR UM1-UM2 - CNRS 5290 - IRD 224, Montpellier, France.|Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cornelie
authors.affiliation: Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), UMR UM1-UM2 - CNRS 5290 - IRD 224, Montpellier, France.|Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Innocent
authors.initials: I
authors.lastname: Djègbè
authors.affiliation: Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Justine
authors.initials: J
authors.lastname: Ahlonsou
authors.affiliation: Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Sidick
authors.initials: S
authors.lastname: Aboubakar
authors.affiliation: Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Christophe
authors.initials: C
authors.lastname: Soares
authors.affiliation: Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Bénin.
authors.forename: Martin
authors.initials: M
authors.lastname: Akogbéto
authors.affiliation: Institut de Recherche pour le Développement (IRD), Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle (MIVEGEC), UMR UM1-UM2 - CNRS 5290 - IRD 224, Montpellier, France.|Department of Entomology, Faculty of Agriculture, Kasetsart University, 50 Ngam Wong Wan Rd, Lat Yao Chatuchak, Bangkok, 10900, Thailand.
authors.forename: Vincent
authors.initials: V
authors.lastname: Corbel
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001541:Benin / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007303:Insect Vectors / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D007814:Larva; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D009032:Mosquito Control; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin
keywords: Anopheles; Insecticide resistance; Malaria; Metabolic gene; Vector control; kdr