title: Insecticide resistance profile of Anopheles gambiae from a phase II field station in Cové, southern Benin: implications for the evaluation of novel vector control products.
abstract: BACKGROUND
  Novel indoor residual spraying (IRS) and long-lasting insecticidal net (LLIN) products aimed at improving the control of pyrethroid-resistant malaria vectors have to be evaluated in Phase II semi-field experimental studies against highly pyrethroid-resistant mosquitoes. To better understand their performance it is necessary to fully characterize the species composition, resistance status and resistance mechanisms of the vector populations in the experimental hut sites.
  
  
  METHODS
  Bioassays were performed to assess phenotypic insecticide resistance in the malaria vector population at a newly constructed experimental hut site in Cové, a rice growing area in southern Benin, being used for WHOPES Phase II evaluation of newly developed LLIN and IRS products. The efficacy of standard WHOPES-approved pyrethroid LLIN and IRS products was also assessed in the experimental huts. Diagnostic genotyping techniques and microarray studies were performed to investigate the genetic basis of pyrethroid resistance in the Cové Anopheles gambiae population.
  
  
  RESULTS
  The vector population at the Cové experimental hut site consisted of a mixture of Anopheles coluzzii and An. gambiae s.s. with the latter occurring at lower frequencies (23 %) and only in samples collected in the dry season. There was a high prevalence of resistance to pyrethroids and DDT (>90 % bioassay survival) with pyrethroid resistance intensity reaching 200-fold compared to the laboratory susceptible An. gambiae Kisumu strain. Standard WHOPES-approved pyrethroid IRS and LLIN products were ineffective in the experimental huts against this vector population (8-29 % mortality). The L1014F allele frequency was 89 %. CYP6P3, a cytochrome P450 validated as an efficient metabolizer of pyrethroids, was over-expressed.
  
  
  CONCLUSIONS
  Characterizing pyrethroid resistance at Phase II field sites is crucial to the accurate interpretation of the performance of novel vector control products. The strong levels of pyrethroid resistance at the Cové experimental hut station make it a suitable site for Phase II experimental hut evaluations of novel vector control products, which aim for improved efficacy against pyrethroid-resistant malaria vectors to WHOPES standards. The resistance genes identified can be used as markers for further studies investigating the resistance management potential of novel mixture LLIN and IRS products tested at the site.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. corine.ngufor@lshtm.ac.uk.|Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. corine.ngufor@lshtm.ac.uk.|Pan African Malaria Vector Research Consortium, London, UK. corine.ngufor@lshtm.ac.uk.
authors.forename: Corine
authors.initials: C
authors.lastname: Ngufor
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. raphaelnguessan@yahoo.fr.|Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. raphaelnguessan@yahoo.fr.|Pan African Malaria Vector Research Consortium, London, UK. raphaelnguessan@yahoo.fr.
authors.forename: Raphael
authors.initials: R
authors.lastname: N'Guessan
authors.affiliation: Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. laurenjos2010@yahoo.fr.
authors.forename: Josias
authors.initials: J
authors.lastname: Fagbohoun
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK. krishanthi.subramaniam@lstmed.ac.uk.
authors.forename: Krishanthi
authors.initials: K
authors.lastname: Subramaniam
authors.affiliation: Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. abibatho@yahoo.fr.
authors.forename: Abibatou
authors.initials: A
authors.lastname: Odjo
authors.affiliation: Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. Fongnikin@live.fr.
authors.forename: Augustin
authors.initials: A
authors.lastname: Fongnikin
authors.affiliation: Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin. akogbetom@yahoo.fr.
authors.forename: Martin
authors.initials: M
authors.lastname: Akogbeto
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK. david.weetman@lstmed.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Weetman
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. mark.rowland@lshtm.ac.uk.|Pan African Malaria Vector Research Consortium, London, UK. mark.rowland@lshtm.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Rowland
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D001541:Benin; D001681:Biological Assay; D005260:Female; D060005:Genotyping Techniques; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D046228:Microarray Analysis; D016019:Survival Analysis
chemical_list: D007306:Insecticides