title: Phenotypic effects of concomitant insensitive acetylcholinesterase (ace-1(R)) and knockdown resistance (kdr(R)) in Anopheles gambiae: a hindrance for insecticide resistance management for malaria vector control.
abstract: BACKGROUND
  Malaria is endemic in sub-Saharan Africa with considerable burden for human health. Major insecticide resistance mechanisms such as kdr(R) and ace-1(R) alleles constitute a hindrance to malaria vector control programs. Anopheles gambiae bearing both kdr and ace-1 resistant alleles are increasingly recorded in wild populations. In order to maintain the efficacy of vector control strategies, the characterization of concomitant kdr and ace-1 resistance, and their pleiotropic effects on malaria vector phenotype on insecticide efficacy are important.
  
  
  METHODS
  Larval and adult bioassays were performed with different insecticide classes used in public health following WHO standard guidelines on four laboratory Anopheles gambiae strains, sharing the same genetic background but harboring distinct resistance status: KISUMU with no resistance allele; ACERKIS with ace-1(R) allele; KISKDR with kdr(R) allele and ACERKDRKIS with both resistance alleles' ace-1(R) and kdr(R) .
  
  
  RESULTS
  Larval bioassays indicate that the homozygote resistant strain harboring both alleles (ACERKDRKIS) displayed slightly but significantly higher resistance level to various insecticides like carbamates (bendiocarb, p < 0.001; propoxur, p = 0.02) and organophosphates (chlorpyriphos-methyl, p = 0.002; fenitrothion, p < 0.001) when compared to ACERKIS strain. However, no differences were recorded between ACERKDRKIS and KISKDR resistance level against permethrin (Pyrethroid, p = 0.7) and DDT (Organochlorine, p = 0.24). For adult bioassays, the percentages of mosquitoes knocked down were significantly lower for ACERKDRKIS than for KISKDR with permethrin (p = 0.003) but not with deltamethrin. The percentage of mortality from adult bioassays was similar between ACERKDRKIS and ACERKIS with carbamates and organophosphates, or between ACERKDRKIS and KISKDR with pyrethroid and DDT. Concerning acetylcholinesterase enzyme, ACERKDRKIS strain showed similarAChE1 activity than that of ACERKIS.
  
  
  CONCLUSIONS
  The presence of both kdr(R) and ace-1(R) alleles seems to increase the resistance levels to both carbamate and organophosphate insecticides and at operational level, may represent an important threat to malaria vector control programs in West Africa.
authors.affiliation: Institut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918, Cotonou, Benin. assobe80@gmail.com.|Institut des Sciences de l'Evolution de Montpellier (UMR 5554, CNRS-UM2-IRD), Université Montpellier 2, Montpellier, France. assobe80@gmail.com.
authors.forename: Benoît S
authors.initials: BS
authors.lastname: Assogba
authors.affiliation: Institut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918, Cotonou, Benin. ldjogbenou22002@yahoo.fr.
authors.forename: Luc S
authors.initials: LS
authors.lastname: Djogbénou
authors.affiliation: Institut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918, Cotonou, Benin. saizonoujacques@yahoo.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Saizonou
authors.affiliation: Institut des Sciences de l'Evolution de Montpellier (UMR 5554, CNRS-UM2-IRD), Université Montpellier 2, Montpellier, France. pascal.milesi@univ-montp2.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Milesi
authors.affiliation: Institut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918, Cotonou, Benin. djoslaure@yahoo.fr.
authors.forename: Laurette
authors.initials: L
authors.lastname: Djossou
authors.affiliation: Institut de Recherche pour le Développement (IRD), MIVEGEC (UMR 224-CNRS 5290-UM1-UM2), Centre de Recherche Entomologique de Cotonou (CREC), Cotonou, Benin. djegbe1@yahoo.fr.
authors.forename: Innocent
authors.initials: I
authors.lastname: Djegbe
authors.affiliation: Centre de Recherche Entomologique de Cotonou (CREC), Health Ministry, Cotonou, Bénin. achiloswek@yahoo.fr.
authors.forename: Welbeck A
authors.initials: WA
authors.lastname: Oumbouke
authors.affiliation: Institut de recherche pour le développement, Unité Mixte de Recherche MIVEGEC (IRD 224-CNRS 5290-UM1-UM2), Montpellier, France. fabrice.chandre@ird.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chandre
authors.affiliation: Faculté des Sciences et Techniques, Laboratoire de Biologie et de Typage Moléculaire en Microbiologie, Université d'Abomey Calavi, 05 BP 1604, Cotonou, Benin. laminesaid@yahoo.fr.
authors.forename: Lamine
authors.initials: L
authors.lastname: Baba-Moussa
authors.affiliation: Institut des Sciences de l'Evolution de Montpellier (UMR 5554, CNRS-UM2-IRD), Université Montpellier 2, Montpellier, France. mylene.weill@univ-montp2.fr.
authors.forename: Mylene
authors.initials: M
authors.lastname: Weill
authors.affiliation: Institut Régional de Santé Publique, Université d'Abomey Calavi, 01BP918, Cotonou, Benin. makoutod@gmail.com.
authors.forename: Michel
authors.initials: M
authors.lastname: Makoutodé
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000235:genetics*; D001681:Biological Assay; D015971:Gene Expression Regulation, Enzymologic; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects
chemical_list: D007306:Insecticides; D000110:Acetylcholinesterase