title: Evidence of multiple pyrethroid resistance mechanisms in the malaria vector Anopheles gambiae sensu stricto from Nigeria.
abstract: Pyrethroid insecticide resistance in Anopheles gambiae sensu stricto is a major concern to malaria vector control programmes. Resistance is mainly due to target-site insensitivity arising from a single point mutation, often referred to as knockdown resistance (kdr). Metabolic-based resistance mechanisms have also been implicated in pyrethroid resistance in East Africa and are currently being investigated in West Africa. Here we report the co-occurrence of both resistance mechanisms in a population of An. gambiae s.s. from Nigeria. Bioassay, synergist and biochemical analysis carried out on resistant and susceptible strains of An. gambiae s.s. from the same geographical area revealed >50% of the West African kdr mutation in the resistant mosquitoes but <3% in the susceptible mosquitoes. Resistant mosquitoes synergized using pyperonyl butoxide before permethrin exposure showed a significant increase in mortality compared with the non-synergized. Biochemical assays showed an increased level of monooxygenase but not glutathione-S-transferase or esterase activities in the resistant mosquitoes. Microarray analysis using the An. gambiae detox-chip for expression of detoxifying genes showed five over-expressed genes in the resistant strain when compared with the susceptible one. Two of these, CPLC8 and CPLC#, are cuticular genes not implicated in pyrethroid metabolism in An. gambiae s.s, and could constitute a novel set of candidate genes that warrant further investigation.
authors.affiliation: Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria. awololas@hotmail.com
authors.forename: T S
authors.initials: TS
authors.lastname: Awolola
authors.forename: O A
authors.initials: OA
authors.lastname: Oduola
authors.forename: C
authors.initials: C
authors.lastname: Strode
authors.forename: L L
authors.initials: LL
authors.lastname: Koekemoer
authors.forename: B
authors.initials: B
authors.lastname: Brooke
authors.forename: H
authors.initials: H
authors.lastname: Ranson
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000235:genetics*; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000235:genetics*; D008288:Malaria / Q000235:genetics / Q000635:transmission; D009032:Mosquito Control; D009549:Nigeria; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation / Q000235:genetics*; D011722:Pyrethrins / Q000494:pharmacology
chemical_list: D007306:Insecticides; D011722:Pyrethrins