title: Widespread pyrethroid and DDT resistance in the major malaria vector Anopheles funestus in East Africa is driven by metabolic resistance mechanisms.
abstract: BACKGROUND
  Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms.
  
  
  RESULTS
  Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance.
  
  
  CONCLUSIONS
  The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management.
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom; Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Charles
authors.initials: C
authors.lastname: Mulamba
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Riveron
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Sulaiman S
authors.initials: SS
authors.lastname: Ibrahim
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Irving
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Kayla G
authors.initials: KG
authors.lastname: Barnes
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Louis G
authors.initials: LG
authors.lastname: Mukwaya
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Josephine
authors.initials: J
authors.lastname: Birungi
authors.affiliation: Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wondji
mesh_terms: D000351:Africa, Eastern; D000818:Animals; D000852:Anopheles / Q000235:genetics*; D003634:DDT / Q000494:pharmacology*; D005260:Female; D007303:Insect Vectors / Q000235:genetics; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects; D011722:Pyrethrins / Q000494:pharmacology*; D015222:Sodium Channels / Q000235:genetics
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D015222:Sodium Channels; D003634:DDT