title: Does insecticide resistance contribute to heterogeneities in malaria transmission in The Gambia?
abstract: BACKGROUND
  Malaria hotspots, areas with consistently higher than average transmission, may become increasingly common as malaria declines. This phenomenon, currently observed in The Gambia, may be caused by several factors, including some related to the local vectors, whose contribution is poorly understood.
  
  
  METHODS
  Using WHO susceptibility bioassays, insecticide resistance status was determined in vector populations sampled from six pairs of villages across The Gambia, each pair contained a low and high prevalence village.
  
  
  RESULTS
  Three vector species were observed (23.5% Anopheles arabiensis, 31.2% Anopheles gambiae, 43.3% Anopheles coluzzii and 2.0% An. coluzzii × An. gambiae hybrids). Even at a fine scale, significant differences in species composition were detected within village pairs. Resistance to both DDT and deltamethrin was more common in An. gambiae, most markedly in the eastern part of The Gambia and partly attributable to differing frequencies of resistance mutations. The Vgsc-1014F target site mutation was strongly associated with both DDT (OR = 256.7, (95% CI 48.6-6374.3, p < 0.001) and deltamethrin survival (OR = 9.14, (95% CI 4.24-21.4, p < 0.001). A second target site mutation, Vgsc-1575Y, which co-occurs with Vgsc-1014F, and a metabolic marker of resistance, Gste2-114T, conferred additional survival benefits to both insecticides. DDT resistance occurred significantly more frequently in villages with high malaria prevalence (p = 0.025) though this did not apply to deltamethrin resistance.
  
  
  CONCLUSIONS
  Whilst causality of relationships requires further investigation, variation in vector species and insecticide resistance in The Gambia is associated with malaria endemicity; with a notably higher prevalence of infection and insecticide resistance in the east of the country. In areas with heterogeneous malaria transmission, the role of the vector should be investigated to guide malaria control interventions.
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.|Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Kevin Ochieng'
authors.initials: KO
authors.lastname: Opondo
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: David
authors.initials: D
authors.lastname: Weetman
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.
authors.forename: Musa
authors.initials: M
authors.lastname: Jawara
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.
authors.forename: Mathurin
authors.initials: M
authors.lastname: Diatta
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.
authors.forename: Amfaal
authors.initials: A
authors.lastname: Fofana
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Florence
authors.initials: F
authors.lastname: Crombe
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.
authors.forename: Julia
authors.initials: J
authors.lastname: Mwesigwa
authors.affiliation: Medical Research Council Unit, PO Box 273, Banjul, The Gambia.|London School of Hygiene and Tropical Medicine, London, UK.|Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK. Martin.Donnelly@lstmed.ac.uk.|London School of Hygiene and Tropical Medicine, London, UK. Martin.Donnelly@lstmed.ac.uk.
authors.forename: Martin James
authors.identifier: http://orcid.org/0000-0001-5218-1497
authors.initials: MJ
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000502:physiology*; D001681:Biological Assay; D003430:Cross-Sectional Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D007305:Insecticide Resistance; D008288:Malaria / Q000453:epidemiology* / Q000635:transmission*; D016019:Survival Analysis