title: Insecticide resistance in Anopheles arabiensis in Sudan: temporal trends and underlying mechanisms.
abstract: BACKGROUND
  Malaria vector control in Sudan relies mainly on indoor residual spraying (IRS) and the use of long lasting insecticide treated bed nets (LLINs). Monitoring insecticide resistance in the main Sudanese malaria vector, Anopheles arabiensis, is essential for planning and implementing an effective vector control program in this country.
  
  
  METHODS
  WHO susceptibility tests were used to monitor resistance to insecticides from all four WHO-approved classes of insecticide at four sentinel sites in Gezira state over a three year period. Insecticide resistance mechanisms were studied using PCR and microarray analyses.
  
  
  RESULTS
  WHO susceptibility tests showed that Anopheles arabiensis from all sites were fully susceptible to bendiocarb and fenitrothion for the duration of the study (2008-2011). However, resistance to DDT and pyrethroids was detected at three sites, with strong seasonal variations evident at all sites. The 1014 F kdr allele was significantly associated with resistance to pyrethroids and DDT (P < 0.001) with extremely high effects sizes (OR > 7 in allelic tests). The 1014S allele was not detected in any of the populations tested. Microarray analysis of the permethrin-resistant population of An. arabiensis from Wad Medani identified a number of metabolic genes that were significantly over-transcribed in the field-collected resistant samples when compared to the susceptible Sudanese An. arabiensis Dongola strain. These included CYP6M2 and CYP6P3, two genes previously implicated in pyrethroid resistance in Anopheles gambiae s.s, and the epsilon-class glutathione-S-transferase, GSTe4.
  
  
  CONCLUSIONS
  These data suggest that both target-site mechanisms and metabolic mechanisms play an important role in conferring pyrethroid resistance in An. arabiensis from Sudan. Identification in An. arabiensis of candidate loci that have been implicated in the resistance phenotype in An. gambiae requires further investigation to confirm the role of these genes.
authors.forename: Hiba
authors.initials: H
authors.lastname: Abdalla
authors.forename: Craig S
authors.initials: CS
authors.lastname: Wilding
authors.forename: Luisa
authors.initials: L
authors.lastname: Nardini
authors.forename: Patricia
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Lizette L
authors.initials: LL
authors.lastname: Koekemoer
authors.forename: Hilary
authors.initials: H
authors.lastname: Ranson
authors.affiliation: Wits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. maureenc@nicd.ac.za.
authors.forename: Maureen
authors.initials: M
authors.lastname: Coetzee
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D001681:Biological Assay; D007303:Insect Vectors / Q000187:drug effects; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D008288:Malaria / Q000635:transmission; D009032:Mosquito Control; D013397:Sudan; D013997:Time Factors
chemical_list: D007306:Insecticides