title: Susceptibility of Anopheles gambiae to insecticides used for malaria vector control in Rwanda.
abstract: BACKGROUND
  The widespread emergence of resistance to pyrethroids is a major threat to the gains made in malaria control. To monitor the presence and possible emergence of resistance against a variety of insecticides used for malaria control in Rwanda, nationwide insecticide resistance surveys were conducted in 2011 and 2013.
  
  
  METHODS
  Larvae of Anopheles gambiae sensu lato mosquitoes were collected in 12 sentinel sites throughout Rwanda. These were reared to adults and analysed for knock-down and mortality using WHO insecticide test papers with standard diagnostic doses of the recommended insecticides. A sub-sample of tested specimens was analysed for the presence of knockdown resistance (kdr) mutations.
  
  
  RESULTS
  A total of 14,311 mosquitoes were tested and from a sample of 1406 specimens, 1165 (82.9%) were identified as Anopheles arabiensis and 241 (17.1%) as Anopheles gambiae sensu stricto. Mortality results indicated a significant increase in resistance to lambda-cyhalothrin from 2011 to 2013 in 83% of the sites, permethrin in 25% of the sites, deltamethrin in 25% of the sites and DDT in 50% of the sites. Mosquitoes from 83% of the sites showed full susceptibility to bendiocarb and 17% of sites were suspected to harbour resistance that requires further confirmation. No resistance was observed to fenitrothion in all study sites during the entire survey. The kdr genotype results in An. gambiae s.s. showed that 67 (50%) possessed susceptibility (SS) alleles, while 35 (26.1%) and 32 (23.9%) mosquitoes had heterozygous (RS) and homozygous (RR) alleles, respectively. Of the 591 An. arabiensis genotyped, 425 (71.9%) possessed homozygous (SS) alleles while 158 (26.7%) and 8 (1.4%) had heterozygous (RS) and homozygous (RR) alleles, respectively. Metabolic resistance involving oxidase enzymes was also detected using the synergist PBO.
  
  
  CONCLUSIONS
  This is the first nationwide study of insecticide resistance in malaria vectors in Rwanda. It shows the gradual increase of insecticide resistance to pyrethroids (lambda-cyhalothrin, deltamethrin, permethrin) and organochlorines (DDT) and the large presence of target site insensitivity. The results demonstrate the need for Rwanda to expand monitoring for insecticide resistance including further metabolic resistance testing and implement an insecticide resistance management strategy to sustain the gains made in malaria control.
authors.affiliation: Malaria and Other Parasitic Diseases Division (MOPDD), Rwanda Biomedical Centre, Ministry of Health, Kigali, Rwanda.|Laboratory of Entomology, Wageningen University and Research, PO Box 16, 6700 AA, Wageningen, The Netherlands.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hakizimana
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Corine
authors.initials: C
authors.lastname: Karema
authors.affiliation: Malaria and Other Parasitic Diseases Division (MOPDD), Rwanda Biomedical Centre, Ministry of Health, Kigali, Rwanda.
authors.forename: Dunia
authors.initials: D
authors.lastname: Munyakanage
authors.affiliation: Malaria and Other Parasitic Diseases Division (MOPDD), Rwanda Biomedical Centre, Ministry of Health, Kigali, Rwanda.
authors.forename: Gad
authors.initials: G
authors.lastname: Iranzi
authors.affiliation: Integrated Vector Management Project, MOPDD, Abt Associates Inc., Kigali, Rwanda.
authors.forename: John
authors.initials: J
authors.lastname: Githure
authors.affiliation: USAID/PMI Office, Kigali, Rwanda.
authors.forename: Jon Eric
authors.initials: JE
authors.lastname: Tongren
authors.affiliation: Laboratory of Entomology, Wageningen University and Research, PO Box 16, 6700 AA, Wageningen, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Takken
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.|Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.|University of Global Health Equity, Kigali, Rwanda.
authors.forename: Agnes
authors.initials: A
authors.lastname: Binagwaho
authors.affiliation: Laboratory of Entomology, Wageningen University and Research, PO Box 16, 6700 AA, Wageningen, The Netherlands. sander.koenraadt@wur.nl.
authors.forename: Constantianus J M
authors.identifier: http://orcid.org/0000-0001-7861-8781
authors.initials: CJ
authors.lastname: Koenraadt
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D001681:Biological Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D009032:Mosquito Control / Q000379:methods*; D000072138:Mosquito Vectors / Q000187:drug effects*; D009154:Mutation; D012432:Rwanda; D016019:Survival Analysis
chemical_list: D007306:Insecticides
keywords: Anopheles gambiae; Bendiocarb; DDT; Fenitrothion; Insecticide resistance; Pyrethroids; Rwanda; Vector control; kdr Mutation