title: A new class of insecticide for malaria vector control: evaluation of mosquito nets treated singly with indoxacarb (oxadiazine) or with a pyrethroid mixture against Anopheles gambiae and Culex quinquefasciatus.
abstract: BACKGROUND
  Universal coverage with long-lasting insecticidal mosquito nets (LLIN) or indoor residual spraying (IRS) of houses remain the primary strategies for the control of mosquito vectors of malaria. Pyrethroid resistant malaria vectors are widespread throughout sub-Saharan Africa and new insecticides with different modes of action are urgently needed if malaria vector control is to remain effective. Indoxacarb is an oxadiazine insecticide that is effective as an oral and contact insecticide against a broad spectrum of agricultural pests and, due to its unique site of action, no cross-resistance has been detected through mechanisms associated with resistance to insecticides currently used in public health.
  
  
  METHODS
  WHO tunnel tests of host seeking mosquitoes were carried out as a forerunner to experimental hut trials, to provide information on dosage-dependent mortality, repellency, and blood-feeding inhibition. A dosage range of indoxacarb treated netting (100-1000 mg/m(2)) was tested against a pyrethroid susceptible strain of Anopheles gambiae. In addition, efficacy of indoxacarb 500 mg/m(2) was compared with a standard pyrethroid formulation against pyrethroid susceptible and resistant Culex quinquefasciatus. Dosages between 25 and 300 mg/m(2) indoxacarb were tested in tunnel tests and in ball-frame bioassays as mixtures with alphacypermethrin 25 mg/m(2) and were compared with singly applied treatments against an insectary reared pyrethroid resistant strain of Cx. quinquefasciatus originally collected in Cotonou, Benin.
  
  
  RESULTS
  There was a dosage-dependent response in terms of indoxacarb induced mortality, with dosages >100 mg/m(2) producing the best mortality response. In tunnel tests indoxacarb 500 mg/m(2) exceeded WHOPES thresholds with >80 % mortality of adult An. gambiae and blood-feeding inhibition of 75 %. No cross-resistance to indoxacarb was detected through mechanisms associated with resistance to pyrethroid insecticides and was equally effective against susceptible and resistant strains of Cx. quinquefasciatus. Indoxacarb 500 mg/m(2) killed 75 % of pyrethroid resistant Cx. quinquefasciatus compared with only 21 % mortality with alphacypermethrin 40 mg/m(2). Mixtures of indoxacarb with pyrethroid produced an additive response for both mortality and blood-feeding inhibition. The best performing mixture (indoxacarb 200 mg/m(2) + alphacypermethrin 25 mg/m(2)) killed 83 % of pyrethroid resistant Cx. quinquefasciatus and reduced blood-feeding by 88 %, while alphacypermethrin only killed 36 % and inhibited blood-feeding by 50 %.
  
  
  CONCLUSIONS
  New insecticides with different modes of action to those currently used in mosquito vector control are urgently needed. Indoxacarb shows great promise as a mixture with a pyrethroid and should be evaluated in experimental hut trials to determine performance against wild free-flying, pyrethroid resistant An. gambiae and wash-resistant formulations developed.
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK. oxandbull@hotmail.com.|Department of Entomology and Parasitology, Kilimanjaro Christian Medical University College, Moshi, Kilimanjaro, Tanzania. oxandbull@hotmail.com.|Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. oxandbull@hotmail.com.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Oxborough
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK. raphael.n'guessan@lshtm.ac.uk.|Laboratoire Nationale, Ministère de la Santé, CREC Laboratories, Centre de Recherche Entomologique de Cotonou, Cotonou 06, BP 2604, Benin. raphael.n'guessan@lshtm.ac.uk.|Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. raphael.n'guessan@lshtm.ac.uk.
authors.forename: Raphael
authors.initials: R
authors.lastname: N'Guessan
authors.affiliation: Department of Entomology and Parasitology, Kilimanjaro Christian Medical University College, Moshi, Kilimanjaro, Tanzania. jvnkit@gmail.com.|Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. jvnkit@gmail.com.
authors.forename: Jovin
authors.initials: J
authors.lastname: Kitau
authors.affiliation: Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. PatrickKijatungu@hotmail.com.|Amani Centre, National Institute for Medical Research, Muheza, Tanzania. PatrickKijatungu@hotmail.com.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Tungu
authors.affiliation: Innovative Vector Control Consortium (IVCC), Pembroke Place, Liverpool, L3 5QA, UK. david.malone@ivcc.com.
authors.forename: David
authors.initials: D
authors.lastname: Malone
authors.affiliation: Department of Entomology and Parasitology, Kilimanjaro Christian Medical University College, Moshi, Kilimanjaro, Tanzania. fwmosha@gmail.com.|Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. fwmosha@gmail.com.
authors.forename: Franklin W
authors.initials: FW
authors.lastname: Mosha
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK. mark.rowland@lshtm.ac.uk.|Pan-African Malaria Vector Research Consortium, (PAMVERC), Moshi, Tanzania. mark.rowland@lshtm.ac.uk.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Rowland
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D001681:Biological Assay; D003465:Culex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007303:Insect Vectors / Q000187:drug effects*; D057148:Insecticide-Treated Bednets; D007306:Insecticides / Q000494:pharmacology*; D008288:Malaria / Q000517:prevention & control; D010078:Oxazines / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D010078:Oxazines; D011722:Pyrethrins; C401104:indoxacarb