title: Can piperonyl butoxide enhance the efficacy of pyrethroids against pyrethroid-resistant Aedes aegypti?
abstract: BACKGROUND
  Pyrethroid resistance can be considered the main threat to the continued control of many mosquito vectors of disease. Piperonyl butoxide (PBO) has been used as a synergist to help increase the efficacy of certain insecticides. This enhancement stems from its ability to inhibit two major metabolic enzyme systems, P450s and non-specific esterases, and to enhance cuticular penetration of the insecticide.
  
  
  OBJECTIVE
  To compare the mortality of a characterized resistant Aedes aegypti strain, Nha Trang, from Vietnam and the susceptible laboratory strain Bora Bora on netting with the pyrethroid deltamethrin (DM) alone and in combination with PBO.
  
  
  METHODS
  Resistance mechanisms were characterized using molecular and bioassay techniques; standard PCR was used to test for the kdr target site mutation. Potential genes conferring metabolic resistance to DM were identified with microarray analysis using the Ae. aegypti 'detox chip'. These data were analysed alongside results from WHO susceptibility tests. P450, CYP9J32, was significantly overexpressed in the DM-resistant strain compared with the susceptible Bora Bora strain. Another five genes involved with oxidative stress responses in mosquitoes were also significantly overexpressed. The Nha Trang strain was homozygous for two kdr mutations. WHO cone bioassays were used to investigate mortality with incorporated DM-treated nets with and without PBO. PBO used in combination with DM resulted in higher mortality than DM alone.
  
  
  CONCLUSIONS
  Synergists may have an important role to play in the future design of vector control products in an era when alternatives to pyrethroids are scarce.
authors.affiliation: Innovation Centre, Vestergaard Frandsen, Lausanne, Switzerland. gvb@vestergaard-frandsen.com
authors.forename: Georgina
authors.initials: G
authors.lastname: Bingham
authors.forename: Clare
authors.initials: C
authors.lastname: Strode
authors.forename: Lien
authors.initials: L
authors.lastname: Tran
authors.forename: Pham Thi
authors.initials: PT
authors.lastname: Khoa
authors.forename: Helen Pates
authors.initials: HP
authors.lastname: Jamet
mesh_terms: D000330:Aedes / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001681:Biological Assay / Q000379:methods; D004357:Drug Synergism; D005260:Female; D017344:Genes, Insect; D007303:Insect Vectors / Q000187:drug effects* / Q000235:genetics; D007305:Insecticide Resistance / Q000187:drug effects / Q000235:genetics; D057148:Insecticide-Treated Bednets; D007306:Insecticides / Q000494:pharmacology*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010574:Pesticide Synergists / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D010574:Pesticide Synergists; D011722:Pyrethrins; D010882:Piperonyl Butoxide