title: The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides.
abstract: BACKGROUND
  Permethrin is the active component of topical creams widely used to treat human scabies. Recent evidence has demonstrated that scabies mites are becoming increasingly tolerant to topical permethrin and oral ivermectin. An effective approach to manage pesticide resistance is the addition of synergists to counteract metabolic resistance. Synergists are also useful for laboratory investigation of resistance mechanisms through their ability to inhibit specific metabolic pathways.
  
  
  RESULTS
  To determine the role of metabolic degradation as a mechanism for acaricide resistance in scabies mites, PBO (piperonyl butoxide), DEF (S,S,S-tributyl phosphorotrithioate) and DEM (diethyl maleate) were first tested for synergistic activity with permethrin in a bioassay of mite killing. Then, to investigate the relative role of specific metabolic pathways inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST) and cytochrome P450 monooxygenase (cytochrome P450) activity in mite extracts. A statistically significant difference in median survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to median survival time of mites exposed to permethrin alone (p<0.0001). Incubation of mite homogenates with DEF showed inhibition of esterase activity (37%); inhibition of GST activity (73%) with DEM and inhibition of cytochrome P450 monooxygenase activity (81%) with PBO. A 7-fold increase in esterase activity, a 4-fold increase in GST activity and a 2-fold increase in cytochrome P450 monooxygenase activity were observed in resistant mites compared to sensitive mites.
  
  
  CONCLUSIONS
  These findings indicate the potential utility of synergists in reversing resistance to pyrethroid-based acaricides and suggest a significant role of metabolic mechanisms in mediating pyrethroid resistance in scabies mites.
authors.affiliation: Queensland Institute of Medical Research and Australian Centre for International and Tropical Health, University of Queensland, Brisbane, Queensland, Australia. Cielo.Pasay@qimr.edu.au
authors.forename: Cielo
authors.initials: C
authors.lastname: Pasay
authors.forename: Larry
authors.initials: L
authors.lastname: Arlian
authors.forename: Marjorie
authors.initials: M
authors.lastname: Morgan
authors.forename: Robin
authors.initials: R
authors.lastname: Gunning
authors.forename: Louise
authors.initials: L
authors.lastname: Rossiter
authors.forename: Deborah
authors.initials: D
authors.lastname: Holt
authors.forename: Shelley
authors.initials: S
authors.lastname: Walton
authors.forename: Simone
authors.initials: S
authors.lastname: Beckham
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
mesh_terms: D056810:Acaricides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D004950:Esterases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007306:Insecticides / Q000378:metabolism / Q000494:pharmacology*; D008298:Maleates / Q000378:metabolism / Q000494:pharmacology; D063086:Organothiophosphates / Q000378:metabolism / Q000494:pharmacology; D026023:Permethrin / Q000378:metabolism / Q000494:pharmacology; D010574:Pesticide Synergists / Q000378:metabolism / Q000494:pharmacology*; D010882:Piperonyl Butoxide / Q000378:metabolism / Q000494:pharmacology; D011722:Pyrethrins / Q000378:metabolism / Q000494:pharmacology*; D012520:Sarcoptes scabiei / Q000187:drug effects* / Q000378:metabolism; D012532:Scabies / Q000188:drug therapy
chemical_list: D056810:Acaricides; D004791:Enzyme Inhibitors; D007306:Insecticides; D008298:Maleates; D063086:Organothiophosphates; D010574:Pesticide Synergists; D011722:Pyrethrins; D026023:Permethrin; C006863:butyl phosphorotrithioate; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D004950:Esterases; C014476:diethyl maleate; D010882:Piperonyl Butoxide