Date Published: January 6, 2009
Publisher: Public Library of Science
Author(s): Cielo Pasay, Larry Arlian, Marjorie Morgan, Robin Gunning, Louise Rossiter, Deborah Holt, Shelley Walton, Simone Beckham, James McCarthy, Mike J. Lehane
Abstract: BackgroundPermethrin 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.Methodology/Principal FindingsTo 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.ConclusionsThese 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.
Partial Text: Scabies is an infectious skin disease caused by the ectoparasite, Sarcoptes scabiei. The mite lives in the skin of hosts where it passes through a series of life stages (eggs, larva, protonymph, tritonymph, and adult). A severe manifestation of the disease i.e., crusted scabies can occur which may predispose to streptococcal pyoderma and the subsequent development of acute post streptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease . Treatment generally entails the application of topical creams for classical scabies, while oral ivermectin is recommended for crusted scabies . Permethrin, used at a concentration of 5%, is the active component of topical creams commonly used to treat the disease. Since its introduction in Australia in 1994 for the treatment of scabies, it has been widely used in endemic communities in mass treatment programs . Recent evidence from a prospective study of in vitro acaricide sensitivity has demonstrated increased tolerance to permethrin of scabies mites collected from indigenous communities across northern Australia (unpublished data).
Detoxifying enzymes and target alteration are equally important mechanisms of insecticide degradation in ticks and mites. While a point mutation in the Vssc gene has been associated with pyrethroid resistance in two strains of cattle ticks, Boophilus microplus, high levels of esterase activity have been observed in another two strains in the absence of this mutation . Resistance to tau-fluvalinate in the honeybee mite, Varroa destructor has been associated with sodium channel insensitivity as well as elevated cytochrome P450s and high levels of esterases ,.