Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009;3(1):e354.
doi: 10.1371/journal.pntd.0000354. Epub 2009 Jan 6.

The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides

Cielo Pasay  1 , Larry Arlian, Marjorie Morgan, Robin Gunning, Louise Rossiter, Deborah Holt, Shelley Walton, Simone Beckham, James McCarthy
Affiliations

The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides

Cielo Pasay et al. PLoS Negl Trop Dis. 2009.

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.

Methodology/principal findings: 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.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Survival of Permethrin (P) Resistant (Res) and Sensitive (Sen) Mites with or without Synergists.
A. Survival of scabies mites using PBO (Piperonyl Butoxide) as synergist to permethrin. B. Survival of scabies mites using DEF (S,S,S-tributylphosphorotrithioate) as synergist to permethrin. C. Survival of scabies mites using DEM (Diethyl Maleate) as synergist to permethrin. Benzyl Benzoate was used as positive control and Mineral Oil was used as negative control. Synergist (PBO, DEF and DEM) only controls were also included in the bioassays.
Figure 2
Figure 2. Results of in-vitro enzyme inhibition by synergists/inhibitors (30 mM).
A. Esterase activity in resistant and sensitive scabies mites in the presence or absence of inhibitor (PBO, DEF and DEM). B. GST activity in resistant and sensitive mites in the presence or absence of inhibitor (PBO, DEF and DEM). C. Cytochrome P450 activity in the presence or absence of inhibitor (PBO, DEF and DEM). *Error bars represent SEM.
Figure 3
Figure 3. Esterase levels of resistant mites with varying concentrations of DEF.
*Error bars represent SEM. **Commercial esterase from rabbit liver was used as assay control.
Figure 4
Figure 4. GST levels of resistant mites with varying concentrations of DEM.
*Error bars represent SEM. **Commercial GST from equine liver was used as assay control.
See this image and copyright information in PMC

References

    1. Mounsey KE, Holt DC, McCarthy J, Currie BJ, Walton SF. Scabies: molecular perspectives and therapeutic implications in the face of emerging drug resistance. Future Microbiol. 2008;3(1):57–66. - PubMed
    1. Carapetis JR, Connors C, Yarmirr D, Krause V, Currie BJ. Success of a scabies control program in an Australian aboriginal community. Pediatric Infect Dis J. 1997;16(5):494–499. - PubMed
    1. Davies TGE, Field LM, Usherwood PNR, Williamson MS. DDT, pyrethrins, pyrethroids and insect sodium channels. IUBMB Life. 2007;59(3):151–162. - PubMed
    1. Anspaugh DD, Rose RL, Koehler PG, Hodgson E, Roe M. Multiple mechanisms of pyrethroid resistance in the German cockroach, Blattella germanica (L.). Pest Biochem Physiol. 1994;50:138–148.
    1. Jamroz RC, Guerrero FD, Pruett JH, Oehler DD, Miller RJ. Molecular and biochemical survey of acaricide resistance mechanisms in larvae from Mexican strains of the southern cattle tick, Boophilus microplus. . J Insect Physiol. 2000;46:685–695. - PubMed

Publication types

MeSH terms