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First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye

Year 2025, Volume: 15 Issue: 1, 90 - 94, 28.03.2025
https://doi.org/10.33808/clinexphealthsci.1458615

Abstract

Objective: Scabies, a longstanding public health concern, is a contagious and pruritic skin condition caused by the parasite Sarcoptes scabiei, affecting an estimated 300 million individuals worldwide annually. Recent increases in incidence can be attributed to challenges in accurate diagnosis and instances of treatment resistance. Permethrin, an insecticide belonging to the pyrethroid group, is the primary choice for scabies treatment. However, recent treatment failures suggest the emergence of permethrin resistance. Pyrethroids, widely employed as insecticides over the past three decades, have led to resistance development across various organisms. Pyrethroid acaricides like permethrin target the neuronal voltage-sensitive sodium channel (VSSC) protein, crucial for action potential generation in excitable cells. Specific mutations in the VSSC gene have been associated with pyrethroid resistance. Our objective is to elucidate the correlation between treatment failure and pyrethroid resistance stemming from VSSC gene mutations in Sarcoptes scabiei mites responsible for scabies cases in the Sivas region, Türkiye.
Methods: In this study, we analyzed 30 scabies cases where initial permethrin treatment proved ineffective. The VSSC gene of scabies mites was partially isolated from genomic DNA to identify potential mutations via DNA sequencing.
Results: Results yielded significant insights into the relationship between permethrin resistance and VSSC gene mutations. Notably, 43.3% of mites exhibited mutated VSSC genes.
Conclusion: This study represents the first investigation into Vssc-associated permethrin resistance in human scabies. The study highlights the importance of detecting genotypic resistance in 43.3% of phenotypically resistant cases.

Ethical Statement

This study was approved by Ethics Committee of Sivas Cumhuriyet University Clinic Ethics Committee (Approval date 03/12/2020; Number: 2020-12/04,)

Supporting Institution

This work is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University

Project Number

T-2021-916

References

  • Mounsey KE. Molecular mechanisms of emerging ivermectin resistance in scabies mites from northern Australia. Charles Darwin University (Australia); 2007.
  • Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. The lancet. 2016;388(10053):1545–602.
  • James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2018;392(10159):1789–858. https://linkinghub.elsevier.com/retrieve/pii/S0140673618322797
  • Turan Ç, Metin N, Utlu Z. Epidemiological evaluation of scabies cases encountered in the last three years as a tertiary health center. Turkiye Parazitol Derg. 2020;44(2):77.
  • Rosumeck S, Nast A, Dressler C. Ivermectin and permethrin for treating scabies. Cochrane Database of Systematic Reviews 1996;2018(4): CD012994. https://doi.org/10.1002/14651858.CD012994
  • Mazzatenta C, Piccolo V, Argenziano G, Bassi A. Is Scabies becoming less sensitive to permethrin therapy? Journal of the European Academy of Dermatology and Venereology 2021;35(9):e607–609. https://doi.org/10.1111/jdv.17339
  • Balestri R, Magnano M, Infusino SD, Rizzoli L, Girardelli CR, Rech G. Scabies is becoming less sensitive to permethrin therapy. Journal of the European Academy of Dermatology and Venereology 2021;35(12):e889–91. https://doi.org/10.1111/jdv.17538
  • Meyersburg D, Kaiser A, Bauer JW. ‘Loss of efficacy of topical 5% permethrin for treating scabies: an Austrian single-center study.’ Journal of Dermatological Treatment 2022;33(2):774–777. https://doi.org/10.1080/09546634.2020.1774489
  • Mounsey KE, Pasay CJ, Arlian LG, Morgan MS, Holt DC, Currie BJ. Increased transcription of Glutathione S-transferases in acaricide exposed scabies mites. Parasit Vectors. 2010;3(1):1–9.
  • Pasay C, Arlian L, Morgan M, Gunning R, Rossiter L, Holt D. The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides. PLoS Negl Trop Dis. 2009;3(1):e354.
  • Pasay C, Arlian L, Morgan M, Vyszenski-Moher D, Rose A, Holt D. High-resolution melt analysis for the detection of a mutation associated with permethrin resistance in a population of scabies mites. Med Vet Entomol. 2008 Mar;22(1):82–88.
  • Miyazaki M, Ohyama K, Dunlap DY, Matsumura F. Cloning and sequencing of thepara-type sodium channel gene from susceptible and kdr-resistant German cockroaches (Blattella germanica) and house fly (Musca domestica). Mol Gen Genet.1996;252(1):61–68. https://doi.org/10.1007/BF02173205
  • Williamson MS, Martinez-Torres D, Hick CA, Devonshire AL. Identification of mutations in the houseflypara-type sodium channel gene associated with knockdown resistance (kdr) to pyrethroid insecticides. Mol Gen Genet. 1996;252(1):51–60. https://doi.org/10.1007/BF02173204
  • Özden MG, Ertürk K, Kartal SP, Yayli S, Göktay F, Doğramacı CA, et al. An extraordinary outbreak of scabies in Turkey. Journal of the European Academy of Dermatology and Venereology 2020;34(12):e818–820. https://doi.org/10.1111/jdv.16699
  • Baykal C, Atci T, Kutlay A, Baykut B, Türkoğlu Z. Scabies outbreak in Turkey in 2018–2019. Journal of the European Academy of Dermatology and Venereology 2021;35(6):e384–385. https://doi.org/10.1111/jdv.17152
  • Turan Ç, Metin N. Impact of Pandemic in the Frequency of Scabies: Possible Scabies Outbreak Scenario Aftermath COVID-19. Türkiye Parazitol Derg. 2021;45(3):190.
  • Özçelik S. A neglected disease: Scabies a retrospective study on children. Türkiye Çocuk Hastalıkları Dergisi. 2021;121–6.
  • Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35(6):1547–1549.
  • Pasay C, Walton S, Fischer K, Holt D, McCarthy J. PCR-based assay to survey for knockdown resistance to pyrethroid acaricides in human scabies mites (Sarcoptes scabiei var hominis). Am J Trop Med Hyg. 2006 Apr;74(4):649–657.
  • Sunderkötter C, Aebischer A, Neufeld M, Löser C, Kreuter A, Bialek R, et al. Increase of scabies in Germany and development of resistant mites? Evidence and consequences. Journal der Deutschen Dermatologischen Gesellschaft. 2019;17(1):15–23.
  • Silver KS, Du Y, Nomura Y, Oliveira EE, Salgado VL, Zhorov BS, et al. Chapter Five - Voltage-Gated Sodium Channels as Insecticide Targets. In: Cohen E, editor. Advances in Insect Physiology [Internet]. Academic Press; 2014. p. 389–433.
  • Andriantsoanirina V, Izri A, Botterel F, Foulet F, Chosidow O, Durand R. Molecular survey of knockdown resistance to pyrethroids in human scabies mites. Clinical Microbiology and Infection 2014;20(2):O139–41.
  • Yürekli A. Is there a really resistance to scabies treatment with permethrin? In vitro killing activity of permethrin on Sarcoptes scabiei from patients with resistant scabies. Dermatol Ther. 2022;35(3):e15260.
  • Currie BJ, Harumal P, McKinnon M, Walton SF. First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clinical Infectious Diseases. 2004;39(1):e8–12.
  • Xu M, Molento M, Blackhall W, Ribeiro P, Beech R, Prichard R. Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog. Mol Biochem Parasitol. 1998;91(2):327–35.
Year 2025, Volume: 15 Issue: 1, 90 - 94, 28.03.2025
https://doi.org/10.33808/clinexphealthsci.1458615

Abstract

Project Number

T-2021-916

References

  • Mounsey KE. Molecular mechanisms of emerging ivermectin resistance in scabies mites from northern Australia. Charles Darwin University (Australia); 2007.
  • Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. The lancet. 2016;388(10053):1545–602.
  • James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2018;392(10159):1789–858. https://linkinghub.elsevier.com/retrieve/pii/S0140673618322797
  • Turan Ç, Metin N, Utlu Z. Epidemiological evaluation of scabies cases encountered in the last three years as a tertiary health center. Turkiye Parazitol Derg. 2020;44(2):77.
  • Rosumeck S, Nast A, Dressler C. Ivermectin and permethrin for treating scabies. Cochrane Database of Systematic Reviews 1996;2018(4): CD012994. https://doi.org/10.1002/14651858.CD012994
  • Mazzatenta C, Piccolo V, Argenziano G, Bassi A. Is Scabies becoming less sensitive to permethrin therapy? Journal of the European Academy of Dermatology and Venereology 2021;35(9):e607–609. https://doi.org/10.1111/jdv.17339
  • Balestri R, Magnano M, Infusino SD, Rizzoli L, Girardelli CR, Rech G. Scabies is becoming less sensitive to permethrin therapy. Journal of the European Academy of Dermatology and Venereology 2021;35(12):e889–91. https://doi.org/10.1111/jdv.17538
  • Meyersburg D, Kaiser A, Bauer JW. ‘Loss of efficacy of topical 5% permethrin for treating scabies: an Austrian single-center study.’ Journal of Dermatological Treatment 2022;33(2):774–777. https://doi.org/10.1080/09546634.2020.1774489
  • Mounsey KE, Pasay CJ, Arlian LG, Morgan MS, Holt DC, Currie BJ. Increased transcription of Glutathione S-transferases in acaricide exposed scabies mites. Parasit Vectors. 2010;3(1):1–9.
  • Pasay C, Arlian L, Morgan M, Gunning R, Rossiter L, Holt D. The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides. PLoS Negl Trop Dis. 2009;3(1):e354.
  • Pasay C, Arlian L, Morgan M, Vyszenski-Moher D, Rose A, Holt D. High-resolution melt analysis for the detection of a mutation associated with permethrin resistance in a population of scabies mites. Med Vet Entomol. 2008 Mar;22(1):82–88.
  • Miyazaki M, Ohyama K, Dunlap DY, Matsumura F. Cloning and sequencing of thepara-type sodium channel gene from susceptible and kdr-resistant German cockroaches (Blattella germanica) and house fly (Musca domestica). Mol Gen Genet.1996;252(1):61–68. https://doi.org/10.1007/BF02173205
  • Williamson MS, Martinez-Torres D, Hick CA, Devonshire AL. Identification of mutations in the houseflypara-type sodium channel gene associated with knockdown resistance (kdr) to pyrethroid insecticides. Mol Gen Genet. 1996;252(1):51–60. https://doi.org/10.1007/BF02173204
  • Özden MG, Ertürk K, Kartal SP, Yayli S, Göktay F, Doğramacı CA, et al. An extraordinary outbreak of scabies in Turkey. Journal of the European Academy of Dermatology and Venereology 2020;34(12):e818–820. https://doi.org/10.1111/jdv.16699
  • Baykal C, Atci T, Kutlay A, Baykut B, Türkoğlu Z. Scabies outbreak in Turkey in 2018–2019. Journal of the European Academy of Dermatology and Venereology 2021;35(6):e384–385. https://doi.org/10.1111/jdv.17152
  • Turan Ç, Metin N. Impact of Pandemic in the Frequency of Scabies: Possible Scabies Outbreak Scenario Aftermath COVID-19. Türkiye Parazitol Derg. 2021;45(3):190.
  • Özçelik S. A neglected disease: Scabies a retrospective study on children. Türkiye Çocuk Hastalıkları Dergisi. 2021;121–6.
  • Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35(6):1547–1549.
  • Pasay C, Walton S, Fischer K, Holt D, McCarthy J. PCR-based assay to survey for knockdown resistance to pyrethroid acaricides in human scabies mites (Sarcoptes scabiei var hominis). Am J Trop Med Hyg. 2006 Apr;74(4):649–657.
  • Sunderkötter C, Aebischer A, Neufeld M, Löser C, Kreuter A, Bialek R, et al. Increase of scabies in Germany and development of resistant mites? Evidence and consequences. Journal der Deutschen Dermatologischen Gesellschaft. 2019;17(1):15–23.
  • Silver KS, Du Y, Nomura Y, Oliveira EE, Salgado VL, Zhorov BS, et al. Chapter Five - Voltage-Gated Sodium Channels as Insecticide Targets. In: Cohen E, editor. Advances in Insect Physiology [Internet]. Academic Press; 2014. p. 389–433.
  • Andriantsoanirina V, Izri A, Botterel F, Foulet F, Chosidow O, Durand R. Molecular survey of knockdown resistance to pyrethroids in human scabies mites. Clinical Microbiology and Infection 2014;20(2):O139–41.
  • Yürekli A. Is there a really resistance to scabies treatment with permethrin? In vitro killing activity of permethrin on Sarcoptes scabiei from patients with resistant scabies. Dermatol Ther. 2022;35(3):e15260.
  • Currie BJ, Harumal P, McKinnon M, Walton SF. First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clinical Infectious Diseases. 2004;39(1):e8–12.
  • Xu M, Molento M, Blackhall W, Ribeiro P, Beech R, Prichard R. Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog. Mol Biochem Parasitol. 1998;91(2):327–35.
There are 25 citations in total.

Details

Primary Language English
Subjects Dermatology
Journal Section Articles
Authors

Ozan Kılıçkaya 0000-0003-2710-2149

Mustafa Tosun 0000-0002-6189-8016

Necati Özpınar 0000-0002-7317-885X

Project Number T-2021-916
Early Pub Date March 23, 2025
Publication Date March 28, 2025
Submission Date March 25, 2024
Acceptance Date December 4, 2024
Published in Issue Year 2025 Volume: 15 Issue: 1

Cite

APA Kılıçkaya, O., Tosun, M., & Özpınar, N. (2025). First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye. Clinical and Experimental Health Sciences, 15(1), 90-94. https://doi.org/10.33808/clinexphealthsci.1458615
AMA Kılıçkaya O, Tosun M, Özpınar N. First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye. Clinical and Experimental Health Sciences. March 2025;15(1):90-94. doi:10.33808/clinexphealthsci.1458615
Chicago Kılıçkaya, Ozan, Mustafa Tosun, and Necati Özpınar. “First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye”. Clinical and Experimental Health Sciences 15, no. 1 (March 2025): 90-94. https://doi.org/10.33808/clinexphealthsci.1458615.
EndNote Kılıçkaya O, Tosun M, Özpınar N (March 1, 2025) First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye. Clinical and Experimental Health Sciences 15 1 90–94.
IEEE O. Kılıçkaya, M. Tosun, and N. Özpınar, “First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye”, Clinical and Experimental Health Sciences, vol. 15, no. 1, pp. 90–94, 2025, doi: 10.33808/clinexphealthsci.1458615.
ISNAD Kılıçkaya, Ozan et al. “First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye”. Clinical and Experimental Health Sciences 15/1 (March 2025), 90-94. https://doi.org/10.33808/clinexphealthsci.1458615.
JAMA Kılıçkaya O, Tosun M, Özpınar N. First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye. Clinical and Experimental Health Sciences. 2025;15:90–94.
MLA Kılıçkaya, Ozan et al. “First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye”. Clinical and Experimental Health Sciences, vol. 15, no. 1, 2025, pp. 90-94, doi:10.33808/clinexphealthsci.1458615.
Vancouver Kılıçkaya O, Tosun M, Özpınar N. First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye. Clinical and Experimental Health Sciences. 2025;15(1):90-4.

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