First Molecular Investigation of VSSC-Linked Permethrin Resistance in Human Scabies in Türkiye
Year 2025,
Volume: 15 Issue: 1, 90 - 94, 28.03.2025
Ozan Kılıçkaya
,
Mustafa Tosun
,
Necati Özpınar
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
Ozan Kılıçkaya
,
Mustafa Tosun
,
Necati Özpınar
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.