Resistance and Pseudo-resistance to permethrin: the importance of controlling scabies
Fabio Rinaldi, Roberta Chirico, Anna Trink, Daniela Pinto
Abstract
The World Health Organization (WHO) stated that scabies (Sarcoptes scabiei var.hominis) is one of the most neglected diseases in the world (World Health Organization, 2020).It is estimated that 200 million people in the world have suffered from a scabies infection at least once in their lifetime (Widaty et al., 2022).The update of "European guideline for the management of scabies" is based on the increasing worldwide incidence of this cutaneous disease.Recommended treatments are Permethrin 5% cream applied head to toe and oral Ivermectin 200 mg/kg (Salavastru et al., 2017).Some articles have reported the emergence of S. scabiei var.hominis resistance to Permethrin.Among the main causes of this problem is treatment failure, which is increasingly documented by physicians and is multifactorial in origin (Lluch-Galceraet al., 2023).We aim to distinguish pseudoresistance from true resistance based on the drug's mechanism of action and mutations.With this letter, we want to underline that we cannot yet talk about true resistance, as there is no statistically significant evidence. Permethrin's mechanism of actionIon channels are proteins embedded in the cell membrane, creating openings, called "pores", frequently become the focal points of neurotoxins (Wakeling et al., 2012).. Permethrin acts on the nerve cell membrane by disrupting the function of voltage-gated sodium channels (VGSCs).This results in delayed repolarization and subsequent paralysis and death of the parasite in all stages (Lobo and Wheller, 2021).VGSCs comprise a central subunit that forms the pore (a subunit) and an additional auxiliary subunit.The a subunit contains four domains (I-IV) each with 6 transmembrane segments (S1-S6).The channel pore, responsible for Na+ selectivity, is constituted by the fifth and sixth transmembrane segments (S5 and S6) along with the interconnecting loop.The S4 segments, containing positively charged amino acids, act as voltage sensors, instigating