Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
J Eur Acad Dermatol Venereol. 2023 Nov;37(11):2355-2361. doi: 10.1111/jdv.19288. Epub 2023 Jul 10.
Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites.
To identify factors contributing to therapy failure.
Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained.
Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary.
The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.
越来越多的证据引发了关于疥疮螨虫对传统扑灭司林治疗敏感性丧失的争论。电压敏感钠通道（VSSC）中的突变与许多节肢动物的击倒抗性（kdr）有关，但从未在人疥疮变种（var.）的疥螨中发现过。
确定导致治疗失败的因素。
从奥地利维也纳的 64 名疥疮感染患者中收集了 67 只螨虫，其中 85.9%的患者对先前基于扑灭司林的治疗有抗药性，并对 VSSC 结构域 II 中的核苷酸多态性进行了基因分型，该结构域与 kdr 有关。获得了有关先前抗疥疮治疗、去污程序以及与接触者可能的再感染以及对重新实施的治疗的反应的信息。
序列比对比较显示，VSSC 结构域 II 的编码区存在以前未识别的突变。在 97.0%的螨虫中检测到新的 A1663T 颠换，导致甲硫氨酸到亮氨酸的非同义取代，M918L，这种突变在其他节肢动物中已知会导致 kdr。此外，在一只螨虫中发现了一个同义的 G1659A 转换，其核苷酸序列与野生型参考完全相同。以前的治疗和去污程序中没有观察到主要的不一致，这可能是导致对扑灭司林基治疗无反应的原因。在 65.6%的参与者中，后续感染得到治愈，主要是通过局部使用扑灭司林和全身使用伊维菌素的联合治疗。然而，在 14.6%的治愈病例中，单独使用扑灭司林即可消除疥疮，尽管在某些情况下需要延长暴露时间。
VSSC 基因中的 kdr 相关 M918L 突变现已出现在 S. scabiei var. hominis 螨虫中。因此，由于 kdr 型抗性导致对扑灭司林的敏感性丧失可能比预期的更为普遍，并且可能对感染疥疮的患者的治疗反应性起决定性作用。
