Abstract：
BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene.
OBJECTIVE: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States.
METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His).
RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution.
CONCLUSIONS: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.
OBJECTIVE: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States.
METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His).
RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution.
CONCLUSIONS: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.
摘要：
背景：在全球范围内，抗真菌耐药的皮肤癣菌病正在上升，角鲨烯环氧酶（SQLE）基因的点突变赋予的对特比萘芬的抗性。
目的：报告美国甲癣患者中SQLE突变的患病率和分布的变化。
方法：从2022年至2023年的18个月期间，从疑似甲癣患者中收集了脚趾甲样本的纵向队列研究。从美国各地提交样品，并进行多重实时聚合酶链反应以检测皮肤癣菌，在四个已知热点进一步筛查SQLE突变(393Leu，397Phe，415Phe和440His）。
结果：共提交了62,056份样本（平均年龄：57.5岁；女性：60.4%）。在38.5%的样本中检测到皮肤癣菌，主要是红色毛癣菌复合体(83.6%)和植叶草毛癣菌复合体(10.7%)。在22,610个皮肤癣菌样本中进行了SQLE突变调查;在2022年第一季度至2023年第二季度之间，SQLE突变的患病率显着增加（每千人29.0至61.9）。Phe397Leu取代是主要突变;Phe415Ser和His440Tyr也已经出现,其先前被报道为皮肤样品中的次要突变。突变率的时间变化可主要归因于Phe415Ser取代。来自老年患者(>70岁)的样品更有可能被包括具有Phe415Ser替代的菌株在内的叶植叶虫复合体感染。
结论：甲癣菌感染患者中SQLE突变的患病率可能被低估。老年人可能有更高的风险。
目的：报告美国甲癣患者中SQLE突变的患病率和分布的变化。
方法：从2022年至2023年的18个月期间，从疑似甲癣患者中收集了脚趾甲样本的纵向队列研究。从美国各地提交样品，并进行多重实时聚合酶链反应以检测皮肤癣菌，在四个已知热点进一步筛查SQLE突变(393Leu，397Phe，415Phe和440His）。
结果：共提交了62,056份样本（平均年龄：57.5岁；女性：60.4%）。在38.5%的样本中检测到皮肤癣菌，主要是红色毛癣菌复合体(83.6%)和植叶草毛癣菌复合体(10.7%)。在22,610个皮肤癣菌样本中进行了SQLE突变调查;在2022年第一季度至2023年第二季度之间，SQLE突变的患病率显着增加（每千人29.0至61.9）。Phe397Leu取代是主要突变;Phe415Ser和His440Tyr也已经出现,其先前被报道为皮肤样品中的次要突变。突变率的时间变化可主要归因于Phe415Ser取代。来自老年患者(>70岁)的样品更有可能被包括具有Phe415Ser替代的菌株在内的叶植叶虫复合体感染。
结论：甲癣菌感染患者中SQLE突变的患病率可能被低估。老年人可能有更高的风险。
