Pathogenic Dermatophytes Survive in Nail Lesions During Oral Terbinafine Treatment for Tinea Unguium

Abstract

Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium.

Variations in ribosomal DNA copy numbers in a genome of Trichophyton interdigitale

“…Among them, the evaluation method for viability was developed using qPCR targeting the ITS region of rDNA, which revealed a correlation between ITS DNA and CFU 48 hours after death in T. interdigitale 21 . In addition, the amounts of rDNA in toe nail and skin specimens from patients with tinea pedis and tinea unguium were quantified using the ITS region of rDNA targeted by qPCR 33‐35 . By combining the investigation of rDNA copy numbers with the quantification of rDNA amounts in specimens, it will be possible to estimate the amount of T. interdigitale in affected sites.…”

“…21 In addition, the amounts of rDNA in toe nail and skin specimens from patients with tinea pedis and tinea unguium were quantified using the ITS region of rDNA targeted by qPCR. [33][34][35] By combining the investigation of rDNA copy numbers with the quantification of rDNA amounts in specimens, it will be possible to estimate the amount of T. interdigitale in affected sites. This finding may provide a more detailed understanding of the mechanisms underlying the attenuation and recalcitrance of dermatophytosis caused by T. interdigitale.…”

A comparative study between two antifungal agents, Luliconazole and Efinaconazole, of their preventive effects in a Trichophyton-infected guinea pig onychomycosis model

“…Quantitative real-time PCR (qPCR) assay using the internal transcribed spacer (ITS) region of T. mentagrophytes DNA was used to detect the viability of the fungi. 22 qPCR has comparable sensitivity to potassium hydroxide (KOH) examination and nail culture assay by colony-forming unit. 23–25 A total of 12 nails per group (1 or 2 nails per foot) was measured.…”

“…In addition, we determined that the fixed-quantity minimum limit value of T. mentagrophytes per nail is 10,000 copies of ITS DNA because the primers for the ITS region of T. mentagrophytes DNA form the primer-dimer below 10,000 copies. 22 …”

The Curious Case of “Case Report” of Infections Caused by Human and Animal Fungal Pathogens: An Educational Tool, an Online Archive, or a Format in Need of Retooling

“…In Table 7, we present the analysis of a few Mycopathologia articles covering clinical and experimental mycology, and the opinions. The articles were from Brazil [95], China [96,97], Colombia [98], Japan [99], the Netherlands [100], and Poland [101]. Interestingly, an impressive number of downloads of a recent article did not lead to high citations [101], while high downloads of a 2016 article garnered impressive citations.…”