The emergence of superficial dermatophytosis due to Trichophyton indotineae and Trichophyton mentagrophytes genotypes VII and II* in the United States: A need for comprehensive testing approaches

We report an exponential rise in dermatophyte infections belonging to the Trichophyton interdigitale/mentagrophytes species complex (TiTmSC), including the recently speciated T. indotineae (Ti, formerly T. mentagrophytes genotype VIII), in New York City and surrounding counties. These include 135 cases of Ti, 39 cases of T. mentagrophytes genotype VII (TmVII), and 14 cases of T. mentagrophytes genotype II* (TmII*), highlighting the urgent need for rapid and high-throughput identification, and characterization of the prevalence, spread, and drug-resistance of these pathogens. A deep learning model utilizing a Convolutional Neural Network (CNN) was developed with the internal transcribed spacer (ITS) region of 28 genotypes of TiTmSC. The model enabled accurate, rapid, and high-throughput identification of Trichophyton species and genotypes directly from Sanger sequencing output files. Antifungal susceptibility testing (AFST) of these pathogens revealed that 57% of the Ti isolates were resistant to the first-line drug terbinafine, and 38-52% of Ti isolates were resistant to azoles. In contrast, all TmVII and TmII* isolates were susceptible to terbinafine, with some degree of resistance observed against azoles. Whole-genome sequencing (WGS) on a subset of Ti, TmVII, and TmII* isolates revealed both clonal spread and independent introductions. The comprehensive approaches on rapid identification, drug resistance profiles, and mechanisms of spread of these emerging dermatophyte pathogens will likely aid in patient care and infection control measures. IMPORTANCEIn this report, we present a comprehensive laboratory investigations on the emergence and rapid spread of drug-resistant Trichophyton indotineae (Ti), T. mentagrophytes genotype VII (TmVII) and T. mentagrophytes genotype II* (TmII*) in New York City and surrounding counties. The whole-genome sequencing results revealed both clonal spread and independent introduction. The comprehensive approaches on rapid identification, drug-resistance profiles, and mechanisms of spread of these emerging pathogens will likely aid in patient care and infection contrl measures.