Emergence of terbinafine-resistant Trichophyton indotineae in Ontario, Canada, 2014-2023

Trichophyton indotineae is an emerging fungal pathogen capable of causing extensive recalcitrant dermatophytosis exacerbated by frequently retained terbinafine resistance. Cases of dermatophytosis due to T. indotineae have increased dramatically in India in recent years. Other countries have reported imported infection cases, causing public health concerns over the potential global spread of this drug-resistant pathogen. We describe T. indotineae from 47 clinical cases in Ontario, Canada, from 2014 to 2023, based on 50 isolates received by the provincial public health laboratory. Although detected in Ontario as early as 2014, cases increased sharply in 2022-2023. The majority of cases were found in 20 to 64-year-olds (83.0%). Cases from 2022 to 2023 were noted in only 8 of 34 public health units, clustering in large urban centers. Based on genomic epidemiology, Ontario isolates were genetically similar to isolates from other countries. Neither temporal nor geographic clustering based on country or public health unit was observed, suggesting Ontario cases represented recent introductions from endemic regions, although limited local transmission cannot be ruled out. Genome diversity (4.4 × 10^-6) was extremely low, consistent with the hypothesized recent emergence and clonal population structure of T. indotineae. Most (71.4%) cases were terbinafine-resistant, with isolates exhibiting either the L393F/L393S (n = 3) or F397L (n = 27) squalene epoxidase substitution. Decreased susceptibility to itraconazole or voriconazole was found among 23.7% of isolates and was frequently associated with CYP51B gene duplication. Terbinafine-resistant T. indotineae infections are escalating in Ontario, meriting enhanced laboratory detection methods and public health efforts to increase the awareness of recalcitrant dermatophytoses in order to promptly initiate appropriate treatment and control transmission.IMPORTANCECases of dermatophytosis caused by emerging pathogen Trichophyton indotineae are increasing worldwide. Many are resistant to first-line treatment option terbinafine, resulting in difficult-to-treat cases. We describe the emergence of cases of T. indotineae infections in Ontario, Canada. The incidence in primarily urban centers increased dramatically in 2022-2023, with a large percentage of isolates resistant to terbinafine. Decreased susceptibility to azoles was also observed for some isolates, raising concern over the potential evolution of multi-drug resistance. Ontario T. indotineae isolates were genetically similar to those from disparate locales worldwide, signifying the global nature of this public health concern. Together with other reports, this study serves to raise public health awareness to promote better laboratory detection procedures, prompt appropriate treatment of recalcitrant dermatophytoses, and inform infection prevention and control measures.