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

Abstract

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.