Drug-Resistant Skin Fungus Trichophyton indotineae Spreads Worldwide

A stubborn skin fungus that shrugs off one of the most widely used antifungal drugs on the planet has spread far beyond the country where it first exploded into view. A comprehensive review published in Frontiers in Tropical Diseases maps the global rise of Trichophyton indotineae, an anthropophilic dermatophyte first formally named in 2020 after years of being mislabeled under the older Trichophyton mentagrophytes complex. The review, led by Dipika Shaw and Prasanna Honnavar of the American University of Antigua College of Medicine together with colleagues in India and the United States, argues that the organism now qualifies as a serious global public health threat, driven by terbinafine resistance, diagnostic blind spots, and the unchecked sale of steroid-antifungal combination creams.

Dermatophytosis, the family of superficial fungal infections that includes ringworm, jock itch, and athlete’s foot, is one of the most common infectious conditions on Earth, affecting roughly a quarter of the world’s population according to the World Health Organization. For decades, the allylamine drug terbinafine served as the reliable first-line oral treatment. That changed dramatically in India beginning around 2016, when dermatologists began reporting an unprecedented wave of chronic, widespread, and recurrent tinea infections that failed to respond to standard therapy. The culprit strains, initially described as Trichophyton mentagrophytes internal transcribed spacer genotype VIII, showed minimum inhibitory concentrations to terbinafine far above the wild-type range and produced atypical clinical pictures with large, steroid-modified lesions. Genetic analyses, including multilocus sequence typing and ITS sequencing, eventually confirmed that these isolates formed a distinct species, which Kano and colleagues named Trichophyton indotineae in 2020.

The taxonomy itself carries practical weight. Until recently, the T. mentagrophytes and T. interdigitale species were tangled in a morphological knot, with zoophilic and anthropophilic variants blurring species boundaries. Multicentric Indian studies, genomic analyses by Pchelin, Singh, and Tang and their teams, and whole-genome comparisons ultimately established T. indotineae as a genetically separate lineage that behaves as a human-adapted pathogen. Because phenotypic appearance alone cannot reliably separate it from close relatives, molecular taxonomy has become essential not just for academic clarity but for surveillance, since understanding which species is spreading and where determines how resistance trends are tracked and interpreted.

The epidemiology revealed by the review is striking. In India, prevalence figures for the organism vary widely, from 6.8 percent to as high as 61.5 percent in northern regions and 6.09 to 27.6 percent in the south, suggesting that climatic conditions are not the dominant driver. Between 2017 and 2019, T. indotineae became the predominant dermatophyte across India, accounting for roughly 82.6 to 94 percent of isolates in multicentre studies, displacing the long-standing leader Trichophyton rubrum. GenBank sequences suggest the organism circulated in the region for more than a decade before the epidemic was formally recognized. Patients now account for an estimated 5 to 10 percent of new dermatology outpatient registrations in northern India, and researchers describe hospital figures as merely the tip of the iceberg in the community.

Beyond the Indian subcontinent, the fungus has established a troubling international footprint. Iran appears to be a second endemic region, with earliest documented cases dating back to 2008 to 2010; a multicentre Iranian study found 28 of 141 T. mentagrophytes complex isolates were T. indotineae, some with terbinafine MICs of 32 milligrams per liter or higher. In a 2019 Baghdad survey, 69.2 percent of complex isolates were identified as T. indotineae, with 39 percent showing terbinafine resistance. Imported and locally acquired cases have been confirmed in Belgium, Canada, Denmark, France, Germany, Greece, Japan, and Switzerland, while Poland has deposited ITS sequences with 100 percent identity to the species. Retrospective sequencing pushed the earliest European detection back to 2011 in Germany. Most diagnosed patients were migrants from South Asian countries, but a Canadian study reporting an average delay of more than a year between migration and lesion onset raises the possibility of local transmission, and refugee or migrant camps with overcrowding may serve as transmission hotspots in non-endemic regions.

Clinically, the infection is dominated by extensive tinea corporis and tinea cruris, often covering large areas of the lower body and groin, with tinea faciei frequently reported. Notably, both men and women are affected equally regardless of age, and the fungus primarily infects people with competent immunity. Diabetes and immunosuppression appear to play only a minor role; instead, the local skin environment and drug pressure determine disease course. Intrafamilial transmission is a hallmark, with roughly half of patients reporting spread within the household, often linked to shared clothing, towels, and other fomites. Tinea capitis has not been established as a recognized manifestation, though the review cautions that earlier scalp infections may have been misassigned without molecular identification.

The molecular basis of terbinafine resistance is now well characterized. Terbinafine works by binding and blocking squalene epoxidase, the fungal enzyme encoded by the SQLE gene that is required to synthesize ergosterol, an essential component of the fungal cell membrane. In resistant strains, point mutations alter the enzyme’s structure so the drug can no longer bind effectively. The dominant substitutions are Leu393Phe and Phe397Leu, with additional mutations including L393S, F397I, F397V, F415I, F415S, F415V, H440Y, S395P, Q408L, and S443P documented. A multicentre Indian study found up to 76 percent of T. indotineae isolates resistant in vitro, and even T. rubrum showed resistance in 57.1 percent of tested isolates, signaling that allylamine resistance extends beyond a single species. Aggregate MIC data show in vitro terbinafine resistance in 78.9 to 82.5 percent of isolates, with MICs of 4 micrograms per milliliter or higher in 70.5 percent of isolates tested by CLSI methods. Resistance to azoles is also emerging, driven by overexpression of efflux pump genes; genomic work on T. rubrum identified 39 ATP-binding cassette transporters and 170 major facilitator superfamily transporters, of which several, including TruMDR1, TruMDR2, TruMDR3, and TruMFS2, are overexpressed on azole exposure and actively expel drugs from fungal cells.

Diagnosis and treatment remain the weakest links. Conventional phenotypic methods cannot reliably distinguish T. indotineae from its relatives, so ITS sequencing is the reference approach, albeit slow and dependent on sequencing facilities and curated databases. Faster alternatives include species-specific PCR targeting the C120-287 locus, PCR-RFLP targeting TOP2, and quantitative PCR assays that detect species-specific ITS polymorphisms directly from clinical specimens, though these still require validation. Improved MALDI-TOF mass spectrometry databases have proven remarkably powerful: adding reference spectra raised identification from 5 percent to 96 percent with 99.6 percent sensitivity. On the therapeutic side, itraconazole remains the most effective systemic alternative, with in vitro resistance relatively rare, while newer topical azoles such as luliconazole, sertaconazole, and efinaconazole show strong efficacy for localized disease. Expert recommendations favor itraconazole 100 milligrams per day as a first-line option and individualized, prolonged therapy continued until complete clinical and mycological cure, guided wherever possible by susceptibility testing.

The review’s authors close with a blunt prescription. Over-the-counter fixed-dose combinations containing potent corticosteroids such as clobetasol with antifungals and antibiotics are a major engine of the epidemic, with 60 to 70 percent of tinea patients reporting prior exposure; steroids deliver temporary relief while suppressing local immunity and distorting lesion appearance. Fungal resistance data is rarely integrated into national surveillance systems, and regulatory oversight of combination creams is inadequate, especially in developing countries. The authors call for a WHO-coordinated dermatophyte surveillance framework, standardized laboratories with molecular diagnostics, antifungal stewardship programs that match drug, dose, and duration to susceptibility results, prescription-only restrictions on steroid-antifungal combinations, and high-quality multicentre randomized controlled trials, which are currently absent, to establish evidence-based regimens for what has become the first truly global epidemic of drug-resistant ringworm.

Subject of Research: Global emergence of terbinafine-resistant dermatophytosis caused by Trichophyton indotineae

Article Title: The global emergence of Trichophyton indotineae: epidemiology, resistance, and management challenges

Article References: Shaw, D., Omar, A., Singh, M., Chandanathil, M., Bhargavi, C., Mysore, N., Bir, D., Ramasamy, S., & Honnavar, P. (2026). The global emergence of Trichophyton indotineae: epidemiology, resistance, and management challenges. Frontiers in Tropical Diseases, 7, Article 1960706. https://doi.org/10.3389/fitd.2026.1960706

Image Credits: AI Generated

DOI: 10.3389/fitd.2026.1960706

Keywords: Trichophyton indotineae, dermatophytosis, terbinafine resistance, antifungal resistance, squalene epoxidase, tinea, itraconazole, efflux pumps, molecular diagnostics, antifungal stewardship, global health, India epidemic