Has the Multidrug-Resistant Dermatophyte *Trichophyton indotineae* Epidemic Finally Reached China?

🔍 Key Finding This study reports the first cases of Trichophyton indotineae in mainland China, imported from India, and finds no evidence of local transmission despite the fungus’ presence for nearly five years. This suggests a possible difference in susceptibility to this multidrug-resistant dermatophyte between individuals of South Asian ancestry and other races.

🔬 Methodology Overview

• Design: Retrospective case series and phylogenetic analysis.
• Sample Collection: 31 strains of the T. mentagrophytes complex isolated from patients at the Affiliated Hospital of Guizhou Medical University between May 2017 and April 2022. Included strains demonstrated successful growth, isolation, purification, and morphological identification as dermatophytes.
• Identification and Phylogeny: Phenotypic identification followed by rDNA ITS sequencing and phylogenetic analysis using maximum-likelihood and Bayesian inference methods. Comparison with 115 reference sequences from GenBank.
• Antifungal Susceptibility Testing: Broth dilution method according to CLSI M38-A2 guidelines for terbinafine, luliconazole, itraconazole, voriconazole, fluconazole, and ketoconazole.
• Squalene Epoxidase (SQLE) Gene Analysis: PCR amplification and sequencing of the SQLE gene to identify mutations associated with terbinafine resistance.
• Literature Search: PubMed and Embase search for published cases/GenBank accession numbers of T. mentagrophytes genotype VIII or T. indotineae to analyze global distribution and patient demographics.

📊 Results

• First report of T. indotineae in mainland China: Two Indian patients in Guiyang, China, were diagnosed with tinea infections (corporis/cruris/faciei) caused by T. indotineae.
• Local transmission not observed: Despite the presence of T. indotineae in Guiyang for nearly 5 years, no transmission among the local Chinese population has been observed. Other countries outside the Indian subcontinent report similar findings.
• Potential host susceptibility differences: The lack of local transmission suggests possible racial differences in immunity or genetic predisposition to T. indotineae infection.
• High terbinafine resistance: One T. indotineae isolate (JYP22048) showed high MIC to terbinafine (4 µg/ml), while the other (JYP18010) had a low MIC (<0.03 µg/ml). JYP22048 carried the Phe397Leu mutation in the SQLE gene, associated with terbinafine resistance.
• Reduced fluconazole susceptibility: Both T. indotineae isolates showed reduced susceptibility to fluconazole (MICs of 16 µg/ml and 32 µg/ml).
• Luliconazole most effective: Luliconazole was the most effective antifungal against both T. indotineae isolates (MIC <0.03 µg/ml).
• Four genotypes of T. mentagrophytes complex identified: Among 31 clinical isolates of the T. mentagrophytes complex collected in Guiyang (2017-2022), four ITS genotypes were identified, including T. interdigitale types I and II (16 cases), T. mentagrophytes type VII (3 cases), T. mentagrophytes type IX (9 cases), and T. indotineae (2 cases).

💡 Clinical Impact Trichophyton indotineae is an emerging multidrug-resistant dermatophyte spreading globally from the Indian subcontinent, and itraconazole should be considered for treating recalcitrant cases. Clinicians should be aware of the increasing prevalence of T. indotineae and its resistance profile, especially in patients of South Asian descent, and consider appropriate diagnostic and treatment strategies.

🤔 Limitations

• Traditional definitions of “anthropophilic”, “zoophilic”, and “geophilic” corresponding to clinical characteristics of inflammation severity are not accurate and have limitations, especially when used to define fungal species boundaries.
• The correlation between T. indotineae and host genetic background needs further clarification to understand taxonomic relationships and host susceptibility.
• Limited research investigates the link between genetic polymorphism, human ancestry, and gender susceptibility to fungal infections.
• Inconsistent reporting of strain collection times in published articles makes tracking the spread of T. indotineae challenging.
• Secondary drug resistance in dermatophytes, including T. indotineae and T. rubrum, due to erratic antifungal drug use needs attention.

✨ What It Means For You Doctors should be aware that Trichophyton indotineae has spread to China and exhibits high resistance to terbinafine, necessitating the use of alternative antifungals like itraconazole. The apparent host specificity of T. indotineae for individuals of South Asian descent warrants further investigation to understand the interplay between host genetics and fungal susceptibility.

Reference Jia S, Long X, Hu W, Zhu J, Jiang Y, Ahmed S, de Hoog GS, Liu W, Jiang Y. The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China. Front Immunol. 2023;13:1113065. https://doi.org/10.3389/fimmu.2022.1113065