Increasing and Alarming Prevalence of Trichophyton indotineae as the Primary Causal Agent of Skin Dermatophytosis in Iran
Corresponding Author
Hossein Mirhendi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Correspondence:
Hossein Mirhendi ([email protected])
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Data curation, Supervision
Search for more papers by this authorShima Aboutalebian
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Investigation, Methodology, Software, Formal analysis, Writing - review & editing
Search for more papers by this authorZahra Jahanshiri
Department of Mycology, Pasteur Institute of Iran, Tehran, Iran
Contribution: Resources
Search for more papers by this authorFaezeh Rouhi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Writing - original draft, Writing - review & editing, Formal analysis
Search for more papers by this authorMohammad-Reza Shidfar
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Contribution: Resources
Search for more papers by this authorAmir-Shayan Chadeganipour
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Resources
Search for more papers by this authorShahla Shadzi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Resources
Search for more papers by this authorMahboobeh Kharazi
Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Contribution: Resources
Search for more papers by this authorMahzad Erami
Department of Infectious Disease, School of Medicine, Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
Contribution: Resources
Search for more papers by this authorMahnaz Hosseini Rizi
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Methodology
Search for more papers by this authorCorresponding Author
Hossein Mirhendi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Correspondence:
Hossein Mirhendi ([email protected])
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Data curation, Supervision
Search for more papers by this authorShima Aboutalebian
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Investigation, Methodology, Software, Formal analysis, Writing - review & editing
Search for more papers by this authorZahra Jahanshiri
Department of Mycology, Pasteur Institute of Iran, Tehran, Iran
Contribution: Resources
Search for more papers by this authorFaezeh Rouhi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Writing - original draft, Writing - review & editing, Formal analysis
Search for more papers by this authorMohammad-Reza Shidfar
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Contribution: Resources
Search for more papers by this authorAmir-Shayan Chadeganipour
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Resources
Search for more papers by this authorShahla Shadzi
Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Resources
Search for more papers by this authorMahboobeh Kharazi
Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Contribution: Resources
Search for more papers by this authorMahzad Erami
Department of Infectious Disease, School of Medicine, Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
Contribution: Resources
Search for more papers by this authorMahnaz Hosseini Rizi
Mycology Reference Laboratory, Isfahan University of Medical Sciences, Isfahan, Iran
Contribution: Methodology
Search for more papers by this authorFunding: This work was supported by the Isfahan University of Medical Sciences, Isfahan, Iran (Grant Number: 1402377).
ABSTRACT
Background
Trichophyton indotineae, formerly described as T. mentagrophytes rDNA-ITS genotype VIII, has recently been identified as a novel species within the T. mentagrophytes complex. It has rapidly replaced T. rubrum as the predominant dermatophyte. In this study, skin dermatophyte isolates collected from patients in Iran were sequence-analysed for species identification. Additionally, the current prevalence of T. indotineae was compared with data from the previous decade.
Methods
A total of 194 dermatophyte isolates were collected from patients in four cities across Iran between July and December 2023, with 73 isolates of the T. mentagrophytes complex from the past decade also included. DNA was extracted from fresh colonies, and the internal transcribed spacer (ITS) 1–5.8S rDNA-ITS2 region was PCR-amplified and sequenced, followed by bioinformatic sequence analysis.
Results
Out of the 194 dermatophyte isolates, 132 samples (68.04%) were identified as T. indotineae, followed by T. tonsurans (14.43%), T. rubrum (7.22%), Microsporum canis (4.64%), T. interdigitale (3.61%), T. mentagrophytes (1.55%) and Arthroderma benhamiae (0.51%). Sequence analysis of 73 isolates from the past decade showed T. indotineae as the most frequently identified species (43.83%), followed by T. interdigitale (32.88%), T. mentagrophytes (21.92%) and Nannizzia fulva (1.37%). These findings indicate an increasing prevalence of T. indotineae in Iran in recent years. We analysed 214 T. mentagrophytes/T. interdigitale isolates, identifying 164 as T. indotineae, including 26 with nucleotide variations. A phylogenetic tree highlighted the genetic diversity within the species complex.
Conclusion
The alarmingly high prevalence of the potentially drug-resistant species T. indotineae signals the necessity of continuous surveillance of skin dermatophytosis in the community.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author. Additionally, the datasets generated and analysed during this study are available in online repositories. The names of the repositories and the associated accession numbers can be found within the article.
References
- 1G. S. de Hoog, K. Dukik, M. Monod, et al., “Toward a Novel Multilocus Phylogenetic Taxonomy for the Dermatophytes,” Mycopathologia 182 (2017): 5–31.
- 2A. Ebert, M. Monod, K. Salamin, et al., “Alarming India-Wide Phenomenon of Antifungal Resistance in Dermatophytes: A Multicentre Study,” Mycoses 63, no. 7 (2020): 717–728.
- 3L. Brescini, S. Fioriti, G. Morroni, and F. Barchiesi, “Antifungal Combinations in Dermatophytes,” Journal of Fungi 7, no. 9 (2021): 727.
- 4R. Kano, U. Kimura, M. Kakurai, et al., “Trichophyton indotineae sp. Nov.: A New Highly Terbinafine-Resistant Anthropophilic Dermatophyte Species,” Mycopathologia 185, no. 6 (2020): 947–958.
- 5P. Chanyachailert, C. Leeyaphan, and S. Bunyaratavej, “Cutaneous Fungal Infections Caused by Dermatophytes and Non-Dermatophytes: An Updated Comprehensive Review of Epidemiology, Clinical Presentations, and Diagnostic Testing,” Journal of Fungi 9, no. 6 (2023): 669.
- 6S. Uhrlaß, S. B. Verma, Y. Gräser, et al., “Trichophyton Indotineae—An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide—A Multidimensional Perspective,” Journal of Fungi 8, no. 7 (2022): 757.
- 7A. Bishnoi, K. Vinay, and S. Dogra, “Emergence of Recalcitrant Dermatophytosis in India,” Lancet Infectious Diseases 18, no. 3 (2018): 250–251.
- 8G. Russo, L. Toutous Trellu, L. Fontao, and B. Ninet, “Towards an Early Clinical and Biological Resistance Detection in Dermatophytosis: About 2 Cases of Trichophyton indotineae,” Journal of Fungi 9, no. 7 (2023): 733.
- 9Z. Salehi, M. Shams-Ghahfarokhi, and M. Razzaghi-Abyaneh, “Antifungal Drug Susceptibility Profile of Clinically Important Dermatophytes and Determination of Point Mutations in Terbinafine-Resistant Isolates,” European Journal of Clinical Microbiology & Infectious Diseases 37 (2018): 1841–1846.
- 10A. Singh, A. Masih, J. Monroy-Nieto, et al., “A Unique Multidrug-Resistant Clonal Trichophyton Population Distinct From Trichophyton mentagrophytes/Trichophyton interdigitale Complex Causing an Ongoing Alarming Dermatophytosis Outbreak in India: Genomic Insights and Resistance Profile,” Fungal Genetics and Biology 133 (2019): 103266.
- 11A. Süß, S. Uhrlaß, A. Ludes, et al., “Extensive Tinea Corporis due to a Terbinafine-Resistant Trichophyton Mentagrophytes Isolate of the Indian Genotype in a Young Infant From Bahrain in Germany,” Die Dermatologie 70 (2019): 888–896.
10.1007/s00105-019-4431-7 Google Scholar
- 12A. Rezaei-Matehkolaei, A. Rafiei, K. Makimura, Y. Gräser, M. Gharghani, and B. Sadeghi-Nejad, “Epidemiological Aspects of Dermatophytosis in Khuzestan, Southwestern Iran, an Update,” Mycopathologia 181 (2016): 547–553.
- 13P. Nenoff, S. B. Verma, S. Uhrlaß, A. Burmester, and Y. Gräser, “A Clarion Call for Preventing Taxonomical Errors of Dermatophytes Using the Example of the Novel Trichophyton mentagrophytes Genotype VIII Uniformly Isolated in the Indian Epidemic of Superficial Dermatophytosis,” Mycoses 62, no. 1 (2019): 6–10.
- 14U. Kimura, M. Hiruma, R. Kano, et al., “Caution and Warning: Arrival of Terbinafine-Resistant Trichophyton interdigitale of the Indian Genotype, Isolated From Extensive Dermatophytosis, Japan,” Journal of Dermatology 47, no. 5 (2020): e192–e193.
- 15R. Sacheli and M.-P. Hayette, “Antifungal Resistance in Dermatophytes: Genetic Considerations, Clinical Presentations and Alternative Therapies,” Journal of Fungi 7, no. 11 (2021): 983.
- 16M. Klinger, M. Theiler, and P. Bosshard, “Epidemiological and Clinical Aspects of Trichophyton Mentagrophytes/Trichophyton Interdigitale Infections in the Zurich Area: A Retrospective Study Using Genotyping,” Journal of the European Academy of Dermatology and Venereology 35, no. 4 (2021): 1017–1025.
- 17M. Siopi, I. Efstathiou, K. Theodoropoulos, S. Pournaras, and J. Meletiadis, “Molecular Epidemiology and Antifungal Susceptibility of Trichophyton Isolates in Greece: Emergence of Terbinafine-Resistant Trichophyton Mentagrophytes Type VIII Locally and Globally,” Journal of Fungi 7, no. 6 (2021): 419.
- 18M. Durdu, H. Kandemir, A. S. Karakoyun, M. Ilkit, C. Tang, and S. de Hoog, “First Terbinafine-Resistant Trichophyton Indotineae Isolates With Phe397Leu and/or Thr414His Mutations in Turkey,” Mycopathologia 1–10 (2023): 2.
- 19S. Dellière, B. Joannard, M. Benderdouche, et al., “Emergence of Difficult-To-Treat Tinea Corporis Caused by Trichophyton Mentagrophytes Complex Isolates, Paris, France,” Emerging Infectious Diseases 28, no. 1 (2022): 224–228.
- 20K. M. T. Astvad, R. K. Hare, K. M. Jørgensen, D. M. L. Saunte, P. K. Thomsen, and M. C. Arendrup, “Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020,” Journal of Fungi 8, no. 2 (2022): 150.
- 21X. Kong, C. Tang, A. Singh, et al., “Antifungal Susceptibility and Mutations in the Squalene Epoxidase Gene in Dermatophytes of the Trichophyton Mentagrophytes Species Complex,” Antimicrobial Agents and Chemotherapy 65 (2021): 21–56.
- 22C. J. Posso-De Los Rios, E. Tadros, R. C. Summerbell, and J. A. Scott, “Terbinafine Resistant Trichophyton Indotineae Isolated in Patients With Superficial Dermatophyte Infection in Canadian Patients,” Journal of Cutaneous Medicine and Surgery 26, no. 4 (2022): 371–376.
- 23T. M. C. Ngo, P. A. T. Nu, C. C. Le, T. N. T. Ha, T. B. T. Do, and G. T. Thi, “First Detection of Trichophyton Indotineae Causing Tinea Corporis in Central Vietnam,” Medical Mycology Case Reports 36 (2022): 37–41.
- 24S. Jia, X. Long, W. Hu, et al., “The Epidemic of the Multiresistant Dermatophyte Trichophyton Indotineae Has Reached China,” Frontiers in Immunology 13 (2023): 1113065.
- 25A. S. Caplan, S. Chaturvedi, Y. Zhu, et al., “Notes From the Field: First Reported US Cases of Tinea Caused by Trichophyton Indotineae—New York City, December 2021–March 2023,” Morbidity and Mortality Weekly Report 72, no. 19 (2023): 536–537.
- 26P. Rana, M. Ghadlinge, and V. Roy, “Topical Antifungal-Corticosteroid Fixed-Drug Combinations: Need for Urgent Action,” Indian Journal of Pharmacology 53, no. 1 (2021): 82–84.
- 27A. Chowdhary, A. Singh, P. K. Singh, A. Khurana, and J. F. Meis, “Perspectives on Misidentification of Trichophyton interdigitale/Trichophyton mentagrophytes Using Internal Transcribed Spacer Region Sequencing: Urgent Need to Update the Sequence Database,” Mycoses 62, no. 1 (2019): 11–15.
- 28M. Erami, S. Aboutalebian, S. J. H. Hezaveh, et al., “Microbial and Clinical Epidemiology of Invasive Fungal Rhinosinusitis in Hospitalized COVID-19 Patients, the Divergent Causative Agents,” Medical Mycology 61 (2023): myad020.
- 29T. J. White, T. Bruns, S. Lee, and J. Taylor, “Amplification and Direct Sequencing of Fungal Ribosomal RNA Genes for Phylogenetics,” PCR Protocols: A Guide to Methods and Applications 18, no. 1 (1990): 315–322.
- 30A. Chowdhary, A. Singh, A. Kaur, and A. Khurana, “The Emergence and Worldwide Spread of the Species Trichophyton Indotineae Causing Difficult-To-Treat Dermatophytosis: A New Challenge in the Management of Dermatophytosis,” PLoS Pathogens 18, no. 9 (2022): e1010795.
- 31T. S. Bui and K. A. Katz, “Resistant Trichophyton Indotineae Dermatophytosis—An Emerging Pandemic, Now in the US,” JAMA Dermatology 160 (2024): 699.
- 32A. Khurana, A. Gupta, K. Sardana, et al., “A Prospective Study on Patterns of Topical Steroids Self-Use in Dermatophytoses and Determinants Predictive of Cutaneous Side Effects,” Dermatologic Therapy 33, no. 4 (2020): e13633.
- 33M. Ebrahimi, H. Zarrinfar, A. Naseri, et al., “Epidemiology of Dermatophytosis in Northeastern Iran,” Current Medical Mycology 5, no. 2 (2019): 16–21.
- 34C. B. Costa-Orlandi, G. M. Magalhães, M. B. Oliveira, E. L. Taylor, C. R. Marques, and M. A. de Resende-Stoianoff, “Prevalence of Dermatomycosis in a Brazilian Tertiary Care Hospital,” Mycopathologia 174, no. 5–6 (2012): 489–497.
- 35S. Aref, S. Nouri, H. Moravvej, M. Memariani, and H. Memariani, “Epidemiology of Dermatophytosis in Tehran, Iran: A Ten-Year Retrospective Study,” Archives of Iranian Medicine 25, no. 8 (2022): 502–507.
- 36S. Zamani, G. Sadeghi, F. Yazdinia, et al., “Epidemiological Trends of Dermatophytosis in Tehran, Iran: A Five-Year Retrospective Study,” Journal of Medical Mycology 26, no. 4 (2016): 351–358.
- 37G. Sadeghi, M. Abouei, M. Alirezaee, et al., “A 4-Year Survey of Dermatomycoses in Tehran From 2006 to 2009,” Journal of Medical Mycology 21, no. 4 (2011): 260–265.
10.1016/j.mycmed.2011.10.001 Google Scholar
- 38M. Ilkit and M. Durdu, “Tinea Pedis: The Etiology and Global Epidemiology of a Common Fungal Infection,” Critical Reviews in Microbiology 41, no. 3 (2015): 374–388.
- 39A. Rezaei-Matehkolaei, K. Makimura, S. de Hoog, et al., “Molecular Epidemiology of Dermatophytosis in Tehran, Iran, a Clinical and Microbial Survey,” Medical Mycology 51, no. 2 (2013): 203–207.
- 40S. Bassiri-Jahromi and A. A. Khaksari, “Epidemiological Survey of Dermatophytosis in Tehran, Iran, From 2000 to 2005,” Indian Journal of Dermatology, Venereology and Leprology 75, no. 2 (2009): 142–147.
- 41C. Tang, X. Kong, S. A. Ahmed, et al., “Taxonomy of the Trichophyton Mentagrophytes/T. Interdigitale Species Complex Harboring the Highly Virulent, Multiresistant Genotype T. Indotineae,” Mycopathologia 186 (2021): 315–326.
- 42Z. Salehi, M. Shams-Ghahfarokhi, and M. Razzaghi-Abyaneh, “Molecular Epidemiology, Genetic Diversity, and Antifungal Susceptibility of Major Pathogenic Dermatophytes Isolated From Human Dermatophytosis,” Frontiers in Microbiology 12 (2021): 643509.
- 43A. S. Caplan, G. C. Todd, Y. Zhu, et al., “Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton Indotineae. JAMA,” Dermatology 160 (2024): 701.
- 44M. Kawasaki, K. Anzawa, A. Wakasa, et al., “Different Genes Can Result in Different Phylogenetic Relationships in Trichophyton Species,” Nihon Ishinkin Gakkai Zasshi 49, no. 4 (2008): 311–318.
- 45S. Crotti, D. Cruciani, S. Spina, et al., “A Terbinafine Sensitive Trichophyton Indotineae Strain in Italy: The First Clinical Case of Tinea Corporis and Onychomycosis,” Journal of Fungi 9, no. 9 (2023): 865.
- 46A. Jabet, A. C. Normand, S. Brun, et al., “Trichophyton Indotineae, From Epidemiology to Therapeutic,” Journal of Medical Mycology 33, no. 3 (2023): 101383.
10.1016/j.mycmed.2023.101383 Google Scholar
- 47S. Taghipour, F. Shamsizadeh, I. M. Pchelin, et al., “Emergence of Terbinafine Resistant Trichophyton Mentagrophytes in Iran, Harboring Mutations in the Squalene Epoxidase (SQLE) Gene,” Infection and Drug Resistance 13 (2020): 845–850.
- 48A. Jabet, S. Brun, A. C. Normand, et al., “Extensive Dermatophytosis Caused by Terbinafine-Resistant Trichophyton indotineae, France,” Emerging Infectious Diseases 28, no. 1 (2022): 229–233.
- 49Y. H. Tartor, W. M. El-Neshwy, A. M. A. Merwad, et al., “Ringworm in Calves: Risk Factors, Improved Molecular Diagnosis, and Therapeutic Efficacy of an Aloe vera Gel Extract,” BMC Veterinary Research 16, no. 1 (2020): 421.
- 50S. B. Verma, S. Panda, P. Nenoff, et al., “The Unprecedented Epidemic-Like Scenario of Dermatophytosis in India: I. Epidemiology, Risk Factors and Clinical Features,” Indian Journal of Dermatology, Venereology and Leprology 87, no. 2 (2021): 154–175.
- 51O. Bontems, M. Fratti, K. Salamin, E. Guenova, and M. Monod, “Epidemiology of Dermatophytoses in Switzerland According to a Survey of Dermatophytes Isolated in Lausanne Between 2001 and 2018,” Journal of Fungi 6, no. 2 (2020): 95.
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