Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Tinea corporis intrafamilial infection in pets due to Microsporum canis.

Microsporum canis, one of the most widespread dermatophytes worldwide, is a zoonotic microorganism that transmits infection from reservoirs such as cats and dogs to humans. This microorganism is associated with Tinea corporis and other clinical manifestations; however, few studies have used genetic surveillance to determine and characterize the process of zoonotic transmission. In this study, we show a clear example of zoonotic transmission from a cat to an intrafamilial environment, where it caused Tinea corporis by infection with M. canis. Molecular characterization using the b-tubulin gene and Random Amplified Polymorphic DNA analysis made it possible to determine that the six isolates of M. canis obtained in this study belonged to the same genetic variant or clone responsible for reservoir-reservoir or reservoir-human transmission.

In vitro antifungal susceptibility of the dermatophytes: a single center study from Eastern Black Sea Region of Turkey.

OBJECTIVE: A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs. PATIENTS AND METHODS: Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine. RESULTS: A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum (13.8% in 49 samples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance. CONCLUSIONS: The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development.

Prevalence and characteristics of Epidermophyton floccosum skin infections: A 12-year retrospective study.

BACKGROUND: Epidermophyton floccosum (E. floccosum), an anthropophilic dermatophyte, is the primary causative agent of skin conditions such as tinea cruris, tinea pedis and tinea corporis. OBJECTIVES: This study aimed to determine the prevalence and characteristics of E. floccosum-induced dermatophytosis, with particular emphasis on the types of infections and demographic profiles. METHODS: In this retrospective study, patient records from the dermatology outpatient clinic were scrutinized, covering the timeframe from January 2009 to December 2020. Eligibility for the study required a dermatophytosis diagnosis verified by microscopic examination and fungal culture. RESULTS: Of the 4669 confirmed dermatophytosis cases, 82 (1.8%) were attributable to E. floccosum infection. The proportions of male and female patients with E. floccosum infections were 50.0% each. The most common presentation was tinea pedis (39.0%), followed by tinea cruris (37.8%) and tinea corporis (26.8%). The mean age at disease onset for tinea cruris was 38.7 ± 18.7 years, which was lower than that for tinea pedis (50.6 ± 14.2 years) and tinea corporis (53.5 ± 16.4 years). However, these age differences were not statistically significant. A continuous decrease in E. floccosum isolation was observed over the study period. CONCLUSIONS: There was a steady decline in the prevalence of E. floccosum dermatophytosis over the 12-year study period. Despite the decreasing trend, tinea cruris, tinea corporis and tinea pedis remained the predominant clinical manifestations of E. floccosum infection.

Impact of sphingolipid synthesis inhibition on the drug susceptibility patterns of Trichophyton species.

The well known dermatophyte infections caused by Trichophyton species are an ambiguous problem to treat using the present arsenal of antifungals. This study expounds on the effect of inhibition of sphingolipid pathway on Trichophyton growth. Findings from the drug susceptibility assays suggest sphingolipid inhibition severely restricts the growth of T. interdigitale and T. tonsurans. The observed synergistic effects of combinations of sphingolipid inhibitor and conventional drugs provide a promising treatment strategy against Trichophyton infection.

Expert Panel Review of Skin and Hair Dermatophytoses in an Era of Antifungal Resistance.

Dermatophytoses are fungal infections of the skin, hair, and nails that affect approximately 25% of the global population. Occlusive clothing, living in a hot humid environment, poor hygiene, proximity to animals, and crowded living conditions are important risk factors. Dermatophyte infections are named for the anatomic area they infect, and include tinea corporis, cruris, capitis, barbae, faciei, pedis, and manuum. Tinea incognito describes steroid-modified tinea. In some patients, especially those who are immunosuppressed or who have a history of corticosteroid use, dermatophyte infections may spread to involve extensive skin areas, and, in rare cases, may extend to the dermis and hair follicle. Over the past decade, dermatophytoses cases not responding to standard of care therapy have been increasingly reported. These cases are especially prevalent in the Indian subcontinent, and Trichophyton indotineae has been identified as the causative species, generating concern regarding resistance to available antifungal therapies. Antifungal-resistant dermatophyte infections have been recently recognized in the United States. Antifungal resistance is now a global health concern. When feasible, mycological confirmation before starting treatment is considered best practice. To curb antifungal-resistant infections, it is necessary for physicians to maintain a high index of suspicion for resistant dermatophyte infections coupled with antifungal stewardship efforts. Furthermore, by forging partnerships with federal agencies, state and local public health agencies, professional societies, and academic institutions, dermatologists can lead efforts to prevent the spread of antifungal-resistant dermatophytes.

A Case of Tinea Faciei due to Trichophyton indotineae with Steroid Rosacea Related to Topical Over-The-Counter Drugs Purchased Outside of Japan.

A Filipino woman in her forties had facial erythema that was being self-treated with over-the-counter (OTC) drugs purchased outside of Japan. The drugs included clobetasol propionate, antibiotic, and antifungal components. Her facial erythema symptoms were worse during summertime. KOH direct examination of annular erythema was positive for fungal hyphae and negative for Demodex folliculorum. Fungal culture revealed Trichophyton indotineae based on internal transcribed spacer sequence analysis. Minimal inhibitory concentration for terbinafine was 0.06 µg/mL. We made a diagnosis of tinea faciei with steroid rosacea. We treated the patient with oral itraconazole. Physicians should be aware of increasing T. indotineae infections and increasing self-medication using topical OTC steroids combined with antifungals and antibiotics not only in India but also among foreign people living in other countries such as Japan.

Identification of primary metabolites in fungal species of Trichophyton mentagrophyte and Trichophyton rubrum by NMR spectroscopy.

BACKGROUND: Superficial mycoses are fungal infections limited to the outermost layers of the skin and its appendages. The chief causative agents of these mycoses are dermatophytes and yeasts. The diagnosis of dermatophytosis can be made by direct mycological examination with potassium hydroxide (10%-30%) of biological material obtained from patients with suspected mycosis, providing results more rapid than fungal cultures, which may take days or weeks. This information, together with clinical history and laboratory diagnosis, ensures that the appropriate treatment is initiated promptly. However, false negative results are obtained in 5%-15%, by conventional methods of diagnosis of dermatophytosis. OBJECTIVES: To study the metabolic profiles of the commonly occurring dermatophytes by NMR spectroscopy. PATIENTS/MATERIALS: We have used 1D and 2D Nuclear Magnetic Resonance (NMR) experiments along with Human Metabolome Database (HMDB) and Chenomx database search for identification of primary metabolites in the methanol extract of two fungal species: Trichophyton mentagrophyte (T. mentagrophyte) and Trichophyton rubrum (T. rubrum). Both standard strains and representative number of clinical isolates of these two species were investigated. Further, metabolic profiles obtained were analysed using multivariate analysis. RESULTS: We have identified 23 metabolites in the T. mentagrophyte and another 23 metabolites in T. rubrum. Many important metabolites like trehalose, proline, mannitol, acetate, GABA and several other amino acids were detected, which provide the necessary components for fungal growth and metabolism. Altered metabolites were defined between Trichophyton mentagrophyte and T. rubrum strains. CONCLUSION: We have detected many metabolites in the two fungal species T. mentagrophyte and T. rubrum by using NMR spectroscopy. NMR spectroscopy provides a holistic snapshot of the metabolome of an organism. Key metabolic differences were identified between the two fungal strains. We need to perform more studies on metabolite profiling of the samples from these species for their rapid diagnosis and prompt treatment.

Case Report: Diagnosing Dermatophytoses in Children.

Dermatophytoses of the skin and scalp are common disorders in the pediatric population. The resemblance of the clinical presentation to other dermatoses can make fungal infections challenging to diagnose. We present three cases of dermatophytoses in children. The presence of fungi within skin lesions was confirmed in all cases. The diagnoses were "id" reaction in response to Trichophyton tonsurans infection, Kerion celsi because of Microsporum canis infection, and hair loss during microsporosis. Based on our review and clinical experience, we suggest diagnostic paths and treatments for dermatophytoses in children.

Multi-drug resistance Trichophyton indotineae in a stray dog.

A 2.5-year-old stray dog showed signs of hair loss, mild skin crusting, and redness on extremities and trunk. The etiologic agent was confirmed as Trichophyton indotineae by sequencing of ITS region. Using the Clinical and Laboratory Standards Institute (CLSI M38-A3) guideline, antifungal susceptibility testing showed multidrug resistance phenotype against terbinafine (16 µg/mL-1), itraconazole, and some other tested antifungals (minimum inhibitory concentration, MIC≥16 µg/mL-1). However, luliconazole was found to be active in- vitro (0.016 µg/mL-1). Upon further studies, sequencing of SQLE gene showed an amino acids substitution of Phe397Leu and Ala448Thr, which is potentially linked to terbinafine resistance in Trichophyton species.

Molecular typing of a collection of Iranian clinical Trichophyton tonsurans isolates based on the non-transcribed spacer region of rDNA and antifungal susceptibility testing of the species.

INTRODUCTION: Wrestling, considered the national sport of Iran, has gained immense popularity among Iranians. Wrestlers frequently encounter skin conditions, with dermatophyte fungal infections, particularly tinea gladiatorum (TG), being a common issue. TG, caused by the Trichophyton genus, has emerged as a major health concern for wrestlers and other contact sport athletes worldwide. This study aimed to assess the genotypic diversity and antifungal susceptibility of Trichophyton tonsurans isolates responsible for TG in Iranian wrestlers from Mazandaran province, northern Iran. MATERIALS AND METHODS: A total of 60 clinical T. tonsurans isolates collected from various cities in Mazandaran, were included in the study. The isolates were identified through PCR-restriction fragment length polymorphism and sequencing methods. Genomic DNA was extracted from these isolates, and the non-transcribed spacer (NTS) region of ribosomal RNA (rRNA) was targeted for genotyping using newly designed primers. Haplotype analysis was performed to explore genetic diversity, and antifungal susceptibility to terbinafine (TRB) and itraconazole (ITC) was assessed. RESULTS: The results revealed five distinct NTS types: NTS-I, NTS-II, NTS-III, NTS-IV and NTS-V, with NTS-IV being the most prevalent. The distribution of NTS types varied across different cities, suggesting potential transmission patterns among wrestlers. Antifungal susceptibility testing showed that all isolates were susceptible to TRB, while one isolate demonstrated resistance to ITC. Genotypic diversity was not correlated with antifungal susceptibility, emphasising the importance of monitoring susceptibility to ensure effective treatment. Haplotype analysis highlighted significant genetic diversity among the T. tonsurans isolates. This diversity may be attributed to factors such as human-to-human transmission, geographic location and lifestyle changes. The study's findings underscore the need for comprehensive genotypic analysis to understand the epidemiology and evolution of T. tonsurans infections in athletes. CONCLUSION: In conclusion, this study provides valuable insights into the genotypic diversity and antifungal susceptibility of T. tonsurans isolates causing TG in Iranian wrestlers. The presence of multiple NTS types and varying susceptibility patterns highlights the complexity of T. tonsurans infections in this population. Further research is warranted to track the transmission routes and genetic evolution of T. tonsurans strains among wrestlers and develop effective control measures.

Deep dermatophytosis caused by Trichophyton rubrum in an elderly patient with CARD9 deficiency: A case report and literature review.

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

A resurgence of tinea cruris caused by Epidermophyton floccosum: An outbreak among Thai naval cadets.

BACKGROUND: A decreasing trend in tinea cruris caused by Epidermophyton floccosum, an anthropophilic dermatophyte, has been observed. METHODS: This retrospective study involved Thai naval cadets aged 18 years or older with suspected groin lesions. Both clinical evaluations and laboratory investigations were conducted. RESULTS: In total, 86 male participants with a median age of 19 years who presented with groin rash were enrolled in the study. Branching septate hyphae from KOH examination were found in 55 patients (64.0 %). Fungal identifications were Epidermophyton floccosum (42 cases; 76.4 %), Trichophyton mentagrophytes complex (3 cases; 5.5 %), and no growth (10 cases; 18.2 %). An E. floccosum outbreak was identified, with a prevalence of 76.4 %. Most lesions exhibited admixed erythema and hyperpigmentation. Approximately two-thirds displayed prominent, easily visible scaling. Scrotal involvement was absent in 95.2 % of lesions, with 87.2 % presenting bilaterally. A gradual symptom onset lasting up to 2 months was observed in 78.9 % of cases. Lesion morphologies included annular (73.8 %), patchy (14.3 %), and polycyclic (9.5 %). Severe itching disrupting daily activities was reported by only 7.1 % of participants. Approximately two-thirds used over-the-counter (OTC) topical medications without consulting a physician. Risk factors related to clothing included sharing clothes (59.5 %), wearing sweaty clothes (100 %), and reusing unwashed clothes (81.0 %). CONCLUSIONS: The E. floccosum tinea cruris outbreak among naval cadets was characterized by a gradual onset and mild symptoms. OTC medication use without physician consultation was prevalent.

Dermatophyte infection: from fungal pathogenicity to host immune responses.

Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients.

Patterns of Common Dermatological Conditions among Children and Adolescents in Pakistan.

Background and Objectives: Dermatological disorders are highly prevalent among children in Pakistan. The present cross-sectional study aims to identify the spectrum of dermatological conditions among children and adolescents in Pakistan. Materials and Methods: A total of 582 patients (50.9% males; 49.1% females) were included in the study based on their age (5.7 ± 4.1 years), dermatological condition, and epidemiology. The youngest patient was aged ten days, whereas the eldest was seventeen. Age criteria were further stratified into three categories: infants and toddlers (≤5 years), children (≥5 to <12 years), and adolescents (≥12 to <18 years). Amongst them, the majority was from Punjab (81.6%), while the other regions included were Azad Jammu and Kashmir (14.4%), Islamabad (3.3%), and Khyber Pakhtunkhwa (0.7%). Results: Scabies was the highest reported skin condition with 281 (45.55%) patients, followed by 114 (19.6%) with eczema, 60 (10.3%) with dermatitis, 33 (5.7%) with tinea capitis, 17 (2.9%) with tinea corporis, 16 (2.7%) with impetigo, and 15 (2.6%) with folliculitis. Other conditions include urticaria, burns, infections, pediculosis, tinea inguinalis, tinea faciei, nappy rashes, alopecia, warts, tinea incognito, tinea cruris, and acne vulgaris. The chi-squared test showed a high prevalence of tinea corporis and acne among adolescents (12-17 years), whereas eczema, dermatitis, and impetigo were more prevalent among infants and toddlers. Conclusions: Pets or livestock and poor hygiene were found to be highly reported risk factors for many dermatological conditions like scabies and fungal infections. Dermatological conditions are common in younger individuals, but unfortunately, many children do not receive the desired medical assistance.

[2021 Epidemiological Survey of Dermatomycoses in Japan].

This is a report of the results of the epidemiological survey on dermatomycoses conducted in 2021. A total of 9,442 patients with dermatomycosis were reported for one year. They include 8,151 (86.3%) with dermatophytosis, 796 (8.4%) with candidiasis, 484 (5.1%) with Malassezia infection, and 11 (0.1%) with deep cutaneous mycosis. In order, the most common types of dermatophytoses were tinea pedis (4,195 cases, 2,341 males and 1,854 females), tinea unguium (2,711 cases, 1,509 males and 1,202 females), tinea corporis (674 cases, 445 males and 229 females), tinea cruris (399 cases, 305 males and 94 females), tinea manus (125 cases, 78 males and 47 females), and tinea capitis (47 cases, 25 males and 22 females). The number of cases of tinea pedis and tinea unguium increased during the summer. A higher percentage of patients were aged 80 or older than in previous surveys. These findings may reflect the increasing percentage of elderly patients seen and the superannuation of the population. As in previous surveys, Trichophyton rubrum and Trichophyton interdigitale were the two most frequently isolated species of fungi causing dermatophytoses. Microsporum canis and Trichophyton tonsurans were the two species most often causing tinea capitis.Regarding cutaneous candidiasis, while candidal intertrigo was the most common in previous surveys, diaper candidiasis in the elderly was the most common in this survey. A background check revealed that this was because a facility included a semi-prophylactic approach to address diaper candidiasis occurring within the ward.Malassezia infections by Malassezia folliculitis clearly increased with each survey. The tendency of certain facilities with many reports of Malassezia folliculitis suggests that it is greatly affected by the presence of physicians familiar with the disease.

Nannizzia species causing dermatophytosis in cats and dogs: First report of Nannizzia incurvata as an etiological agent in Brazil.

Dermatophytosis is a superficial cutaneous infection, most commonly caused by fungal species such as Microsporum canis, Nannizzia gypsea (Microsporum gypseum), and Trichophyton mentagrophytes in dogs and cats. The zoonotic potential of these species is concerning, as companion animals are increasingly close to their owners. Therefore, the objectives of the study were to evaluate the current prevalence of Nannizzia-causing canine and feline dermatophytosis in Curitiba and Metropolitan Region, as well as perform phenotypic and phylogenetic characterizations of these isolates. Thus, 241 skin and fur samples from 163 dogs and 78 cats were analyzed from 2020 to 2021. The samples were obtained from animals of three sources: Veterinary Hospital of the Federal University of Paraná, animal shelters, and private clinics. The diagnosis was performed through phenotypic characterization and sequencing ITS rDNA region. Among 97 positive samples for dermatophytes, Nannizzia was identified in 14 (14.4%) samples, while other dermatophyte genera were found in the remaining 83 (85.6%) samples. Among the canine samples, nine (90%) were N. gypsea, and one (10%) was N. incurvata. Whereas in feline samples, three (75%) were N. gypsea, and one (25%) was N. incurvata. It was concluded that among 97 animals infected with dermatophytes, dogs (24.4%; 10/41) were significantly more affected by Nannizzia than cats (7.1%; 4/56) (P < .05). According to molecular analyses, the ITS rDNA region provided satisfactory results for species-level identification of Nannizzia, confirming the first report of N. incurvata as an etiological agent of canine and feline dermatophytosis in Brazil.

Nannizzia genus affected significantly more dogs (24.4%) than cats (7.1%) (P < .05). The ITS rDNA exhibited higher accuracy for identifying dermatophytes compared to phenotypic diagnosis, allowing the confirmation of the first reports of N. incurvata as an etiological agent of dermatophytosis in dogs and cats in Brazil.

Tiña por Nannizzia nana: caso clínico y revisión bibliográfica / Ringworm by Nannizzia nana: Clinical case and literature review

Introducción Las dermatofitosis humanas son el grupo más extendido de infecciones causadas por hongos. Estos son capaces de invadir los tejidos que contienen queratina de los animales. Nannizzia nana (N. nana) puede causar tiña en cerdos y que de manera excepcional puede producir infecciones en humanos. Métodos Realizamos una búsqueda en PubMed de artículos publicados desde el 1 de enero de 1990 hasta el 31 de marzo del 2022 para identificar casos adicionales. Los términos de búsqueda empleados fueron «Microsporum nanum» y «Nannizzia nana». Resultados Tras la revisión bibliográfica identificamos un total 16 casos de dermatofitosis por N. nana desde 1990. En la mayoría de los pacientes, el diagnóstico clínico fue tinea corporis y los antifúngicos más utilizados fueron terbinafina y griseofulvina. Conclusión N. nana es una especie de dermatofito aislada infrecuentemente en humanos, pero que representa una fuente potencial de dermatofitosis en personas que entran en contacto directo o indirecto con animales y con el suelo (AU)

Introduction Human dermatophytoses are the most widespread infections caused by fungi. These are capable of invading the keratin-containing tissues of animals. Nannizzia nana (N. nana) can cause ringworm in pigs and rarely cause infections in humans. Methods We conducted a search using PubMed for articles published from January 1, 1990 to March 31, 2022 to identify additional cases. The search terms used were “Microsporum nanum” and “Nannizzia nana”. Results After reviewing the literature, we identified a total of 16 cases of dermatophytosis due to N. nana since 1990. In most of the patients, the clinical diagnosis was tinea corporis and the most widely used antifungals were: terbinafine and griseofulvin. Conclusion N. nana is a dermatophyte species isolated infrequently in humans, but it represents a potential source of dermatophytosis in people who come into direct or indirect contact with animals and soil (AU)