Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq.

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2-4 and 4 µg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.

Dermatophytomas in Onychomycosis: A Scoping Review of Prevalence, Diagnosis, and Treatment.

BACKGROUND: Dermatophytoma, also described as a longitudinal streak/spike, is a form of onychomycosis that presents as yellow/white streaks or patches in the subungual space, with dense fungal masses encased in biofilm. This scoping review of the literature was conducted to address a general lack of information about the epidemiology, pathophysiology, and treatment of dermatophytomas in onychomycosis. METHODS: A search was performed in the PubMed and Embase databases for the terms "longitudinal spike" or "dermatophytoma." Outcomes of interest were definition, prevalence, methods used for diagnosis, treatments, and treatment efficacy. Inclusion and exclusion of search results required agreement between two independent reviewers. RESULTS: Of a total of 51 records, 37 were included. Two reports provided the first unique definitions/clinical features of dermatophytomas. Overall, many descriptions were found, but one conclusive definition was lacking. Prevalence data were limited and inconsistent. The most frequently mentioned diagnostic techniques were clinical assessment, potassium hydroxide/microscopy, and fungal culture/mycology. Oral terbinafine and topical efinaconazole 10% were the most frequently mentioned treatments, followed by topical luliconazole 5% and other oral treatments (itraconazole, fluconazole, fosravuconazole). In studies with five or more patients without nail excision, cure rates were highest with efinaconazole 10%, which ranged from 41% to 100% depending on the clinical and/or mycologic assessment evaluated. Other drugs with greater than or equal to 50% cure rates were topical luliconazole 5% (50%), oral fosravuconazole (57%), and oral terbinafine (67%). In studies that combined oral terbinafine treatment with nail excision using surgical or chemical (40% urea) methods, cure rates ranged from 50% to 100%. CONCLUSIONS: There is little published information regarding dermatophytomas in onychomycosis. More clinical research and physician education are needed. Although dermatophytomas have historically been considered difficult to treat, the efficacy data gathered in this scoping review have demonstrated that newer topical treatments are effective, as are oral antifungals in combination with chemical or surgical methods.

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.

Dermatophytosis in domestic cats: Identification, and treatment in an Indian context.

The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased incidence of dermatophytosis among feline companions. Despite this growing concern, there is a noticeable scarcity of studies in India delving into the etiological factors contributing to dermatophytosis in cats. This disease is a threat to animal health and carries public health significance, given that cats are recognized reservoir hosts for Microsporum canis, a common dermatophyte affecting humans and animals. This study endeavours to identify the dermatophytes affecting cats and establish a standardized therapeutic regimen while accounting for the local stigma surrounding the regular bathing of cats. The study involved the examination of 82 cats presenting dermatological lesions, when subjected to cultural examination in dermatophyte test medium revealed 36 afflicted with dermatophytes. Isolates were presumptively identified by staining using lactophenol cotton blue, Chicago sky blue 6B, and Calcofluor white stains. Molecular-level identification of the isolates was confirmed through PCR-RFLP, amplifying the Internal Transcribed Spacer Sequence of 16 s rDNA, followed by restriction digestion using the Mva1 enzyme. Among the thirty-six isolates, 29 were identified as M. canis, while the remaining 7 were M. gypseum. The cases were categorized into five groups and treated with Lime Sulphur dip, 4 % chlorhexidine shampoo, a shampoo containing 2 % miconazole and 4 % chlorhexidine, oral itraconazole alone, and a combination of oral itraconazole with lime-Sulphur dip. Statistical analysis revealed that the response was notably swifter with lime Sulphur dip when considering only topical therapy. Moreover, the mycological cure was most expeditious when combining Lime Sulphur dip with oral itraconazole. These findings underscore the pivotal role of topical biocides in feline dermatophytosis treatment, potentially reducing the reliance on specific antifungals and thereby contributing to the mitigation of antimicrobial resistance emergence.

Dermatophytosis in cats: A comprehensive study on diagnostic methods and their accuracy.

Background: Dermatophytosis is a contagious fungal infection that affects mainly cats. It poses significant challenges in veterinary medicine due to its zoonotic potential and impact on animal and public health. Rapid and reliable diagnosis is crucial for preventing the spread of the disease, guiding treatment decisions, and monitoring disease control efforts. Although there are several studies on diagnostic methods in feline dermatophytosis, the comparison between them from the same sample lacks data. The absence of a universally accepted gold standard diagnostic method highlights the need for a multifaceted approach to diagnosing feline dermatophytosis. Aim: This study aims to assess the accuracy and efficacy of different diagnostic techniques comprehensively. Methods: For this, 48 samples of cats were analyzed by dermoscopy, direct hair examination, fungal culture using various media (Mycosel, Sabouraud, and Dermatophyte Test Medium), and polymerase chain reaction (PCR). Results: Direct examination and dermoscopy yielded unsatisfactory results. Mycosel and Sabouraud were suboptimal. DTM demonstrated superior selectivity, making it the most reliable among traditional methods. PCR was the top performer, exhibiting singular sensitivity, specificity, and accuracy. Conclusion: The study suggests that PCR may be the preferred choice for diagnosing feline dermatophytosis in clinical practice, especially when rapid and accurate results are essential.

Inappropriate Use of Steroids in Superficial Dermatophytosis: An Uncommon Case of Erythroderma.

Erythroderma is a dermatological emergency presenting with generalized erythema and scaling involving <90% of the body surface.1 There are various causes of erythroderma, such as psoriasis, atopic dermatitis, phytophotodermatitis, pityriasis rubra pilaris, pemphigus foliaceus, cutaneous T-cell lymphoma, and drug eruptions.2 However, erythroderma induced by dermatophytosis is encountered rarely. We, here, describe a case of erythroderma developed secondary to extensive dermatophytosis.

Antifungal activity of aminopyrrolnitrin against Trichophyton verrucosum in a guinea pig model of dermatophytosis.

BACKGROUND: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity. OBJECTIVES: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model. METHODS: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 µg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 µg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days. RESULTS: The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 µg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC. CONCLUSION: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.

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.

The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum.

Trichophyton rubrum is a human fungal pathogen that causes dermatophytosis, an infection that affects keratinized tissues. Integrated molecular signals coordinate mechanisms that control pathogenicity. Transcriptional regulation is a core regulation of relevant fungal processes. Previous RNA sequencing data revealed that the absence of the transcription factor StuA resulted in the differential expression of the MAPK-related high glycerol osmolarity gene (hog1) in T. rubrum. Here we validated the role of StuA in regulating the transcript levels of hog1. We showed through RT-qPCR that transcriptional regulation controls hog1 levels in response to glucose, keratin, and co-culture with human keratinocytes. In addition, we also detected hog1 pre-mRNA transcripts that underwent alternative splicing, presenting intron retention in a StuA-dependent mechanism. Our findings suggest that StuA and alternative splicing simultaneously, but not dependently, coordinate hog1 transcript levels in T. rubrum. As a means of preventing and treating dermatophytosis, our results contribute to the search for new potential drug therapies based on the molecular aspects of signaling pathways in T. rubrum.

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.

Improper Use of Topical Corticosteroids in Tinea Infections in a Tertiary Care Hospital.

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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.

An update on antifungal resistance in dermatophytosis.

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.

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.

Demography, commonly diagnosed disorders and mortality of guinea pigs under primary veterinary care in the UK in 2019-A VetCompass study.

INTRODUCTION: Guinea pigs are popular as domestic pets but there is limited information on the health of the wider pet population. This study aimed to report demography, commonly diagnosed disorders and mortality of guinea pigs under UK primary veterinary care. METHODS: Diagnosis and mortality information on guinea pigs was extracted from anonymised UK primary-care clinical records in VetCompass. RESULTS: From 51,622 guinea pigs under primary veterinary care during 2019, a specific breed was not recorded in 50,098 (97.05%). Of guinea pigs with information recorded, 23,206 (47.33%) were female and 25,828 (52.67%) were male. There were 1,020 (2.08%) neutered and 48,014 (97.92%) entire. Median adult bodyweight overall was 1.05kg (interquartile range [IQR] 0.90-1.19, range 0.40-2.66). From a random sample of 3,785/51,622 (7.33%) guinea pigs, the most prevalent disorders were overgrown nail(s) (n = 1,005, 26.55%, 95% confidence interval [CI] 25.15-27.99), dermatophytosis (228, 6.02%, 95% CI 5.29-6.83) and corneal ulceration (189, 4.99%, 95% CI 4.32-5.74). Among the 30 most common disorders, females showed predisposition for 3 disorders and males showed predisposition for 5 disorders. The disorder with the youngest age of affected animals was dermatophytosis (1.11 years) while weight loss had the oldest age of affected animals (4.64 years). From 757 recorded deaths, the median age at death overall was 4.03 years (IQR 2.56-5.44, range 0.17-10.00). Among deaths with a recorded cause, the most common causes of death were anorexia (n = 82, 13.87%, 95% CI 11.19-16.93), collapsed (58, 9.81%, 95% CI 7.54-12.50) and peri-anaesthetic death (20, 3.38%, 95% CI 2.08-5.18). CONCLUSIONS: These results can assist veterinarians and owners by providing demographic, disorder and mortality benchmarks that support improved clinical care and welfare outcomes in guinea pigs. Many common disorders in guinea pigs were husbandry related.

Dermatophytes and skin dermatophytoses in Southeast Asia-First epidemiological survey from Cambodia.

BACKGROUND: Dermatomycoses count to the most frequent dermatoses in Cambodia. OBJECTIVES: The aim of this survey was to investigate the occurrence of dermatophytes in this Southeast Asian country. METHODS: From June 2017 to July 2018, skin scrapings were taken from 67 patients with superficial dermatophytosis for mycological diagnostics. Identification of dermatophytes was confirmed by sequencing of the 'internal transcribed spacer'-(ITS) region of the rDNA, and the gene of the Translation Elongation Factor (TEF)-1α. RESULTS: Patients were suffering from tinea corporis and tinea inguinalis/cruris 42/67 (63%), tinea capitis/faciei 14/67 (21%), tinea corporis/capitis/faciei 6/67 (9%), tinea manuum/pedis 2/67 (3%), tinea pedis 2/67 (3%) and tinea manuum 1/67 (1%). Both, by culture and/or PCR, a dermatophyte was detected in 52 (78%) out of 67 samples. Culture positive were 42 (81%) of 52, PCR positive were 50 (96%). The following dermatophytes were found: Trichophyton (T.) rubrum, 36/52 strains (69%, 29 by culture), T. mentagrophytes/T. interdigitale (TM/TI) 9/52 (17%, six by culture) and Microsporum (M.) canis 5/52 strains (10%, by culture). One strain of Nannizzia (N.) incurvata 1/52 (2%) and N. nana 1/52 (2%) was isolated. Based on sequencing, we demonstrated that two T. mentagrophytes strains out of the nine TM/TI represented the new ITS genotype XXV Cambodia. We found one T. mentagrophytes strain genotype VIII (now, reclassified as T. indotineae). This isolate was terbinafine resistant, and it exhibited the amino acid substitution Phe397Leu in the squalene epoxidase. Three strains of T. interdigitale genotype II* were isolated. CONCLUSION: This is the first survey on epidemiology of dermatophytes in Cambodia. Currently, T. rubrum represents the most frequent species in Cambodia. One Indian strain genotype VIII T. mentagrophytes was found. A highlight was the first description of the new T. mentagrophytes genotype XXV Cambodia.