Clinical and epidemiological characteristics of tinea capitis in northern Taiwan during 2014-2019: An unusual bimodal distribution of patients and comparison of paediatric and adult cases.

Tinea capitis (TC) mainly occurs in children, and related studies in adults are rare. We aimed to investigate the current epidemiological, clinical and mycological characteristics of TC and to compare adult and paediatric patients in northern Taiwan. We conducted a retrospective study at Chang Gung Memorial Hospital, Linkou Branch, from 2014 to 2019. The dataset included age, sex, records of underlying diseases, animal contact history, frequent hair salon visits, clinical patterns, treatment and outcome via chart or phone call reviews. The average ages of 72 children and 104 adults recruited were 6.0 and 74.0 years, respectively. A female predominance was noted in both groups, and the ratio of females was significantly higher in adults (94.2% vs 59.7%, P < .0001). Microsporum canis (76.4%) and Trichophyton mentagrophytes (11.1%) in children, and M. canis (49.0%) and T. violaceum (31.7%) in adults were the most common pathogens. Adults were more likely to be infected with T. violaceum (OR = 10.14, 95% CI = 2.04-50.26) than children. In contrast, adults were less likely to be infected with M. canis than children (OR = 0.31, 95% CI = 0.11-0.90). Furthermore, adults visited hair salons more, had less animal contact and were more immunosuppressed than children. TC is not unusual in the adult population. Dermatologists are advised to realise risk factors such as immunosuppression and regular hair salon visit in adult TC.

Superficial mycoses, a matter of concern: Global and Indian scenario-an updated analysis.

Superficial mycoses of skin, nails and hair are among the common fungal infections. They are caused by dermatophytes, non-dermatophyte moulds, yeasts and yeast-like fungi. Such fungal infections are widespread all over the world and are predominant in tropical as well as subtropical regions. Environmental factors, such as warm, humid and pitiable hygienic conditions, are conducive for their growth and proliferation. Although it does not cause mortality, it is known to be associated with excessive morbidity which may be psychological or physical. This affects the quality of life of the infected individuals which leads to a negative impact on their occupational, emotional and social status. Such infections are increasing on a global scale and, therefore, are of serious concern worldwide. This review article covers the global and Indian scenario of superficial mycoses taking into account the historical background, aetiological agents, prevalence, cultural and environmental factors, risk factors, pathogenesis and hygienic practices for the prevention of superficial mycoses.

Non-dermatophyte fungi in onychomycosis-Epidemiology and consequences for clinical practice.

Onychomycoses are difficult-to-treat fungal infections with a high recurrence rate that relates to the anatomic and pathophysiological conditions in the nail organ and the required extended duration of treatment. Clinical-epidemiological studies demonstrated that non-dermatophyte molds and yeasts are the primary causative agents in 20%-30% of onychomycoses. Mixed infections with dermatophytes are observed as well. Therefore, the causative agents should be determined by fungal culture and the antifungal treatment regimen should reliably cover non-dermatophytes, if appropriate. Systemic-topical combination therapy involving a broad-spectrum, locally applied antifungal may increase the mycological and clinical cure rates compared to monotherapy with systemic drugs.

Population differentiation, antifungal susceptibility, and host range of Trichophyton mentagrophytes isolates causing recalcitrant infections in humans and animals.

The major problems in determining the causative factors of the high prevalence of dermatophytoses include the lack of a well-standardized antifungal susceptibility testing method, the low consistency of in vitro and clinical minimal inhibitory concentration values, the high genomic diversity of the population, and the unclear mechanism of pathogenicity. These factors are of particular importance when the disease is recalcitrant and relapses. Herein, we identified and characterized Trichophyton mentagrophytes isolates obtained from therapy-resistant cases in humans and animals. We used genomic diversity analysis of 17 human and 27 animal clinical isolates with the MP-PCR technique, determined their phenotypic enzymatic activity and host range, and performed antifungal susceptibility testing to currently available antifungal drugs from various chemical groups. Genomic diversity values of 35.3% and 33.3% were obtained for clinical isolates from humans and animals, respectively, yet without any relationship to the host species or antifungal drug to which resistance in therapy was revealed. The highest activity of keratinase enzymes was recorded for fox, guinea pig, and human hairs. These hosts can be considered as the main species in the host range of these isolates. A phenyl morpholine derivative, i.e. amorolfine, exhibited superior activity against strains obtained from both humans and animals with the lowest MIC50. Interestingly, high compliance of terbinafine in vitro resistance with clinical problems in the treatment with this substance was shown as well. The high resistance of dermatophytes to drugs is the main cause of the recalcitrance of the infection, whereas the other features of the fungus are less important.

Viability of pathogenic dermatophytes during a 4-week treatment with 1% topical luliconazole for tinea pedis.

The viability of pathogenic fungi in the scale was investigated during topical administration of 1% luliconazole (LLCZ). Thirteen tinea pedis patients found to be positive on KOH examination were assessed by mycological examinations and quantitative real-time polymerase chain reaction (PCR) targeted internal transcribed spacer (ITS) in ribosomal RNA gene at the initial visit and after 2 and 4 weeks of treatment. Assays showed that the average copy number of ITS DNA had significantly decreased to 22.9% at 2 weeks and 4.8% at 4 weeks compared with the initial visit. LLCZ topical treatment could defeat almost pathogenic dermatophytes in the scales within 4 weeks.

A skin disease and needs assessment analysis of the displaced Rohingya population in the Kutupalong refugee camp, Bangladesh.

The physical, psychological and financial burden of skin disease in low- to middle-income countries, where access to skincare is limited, is poorly understood. A group that we know very little about in this regard are refugees. There are limited data on the range of skin diseases and skincare needs of this group. To better understand the skincare needs of the displaced Rohingya population residing in the Kutupalong refugee camp, Bangladesh, we collected data on demographics, living conditions and range of dermatoses. In the 380 patients assessed, fungal skin infections, predominantly dermatophytes, were by far the most common skin disease seen (n = 215), followed by dermatitis (n = 81). Skin disease can be the presenting feature in many systemic conditions and may cause significant secondary complications itself. Developing a better understanding of the skincare needs of the refugee population is essential for future healthcare planning for this vulnerable group.

Assembly and analysis of the whole genome of Arthroderma uncinatum strain T10, compared with Microsporum canis and Trichophyton rubrum.

BACKGROUND: Arthroderma uncinatum is a geophilic dermatophyte that occasionally causes superficial infections in humans leading to skin diseases. OBJECTIVES: To better understand the ecology and potential pathogenicity of A uncinatum, we analysed its whole genome. We compared A uncinatum with the genome of the zoophilic dermatophyte Microsporum canis and with the anthropophilic species Trichophyton rubrum. The compared species differ significantly in the frequency of human infection. METHODS: We reported the genome sequence of strain T10 of A uncinatum based on SMRT (single-molecule real-time) technology (PacBio). RESULTS: We obtained a near-complete 23.56 Mb genome, with 7153 predicted gene models and ~20% repetitive sequences. We subsequently determined the specific genetic differences between A uncinatum, M canis and T rubrum. The functional enrichment analysis suggests that A uncinatum is particularly enriched in specific virulence genes. This suggests that the ancestral condition in dermatophytes is with high virulence, which has decreased in the course of evolution to enhance coexistence with animal or human hosts.

Differential gene expression in HaCaT cells may account for the various clinical presentation caused by anthropophilic and geophilic dermatophytes infections.

BACKGROUND: Despite the worldwide prevalence of dermatophyte infections, only a few genes are reported to be related to dermatophyte infections. In addition, the mechanism by which different ecological dermatophytes infection leads to varying intensity of inflammation remains unclear. OBJECTIVES: To investigate the mechanism of varying intensity of skin inflammation caused by different ecological dermatophytes infection. METHODS: We infected HaCaT cells with anthropophilic and geophilic dermatophytes to mimic various ecological dermatophyte infections. RNA-sequencing (RNA-seq) was employed to identify the change in the gene expression of HaCaT cells. To verify the expression of differentially expressed genes (DEGs), we selected 18 HaCaT cells genes to conduct qPCR experiments. In addition, immunoblotting was conducted to validate key genes from the MAPK signalling pathway. RESULTS: After HaCaT cells were infected with the anthropophilic Trichophyton rubrum (T rubrum) and the geophilic Microsporum gypseum (M gypseum), 118 and 619 differentially expressed genes were identified in HaCaT cells, respectively. These genes may provide a clue as to how keratinocytes respond to anthropophilic and geophilic dermatophytes. We also found that JUN may play a critical role in keratinocytes infected with M gypseum. CONCLUSIONS: Differential gene expression in HaCaT cells may account for the various clinical presentation caused by anthropophilic and geophilic dermatophytes infections. In addition, the intense inflammatory reaction of M gypseum infection may be triggered by activating the JNK-JUN signalling pathway.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Adult tinea capitis in China: A retrospective analysis from 2000 to 2019.

BACKGROUND: Tinea capitis (TC) is an infection of the scalp hair due to dermatophytes. Most commonly seen in prepubescent children, but data of adults tinea capitis (ATC) in China mainland are limited. OBJECTIVES: We aimed to evaluate epidemiological, clinical and mycological characteristics of ATC in China from 2000 to 2019. METHODS: We retrospectively analysed all ATC reported cases in China mainland, confirmed by mycological examination, by searching PubMed, Wanfang, Weipu and CNKI database. RESULTS: In sum, 40 papers involving 269 clinical cases were included. The average morbidity of ATC was calculated as 9.04% after standardisation. The sex ratio is 1:5.2 (31 male, 163 female); 76 people between 18 and 44 age level and 137 people between 45 and 89 age level were diagnosed as ATC. Culture or ITS sequencing identified Trichophyton violaceum in 70 cases (35.2%), Microsporum canis in 42 cases (21.1%), Trichophyton mentagrophyte in 32 cases (16.1%), Trichophyton rubrum in 23 cases (11.5%), Microsporum gypseum in 18 cases (9.0%), Trichophyton tonsurans in 6 cases (3.0%), Trichophyton schoenleini in 4 cases (2.0%), Epidermophyton floccosum in 2 cases (1.0%), Trichophyton verrucosum and Microsporum ferrugineum in one case (0.5%). ATC was easily to be diagnosed as furfur, seborrhoeic dermatitis (13%) or pustular and dermatocellulitis (11.15%).Six immunocompromised persons were recorded (2.2%). CONCLUSIONS: ATC mainly involves postmenopausal women. Trichophyton violaceum, M canis, T mentagrophyte remain the most common aetiological agent of ATC in China. Trichophyton rubrum own the much higher frequency in ATC than in children. For diversified clinical manifestations, recognising ATC profiles will help clinicians avoid misdiagnosis.

Changing Concepts and Current Definition of Majocchi's Granuloma.

Dermatophytic granuloma characterized by perifollicular granulomatous inflammation was first described by Domenico Majocchi and was later named after him, Majocchi's granuloma (MG). Although the initial description was related to a dermatophyte Trichophyton tonsurans, later reports linked MG to non-dermatophytes (Phoma, Aspergillus, Malbranchea), which led to a confusion of disease patterns caused by cutaneous pathogens and general opportunistic microorganisms. Furthermore, several causative agents of MG described in the literature were not confirmed as such. Our review addressed the following aspects: (1) significance of histopathological finding for MG diagnosis, (2) dermatophytes as exclusive agents of MG, (3) spectrum of etiological agents causing different types of invasive dermatophytic infections, and (4) treatment options.

Genes Encoding Proteolytic Enzymes Fungalysin and Subtilisin in Dermatophytes of Human and Animal Origin: A Comparative Study.

Dermatophytes are among the most successful fungal pathogens in humans, but their virulence mechanisms have not yet been fully characterized. Dermatophytic fungi secrete proteases in vivo, which are responsible for fungal colonization and degradation of the keratinized tissue during infection. In the present study, we used PCR to investigate the presence of genes encoding fungalysins (MEP) and subtilisins (SUB) in three dermatophyte species whose incidence is increasing in Europe: the anthropophilic Trichophyton rubrum (n = 58), zoophilic Microsporum canis (n = 33), and Trichophyton benhamiae (n = 6). MEP2 and SUB4 genes were significantly correlated with T. rubrum; MEP3 and SUB1 were mostly frequently harbored by M. canis; and MEP1, 2, and 4 and SUB3-7 were most frequently harbored by T. benhamiae isolates (p < 0.05). Furthermore, MEP1-5 and SUB1-3 genes were significantly more prevalent among human clinical isolates of M. canis (n = 17) than among asymptomatic cat isolates of M. canis (n = 16; p < 0.05). Unidentified MEP and/or SUB genes in some isolates in the current study may suggest that other gene repertoires may be involved in the degradation of keratin. The presented analysis of the incidence of MEP and SUB virulence genes in three dermatophyte species of diverse origins provides an insight into the host-fungus interaction and dermatophyte pathogenesis.

Recent advances in the diagnosis of dermatophytosis.

Dermatophytosis is a disease of global significance caused by pathogenic keratinolytic fungi called dermatophytes in both animals and humans. The recent taxonomy of dermatophytes classifies them into six pathogenic genera, namely Microsporum, Trichophyton, Epidermophyton, Nannizzia, Lophophyton and Arthroderma. It is because of the delayed diagnostic nature and low accuracy of dermatophyte detection by conventional methods that paved the path for the evolution of molecular diagnostic techniques, which provide the accurate and rapid diagnosis of dermatophytosis for an appropriate, timely antifungal therapy that prevents the nonspecific over-the-counter self-medication. This review focuses on the importance of rapid and accurate diagnosis of dermatophytosis, limitations of conventional methods, selection of targets in diagnosis, and factors affecting sensitivity and specificity of various molecular diagnostic technologies in the diagnosis of dermatophytosis. Generally, all the molecular techniques have a significant edge over the conventional methods of culture and microscopy in the dermatophytosis diagnosis. However, in mycology laboratory, the suitability of any molecular diagnostic technique in the diagnosis of dermatophytosis is driven by the requirement of time, economy, complexity, the range of species spectrum detected and the scale of diagnostic output required. Thus, various choices involved in the pursuit of a diagnosis of dermatophytosis are determined by the available conditions and the facilities in the laboratory.

Antifungal Activity of Gentamicin B1 Against Systemic Plant Mycoses.

BACKGROUND: Gentamicin is a broad-spectrum aminoglycoside antibiotic produced by Micromonospora purpurea bacteria, effective against Gram-negative bacterial infections. Major fractions of the gentamicin complex (C1, C1a, C2, C2a) possess weak antifungal activity and one of the minor components (A, A1-A4, B, B1, X), gentamicin B1 was found to be a strong antifungal agent. METHODS: This work uses in vitro and in vivo dilution methods to compare the antifusarial, antiaspergillic and anticryptococcal effects of gentamicin derivatives and structurally-related congeners. RESULTS: The in vitro antifusarial activity of gentamicin B1 (minimum inhibitory concentration (MIC) 0.4 µg/mL) and structurally-related compounds (MIC 0.8-12.5 µg/mL) suggests that the purpuroseamine ring substituents are responsible for the specific antimycotic effect. The functional groups of the garoseamine and 2-deoxystreptamine rings of gentamicin derivatives are identical in gentamicin compounds and are unlikely to exert a significant antifungal effect. Among soil dermatophytes, Microsporum gypseum was more susceptible to gentamicin B1 (MIC 3.1 µg/mL) than Trichophyton gypseum (MIC 25 µg/mL). The in vitro antifungal effect of gentamicin B1 against plant pathogenic fungi was comparable to primary antifungal agents. CONCLUSION: Gentamicin is already in medical use. In vitro and preclinical in vivo synergisms of gentamicin B1 with amphotericin B suggest immediate clinical trials starting with subtoxic doses.

Improved Methods for Assessing Therapeutic Potential of Antifungal Agents against Dermatophytes and Their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate.

Onychomycosis is a common, difficult-to-treat nail infection that is mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects. The development of treatments for onychomycosis is challenging because standard in vitro tests are not predictive of antifungal efficacy within the nail. We have developed a new antifungal agent, NP213, for the treatment of onychomycosis. NP213 is based on endogenous host defense peptides produced within the nail. We compared the in vitro activity of NP213 and existing antifungal agents using conventional antimicrobial susceptibility test (AST) systems and more physiologically relevant models based on the human nail. We observed that the standard in vitro AST methodologies failed to predict the efficacy of antifungal agents within the nail. To address that, we present a more physiologically relevant modified AST method. This method, alongside other standard in vitro assessments of activity (including mechanism-of-action and time-of-kill studies), better reflected the activity of NP213 and other antifungal agents within the nail than standard in vitro AST methods. NP213 is a rapidly acting, fungicidal peptide that is superior to existing antifungal agents in vitro It penetrated the nail more effectively than other antifungals, as confirmed by using an optimized in vitro nail infection model. The data presented here support the current clinical development status of NP213 as a novel agent for treating onychomycosis. We propose that the modified tests developed and applied for NP213 characterization are the most relevant to use for screening any potential therapeutic candidates for onychomycosis.

Keratin hydrolysis by dermatophytes.

Dermatophytes are the most common cause of superficial fungal infections (tinea infections) and are a specialized group of filamentous fungi capable of infecting and degrading keratinised tissues, including skin, hair, and nail. Essential to their pathogenicity and virulence is the production of a broad spectrum of proteolytic enzymes and other key proteins involved in keratin biodegradation and utilization of its breakdown products. The initial stage of biodegradation of native keratin is considered to be sulfitolysis, in which the extensive disulfide bridges present in keratin are hydrolyzed, although some secreted subtilisins can degrade dye-impregnated keratin azure without prior reduction (Sub3 and Sub4). Sulfitolysis facilitates the extracellular biodegradation of keratin by the dermatophytes' extensive array of endo- and exoproteases. The importance of dermatophyte proteases in infection is widely recognized, and these enzymes have also been identified as important virulence determinants and allergens. Finally, the short peptide and amino acid breakdown products are taken up by the dermatophytes, using as yet poorly characterised transporters, and utilized for metabolism. In this review, we describe the process of keratin biodegradation by dermatophytes, with an especial focus on recent developments in cutting edge molecular biology and '-omic' studies that are helping to dissect the complex process of keratin breakdown and utilization.

In vitro models of dermatophyte infection to investigate epidermal barrier alterations.

Fungal infections of the skin, known as dermatophytoses, are initiated at the epidermal barrier and lead to dysfunctions of the stratum corneum and cornified skin appendages. Dermatophytosis affects a significant part of the human population and, despite the availability of effective treatments, its prevalence is still increasing. Numerous dermatophyte species are able to induce lesions in both animals and humans, with different clinical pictures and host inflammatory responses. The understanding of the infectious process and of tissue responses has been impeded by discrepancies between observations in vivo or in research models. Indeed, cells cultured as monolayers do not undergo the keratinization process required to study the adherence and invasion of dermatophytes. Animal models lack relevance to study human dermatophytosis because of species-specific differences in the development of lesions and inflammatory responses. This review focuses on the recent development of cultured human skin equivalents, which partly overcomes those limitations and allows improved understanding of the pathogenesis of dermatophytosis in human being, especially the impacts of infection on epidermal barrier integrity.

New insights in dermatophyte research.

Dermatophyte research has renewed interest because of changing human floras with changing socioeconomic conditions, and because of severe chronic infections in patients with congenital immune disorders. Main taxonomic traits at the generic level have changed considerably, and now fine-tuning at the species level with state-of-the-art technology has become urgent. Research on virulence factors focuses on secreted proteases now has support in genome data. It is speculated that most protease families are used for degrading hard keratin during nitrogen recycling in the environment, while others, such as Sub6 may have emerged as a result of ancestral gene duplication, and are likely to have specific roles during infection. Virulence may differ between mating partners of the same species and concepts of zoo- and anthropophily may require revision in some recently redefined species. Many of these questions benefit from international cooperation and exchange of materials. The aim of the ISHAM Working Group Dermatophytes aims to stimulate and coordinate international networking on these fungi.

Phenotypic characterization of enzymatic activity of clinical dermatophyte isolates from animals with and without skin lesions and humans.

AIMS: The pathogenesis of dermatophytoses is associated with the secretion of enzymes degrading the infected tissue components. Although many studies on enzymatic activity of dermatophytes have been conducted over the years, there have been no concrete proposals on the construction of the profile of enzymes characteristic of individual species, genus or ecological types of dermatophytes. The aim of this study was to assess the capability of clinical dermatophyte isolates from both symptomatic and asymptomatic animals and humans to produce different enzymes. METHODS AND RESULTS: Clinical isolates of 234 dermatophyte strains collected during routine examination of animal health were used in this study. The enzymatic production of keratinase, elastase, phospholipase, lipase, protease, DNase and gelatinase as well as the haemolytic activity were evaluated using specific test media. The overall degree of enzymatic activity of the analysed clinical isolates of the dermatophytes was 67%. All tested clinical isolates of different species of dermatophytes showed keratinase activity and 96% additionally exhibited phospholipase activity. The weakest activity among the tested enzymes was demonstrated for elastase and gelatinase. 83% of the isolates of the dermatophytes showed haemolytic activity. CONCLUSION: Our data indicate that clinical isolates of dermatophytes from different species produce enzymes with different levels of activities. SIGNIFICANT AND IMPACT OF THE STUDY: Profile of enzymes characteristic of individual species, genus or ecological types of dermatophytes is possibly dependent upon factors related to the host. The relationship between each enzyme and the occurrence of skin lesions in animals and humans or asymptomatic animal carriers varies on whether the infection is caused by Trichophyton mentagrophytes, Trichophyton verrucosum or Microsporum canis. Interestingly, only keratinase seems to be correlated with the appearance of dermatophyte infections, irrespective of the pathogen species, and elastase is a characteristic enzyme for dermatophyte strains infecting humans. Haemolysis seems to be dependent on host factors and is more common in the case of human dermatophyte isolates.