Disseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review.

BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. CASE PRESENTATION: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.

Contribution of host species and pathogen clade to snake fungal disease hotspots in Europe.

Infectious diseases are influenced by interactions between host and pathogen, and the number of infected hosts is rarely homogenous across the landscape. Areas with elevated pathogen prevalence can maintain a high force of infection and may indicate areas with disease impacts on host populations. However, isolating the ecological processes that result in increases in infection prevalence and intensity remains a challenge. Here we elucidate the contribution of pathogen clade and host species in disease hotspots caused by Ophidiomyces ophidiicola, the pathogen responsible for snake fungal disease, in 21 species of snakes infected with multiple pathogen strains across 10 countries in Europe. We found isolated areas of disease hotspots in a landscape where infections were otherwise low. O. ophidiicola clade had important effects on transmission, and areas with multiple pathogen clades had higher host infection prevalence. Snake species further influenced infection, with most positive detections coming from species within the Natrix genus. Our results suggest that both host and pathogen identity are essential components contributing to increased pathogen prevalence.

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.

Identification of Familial Infections Using Multilocus Microsatellite Typing in Tinea Corporis due to Microsporum canis.

Microsporum canis is a type of dermatophyte that causes zoonotic dermatophytosis in cats and dogs. We report three cases of tinea corporis due to M. canis from a single household with a domestic cat as a pet. The cases included a woman in her thirties (mother), a girl in her teens (older sister), and a girl in her teens (younger sister). Following sudden hair loss in the domestic cat, annular erythema with pruritus and scales appeared on the face, neck, and limbs of the older sister, younger sister, and mother, sequentially; they subsequently visited our hospital. Potassium hydroxide direct microscopy revealed filamentous fungi on all three women. In addition, short-haired colonies with a white to yellowish-white color and extending in a radial manner were found in cultures using a flat plate agar medium. A slide culture with the same medium indicated pointed spindle-shaped macroconidia with 7-8 septa. Therefore, the cases were diagnosed as tinea corporis due to M. canis. Genetic analysis of the cells of the cat and the mother, older sister, and younger sister using multilocus microsatellite typing (MLMT) indicated that all cases were classified into the same genotype, suggesting that the transmission route of these cases was familial. Here, we show that MLMT is useful in identifying the infection route in cases of tinea corporis due to M. canis.

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.

Analysis of the culturable gut yeast microbiota of dogs with digestive disorders.

Despite the increasing interest in studying the gut mycobiota of dogs, the association between fungal colonization and the development of digestive disorders in this species remains largely understudied. On the other hand, the high prevalence of antifungal-resistant yeasts detected in previous studies in samples from animals represents a major threat to public health. We analyzed the presence of culturable yeasts in 112 rectal swab samples obtained from dogs with digestive disorders attended in a veterinary teaching hospital. Our results revealed that Malassezia pachydermatis was frequently isolated from the studied dog population (33.9% of samples), and that the isolation of this yeast was significantly associated to the age of animals, but not to their sex, disease group, or the presence of vomits and/or diarrhea. In contrast, other yeast species were less prevalent (17.9% of samples in total), and their isolation was not significantly associated to any variable included in the analysis. Additionally, we observed that 97.5% of the studied M. pachydermatis isolates (n = 158, 1-6 per positive episode) displayed a minimum inhibitory concentration (MIC) value >4 µg/ml to nystatin, 31.6% had a MIC ≥32 µg/ml to fluconazole, and 27.2% had a MIC >4 µg/ml to amphotericin B. The antifungal susceptibility profiles of non-Malassezia (n = 43, 1-7 per episode) were more variable and included elevated MIC values for some antifungal-species combinations. These results confirm that the intestine of dogs is a reservoir of opportunistic pathogenic yeasts and suggest that the prevalence of M. pachydermatis colonization depends more on the age of animals than on any specific digestive disorder.

Subtilisin 3 production from Microsporum canis is independent of keratin substrate availability.

Dermatophytes are highly infectious fungi that cause superficial infections in keratinized tissues in humans and animals. This group of fungi is defined by their ability to digest keratin and encompasses a wide range of species. We investigated a critical adhesion protein, subtilisin 3, utilized by Microsporum canis during initial stages of infection, analyzing its production and expression under varying growth conditions. Additionally, as this protein must be expressed and produced for dermatophyte infections to occur, we developed and optimized a diagnostic antibody assay targeting this protein. Subtilisin 3 levels were increased in culture when grown in baffled flasks and supplemented with either l-cysteine or cat hair. As subtilisin 3 was also produced in cultures not supplemented with keratin or cysteine, this study demonstrated that subtilisin 3 production is not reliant on the presence of keratin or its derivatives. These findings could help direct future metabolic studies of dermatophytes, particularly during the adherence phase of infections.

In vitro virulotyping, antifungal susceptibility testing and DNA fingerprinting of Microsporum canis strains of canine and feline origin.

Microsporum canis is considered the common dermatophyte agent associated with ringworm in felines and canines. In the present study, we sampled n = 548 felines and canines for the probable isolation of M. canis. The rate of isolation from the cats and dogs was 70.27 % (52/74) and 1.68 % (8/474), respectively and Persian cats were found to be highly susceptible to M. canis infection. The strains were evaluated for their production of phospholipase, lipase, catalase, and hemolysis and their ability to grow at 35 â„ƒ. All the strains were identified as low producers of catalase and n = 17 strains exhibited high thermotolerance ability. Terbinafine was found to be the most effective antifungal drug and fluconazole was the least effective, in vitro. AFLP analysis revealed three genotypes of M. canis with 15 sub-clusters showing ≥ 90 % similarity and 7 sub-clusters exhibiting 100 % similarity. However, the phenotypic characters cannot be attributed based on the AFLP profiles.

Genetic mechanisms and biological processes underlying host response to ophidiomycosis (snake fungal disease) inferred from tissue-specific transcriptome analyses.

Emerging infectious diseases in wildlife species caused by pathogenic fungi are of growing concern, yet crucial knowledge gaps remain for diseases with potentially large impacts. For example, there is detailed knowledge about host pathology and mechanisms underlying response for chytridiomycosis in amphibians and white-nose syndrome in bats, but such information is lacking for other more recently described fungal infections. One such disease is ophidiomycosis, caused by the fungus Ophidiomyces ophidiicola, which has been identified in many species of snakes, yet the biological mechanisms and molecular changes occurring during infection are unknown. To gain this information, we performed a controlled experimental infection in captive Prairie rattlesnakes (Crotalus viridis) with O. ophidiicola at two different temperatures: 20 and 26°C. We then compared liver, kidney, and skin transcriptomes to assess tissue-specific genetic responses to O. ophidiicola infection. Given previous histopathological studies and the fact that snakes are ectotherms, we expected highest fungal activity on skin and a significant impact of temperature on host response. Although we found fungal activity to be localized on skin, most of the differential gene expression occurred in internal tissues. Infected snakes at the lower temperature had the highest host mortality whereas two-thirds of the infected snakes at the higher temperature survived. Our results suggest that ophidiomycosis is likely a systemic disease with long-term effects on host response. Our analysis also identified candidate protein coding genes that are potentially involved in host response, providing genetic tools for studies of host response to ophidiomycosis in natural populations.

[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.

Part 1: Understanding the role of Malassezia spp. in skin disorders: Malassezia yeasts as commensal or pathogenic organisms of human and animal skin.

INTRODUCTION: Malassezia spp. are a group of lipid-dependent basidiomycetes yeasts acting as commensal organisms of the human and animal skin. However, under some not well-defined circumstances, these yeasts may switch to opportunistic pathogens triggering a number of skin disorders with different clinical presentations. The genus comprises of 18 lipid-dependent species with a variable distribution in the hosts and pathologies thus suggesting a host- and microbe-specific interactions. AREA COVERED: This review highlighted and discussed the most recent literature regarding the genus Malassezia as a commensal or pathogenic organisms highlighting Malassezia-associated skin disorders in humans and animals and their antifungal susceptibility profile. A literature search of Malassezia associated skin disorders was performed via PubMed and Google scholar (up to May 2023), using the different keywords mainly associated with Malassezia skin disorders and Malassezia antifungal resistance. EXPERT OPINION: Malassezia yeasts are part of the skin mycobiota and their life cycle is strictly associated with the environment in which they live. The biochemical, physiological, or immunological condition of the host skin selects Malassezia spp. or genotypes able to survive in a specific environment by changing their metabolisms, thus producing virulence factors or metabolites which can cause skin disorders with different clinical presentations.

Comparative analysis in diagnosis by real-time polymerase chain reaction versus direct microscopy, culture, and histology in fungal infections of the nails, scalp, and skin.

BACKGROUND: The diagnosis of superficial fungal infections is the subject of intensive research in many countries around the world. The diagnostic methods used are diverse, including both conventional and innovative techniques. METHODS: This study evaluates the sensitivity, specificity, and efficacy of the real-time polymerase chain reaction (PCR) methodology and compares them with those of the conventional methods - direct microscopic, cultural, and histological examinations of materials from hair, skin, and nails - in order to demonstrate the benefits and significance of real-time PCR for the diagnosis of dermatophytic infections. RESULTS: The values obtained for the sensitivity, specificity, and efficacy of direct microscopic, cultural, histological, and real-time PCR studies are as follows: 63.71, 88.89, and 72.96% (P < 0.001); 58.06, 100, and 73.47% (P < 0.001); 85.96, 100, and 90.70% (P < 0.001); 88.52, 100, and 92.63% (P < 0.001). CONCLUSION: The use of real-time PCR in the diagnosis of dermatophytic infections is a relatively new approach in mycology and is subject to testing and experience from its use. The results are promising, but the method has not yet established itself as a new gold standard in the diagnosis of superficial fungal infections caused by dermatophytes, though its application would be very useful in identifying isolates without conidiogenesis or absence of growth.

Fungal Skin Disease Classification Using the Convolutional Neural Network.

Skin is the outer cover of our body, which protects vital organs from harm. This important body part is often affected by a series of infections caused by fungus, bacteria, viruses, allergies, and dust. Millions of people suffer from skin diseases. It is one of the common causes of infection in sub-Saharan Africa. Skin disease can also be the cause of stigma and discrimination. Early and accurate diagnosis of skin disease can be vital for effective treatment. Laser and photonics-based technologies are used for the diagnosis of skin disease. These technologies are expensive and not affordable, especially for resource-limited countries like Ethiopia. Hence, image-based methods can be effective in reducing cost and time. There are previous studies on image-based diagnosis for skin disease. However, there are few scientific studies on tinea pedis and tinea corporis. In this study, the convolution neural network (CNN) has been used to classify fungal skin disease. The classification was carried out on the four most common fungal skin diseases: tinea pedis, tinea capitis, tinea corporis, and tinea unguium. The dataset consisted of a total of 407 fungal skin lesions collected from Dr. Gerbi Medium Clinic, Jimma, Ethiopia. Normalization of image size, conversion of RGB to grayscale, and balancing the intensity of the image have been carried out. Images were normalized to three sizes: 120 × 120, 150 × 150, and 224 × 224. Then, augmentation was applied. The developed model classified the four common fungal skin diseases with 93.3% accuracy. Comparisons were made with similar CNN architectures: MobileNetV2 and ResNet 50, and the proposed model was superior to both. This study may be an important addition to the very limited work on the detection of fungal skin disease. It can be used to build an automated image-based screening system for dermatology at an initial stage.

Current status and research progress of nanoparticle application in superficial fungal infection.

Superficial fungal infections (SFIs) are characterized by diverse etiologies, complex pathogenesis, and marked geographical differences in patient symptoms. Conventional management of SFIs is associated with complications such as hepatotoxicity, skin problems, severe headaches, and clinical difficulties including intractable relapses and drug-drug interactions in patients with chronic diseases remain to be addressed. Moreover, in topical treatment, low penetration of antifungal drugs in hard tissues such as finger (toe) nails and drug-resistant fungi are emerging concerns in current antifungal therapy. Nanotechnology has been a leading research topic in recent years for new dosing forms of antifungal drugs, chemical modification of traditional drugs, and pharmacokinetic improvement, providing potential opportunities for the effective treatment of SFIs. The present study reviewed the direct use of nanoparticles in SFIs and the use of nanoparticles as carriers in SFIs and discussed their future medicinal applications. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/01-12915-PM-29863.jpg.