Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Sequence Variation of Candida albicans Sap2 Enhances Fungal Pathogenicity via Complement Evasion and Macrophage M2-Like Phenotype Induction.

Candida albicans (C. albicans) is an opportunistic pathogen increasingly causing candidiasis worldwide. This study aims to investigate the pattern of systemic immune responses triggered by C. albicans with disease associated variation of Sap2, identifying the novel evasion strategies utilized by clinical isolates. Specifically, a variation in clinical isolates is identified at nucleotide position 817 (G to T). This homozygous variation causes the 273rd amino acid exchange from valine to leucine, close to the proteolytic activation center of Sap2. The mutant (Sap2-273L) generated from SC5314 (Sap2-273V) background carrying the V273L variation within Sap2 displays higher pathogenicity. In comparison to mice infected with Sap2-273V strain, mice infected with Sap2-273L exhibit less complement activation indicated by less serum C3a generation and weaker C3b deposition in the kidney. This inhibitory effect is mainly achieved by Sap2273L -mediated stronger degradation of C3 and C3b. Furthermore, mice infected with Sap2-273L strain exhibit more macrophage phenotype switching from M0 to M2-like and more TGF-ß release which further influences T cell responses, generating an immunosuppressed cellular microenvironment characterized by more Tregs and exhausted T cell formation. In summary, the disease-associated sequence variation of Sap2 enhances pathogenicity by complement evasion and M2-like phenotype switching, promoting a more efficient immunosuppressed microenvironment.

Pathogen Analysis of Superficial Mucocutaneous Mycosis in a Tertiary A-level Hospital from 2007 to 2018.

OBJECTIVE: This study aimed to analyze the fungal species of pathogens isolated from patients with superficial mucocutaneous mycosis from May 2007 to December 2018. METHODS: A retrospective analysis was carried out to determine the pathogenic fungi isolated from patients with superficial fungal infections in the Medical Mycology Clinical Laboratory, Department of Dermatology and Venereology, Union Hospital, from May 2007 to December 2018. RESULTS: A total of 7639 strains were obtained, belonging to 21 genera and 36 species. They mainly consisted of Candida (3707/7639, 48.53%) and dermatophytes (3594/7639, 47.05%). The specimens were skin scales, nail shavings, secretions on the nail grooves, broken or diseased hair and dandruff, secretions or pseudomembrane of the external genitalia, and the oral mucosa. A total of 7300 patients were enrolled in this study, including 3301 males and 3999 females aged 2 months to 92 years old with a median age of 46.04 years old except for 633 patients whose ages were unknown. Two strains of different species were isolated from each of 339 patients at different body sites. The most frequent species were Trichophyton rubrum complex (2906/7639, 38.04%), Candida albicans (2619/7639, 34.28%), and unclassified Candida spp. Dermatophytes were mostly isolated from glabrous skin (2138/3594, 59.49%), with T. rubrum complex being the predominant species. Candida strains were most commonly isolated from mucosal sites (1979/3707, 53.39%), and C. albicans was the most prevalent causative agent. CONCLUSION: The main distribution of pathogenic fungal species isolated from patients with superficial mycosis from 2007 to 2018 in Wuhan, Hubei province and the surrounding areas was that Candida slightly outnumbered dermatophytes. Among all of the isolated strains, T. rubrum complex was the most abundant.

Aetiological changes of tinea capitis in the Hubei area in 60 years: Focus on adult tinea capitis.

BACKGROUND: Tinea capitis is a common dermatophyte infection of the scalp primarily affecting children, with less frequent, though not rare, observation in adults. OBJECTIVE: This study aimed to assess changes in the causative agents of adult tinea capitis over a 60-year period in the Hubei area. METHODS: A retrospective, single-centre study was performed on 164 adults with tinea capitis between 1960 and 2020. RESULTS: Out of 1113 cases of tinea capitis, 164 patients were adults, representing 14.7% of all patients. Adult tinea capitis was slightly more prevalent in males (91, 55.5%) than in females (73, 44.5%), but gender difference was not statistically significant between adults and children. Adult tinea capitis was most prevalent between the ages of 18 and 29 years, with a mean age of 22 years. Trichophyton schoenleinii was the most common dermatophyte in adult tinea capitis (78, 47.6%), followed by Trichophyton violaceum (58, 35.4%). Most adult tinea capitis cases before the 1980s were caused by T. schoenleinii, but T. violaceum has become the leading pathogen for recent adult tinea capitis cases. CONCLUSION: Tinea capitis is not a disease exclusive to children. On the contrary, an upward trend of tinea capitis in adults has been observed in recent years. T. violaceum has become the dominant causative agent of adult tinea capitis in the Hubei area, replacing T. schoenleinii. These results provide a better understanding of the treatment and prevention of tinea capitis in adults.

Cerebral Phaeohyphomycosis Caused by Exophiala dermatitidis in a Chinese CARD9-Deficient Patient: A Case Report and Literature Review.

Exophiala dermatitidis, a dematiaceous fungus typically found in decaying organic matter worldwide, is a rare cause of fungal infections. Cerebral phaeohyphomycosis is a sporadic but often fatal infection of the brain caused by E. dermatitidis. However, due to limited reports, little is known about its specific predisposing factors, clinical manifestation, and optimal treatment modality. Here, we report a clinical presentation and management of cerebral phaeohyphomycosis in a Chinese patient. An otherwise healthy, young male who was diagnosed with neck fungal lymphadenitis caused by E. dermatitidis 7 months prior and was treated with itraconazole, presented later with progressive intracranial hypertension and persistent coma. Culture of the neck lymphoid tissue produced growth of a black yeast-like fungus, which was identified as E. dermatitidis by sequencing of the ribosomal DNA internal transcribed spacer (ITS) domains. Accordingly, a cerebral biopsy was performed, and the pathological report showed mycelia and fungal granulomas. We also sequenced CARD9 in the patient and found him to be homozygous for loss-of-function mutation; his parents were heterozygous for the same mutation. This is a first case report of cerebral phaeohyphomycosis caused by E. dermatitidis in a CARD9-deficient Chinese patient. He eventually succumbed to brain herniation and severe lung infection with a poor response to therapy. Thus, previously healthy patients with unexplained invasive E. dermatitidis infection, at any age, should be tested for inherited CARD9 deficiency.

The 'species complex' issue in clinically relevant fungi: A case study in Scedosporium apiospermum.

The genus Scedosporium currently comprises six species, Scedosporium apiospermum, Scedosporium boydii, Pseudallescheria angusta, Scedosporium minutisporum, Scedosporium dehoogii, and Scedosporium aurantiacum, most of which can be distinguished with the primary fungal DNA barcode, the ITS1/2 region of the rDNA gene cluster. In the present study, four additional genetic loci were explored from a phylogenetic point of view enabling a barcoding approach based on K2P pairwise distances to resolve the taxa Scedosporium. We included partial γ-actin (ACT), ß-tubulin (BT2), elongation factor 1α (TEF1), and the small ribosomal protein 60S L10 (L1) (RP60S). Phylogenetic inference of each marker individually showed that four out of six species within Scedosporium can be distinguished unambiguously, while strains of S. apiospermum, S. boydii, and P. angusta showed occasional recombination, and accordingly, no genealogical concordance between markers was obtainable. We defined S. apiospermum, S. boydii, and P. angusta as the 'S. apiospermum species complex' since observed differences were not consistent between lineages, and no clinical differences are known between entities within the complex. While BT2 revealed the best performance among the genetic loci tested at the lineage level, barcoding of the ITS region is sufficient for distinction of all entities in Scedosporium at the species or 'complex' level.

In Vitro and In Vivo Activities of Essential Oil from the Seed of Anethum graveolens L. against Candida spp.

The essential oil produced from the seed of Anethum graveolens L. (Umbelliferae) was tested in vitro and in vivo anti-Candida activity. The microbroth dilution method was used in the minimal inhibitory concentration (MIC), according to M27-A3 of the guidelines of the Clinical and Laboratory Standard Institute (CLSI). And then, efficacy evaluation of essential oil in the prophylaxis and treatment of experimental vaginal candidiasis was performed in immunosuppressed mice. The anti-Candida activity was analyzed by microbiological and histological techniques and was compared with that of fluconazole (FCZ). The results showed essential oil was active in vitro against all tested strains, with MICs ranging from 0.312 µL/mL (for C. tropicalis, C. parapsilosis, and C. krusei) to 0.625 µL/mL (for 6 isolated C. albicans strains). Essential oil (2% v/v) was highly efficacious in accelerating C. albicans 09-1555 clearance from experimentally infected mice vagina by prophylaxis and therapeutic treatments. In both therapeutic efficacy and prophylaxis studies, the histological findings confirmed the microbiological results. The experimental results revealed that the tested essential oil is effective against vulvovaginal candidiasis in immunosuppressed mice.

Isolation and identification of black yeasts by enrichment on atmospheres of monoaromatic hydrocarbons.

Black yeast members of the Herpotrichiellaceae present a complex ecological behavior: They are often isolated from rather extreme environments polluted with aromatic hydrocarbons, while they are also regularly involved in human opportunistic infections. A selective technique to promote the in vitro growth of herpotrichiellaceous fungi was applied to investigate their ecophysiology. Samples from natural ecological niches and man-made environments that might contain black yeasts were enriched on an inert solid support at low humidity and under a controlled atmosphere rich in volatile aromatic hydrocarbons. Benzene, toluene, and xylene were provided separately as the sole carbon and energy source via the gas phase. The assayed isolation protocol was highly specific toward mesophilic Exophiala species (70 strains of this genus out of 71 isolates). Those were obtained predominantly from creosote-treated railway ties (53 strains), but isolates were also found on wild berries (11 strains) and in guano-rich soil samples (six strains). Most of the isolates were obtained on toluene (43 strains), but enrichments on xylene and benzene also yielded herpotrichiellaceous fungi (17 and 10 isolates, respectively). Based upon morphological characterizations and DNA sequences of the full internal transcriber spacers (ITS) and the 8.5S rRNA genes, the majority of the obtained isolates were affiliated to the recently described species Exophiala xenobiotica (32 strains) and Exophiala bergeri (nine strains). Members of two other phylogenetic groups (24 and two strains, respectively) somewhat related to E. bergeri were also found, and a last group (three strains) corresponded to an undescribed Exophiala species.

Identification of Trichosporon spp. strains by sequencing D1/D2 region and sub-typing by sequencing ribosomal intergenic spacer region of ribosomal DNA.

To re-identify and further group 25 isolates of Trichosporon spp. identified morphologically previously, sequences of D1/D2 region of large subunit (LSU) of ribosomal DNA (rDNA) of 25 tested strains for identification and those of ribosomal intergenic space 1 (IGS1) region of 11 strains for subgrouping were detected. The identifications of tested strains were changed except 6 strains. According to the alignment of the IGS1 region, 6 T. asahii isolates tested fell into 4 groups and 5 T. faecale isolates into 3 groups. Polymorphism of 2 T. japonicum isolates was found in 10 positions. With the alignments obtained in this research compared with the relative GenBank entries, it was found that T. asahii, T. faecale and T. japonicum species were divided into 7, 3 and 2 subtypes respectively. Morphological and biophysical methods are not sufficient for Trichosporon spp. identification. Sequencing becomes necessary for Trichosporon diagnosis. There is obvious diversity within a species.

Susceptibility of Pseudallescheria boydii and Scedosporium apiospermum to new antifungal agents.

Hyalohyphomycoses caused by Pseudallescheria boydii and Scedosporium apiospermum have recently been on the increase. To find the appropriate treatment for this emerging disease, we examined the antifungal susceptibility of 10 isolates of P. boydii and 17 isolates of S. apiospermum, most of which were isolated from clinical specimens. When the NCCLS M38-P microdilution method was used, itraconazole showed strong antifungal activities, while amphotericin B had little efficacy. A new triazole agent, voriconazole showed a strong effect against isolates of P. boydii and S. apiospermum (MIC50 0.06 micro g/ml), whereas micafungin, a newly developed echinocandin, had little effect (MIC50 >16 micro g/ml). There was no significant difference in the susceptibilities between P. boydii and S. apiospermum isolates against any antifungal agents. Our study suggests that voriconazole is a promising new drug in these infections, and that the same antifungal strategy can be employed in the infections by P. boydii and S. apiospermum.