Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Retrospective Analysis of Tinea Capitis in Xinjiang, China.

Tinea capitis is a cutaneous infection of dermatophytes and predominant in children. It is one of common infectious diseases of children in Xinjiang, particularly in the southern Xinjiang. The aim of this study is to analyze the clinical and mycological characteristics of patients with tinea capitis in Xinjiang China. Medical records from 2010 to 2021, Mycology Laboratory Department of Dermatology in the First Affiliated Hospital of Xinjiang Medical University, retrospectively investigated the clinical and mycological characteristics of 198 patients with tinea capitis. Hairs have been obtained for fungal examination, and analysis with 20% KOH and Fungus Fluorescence Staining Solution has been conducted. Identification of fungi was using of morphological and molecular biological methods. Among total number of 198 patients, 189 (96%) were children with tinea capitis, of which 119 (63%) were male and 70 (37%) were female; 9 (4%) were adult patients with tinea capitis, of which 7 were female and 2 were male. Preschool children between the ages of 3 and 5 years had the highest distribution (54%), followed by those between the ages of 6 and 12 years (33%), the ages under 2 years (11%) and the ages of 13-15 years (2%) respectively. Among all patients, 135 (68.18%) were Uygur, 53 (26.77%) were Han, 5 (2.53%) were Kazak, 3 (1.52%) were Hui, 1 (0.5%) was Mongolian and nationality information of 1 patient (0.5%) is unknown. The indentification results of the isolates showed that 195 (98%) patients had single-species infections and 3 (2%) patients had double mixed infections. Among single-species infection patients, Microsporum canis (n = 82, 42.05%), Microsporum ferrugineum (n = 56, 28.72%) and Trichophyton mentagrophytes (n = 22, 11.28%) were the most prevalent species. Other dermatophytes included Trichophyton tonsurans (n = 12, 6.15%), Trichophyton violaceum (n = 10, 5.13%), Trichophyton schoenleinii (n = 9, 4.62%) and Trichophyton verrucosum (n = 4, 2.05%). Among 3 cases of mixed infections, 1 was M. canis + T. tonsurans (n = 1), and the other 2 were M.canis + T.mentagrophytes (n = 2). In conclusion, the majority of tinea capitis patients in Xinjiang, China are Uygur male children aged 3-5 years. M. canis was the most prevalent species causing tinea capitis in Xinjiang. These results provide useful information for the treatment and prevention of tinea capitis.

Hyperactivation of the NLRP3 Inflammasome in Myeloid Cells Leads to Severe Organ Damage in Experimental Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3-R258W mice carrying the gain-of-function mutation. Nlrp3-R258W mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3-R258W mice. In addition, hyperactivation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3-R258W mutation expressed in myeloid cells, because Cre recombinase-mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus.

Analysis on curative effects and safety of 2% liranaftate ointment in treating tinea pedis and tinea corporis & cruris.

The paper is intended to analyze and evaluate the specific curative effect and safety of 2% liranaftate ointment in treating patients with tinea pedis and tinea cruris. 1,100 cases of patients with tinea pedis and tinea corporis & cruris were selected as research objects and were divided into two groups according to the random number table method. They were treated with different methods: 550 cases of patients were treated with 2% liranaftate ointment for external use in the observation group and the rest 550 cases of patients were treated with 1% bifonazole cream in the control group. The treatment time was two weeks for patients with tinea corporis & cruris and four weeks for those with tinea pedis respectively. Meanwhile, the one-month follow-up visit was conducted among the patients to compare the curative effects of two groups. After the medication, the curative effectiveness rate was 87.65% (482/550) in the observation group, while that was 84.91% (467/550) in the control group. After the average follow-up visits of (15.5±2.4), the curative effectiveness rate 96.55% (531/550) in the observation group, while that was 91.45% (503/550) in the control group. Two groups of patients recovered well with a low incidence of adverse reactions in the treatment, and the overall curative effect was good with the inter-group difference at P>0.05, so it was without statistical significance. The curative effect of 2% liranaftate ointment is safe and obvious in treating tinea pedis and tinea corporis & cruris, so it is valuable for clinical popularization and application.

Pathogenic fungus Microsporum canis activates the NLRP3 inflammasome.

Microsporum canis is a pathogenic fungus with worldwide distribution that causes tinea capitis in animals and humans. M. canis also causes invasive infection in immunocompromised patients. To defy pathogenic fungal infection, the host innate immune system is the first line of defense. As an important arm of innate immunity, the inflammasomes are intracellular multiprotein complexes that control the activation of caspase-1, which cleaves proinflammatory cytokine pro-interleukin-1ß (IL-1ß) into its mature form. To determine whether the inflammasome is involved in the host defense against M. canis infection, we challenged human monocytic THP-1 cells and mouse dendritic cells with a clinical strain of M. canis isolated from patients with tinea capitis. We found that M. canis infection triggered rapid secretion of IL-1ß from both THP-1 cells and mouse dendritic cells. Moreover, by using gene-specific shRNA and competitive inhibitors, we determined that M. canis-induced IL-1ß secretion was dependent on NLRP3. The pathways proposed for NLRP3 inflammasome activation, namely, cathepsin B activity, K(+) efflux, and reactive oxygen species production, were all required for the inflammasome activation triggered by M. canis. Meanwhile, Syk, Dectin-1, and Card9 were found to be involved in M. canis-induced IL-1ß secretion via regulation of pro-IL-1ß transcription. More importantly, our data revealed that M. canis-induced production of IL-1ß was dependent on the NLRP3 inflammasome in vivo. Together, this study unveils that the NLRP3 inflammasome exerts a critical role in host innate immune responses against M. canis infection, and our data suggest that diseases that result from M. canis infection might be controlled by regulating the activation of inflammasomes.

Clinical Distribution and Drug Susceptibility Characterization of Invasive Candida Isolates in a Tertiary Hospital of Xinjiang Province.

Objective: This study aims to investigate the clinical distribution characteristics and drug susceptibility profiles of invasive Candida isolates in a tertiary hospital in Urumqi. Methods: The examination was conducted on samples obtained from patients who were clinically diagnosed with invasive candidiasis in this hospital. A total of 109 strains of Candida strains were identified through the use of internal transcribed spacer (ITS) sequencing and fungal cultivation methods.The clinical distribution of the strains was analyzed. Antifungal drug susceptibility tests were performed using the Sensititre YO10 fungal drug susceptibility plate based on the micro-broth dilution method. Results: Candida albicans had the highest percentage (51.38%) among 109 Candida isolates, followed by C. glabrata (18.35%) and C. tropicalis (15.60%). The isolates were predominantly found in the respiratory department (41.28%), intensive care unit (ICU) (31.19%), and infection department (9.17%).The results of drug susceptibility tests indicated that amphotericin B, 5-fluorocytosine, and echinocandins exhibited good in vitro antifungal activity, with a susceptibility rate of over 96%. However, the azoles demonstrated low antifungal activity, especially posaconazole and voriconazole, which had high resistance rates of 64.71% for C. tropicalis and 70% for C. glabrata, respectively. Conclusion: In our hospital, Candida albicans was identified as the primary causal agent of invasive candidiasis. In terms of in vitro antifungal activity, echinocandins, amphotericin B, and 5-fluorocytosine demonstrated efficacy against invasive Candida infections. However, it was important to note that C. glabrata and C. tropicalis exhibited low susceptibility to azoles.

Molecular Characteristics of Macrolide Resistance in Treponema pallidum from Patients with Latent Syphilis in Xinjiang, China.

Background: Macrolide resistance in Treponema pallidum (T. pallidum) has been increasing in recent years worldwide. However, few data are available on macrolide resistance in T. pallidum from Xinjiang province, located in the western part of China, which is an area with a high incidence of syphilis. In this study, we investigated the molecular characteristics of macrolide resistance in T. pallidum from patients with latent syphilis in Xinjiang, China. Methods: In total, 204 whole blood samples were collected from patients with latent syphilis during 2016 to 2017, in the First Hospital of Xinjiang Medical University. Genomic DNA of blood samples was extracted using a QIAamp DNA Mini Kit and T. pallidum was detected by PCR with the specific polA gene of T. pallidum. The 23S rRNA gene of T. pallidum was amplified among the T. pallidum-positive samples by nested PCR, and macrolide resistance-associated mutation sites A2058G and A2059G in the 23S rRNA gene were identified using restriction enzymes MboII and BsaI. Results: The specific polA gene of T. pallidum (T. pallidum positive) was detected in 27 blood samples (13.2%) from 204 patients with latent syphilis. The 23S rRNA gene was then amplified in all 27 T. pallidum-positive samples, among which 24/27 samples (88.9%) harbored the A2058G mutation in the 23S rRNA gene and 3/27 (11.1%) had the A2059G mutation. Conclusion: Our results indicated that T. pallidum macrolide resistance should not be ignored in Xinjiang, China, and that A2058G was the predominant macrolide resistance mechanism. Blood may be a suitable specimen for the detection of resistant mutations of T. pallidum in patients with latent syphilis who do not show any clinical symptoms.

Characterisation of a clinical isolated Aspergillus lentulus strain using a Galleria mellonella infection model.

BACKGROUND: In recent years, the number of invasive aspergillus infection cases caused by Aspergillus lentulus (A. lentulus) has gradually increased and this fungus is usually difficult to distinguish from Aspergillus fumigatus in morphology. All of these presents a great challenge to the treatment of invasive fungal infections caused by A. lentulus. The present study aims to discuss the antifungal resistance, virulence and inflammatory factors' changes after the infection of larvae of A. lentulus separated from patients with chronic obstructive pulmonary disease (COPD) to reflect the host immune response. METHODS: A. lentulus isolated from COPD patients was identified by morphology and molecular biology, and its drug sensitivity was determined in vitro. Then the virulence factors and inflammatory response related factors of A. lentulus were determined by the model of A. lentulus infecting larvae. These were divided into three groups: A. lentulus standard strain, A. lentulus strain isolated from patients; PBS control. The infection model was formed by injecting the suspension of A. lentulus at a concentration of 1×106 CFU into larvae, in order to determine the (1,3)-ß-D-glucan and galactomannan levels, and determine the caspase-1 and TNF-α concentration in Galleria mellonella larvae by RT-PCR. RESULTS: The results revealed that A. lentulus had good sensitivity to itraconazole, voriconazole and micafungin, while (1,3)-ß-D-glucan was negative in the two groups. The level of galactomannan in the two groups was higher than that in the control group, and the difference was statistically significant (P<0.05). However, there was no statistical difference between the standard strain group and patient strain group (P>0.05). After the infection of larvae, caspase-1 and TNF-α in the Galleria mellonella larvae increased in the two groups, and these elevated levels were statistically significant in both groups (P<0.05). However, there was no significant difference between the two groups (P>0.05). CONCLUSIONS: There is no significant difference in virulence factor and host inflammatory response between A. lentulus isolated from COPD patients and standard strains. Galactomannan has more advantages in the early detection of A. lentulus invasive infection. Furthermore, the caspase-1-mediated inflammasome pathway may be involved in the host immune response to A. lentulus.

Specific oligonucleotide primers for identification of Hortaea werneckii, a causative agent of tinea nigra.

Hortaea werneckii, a black yeast-like hyphomycete that is widely distributed in tropical and subtropical environments, can cause superficial mycotic infection in humans. This fungus was recently isolated from superficial infectious lesions of a guinea pig in Japan. An oligonucleotide primer set specific for Hortaea werneckii was designed on the basis of the internal transcribed spacer regions of the ribosomal DNA (rDNA). Polymerase chain reaction (PCR) with this primer set yielded a 306 bp PCR amplicon from only H. werneckii. This primer set did not amplify DNAs of 42 other related dematiaceous species, including the medically important dematiaceous fungi Cladophialophora carrionii, Fonsecaea pedrosoi, Phialophora verrucosa, and Exophiala dermatitidis, and eight species of medically important yeasts, including Candida (C.) albicans, C. dublinensis, C. glabrata, C. parapsilosis, C. tropicalis, Cryptococcus neoformans var. neoformans, Malassezia furfur, and Trichosporon asahii var. asahii. PCR with this primer set may be a useful technique for rapid identification of H. werneckii.

Identification of the first isolates of Trichosporon asahii var asahii from disseminated trichosporonosis in China.

Infection with Trichosporon asahii is a major cause of deep-seated and disseminated trichosporonosis, which is associated with a high mortality rate. Disseminated trichosporonosis in individuals with no underlying disease has not been reported. In this study, we report the identification of the first isolate of Trichosporon asahii var. asahii in China. Two isolates were obtained from the liver and skin of a patient with disseminated trichosporonosis who displayed no evidence of underlying disease. The morphologic and physiologic characteristics of the two isolates differed slightly from those of usual strains of T. asahii var. asahii, including the type strain CBS 2479. Ubiquinone-9 was identified as the major ubiquinone in both isolates. Sequence analysis of the LSUrDNA D1/D2, ITS, and IGS1 regions from the two isolates showed them to be T. asahii var. asahii, and random amplified polymorphic DNA analysis strongly suggested that they were the same strain.

Identification of pathogenic dematiaceous fungi and related taxa based on large subunit ribosomal DNA D1/D2 domain sequence analysis.

The nucleotide sequences of the D1/D2 domains of large subunit (26S) ribosomal DNA for 76 strains of 46 species of pathogenic dematiaceous fungi and related taxa were determined. Intra-species sequence diversity of medically important dematiaceous fungi including Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea compacta, Cladophialophora carrionii, Cladophialophora bantiana, Exophiala dermatitidis, Exophiala jeanselmei, Exophiala spinifera, Exophiala moniliae, and Hortaea werneckii were extremely small; as few as 0 changes were detected in C. bantiana, Fonsecaea and Exophiala species, 1 bp in C. carrionii and H. werneckii, and 2 bp in P. verrucosa. Inter-species nucleotide diversity between most species was higher. These data suggested that the D1/D2 domain is sufficiently variable for identification of pathogenic dematiaceous fungi and relevant species. The phylogenetic trees constructed from the sequence data revealed that most human pathogenic species formed a single cluster and that Cladosporium and Phialophora species were distributed polyphyletically into several clusters.

The first isolation of Hortaea werneckii from a household guinea pig.

Hortaea werneckii, a black yeast and the causative agent of tinea nigra (a superficial type of dermatomycosis), is a human pathogen and is also found in the environment. It is not highly pathogenic but in the last fifteen to twenty years has been isolated from various human and environmental sources in Japan. As far as we know, there has been no report on the isolation of H. werneckii from animals. Recently, we found a case of a guinea pig with dark superficial lesions on the palm and dorsal areas. Cultural and morphological studies of scrapings from the lesion showed that the causative agent was a black yeast, which was identified as H. werneckii by morphological study and molecular biological screening. D1/D2 region of the 26S large subunit rDNA gene of this isolate was identical to those of 11 other H. werneckii isolates used as reference strains in this study. This is the first case recorded of tinea nigra caused by H. werneckii in a guinea pig.

Effects of propranolol and isoproterenol on infantile hemangioma endothelial cells in vitro.

The aim of the present study was to investigate the effects of propranolol and isoproterenol on the growth curve of infantile hemangioma endothelial cells (IHECs) in vitro and determine the functions of the ß-adrenergic receptor in the pathogenesis of infantile hemangioma. IHECs were divided into three groups: The control group, the propranolol group (PG) and the isoproterenol group (IG). The PG and IG were administered with high, medium and low concentrations of the corresponding drugs. The cell growth in each group was determined using the MTT assay. A high propranolol concentration resulted in the inhibition of cell growth. By comparison, isoproterenol promoted cell growth. Within a specific time-frame (72-96 h), high drug concentrations (20 µg/ml) elicited strong effects on the cells. At certain concentrations, propranolol inhibited cell growth once the proliferation stage of IHECs had been affected for a specific length of time, whereas isoproterenol yielded opposite results. The ß-adrenergic receptor elicits an important effect in the pathogenesis of infantile hemangioma.

Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome.

The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1ß. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1ß production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1ß secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1ß secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K⁺ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.

Specific oligonucleotide primers for identification of Cladophialophora carrionii, a causative agent of chromoblastomycosis.

Cladophialophora carrionii is one of the relatively common causative agents of chromoblastomycosis. We have developed the specific oligonucleotide primer set based on the internal transcribed spacer regions of ribosomal DNA for the rapid identification of this pathogen. PCR with this primer set amplified a 362-bp amplicon from C. carrionii strains. From other relevant dematiaceous species, including medically important dematiaceous fungi, such as Fonsecaea pedrosoi, Phialophora verrucosa, and Exophiala dermatitidis, and eight species of medically important yeasts, such as Candida albicans and Cryptococcus neoformans var. neoformans, the primer set did not produce any amplicon. PCR with this primer set may be a useful tool for the identification of C. carrionii.

Rapid identification of the genus fonsecaea by PCR with specific oligonucleotide primers.

An oligonucleotide primer set based on internal transcribed spacer regions of ribosomal DNA for PCR which gives the amplicon for only the DNA from Fonsecaea species was designed. This set yielded an amplicon with 333 bp for all strains of Fonsecaea pedrosoi and Fonsecaea compacta examined but no amplicons for related dematiaceous fungi and pathogenic yeasts. PCR using this primer set was considered to be a useful method for the rapid identification of the genus FONSECAEA: