Medical mycology最新文献

The dose-dependent risk of opportunistic fungal infections and associated mortality from systemic glucocorticoids remains poorly defined in non-HIV, non-transplant (NHNT) populations. This study evaluated the cumulative incidence of opportunistic fungal infections and the association between glucocorticoid dose, infection risk, and 1-year mortality in NHNT adults. In this observational cohort study (NCT05707156), adults without HIV or solid organ transplants who received systemic glucocorticoids for ≥14 days between 2022 and 2024 were identified using the TriNetX research network. Glucocorticoid doses, standardized to prednisone equivalents (PEQ), were categorized as ≤10 mg/day, 11-20 mg/day, and >20 mg/day based on clinically relevant thresholds. Cumulative duration beyond the initial ≥14 days was unavailable. Multivariable logistic regression identified predictors of opportunistic fungal infections. Cox proportional hazards and Kaplan-Meier analyses evaluated associations between glucocorticoid dose and 1-year all-cause mortality. Among 7839 patients, 6% developed opportunistic fungal infections, predominantly histoplasmosis (96%). Compared with ≤10 mg/day, neither 11-20 mg/day (OR 0.85, 95% CI 0.18-3.91) nor >20 mg/day (OR 0.89, 95% CI 0.24-3.33) was independently associated with infection risk. Crude 1-year mortality was higher in the >20 mg group (1.1%) versus ≤10 mg (0.5%) and 11-20 mg (0.4%) groups (P = .002), but glucocorticoid dose was not independently associated with mortality after adjustment. Increased mortality was associated with older age (HR 1.03/year), female sex (HR 1.96), and higher Charlson Comorbidity Index (HR 1.17 per point). Higher glucocorticoid doses did not independently predict opportunistic fungal infection risk or mortality, illustrating the limitations of dose-based risk stratification.

Although serological testing may be influenced by several factors, it remains essential for diagnosing paracoccidioidomycosis (PCM) and monitoring patients' response to treatments. This retrospective, multicenter study evaluated the diagnostic accuracy of the double immunodiffusion (ID) and dot blot (DB) assays using antigenic extracts from the reference strain (RAgPb) and 10 autochthonous Paracoccidioides spp. isolates. We analyzed sera from 370 microbiologically confirmed PCM cases registered in Argentina over a 10-year period (2013-2022). While 318 (86%) showed an identity reaction using ID with the RAgPb, 52 (14%) sera were initially identified as false negatives by referral centers. Upon retesting, 34/52 turned positive, highlighting the operator- and procedure-dependent variability that impacts ID sensitivity. The remaining 18 (5%) sera were tested using autochthonous antigens and showed reactivity by ID and DB, whereas all remained negative when RAgPb was used. These findings underscore the impact of antigenic variability and support the use of native antigens to enhance sensitivity. The DB assay demonstrated higher sensitivity, faster results, and simplicity, making it also suitable for routine diagnosis. No statistically significant differences (P > .05; odds ratio = 2.69) were observed between PCM clinical form and ID results. This study emphasizes the importance of including region-specific antigens and standardized protocols to improve PCM diagnosis and minimize false negatives in endemic areas.

Coccidioidomycosis (Valley Fever) is endemic to California's Central Valley, a region marked by socioeconomic disadvantage and health disparities. We retrospectively reviewed 72 adults with new or active disease seen at a tertiary referral center between January and June 2022. and Nearly all patients lived in areas with high Social Deprivation Index (SDI) and low Healthy Places Index (HPI) scores (assigned by residential ZIP code), reflecting marked neighborhood-level disadvantage. Over half required hospitalization and one-third developed complicated pulmonary or disseminated disease. Lower HPI scores were modestly associated with hospitalization, suggesting community disadvantage may contribute to Valley Fever disparities.

Seawater and freshwater of rivers or lakes and their surrounding sand or soil have been shown to harbour bacteria and fungi. Among these microorganisms, the fungi of clinical interest can impact human health in various ways, posing an important risk to public health. In this article, we will present data of a 2-year survey of fungal contamination of seawater and sand on multiple beaches from Romania and Israel, and discuss the possible effects of the various climatic factors with respect to the mycobiota found in the two sites: the Black Sea versus the Mediterranean Sea. The samples were collected quarterly in 2018 and 2021 from 6 Israeli and 20 Romanian coastal beaches and subsequently processed in the lab for evaluation of fungal burden and mycobiota diversity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spexctrometry (MALDI-TOF MS) and internally transcribed spacer sequencing were used for fungal identification. In Israel, the most common moulds isolated were the Aspergilli, both in sand and water. In Romania, dematiaceous fungi are predominant, followed by Penicillium isolates. The yeast genera isolated both in sand and seawater of Black and Mediterranean seas were Candida, Cryptococcus, Rhodotorula, Trichosporon, and Geotrichum. The study revealed that fungi are constantly contaminating the sand and seawater in both coastlines; there is a difference between mycobiota in Israeli and Romanian beaches mainly related to different climatic conditions; yeast contamination seems to be related with human activities and pollution episodes, especially during high season; many of the yeast and mould species have the potential to cause human disease, particularly in immunocompromised or debilitated individuals.

Quantitative cryptococcal culture of the cerebrospinal fluid (CSF) is commonly used in cryptococcal meningitis research. We assessed the 'marble method' to evenly spread CSF onto two Sabouraud dextrose agar plates compared with the 'droplet method' using drops of CSF evenly placed around two halves of one agar plate. We found high concordance between the two methods. The Bland-Altman plot showed that the droplet method differed from the marble method by an average of -0.044 log10 CFU/ml CSF, with 95% limits of agreement from -0.324 to 0.235, indicating a small bias in favor of the marble method (P < 0.001). The droplet method of quantitative cryptococcal culture had no clinical difference compared to the marble method.

Candida glabrata is a major fungal pathogen capable of causing life-threatening disseminated infections, especially in immunocompromised individuals. Oxygen levels vary widely across host niches, and hypoxia is increasingly recognized as a key modulator of fungal pathogenicity. However, how low-oxygen environments influence adhesion and virulence in C. glabrata remains poorly understood. Here, we investigated C. glabrata adhesion under rigorously controlled oxygen conditions using a sealed hypoxic workstation and identified genes responsible for hypoxia-induced adhesion. Adhesion to human epithelial and endothelial cells was significantly enhanced under hypoxic conditions. RNA-seq analysis revealed that among differentially expressed genes, the adhesin gene EPA6 was consistently upregulated under anaerobic conditions in multiple strains. Using gene deletion and complementation, we found that EPA6 is required for adhesion under hypoxia. Using three distinct in vivo models (intravenous infection, gastrointestinal colonization, and systemic dissemination from the gut), we showed that EPA6 was crucial for fungal burden and pathogenicity. Because the epa6Δ mutant had normal growth and stress tolerance, we consider that its attenuated virulence (reduced colonization and dissemination) resulted from reduced adhesion. This study provides the first demonstration of fungal adhesion under precisely monitored oxygen conditions that mimic those in host physiology. These findings demonstrate that hypoxia promotes C. glabrata adhesion and dissemination through EPA6, highlighting a key virulence mechanism.

Cryptococcal meningitis (CM) remains one of the leading causes of morbidity and mortality among people living with HIV, particularly in low and middle-income countries where access to standard antifungal therapy is limited. Despite global advances in HIV care, early diagnosis and effective treatment of cryptococcal disease continue to represent major challenges in resource-limited settings. We conducted a retrospective registry-based cohort study of HIV patients and a first episode of CM admitted to a Peruvian national referral hospital between 2005 and 2015. Cox proportional hazards models were used to identify independent variables related to 30- and 90-day mortality. A total of 83 patients were included, 87% were males with a median age (interquartile range) of 33.8 (28.7-45.1) years. At baseline, 27.7% of patients had received antiretroviral therapy. Mortality at 30 and 90 days was 26.5% and 31.3%, respectively. In multivariable Cox models, the limited sample availability (59 for baseline and 83 for treatment analyses), constrained the precision estimates; nevertheless, altered consciousness, hyponatremia, and headache as independent predictors of mortality [30-day Hazard Ratios (HR): 7.6 (2.2-26.0); 5.4 (1.6-18.2); 0.1 (0.02-0.4); and 90-day HR: 7.1 (2.0-26.0); 10.9 (2.8-41.8); 0.1 (0.02-0.4), respectively]. In treatment analyses, fluconazole monotherapy or the absence of antifungals were significantly associated with higher mortality [30-day HR: 2.7 (1.1-6.8); 21.1 (7.8-57.5) and 90-day HR: HR: 2.8 (1.1-7.3); 20.1 (7.4-54.5), respectively]. In resource-limited settings, mortality from HIV-associated CM remains unacceptably high. These findings underscore the urgent need to enhance early diagnostic strategies and ensure access to optimal antifungal therapy to improve survival outcomes.

This study evaluated squalene epoxidase (SQLE) mutations, and the antifungal susceptibility profile of Trichophyton species isolated from patients with recalcitrant dermatophytosis in Pakistan. The study was conducted at the Aga Khan University Hospital Laboratory, Karachi, between January 2023 and February 2024. Identification of the isolates was performed through sequencing of the internal transcribed spacer (ITS) region. Antifungal susceptibility testing for terbinafine, itraconazole, and voriconazole was performed using the broth microdilution method based on modified European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Minimum inhibitory concentrations (MICs) were interpreted using EUCAST epidemiological cutoff values to classify isolates as wild-type or non-wild-type. DNA extraction was carried out using the QIAamp DNA Mini Kit, and ITS and SQLE gene regions were amplified and sequenced via Sanger sequencing. A total of 37 Trichophyton isolates were included, of which 17 (45.9%) were Trichophyton mentagrophytes, 16 (43.2%) were T. indotineae, 2 (5.40%) were T. rubrum, and 2 (5.40%) were T. interdigitale identified through ITS sequencing. Non-wild-type MICs to terbinafine were observed in 28 (75.7%) isolates, while eight isolates (21.6%) also showed non-wild-type MICs to itraconazole; no isolates demonstrated non-wild-type MICs to voriconazole. The most prevalent SQLE gene mutations were F397L (54%), Q408R (32.4%), and A448T (21.6%). This study represents the first report from Pakistan of antifungal resistance and SQLE gene mutations in Trichophyton strains from patients with recalcitrant dermatophytosis. The high prevalence of resistance underscores the urgent need for capacity building in antifungal susceptibility testing and highlights the importance of guiding appropriate treatment strategies to manage resistant dermatophytosis in the region effectively.

Tinea corporis and tinea cruris are common dermatophyte infections of increasing public health concern, yet national US data are limited. We estimated incidence, risk factors, and diagnostic and treatment practices among a large Medicaid-insured outpatient cohort. Among ∼6 800 000 enrollees, 54 108 were diagnosed with tinea corporis (79.1/10 000 person-years) and 8386 with tinea cruris (12.2/10 000 person-years). Tinea corporis primarily affected young children and Black patients, while tinea cruris was prevalent among middle-aged men. Overall, <10% received diagnostic testing, and 7%-10% were treated with combination antifungal-corticosteroid products, highlighting the opportunities to increase testing and promote judicious antifungal use amid emerging resistance.

Reptiles can host and potentially spread a wide range of microorganisms, yet the composition and zoonotic potential of their associated fungi remain poorly characterized. This study investigated the cutaneous mycobiota of free-ranging snakes sampled during the "Festa dei Serpari" in Cocullo, Italy, with a specific focus on yeasts and the detection of Ophidiomyces ophidiicola among filamentous fungi. A total of 143 snakes from four species (i.e., Elaphe quatuorlineata, Hierophis viridiflavus, Natrix helvetica, and Zamenis longissimus) were examined. Sterile swabs from healthy and lesioned skin were cultured and analyzed using molecular methods. Yeast isolates included Pichia kudriavzevii, Blastobotrys raffinosifermentans, Cryptococcus neoformans, and Debaryomyces spp. Overall, 64.24% of samples showed fungal growth, with yeasts accounting for 11.52% of positive cultures, while O. ophidiicola was not detected. These results highlight the diversity of yeast communities associated with snakes and emphasize the importance of monitoring O. ophidiicola and fungal pathogens of zoonotic concern to elucidate the role of reptiles as potential sentinels of emerging pathogens.