Medical mycology最新文献

The introduction of CFTR modulator therapies (CFTRmt) has changed cystic fibrosis (CF) management. By improving airway rheology and function in people with CF (pwCF), CFTRmt are expected to modify cyto-microbiological features. This French multicenter study aimed to assess changes in airway fungal ecology before and during the CFTRmt era. Data from pwCF followed at CF reference centers in Besançon, Bordeaux, Limoges, and Rennes were collected before CFTRmt use (2014) and after their widespread implementation (2022), including elexacaftor/tezacaftor/ivacaftor (ETI) as well as other CFTR modulator therapies used in France. Mycological outcomes included the total number of yearly cultures and the number of positive cultures per fungus and per patient, regardless of CFTRmt. A total of 1 555 and 1 400 sputum samples from 438 and 483 pwCF were analyzed in 2014 and 2022, respectively. The 2022 population was significantly older, in agreement with French ETI-prescription limited to pwCF aged at least 12 in 2022. Regardless of year, patients with positive fungal cultures were older than those with negative ones. Positive cultures for Aspergillus section Fumigati significantly decreased under CFTRmt at both population and individual levels. Conversely, positive cultures for Aspergillus section Nigri, Penicillium sp. and Candida albicans increased under CFTRmt, in correlation with the type of CFTRmt for Aspergillus section Nigri. CFTR modulators appear to modify the airway mycobiome and fungal ecology depending on CFTRmt type. Among several factors that may account for these mycobiome changes between 2014 and 2022, environmental changes, including climate-related shifts in Aspergillus distribution, may contribute potentially.

Neutralizing anti-cytokine autoantibodies (ACAAs) have been associated with cryptococcal meningitis (CM), but the influence of HIV co-infection remains undefined. We investigated plasma ACAA profiles and function in a cross-sectional Vietnamese cohort stratified by HIV and CM status (n = 20 per group). We quantified plasma ACAAs against interferons (IFNs), interleukins (ILs), and granulocyte-macrophage colony-stimulating factor (GM-CSF) using a particle-based assay, and assessed their neutralizing activity in high-titer samples. Associations between ACAA levels and CM were analyzed using Firth-penalized logistic regression, adjusting for age, sex, and CD4 count (in HIV-positive models). In HIV-negative individuals, higher anti-GM-CSF levels were associated with CM (odds ratio [OR] per log-unit increase, 1.84; 95% confidence interval [CI], 1.07-3.18). This association was predominantly observed in Cryptococcus gattii cases and was accompanied by functional neutralizing activity. Furthermore, adding pre-specified plasma IgG2 improved overall model fit and showed a strong inverse association with CM (OR, 0.03; 95% CI, 0.003-0.29). Conversely, HIV-positive CM cases had lower overall ACAA levels than non-CM controls. After adjusting for hypogammaglobulinemia/IgG1, significant inverse associations persisted for anti-IL-10, anti-IL-12, anti-IL-15, and anti-IL-22 with CM status. Type I IFN-binding ACAAs were largely non-neutralizing. These findings reveal distinct pathogenic mechanisms. In HIV-negative CM, neutralizing anti-GM-CSF antibodies, often in C. gattii infection, and low IgG2 were independently associated with disease. In HIV-positive CM, ACAA reductions without cytokine neutralization may reflect underlying antibody and/or B-cell deficiency. Longitudinal studies are needed to clarify the clinical implications of ACCAs, particularly in HIV-negative CM.

Blastomyces species complex causes infection in persons with intact and impaired immune defenses. The diagnosis of blastomycosis is challenging because it mimics infectious and non-infectious diseases. Blastomyces adhesin-1 (BAD-1) protein is a major virulence factor in B. dermatitidis and B. gilchristii and induces a humoral immune response during infection. The goal of this retrospective, case-control study conducted at the University of Wisconsin-Madison is to investigate the test characteristics of the newly developed second generation BAD-1 IgG Enzyme Immunoassay (EIA) antibody test for the diagnosis of blastomycosis. The study was performed in an endemic area in a diverse patient population including persons with underlying immunocompromise. Thirty-six case patients with proven or probable blastomycosis were compared to 370 controls. Serum BAD-1 IgG was positive in 50% of the case patients and in 9.7% of the controls, which resulted in a sensitivity of 50% and specificity of 90.2%. The highest sensitivity (80%) occurred in non-immunocompromised persons with chronic blastomycosis and the lowest sensitivity occurred in those with acute blastomycosis (35.0%) or immunocompromise (37.5%). Sensitivity was not influenced by dissemination or severity of disease. In conclusion, this study demonstrates that the BAD-1 IgG EIA can serve as adjunctive test for the diagnosis of blastomycosis in select patient populations living in regions endemic for blastomycosis.

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.

We determined the optimal method to culture Mucorales species from air samples. Subsequently, we investigated the diversity of Mucorales species in Dutch air and compared these species with those causing mucormycosis in patients. We optimized the Mucorales culturing protocol by testing different growth conditions with samples from a newly developed air sampling approach. We used 120 air samples taken throughout the Netherlands in the project called Schimmelradar (September-October 2023). These samples were supplemented with additional air samples taken in the Netherlands (February 2024). The Mucorales species cultured from these air samples were compared to 17 clinical isolates (2016-2023) from a Dutch university medical center. Mucormycosis infections were classified using the EORTC-criteria. All Mucorales were identified at genus level by culture morphology, and a subset was analyzed at species level using MALDI-TOF MS, microscopy and ITS PCR. A combination of Sabouraud dextrose agar, voriconazole and incubation at 30°C yielded the broadest variety of Mucorales species from air samples. Species found in Dutch air included Rhizomucor pusillus, Rhizopus microsporus, and Mucor circinelloides. Clinical data showed that Rhizopus microsporus and Mucor circinelloides were most frequently identified in mucormycosis infections. We validated a selective method for the culture of Mucorales species from air samples using a delta trap air sampling method. Three of the 10 species cultured from air samples, were also detected in clinical isolates. Although inhalation is assumed as primary route of infection, this is the first study demonstrating the similarity of Mucorales species between air and clinical samples.

Seborrheic dermatitis (SD) is a common skin condition affecting the scalp and other sebaceous-rich areas. Most recent studies have focused on the microbiota of individuals with SD and healthy controls, suggesting an association of microbial dysbiosis. The variations in the microbiota at lesional and non-lesional sites of SD patients and healthy controls remain unexplored. The present study aimed to characterize the microbiota in seborrheic dermatitis patients. We conducted a cross-sectional study to analyse microbial composition and diversity of fungi and bacteria on the lesional and non-lesional sites of SD patients (n = 60) and from the scalp of healthy individuals (n = 30) using culture-based methods and high-throughput sequencing (n = 8 each group) of the ITS2 region of fungal rDNA and the V3-V4 region of bacterial 16S rRNA. The culture-based approach revealed a significant association between the combination of 'Malassezia and aerobic bacteria' and lesions in patients, especially in severe cases. Malassezia restricta, Staphylococcus capitis and Staphylococcus epidermidis were the most common isolates. Microbiome results revealed lower species richness of both fungal (observed features, p = 0.0105 and Chao1, p = 0.0487) and bacterial (observed features, p = 0.0016 and Chao1, p = 0.001) communities with higher relative abundance of M. restricta (61%, p < 0.0001) and Staphylococcus (40%, p < 0.0001) and Corynebacterium (16%, p < 0.0001) on lesional sites than on non-lesional sites. A decrease in alpha diversity of both fungal and bacterial flora, on the lesional site compared to the non-lesional site, suggests an association between site-specific dysbiosis and SD.

In this article, we evaluate a possible postzone effect for the Histoplasma antigen Lateral Flow Assay (LFA). We re-tested urine samples that were Histoplasma-positive with the LFA, both for an undiluted and diluted sample. Of the twelve samples, a postzone effect was observed in six, and in one sample this led to a false negative result in the undiluted sample. For two samples, dilution of the sample led to a weaker LFA result. We recommend cautiousness when interpreting negative samples based on LFA alone, especially when clinical suspicion of histoplasmosis is high.

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.