Medical mycology最新文献

The emergence of azole-resistant Candida tropicalis poses a significant threat in healthcare settings. It contributed to high morbidity and mortality, particularly in those undergoing chemotherapy for haematological diseases. In this study, we investigated a suspected outbreak in the haematology ward of Hospital Sultanah Bahiyah involving three patients, using whole genome sequencing (WGS). Azole-resistant Candida tropicalis was isolated from all patients during episodes of neutropenic sepsis following chemotherapy. The index patient developed breakthrough candidaemia while receiving fluconazole prophylaxis. Subsequently, the second and third patients developed candidaemia occurring four days apart. Consequently, phylogenetic analysis confirmed that these isolates formed a clade closely related to other C. tropicalis strains, indicating a clonal nosocomial transmission. Further analysis demonstrated that, among key azole resistance genes, mutations were specifically identified in ERG11. Our findings underscore the critical role of genomic surveillance in uncovering transmission chains of multidrug-resistant fungal pathogens and highlight an urgent need for reinforced infection control measures to contain the spread of this clone.

To assess the performance of a fully automated chemiluminescence immunoassay (CLIA) for the quantitative detection of (1, 3)-β-D-glucan (BDG) in serum samples for the diagnosis of invasive fungal diseases (IFD) and compare the results with the photometric assay, serum samples were collected from 604 patients with clinically suspected IFD between December 2022 and September 2023. According to the 2019 EORTC/MSG guideline, patients were divided into the IFD group (comprising 43, 224, and 81 proven, probable, and possible cases, respectively) and the non-IFD group (256 cases), and BDG in serum samples was measured using both the CLIA and photometric assays. The sensitivity of the CLIA assay for invasive aspergillosis (IA), pneumocystis pneumonia (PCP), and invasive candidiasis (IC) was 88.66% (95% CI, 80.22 to 93.93%), 82.35% (95% CI, 55.80 to 92.18%) and 75.90% (95% CI, 68.54 to 82.04%), respectively, with a specificity of 97.27% (95% CI, 94.21 to 98.80%). The sensitivity of the photometric assay for IA, PCP, and IC was 89.69% (95% CI,81.44 to 94.67%), 76.47% (95% CI, 49.76 to 92.18%), and 72.89% (95% CI, 65.35 to 79.35%), respectively, with a specificity of 100.00% (95% CI, 98.16 to 100.00%). The sensitivity of the CLIA assay was superior to that of the photometric assay (79.60% vs. 77.59%) in diagnosing proven/probable/possible IFD, but the specificity was lower than that of the photometric assay (97.27% vs. 100.00%). The performance of the CLIA assay was highly consistent with that of the photometric assay, both quantitatively (rs = 0.833) and qualitatively (kappa = 0.913). Lowering the cut-off value of the CLIA assay from 90.00 to 85.23 pg/ml improved diagnostic efficiency, with a sensitivity and specificity of 80.17% and 96.88%, respectively. Overall, the diagnostic performance of the two assays was comparable, with the CLIA assay having a higher sensitivity for the diagnosis of IFD. Considering the convenience of automated analysis and point-of-care testing, the CLIA assay is a promising alternative to conventional assays for diagnosing IFD.

Blastomycosis is a rare, fungal infection often with symptoms resembling bacterial or viral pneumonia, and sometimes lung cancer. Delay in diagnosing blastomycosis is associated with worse clinical outcomes, but factors contributing to diagnostic delays remain poorly understood. This study aims to estimate the incidence and duration of diagnostic delays for blastomycosis and identify risk factors associated with missed diagnostic opportunities. We conducted a retrospective cohort study using longitudinal insurance claims data from the Merative MarketScan Research Databases (2001-2022). Patients with blastomycosis were identified using ICD-9/10 codes, and diagnostic delays were estimated using a case-crossover analysis. We estimated the number of potential missed diagnostic opportunities (i.e., healthcare visits prior to the blastomycosis diagnosis with symptoms suggestive of the disease) and identified potential risk factors for delays. A total of 3825 patients with blastomycosis were identified. Of these, 41% experienced at least one missed diagnostic opportunity, with an average of 3.2 missed visits before diagnosis. The average diagnostic delay was 26.82 days (95% confidence interval: 24.57-28.96), with 17% of patients having delays lasting over a month. Missed opportunities occurred primarily in outpatient settings (59.4%). Risk factors for delayed diagnosis included history of diabetes, prior pulmonary conditions (e.g., chronic obstructive pulmonary disease), and respiratory therapies (e.g., antibiotics, inhalers). Diagnostic delays for blastomycosis are common. The association of delays with pre-existing pulmonary conditions underscore the need for heightened clinical suspicion in patients with respiratory symptoms. Education about risk factors for missed opportunities may be helpful in improving timely diagnosis and hopefully will impact patient outcomes.

Gloniopsis spp. are emerging dematiaceous fungi implicated in subcutaneous infections. Its phylogenetically close relation to Rhytidhysteron rufulum based on internal transcribed spacer (ITS) region alone often leads to misidentification of Gloniopsis spp. as R. rufulum. The study aimed to decipher clinical spectrum, molecular characterization, and antifungal susceptibility of Indian R. rufulum and Gloniopsis isolates. We retrieved 13 isolates identified as either R. rufulum or Gloniopsis from subcutaneous lesions in our culture collection and confirmed identification by Sanger sequencing. Phenotypic and genotypic characterization (targeting ITS, TUB, and LSU) was performed, followed by antifungal susceptibility testing (AFST). We also performed systematic review of all cases of 'Rhytidhysteron' or 'Gloniopsis' reported till date. Of 13 patients, majority were male with diabetes or renal transplantation. Diabetes mellitus was particularly noted in all patients infected with G. calami. Microscopic examination showed pigmented septate aerial hyphae in G. calami and septate hyphae with swellings in G. percutanea. All our isolates belonged to genus Gloniopsis rather than Rhytidhysteron. We report G. calami in human infection, for the first time. Molecular identification based on ITS, TUB, and LSU sequencing accurately differentiates among the species; however, TUB GenBank database needs to be expanded. AFST is challenging, but available data elucidate role of triazoles as potent therapy, along with surgical excision. This is the first study delineating clinical and microbiological characteristics and antifungal susceptibility of Gloniopsis species from India. Globally, maximum reports of infection by Gloniopsis spp. are from India, possibly due to its tropical temperature conducive for fungal growth, and warrants epidemiological investigation.

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 12 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.

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 multicentre study aimed to assess changes in airway fungal ecology before and during the CFTRmt era. Data from pwCF followed at CF reference centres 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 1555 and 1400 sputum samples from 438 and 483 pwCF were analysed 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.

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 European Organisation for Research and Treatment of Cancer (EORTC) criteria. All Mucorales were identified at genus level by culture morphology, and a subset was analyzed at species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry, microscopy, and Internal Transcribed Spacer Polymerase Chain Reaction (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 Rhizop. microsporus and M. 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.

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.

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 SD 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 S. epidermidis were the most common isolates. Microbiome results revealed lower species richness of both fungal (observed features, P = .0105 and Chao1, P = .0487) and bacterial (observed features, P = .0016 and Chao1, P = .001) communities with higher relative abundance of M. restricta (61%, P < .0001) and Staphylococcus (40%, P < .0001) and Corynebacterium (16%, P < .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.

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.