Abstract Recurrent vulvovaginal candidiasis (RVVC) is a condition characterized by recurrent episodes of vulvovaginal candidiasis, caused primarily by Candida albicans. Host genetic variations may play a role in the susceptibility to this disease. We performed whole-exome sequencing (WES) in patients with RVVC to identify potentially deleterious genetic variants in candidate genes, assess their impact on gene expression. We searched for patients with severe RVVC (> 10 episodes per year) and who had additional affected family member(s). WES was performed on gDNA from the index patients. Vaginal scraping samples were obtained from the affected females, and total RNA was obtained to evaluate the expression of candidate genes by qPCR. We identified 12 adult females affected with severe RVVC across 11 families, of whom three had more than one affected female. In silico analyses of WES results revealed potentially deleterious variants in MUC4, MUC5B, and MUC21 genes. A significant decrease in the expression of the MUC5B and MUC21 genes was observed in patients with RVVC compared to healthy women. These results suggest that potentially deleterious variants could affect the expression of the genes encoding different members of the mucin family, indicating that mucins may play a significant role in the pathogenesis of RVVC.
Abstract Penguins are highly susceptible to airborne mycoses, and aspergillosis due to Aspergillus fumigatus (recently classified as priority pathogen by WHO) is common in captivity; however, environmental fungal diversity and exposure risk in natural, non-temperate breeding habitats remain poorly described. We aimed to characterize the seasonal burden and diversity of culturable fungi in wild king penguin (Aptenodytes patagonicus) colonies and to assess A. fumigatus diversity and phenotypes. During one year, monthly environmental sampling was performed from four different soils of Crozet archipelago, in French Southern Territories, around three penguin colonies. Samples were cultured on malt extract agar at 35 ± 2°C. Isolates were quantified (CFU) and identified by microscopy, MALDI-TOF MS, and DNA sequencing. A. fumigatus isolates underwent genotyping and phenotyping for antifungal susceptibility, as well as for tolerance to high salinity and extreme temperatures. Overall, fungal loads in penguin environments showed marked seasonality (3–1 100 CFU/month), peaking during breeding/chick rearing summer period (∼22% positive sites). After April, fungal burden declined (mean 150 CFU/month; 8.8% positive sites). Aspergillus section Fumigati represented 21–100% of isolates (150–950 CFU/month). A. fumigatus genotypes were diverse, with no detected antifungal resistance or extreme growth phenotypes. Fungal burden in penguin natural habitats was closely linked to bird presence and breeding activity. These findings provide new insights into fungal exposure in wild groups and emphasize the importance of a One Health approach to better understand the interactions between environment, wildlife, and infectious disease risk in fragile ecosystems.
Abstract The Aspergillus galactomannan chemiluminescence immunoassay (GM–CLIA) is a novel non-culture-based test applied in the detection of GM antigen in serum and bronchoalveolar lavage fluid (BALF). This multicenter, retrospective, and controlled study aims to investigate its diagnostic value for invasive aspergillosis (IA). A total of 246 serum and 228 BALF samples were obtained from IA patients (n = 229) and non-IA (n = 236) patients between March 2023 and July 2024. The performance of GM-CLIA was compared with that of Aspergillus GM sandwich enzyme immunoassay (GM-EIA) through Spearman rank correlation analysis and assessed via sensitivity, specificity, positive/negative predictive values (PPV/NPV), and receiver operating characteristic (ROC) curve analysis. Analytical performance was evaluated through interference, precision, limit of detection (LoD), and cross-reactivity experiments. The sensitivity, specificity, PPV, and NPV of serum GM–CLIA were 93.97%, 97.46%, 97.32%, and 94.26%, respectively. For BALF GM–CLIA, the corresponding values were 93.58%, 95.76%, 95.33%, and 94.17%. ROC analysis yielded high area under the curve (serum: 0.977; BALF: 0.982) with optimal cut-offs of 0.625 (serum) and 0.615 (BALF). The levels of GM by CLIA and EIA (rs = 0.838, P < 0.0001) strongly correlated. No interference was observed from hemoglobin, bilirubin, or triglycerides at certain concentrations. Repeatability, indoor, and inter-batch precision met predefined criteria, with no cross-reactivity in non-Aspergillus pathogens. The LoD for detecting GM–CLIA was 0.09 ng/ml. In summary, GM–CLIA was evaluated in both sample types, demonstrating high specificity and sensitivity in diagnosing IA. Thus, clinical implementation of CLIA may significantly improve diagnostic efficiency and patient outcomes.
Abstract Fungal pneumonias and tuberculosis (TB) remain major causes of mortality among people living with advanced HIV disease (PLWHA). Their overlapping clinical manifestations delay diagnosis in developed and resource-limited settings, with greater impact where access to rapid diagnostic tools is limited. This study evaluated the performance of a multiplex quantitative PCR (qPCR) assay for simultaneous detection of Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis jirovecii, and Mycobacterium tuberculosis complex in respiratory samples from PLWHA. A cross-sectional study was conducted at the Instituto Nacional de Infectologia Evandro Chagas (Rio de Janeiro, Brazil) between December 2023 and March 2025. Adults with HIV infection (CD4 < 200 cells/mm³) and clinical or radiological evidence of pulmonary infection were enrolled. Standard diagnostic methods included culture, microscopy, antigen detection (CrAg-LFA, urinary Histoplasma antigen, TB-LAM), GeneXpert® MTB/RIF, and commercial qPCR for P. jirovecii. The multiplex assay targeted the ITS region (H. capsulatum and C. neoformans), mtLSU (P. jirovecii), and IS6110 (M. tuberculosis). Among 198 screened participants, 88 met inclusion criteria (mean CD4 count: 56 cells/µl). Diagnosis included TB (56.8%), pneumocystosis (34.1%), histoplasmosis (10.2%), and cryptococcosis (11.4%); 25% presented coinfections. The multiplex qPCR showed 100% sensitivity for histoplasmosis, 80% for pneumocystosis, and 40% for both cryptococcosis and TB, with specificities ≥ 82% and 100% for TB. Overall accuracy ranged from 66% to 86%. Mortality was 12.5%, highest among cryptococcosis cases (20%). The assay provided accurate detection of H. capsulatum and P. jirovecii, although performance was limited for TB and cryptococcosis, supporting its use as a complementary molecular tool for differential diagnosis in PLWHA.
Abstract Candida albicans is a commonly encountered dimorphic fungus that normally resides in the human body. Once the host is immune-compromised or endures long-term antibiotic treatment, C. albicans will transform into an opportunistic pathogen that can cause from superficial mucosal diseases (e.g., oropharyngeal candidiasis) to life-threatening invasive infections (e.g., candidemia). Since the resistance rate of clinical C. albicans is rapidly increasing, there is an urgency to expand the current antifungal armamentarium. It has been shown that a growing body of host receptors can recognize the cell wall components of C. albicans (e.g., β-glucan, chitin, and mannan), and trigger potent innate immune responses with enhanced phagocytosis, reactive oxygen species, and inflammatory cytokine production. In this review, we classify the host receptors into two categories: the receptors that directly interact with the epitopes of C. albicans, and those that act as co-receptors to aid in epitope recognition. The former receptors include Dectin-1/2/3, Mincle, MR, DC-SIGN, MBL, CR3, LYSMD3, NKp30, and SPINK7, whereas the latter ones consist of TLR2/4, EphA2/B2, galectin-3, gC1qR, AhR, EGFR, and HER2. We not only characterize the antifungal modes of these host receptors during C. albicans infection, but also summarize the features underlying the recognition of C. albicans epitopes by these receptors. The advancements in PRRs can largely expand our scientific understanding of antifungal mechanisms, and lay a solid foundation for the development of new antifungal agents for the clinical treatment of systemic infections caused by C. albicans.
