Medical mycology最新文献

Central nervous system mucormycosis (CNS-M) is a severe disease with difficult and often delayed diagnosis, leading to high mortality. The aim of this new study was to assess clinical and radiological presentation according to underlying conditions and dissemination routes to optimize diagnostic strategies. We conducted a retrospective national study including 54 CNS-M cases diagnosed between 2005 and 2020, with brain imaging reviewed by two neuroradiologists. CNS-M resulted from presumed hematogenous dissemination in 29 patients (54%) and from direct extension in 25 (46%), known as rhino-orbito-cerebral mucormycosis (ROCM). No neurological symptoms were found in 10/54 (19%), regardless of dissemination route. Hematogenous CNS-M mainly affected highly immunocompromised (HM or SOT) patients (90%), including 43% neutropenic. Radiology showed abscesses (87%) and small-vessel disease (39%). In ROCM, two patterns emerged depending on osteolysis (19/25, 76%) or its absence (6/25, 24%). ROCM without bone lysis, mostly in severely immunosuppressed patients, caused meningitis without abscess, whereas osteolytic ROCM led to abscess formation (11/18, 60%). Without osteolysis, perineural spread along the optic nerve occurred in 2/3 cases. Serum Mucorales PCR was positive in 91% of hematogenous and 64% of ROCM cases. Fungal co-infections occurred in 26%. This study underscores distinct invasion patterns and the need for extensive workup in CNS-M, highlighting the diagnostic value of MRI with gadolinium and serum Mucorales qPCR based on dissemination route and underlying condition. MRI is particularly useful in ROCM for detecting meningitis (80%), large-vessel disease (30%), and perineural involvement (8%).

LysM proteins are widely distributed in fungi of diverse lifestyles, including pathogens of humans and animals. Using bioinformatic methods, LysM proteins have been identified in representative yeasts of medical importance. However, LysM proteins have been found in only four ascomycete yeasts (Candida subhashii, C. tropicalis, Debaryomyces fabryi, and D. hansenii). In contrast, almost all basidiomycete yeasts contain at least one LysM effector but lack subgroup C chitinases. Notably, a unique LysM effector is highly conserved among all the lipid-dependent Malassezia species. The repertoire of LysM proteins in medically important yeasts appears to be more determined by the fungal lifestyle than by host colonization.

Candidemia is a common healthcare-associated infection associated with substantial morbidity and mortality. Candida parapsilosis is among the most common causative species; it has a notable ability to form biofilms and colonize skin, facilitating patient-to-patient spread, and it is increasingly associated with fluconazole resistance. We aimed to describe temporal trends, clinical characteristics, and antifungal resistance patterns among C. parapsilosis candidemia hospitalizations in the United States during 2016-2024. We used the Premier Healthcare Database (which represents >500 hospitals contributing laboratory data) to identify hospitalizations with ≥1 blood culture positive for C. parapsilosis. We calculated rates of C. parapsilosis candidemia hospitalizations and described characteristics overall and stratified by time period (2016-2019, 2020-2021, 2022-2024). We also compared characteristics of hospitalizations with vs. without fluconazole resistance. Among 1943 C. parapsilosis candidemia hospitalizations, prevalence peaked during the COVID-19 pandemic (10.4 per 100 000 hospitalizations in 2020-2021) and was highest among adults aged 45-64 years, male patients, and non-Hispanic Black patients. Many hospitalizations involved intensive care unit admission (67%), central venous catheter use (51%), and mechanical ventilation (37%). Fluconazole resistance rates increased from 3.1% in 2016-2019 to 11.7% in 2022-2024. In-hospital death or discharge to hospice was more frequent among hospitalizations involving fluconazole-resistant isolates vs. those without fluconazole-resistant isolates (42% vs. 28%, P = .017). Increased fluconazole resistance in C. parapsilosis is a growing public health concern. Surveillance, infection prevention and control practices, and routine antifungal susceptibility testing are essential to inform clinical management and public health strategies.

Aspergillus fumigatus is a human pathogen and a ubiquitous environmental mould. Consequently, A. fumigatus may be exposed to agricultural fungicides widely used for crop protection. The use of azole fungicides in the environment has been implicated in the emergence of azole antifungal resistance in A. fumigatus. In vitro susceptibility of a collection of both clinical (n = 14) and environmental (n = 6) A. fumigatus isolates was determined against fungicides with different modes of action (demethylation inhibitors, Succinate DeHydrogenase Inhibitor (SDHI), Quinone outside Inhibitors (QoI), Methyl Benzimidazole Carbamate (MBC) and polyene). Sequencing of tubA, CYTB and SDHB, which encode the cellular targets of these fungicides, was performed. Eventually, the impact of resistance on the basal growth kinetics was assessed using a selection of two susceptible and two resistant isolates. Cross-resistance between medical triazole antifungal and agricultural triazole fungicides was confirmed, except for isolates with G54R/E substitutions in the cyp51A protein. No correlation was observed between resistance to triazole antifungals and imidazole fungicides. We identified seven MBC- (five environmental and two clinical isolates), five QoI- (three environmental and two clinical isolates) and one environmental SDHI-resistant isolates. Resistant phenotypes were associated with amino acid substitutions in beta-tubulin (F219Y and E217A), cytB (G143A) and sdhB (H270Y). Multi-fungicide resistance was not systematically associated with reduced growth kinetic. Multi-fungicide resistance, including at least resistance to one non-azole fungicide, was identified in sevenA. fumigatus isolates, of which two were clinical isolates. This last observation supports the hypothesis of the environmental pathway leading to antifungal resistance in A. fumigatus.

Chronic pulmonary aspergillosis (CPA) comprises a spectrum of lung disorders caused by ubiquitous fungi of the genus Aspergillus, with Aspergillus fumigatus being the most frequently identified pathogen. The disease is globally prevalent and associated with significant morbidity and mortality. Here, we investigated the species distribution, antifungal susceptibility and genetic relatedness of Aspergillus isolates from CPA patients and environmental sources in South India. All tested isolates were susceptible to common antifungals, and A. fumigatus was overall the most common species. Isolates from patients and the environment occasionally displayed identical genotypes, suggesting CPA patients acquire the disease from the environment.

Histoplasmosis and cryptococcosis are major opportunistic infections among patients who are immunosuppressed. This prospective study evaluates the utility of routine antigen screening for Histoplasma and Cryptococcus in patients referred for CD4 count testing at Synlab, Medellin, Colombia. A total of 323 plasma specimens with CD4 counts < 500 cells/µl collected between November and December 2024 were analyzed using commercial antigen detection assays. Overall, 4% of specimens were positive for one of the antigens tested, 2% for each pathogen. Many of the positives were detected in samples with CD4 > 200, demonstrating the need to screen patients above this threshold. The geographical distribution of positives could suggest the value of regionalized screening strategies. Our findings support the integration of early antigen screening into routine care of patients with immunosuppression.

Invasive aspergillosis (IA), caused by Aspergillus, requires prompt diagnosis and treatment. Here, the efficacy of a chemiluminescence immunoassay (CLIA) for detecting Aspergillus galactomannan (GM) antigen in serum and bronchoalveolar lavage fluid (BALF) was evaluated. Overall, 265 patients with suspected IA were enrolled between March and May 2023 and were stratified into IA (n = 48) and non-IA (n = 217) cohorts. A total of 265 samples (208 serum, 57 BALF) were analyzed with GM-CLIA. The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were calculated. Diagnostic performance was assessed with receiver operating characteristic (ROC) curves. GM-CLIA demonstrated sensitivity/specificity values of 88.00%/93.44% in serum and 91.30%/76.47% in BALF. The sensitivity for all samples was 89.58% with a specificity of 90.78%, while PPV and NPV were 69.25% and 97.52%, respectively. The AUC (area under the ROC curve) was 0.93 (95% confidence interval [CI], 0.89-0.97, P < .001), with an optimal cutoff value of 0.70 ng/ml. The GM-CLIA enables automated detection of individual samples (serum/BALF) on a fully integrated chemiluminescence platform. This system delivers high specificity (90.78%), sensitivity (89.58%), enabling prompt diagnosis and treatment of IA.

Candida auris is an emerging fungal pathogen with high rates of multidrug resistance, posing a significant global health threat. Immunosuppressed patients are particularly vulnerable to multidrug-resistant (MDR) C. auris infections. This systematic review and meta-analysis (SR-MA) aimed to assess the global prevalence of MDR-C. auris isolates in humans and their resistance to antifungal drugs, primarily fluconazole (FLZ), voriconazole (VOR), and amphotericin B (AmB). A comprehensive search was conducted in PubMed, Scopus, and ScienceDirect databases on published studies regarding clinical C. auris isolates and the use of antifungal susceptibility testing assay from 17 March 2015 to 1 February 2024. Meta-analysis was conducted using random-effects models to determine the estimated pooled prevalence of MDR-C. auris isolates and their antifungal resistance profiles from immunosuppressed humans. A total of 81 research studies were included in the final analysis, with the overall pooled prevalence of the three most important antifungal drugs; FLZ (92.5% | 95% CI: 89.5-94.7), VOR (49.0% | 95% CI: 37.6-60.4), and AmB (51.0% | 95% CI: 42.3-59.7). According to the subgroup analyses, FLZ-resistant C. auris was the most prevalent isolate observed in the five continents reporting compared to the VOR- and AmB-resistant C. auris having lower pooled prevalence. Further, higher pooled prevalence of MDR-C. auris isolates were observed from males (68.2%, n = 578) compared to females (37.1%, n = 283). Finally, the global pooled prevalence for mortality in immunosuppressed patients with MDR-C. auris from 13 research studies was 41.5% (95% CI: 29.9-54.2). This SR-MA study establishes the variation of MDR-C. auris resistance patterns observed from different continents and the importance to conduct further research studies using potent antifungal drugs. Accordingly, it is imperative to establish stringent surveillance on the increasing prevalence of antifungal resistance particularly in low-income regions with limited research resources to prevent increasing prevalence of MDR-C. auris.

Neurotropic dematiaceous fungi are primary agents of cerebral phaeohyphomycosis, a life-threatening brain infection with high mortality. However, the genomic basis underlying their virulence, stress tolerance, and antifungal resistance is poorly understood. In this study, we present high-quality hybrid genome assemblies of three major neurotropic dematiaceous fungi, Cladophialophora bantiana, Fonsecaea monophora, and Cladosporium cladosporioides, using Nanopore long-read and Illumina short-read sequencing platforms. The assembled genomes ranged from 31.5 to 39.9 Mb, with high completeness (>98.9%). Functional annotation revealed diverse coding and non-coding elements associated with stress responses, iron metabolism, and antifungal resistance. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses uncovered metabolic versatility, enriched xenobiotic degradation pathways, and lineage-specific functional divergence. Notably, C. bantiana and F. monophora exhibited greater genomic plasticity, higher transposable element content, and broader repertoires of virulence factors, extracellular peptidases, and secondary metabolite biosynthetic gene clusters, suggesting enhanced pathogenic potential. All three genera harbored conserved stress tolerance mechanisms, melanin biosynthesis pathways, and pathogenicity-related genes linked to immune evasion and neuroinvasion. Additionally, we identified distinct multidrug efflux transporter families linked to antifungal resistance. Orthology analysis revealed a shared core proteome alongside genus-specific adaptations likely underpinning niche specialization. While the findings highlight critical genomic features driving fungal resilience and neurotropism, functional validation through transcriptomics and phenotypic assays remains essential. Despite current limitations in experimental tractability, this work provides a foundational resource for understanding the molecular basis of fungal pathogenesis and offers valuable targets for future diagnostic and therapeutic strategies against cerebral phaeohyphomycosis and related infections.

The changing epidemiology and diagnostic challenges of coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis in Latin America are reviewed. The agents responsible for these three systemic endemic mycoses are dimorphic fungi from the Onygenales order, all of which are classified as World Health Organization fungal priority pathogens. However, the mycoses they cause span a notable diversity of contrasting etiologies, target populations, geographic distributions, and factors (including climate changes) that determine their incidence. New, updated maps are presented that reflect the current geographical distributions of these systemic endemic mycoses within Latin America, and the epidemiological dynamics that gave rise to them.