The antemortem diagnosis of aspergillosis in birds remains a complex challenge. A variety of diagnostic methods are currently available, including direct detection of Aspergillus components, antibody-based assays, and nonspecific markers such as serum protein electrophoresis (SPE), but their diagnostic performances remain limited. The objective of this study was to assess and compare the performances of several diagnostic approaches, specifically, galactomannan index measurement, beta-D-glucan assay, 3-hydroxybutyrate quantification, SPE, and mannoprotein detection tests. A secondary objective was to develop a predictive model of aspergillosis incorporating optimal test thresholds identified in the first phase, combined with clinical signs. A total of 101 serum and 31 plasma samples were collected from 118 aquatic bird of various species in France. Birds were classified into three categories: control individuals (n = 88), suspected aspergillosis cases (n = 7), and confirmed cases (n = 23). While individually considered tests displayed limitations in specificity, predictive modeling revealed that elevated levels of 3-hydroxybutyrate above 0.52 mmol/L (Se = 96%, Sp = 51%) combined with beta-globulins above 6.90 g/L (Se = 78%, Sp = 51%), in conjunction with concurrent respiratory clinical signs, were significantly associated with the occurrence of aspergillosis. A multivariable logistic model combining these variables achieved excellent diagnostic performance, with AUCs up to 0.98 and sensitivity above 98%. These findings suggest that these parameters, particularly when considered alongside clinical signs, may serve as more reliable indicators for detecting aspergillosis in birds.

Wickerhamomyces anomalus is a yeast rarely involved in human invasive fungal diseases (IFD). We retrospectively analyzed 44 episodes of W. anomalus IFD in France during 2012–2024. Injecting drug use (IDU) was the main risk factor among 26/35 (74.3%) incident cases. Most infections were community acquired; overall 3-month mortality rate was 1/30 (3.3%). Short tandem repeat (STR) genotyping and whole-genome sequencing analyses revealed substantial genetic diversity among isolates. However, 1 STR genotype was shared by 2 IDU patients, suggesting common exposure. In addition, 1 isolate obtained from a cotton filter used for drug preparation was identical by STR genotyping to the bloodstream isolate from the same patient, indicating direct inoculation via contaminated material or poor injection practices. Our findings highlight the increased risk for W. anomalus IFD among IDU patients and emphasize the importance of targeted preventive measures within that population.

Background . Fungal bone and joint infections (BJIs) are rare, and their epidemiology and clinical outcomes remain unclear. Methods . We conducted a retrospective multicentric cohort study of patients diagnosed with fungal BJIs between 2014 and 2021 in six hospitals in Western France. Results . We included 103 patients with fungal BJIs : median age was 66 [interquartile range, 51-73] years, 66% (68/103) were male, and 23% (24/103) were immunosuppressed. There were 39% (40/103) implant-associated BJIs. Yeast BJIs represented 81% (83/103) of cases, with Candida albicans (54/83, 65%) being the leading pathogen. Mold BJIs were mostly due to Aspergillus fumigatus (10/20, 50%). Co-infection with bacteria was found in 60% (62/103) of cases. The most frequent surgical procedure was debridement (52/103, 50%). Fluconazole was prescribed for 82% (68/83) of patients with yeast BJIs, whereas voriconazole (16/20, 80%) was mainly used for mold BJIs. Antifungal therapy was administered for a median of 91 [42-180] days. Failure of fungal BJI treatment was observed in 27% (28/103), and two-year all-cause mortality was 21% (22/103). Patients suffered from sequelae in 62% (50/81) with a high rate of disability (38/81, 47%). Conclusions . Fungal BJIs represent a wide range of infections associated with a poor prognosis.

BACKGROUND:Ibrutinib is a recognized risk factor for invasive fungal disease (IFD) recognized in the 2019 revised criteria of the European Organisation for Research and Treatment of Cancer. Cerebral aspergillosis (CA) under ibrutinib has been relatively frequently reported, but its particular characteristics remain insufficiently described. METHODS:The CEREALS study was a nationwide retrospective cohort of 119 patients diagnosed with CA between 2006 and 2018. We analysed 10 patients who developed CA following ibrutinib therapy and compared their clinical, radiological and outcome data with those of other patients with haematological malignancies from this cohort. RESULTS:Nine patients received ibrutinib for chronic lymphocytic leukaemia and one for diffuse large B-cell lymphoma after a median of two prior treatment lines. None received anti-mould prophylaxis, although 80% of them presented additional IFD risk factors. CA occurred a median of 2.9 months after ibrutinib initiation. All cases resulted from haematogenous dissemination, with extracerebral involvement in 70% of the patients, mostly the lungs. Brain imaging revealed supratentorial abscesses without meningeal involvement in all patients, typically manifesting with focal neurological deficits. Serum galactomannan was positive in 33% of tested patients, exclusively in neutropenic individuals. Six-week mortality was 40%. Compared with other haematological malignancy patients in the CEREALS cohort, ibrutinib-associated CA showed exclusive haematogenous spread, infrequent serum galactomannan positivity and lower mortality (40% versus 62%). CONCLUSIONS:Cerebral aspergillosis during ibrutinib therapy shows particular features. An invasive microbiological workup is often required, as serum galactomannan appears to have limited sensitivity in this context.

Résumé L’alternariose constitue une infection opportuniste due à des moisissures pigmentées du genre Alternaria, ubiquitaire dans l’environnement. Elle survient surtout chez les patients immunodéprimés, en premier lieu les transplantés rénaux, mais aussi beaucoup plus rarement chez des sujets immunocompétents après inoculation cutanée traumatique. La présentation est dominée par des atteintes cutanées et sous-cutanées (nodules, plaques infiltrées, ulcérations des zones exposées), plus rarement respiratoires. Le diagnostic repose sur la réalisation de prélèvements superficiels ou profonds, l’examen direct montrant des filaments septés et pigmentés, et la culture des colonies brun-noir ; une confirmation moléculaire peut être utile. L’interprétation doit rester prudente car Alternaria demeure un contaminant fréquent. La prise en charge associe le plus souvent un azolé (itraconazole ou voriconazole), une exérèse chirurgicale des lésions localisées si possible, et une réduction de l’immunosuppression ; l’évolution est généralement favorable mais des rechutes sont possibles.

Wickerhamomyces anomalus is a yeast rarely involved in human invasive fungal diseases (IFD). We retrospectively analyzed 44 episodes of W. anomalus IFD in France during 2012-2024. Injecting drug use (IDU) was the main risk factor among 26/35 (74.3%) incident cases. Most infections were community acquired; overall 3-month mortality rate was 1/30 (3.3%). Short tandem repeat (STR) genotyping and whole-genome sequencing analyses revealed substantial genetic diversity among isolates. However, 1 STR genotype was shared by 2 IDU patients, suggesting common exposure. In addition, 1 isolate obtained from a cotton filter used for drug preparation was identical by STR genotyping to the bloodstream isolate from the same patient, indicating direct inoculation via contaminated material or poor injection practices. Our findings highlight the increased risk for W. anomalus IFD among IDU patients and emphasize the importance of targeted preventive measures within that population.

Members of the microsporidial genus Encephalitozoon have the capacity to infect both mammals and birds, and E. cuniculi is most commonly found in rabbits. With a seroprevalence ranging up to 85%, E. cuniculi can be a problem in pet rabbits as well as in food production and laboratory animal science. While most infections are likely subclinical, there are three main clinical presentations: neurological, renal, and ocular. Typical clinical signs including vestibular disease and phacoclastic uveitis may develop with initial or relapsing infection, while renal infection is usually progressive and associated with non-specific clinical signs. High-sensitivity/specificity ante mortem diagnostic options are lacking, and serological testing most often provides adjunct rather than definitive information such that physical examination and other diagnostics are used more so for ruling out other differentials and comorbidities, rather than confirming infection. In the veterinary community, treatment regimens are variable given the lack of thorough studies and a consensus. The aim of this document is to present the available literature to give a concise review of this organism and its infection of rabbits as well as to propose guidelines and protocols for diagnostics and treatment regimens. In addition, the current challenges and recommendations for further studies are discussed.

Invasive fungal diseases are life-threatening complications, particularly in immunocompromised patients, and require rapid and accurate diagnosis to improve clinical outcomes. Although major advances in fungal diagnostics that includes antigen detection, molecular assays, and Matrix-Assisted Laser Desorption/Ionization - Time Of Flight (MALDI-TOF) mass spectrometry, have transformed diagnostic strategies, access to these tools remains heterogeneous. In France, national data on diagnostic capacities for invasive fungal diseases have been lacking. Using the framework of the national prospective surveillance program for invasive fungal diseases (SINFONI network), we conducted a survey to assess laboratory diagnostic practices in France. A secured 116-item questionnaire was distributed to 58 participating laboratories, of which 48 responded (83%). Automated blood culture systems and MALDI-TOF mass spectrometry for yeast identification were universally available, with 40 (83%) of the 48 participating laboratories also using MALDI-TOF for mould identification. Antifungal susceptibility testing was performed on-site in 47 (98%) centres for yeasts and in 37 (77%) for moulds. Antigen-based biomarkers were widely available on-site, particularly cryptococcal antigen (n = 43, 90%) and Aspergillus galactomannan (n = 39, 81%), whereas β-D-glucan testing was available in only 26 (54%) of the centres. PCR-based diagnostics were implemented on-site in 43 (88%) centres, most commonly for Pneumocystis jirovecii, Aspergillus spp., and Mucorales. Systematic screening for Candidozyma auris colonization in at-risk patients was performed in 30 (63%) centres, predominantly using culture-based methods (n = 24). Overall, this survey provides the first national overview of diagnostic capacities for invasive fungal diseases in France, highlighting a strong laboratory mycology infrastructure while identifying remaining gaps in access to specific biomarkers, molecular assays, and mould antifungal susceptibility testing.

The European Confederation of Medical Mycology Candida III was a pan-European, multicenter observational study of adult patients with blood culture-proven candidemia. Among a total of 632 patients with candidemia across 64 institutions in 20 European countries, a subanalysis of 396 (63%) cases occurring outside the intensive care unit (ICU) was conducted. Compared with ICU patients, non-ICU patients had a higher comorbidity burden (median Charlson comorbidity index [CCI] 6 vs 5 in ICU patients, P = .006). Hematologic and oncologic malignancies were more frequent among non-ICU cases (45.5% vs 28.4%, P < .001), whereas both chronic kidney and cardiovascular disease were more prevalent in ICU patients (P < .001). Non-ICU patients had significantly lower mortality in Kaplan-Meier survival analysis (P > .001). Postsurgical non-ICU patients (n = 45) had the highest survival rate (73.3%, P = .003) and the longest hospital stay, even after excluding all cases with a fatal outcome before day 30. In non-ICU patients, older age, hemato-oncologic malignancies, chronic liver disease, and COVID-19 were all independently associated with mortality risk, while treatment consultation by an infectious disease or clinical microbiology consultant, and initial treatment with an echinocandin, respectively, higher EQUAL Candida scores were associated with lower mortality risk in the multivariable Cox regression models. In conclusion, despite higher comorbidity rates, non-ICU patients with candidemia had higher survival rates.

BACKGROUND:Pneumocystis pneumonia (PCP) is a well-known infectious complication of organ transplantation requiring prophylaxis at least within the first 6 month to 1 year post transplantation. RESEARCH QUESTION:Few data exist comparing the characteristics of Pneumocystis pneumonia associated with kidney, heart, liver or lung transplant recipients. STUDY DESIGN & METHOD:We here conducted a cross-sectional study nested within the surveillance of our national reference center for invasive mycoses to analyze the prospectively declared cases of PCP occurring in solid organ transplant recipients over a period of 11 years. RESULTS:We found that the median occurrence of PCP post-transplantation varies from the organ recipients with PCP occurring earlier in liver recipients and later in other organs reaching a median of 3.9 years in kidney recipients. We also found a clear increase the proportion of positive mycological criteria in PCP cases occurring within 2 years post-transplantation. Age and ICU hospitalization were major variables associated with 3 month-mortality with liver and lung recipient having a better outcome than renal transplant patients upon adjustment including age. A trend toward the role of additional risk factors (such as HIV, Cancer of hematological malignancy) in the outcome of PCP was also observed. INTERPRETATION:Altogether, this study described on a large patient cohort, some key mycological and clinical information associated with PCP in solid organ transplant patients. The characteristics of PCP in kidney and heart recipients seems similar.

Penicillium, Talaromyces, and Purpureocillium species (so called Penicillium-like) are increasingly recognised as opportunistic fungal pathogens capable of causing a wide range of infections, from superficial to invasive. Although ocular infections caused by these environmental fungi have been reported in the literature, they remain relatively underrecognised. We conducted a multicentric retrospective study of Penicillium-like ocular cases reported in the RESeau de Surveillance des Infections Fongique (RESSIF) database of the French National Reference Center for Invasive Mycoses and Antifungals between 2012 and 2021. Among 55 cases of Penicillium-like invasive infections reported to the RESSIF network in France, a total of 24 cases (44%) were identified, which predominantly presented as keratitis (n = 22, 92%). Predisposing factors were as follows: contact lens wear (n = 11, 46%), topical corticosteroid use (n = 9, 37.5%), ocular trauma (n = 5, 21%), pre-existing corneal disease (n = 4, 17%), and previous ocular surgery (n = 2, 8%). Purpureocillium lilacinum was the predominant pathogen (n = 19, 79%), followed by four Penicillium species and one Talaromyces species. Direct examination of ocular samples was positive in 13 cases (54%). Antifungal susceptibility testing (European Committee on Antimicrobial Susceptibility Testing) revealed that all species exhibited high minimal inhibitory concentrations to amphotericin B (> 1 mg/l). Most patients were treated with a combination of topical voriconazole and amphotericin B (n = 15, 62.5%), which was administered alongside oral voriconazole in nine cases (37.5%). Surgical intervention was required in six cases (25%) and included keratoplasty (n = 4) and enucleation (n = 2). This study provides a valuable overview of Penicillium-like fungal ocular infections and highlights the importance of systematically surveilling filamentous fungal keratitis.

Invasive aspergillosis (IA) caused by Aspergillus flavus remains poorly described. We retrospectively analyzed 54 cases of IA caused by A. flavus reported in France during 2012-2018. Among cases, underlying IA risk factors were malignancy, solid organ transplantation, and diabetes. Most (87%, 47/54) infections were localized, of which 33 were pleuropulmonary and 13 were ear-nose-throat (ENT) infection sites. Malignancy (70% [23/33]) and solid organ transplantation (21% [7/33]) were the main risk factors in localized pulmonary infections, and diabetes mellitus was associated with localized ENT involvement (61.5%, [8/13]). Fungal co-infections were frequent in pulmonary (36%, 12/33) but not ENT IA (0 cases). Antifungal monotherapy was prescribed in 45/50 (90%) cases, mainly voriconazole (67%, 30/45). All-cause 30-day case-fatality rates were 39.2% and 90-day rates were 47.1%, and rates varied according to risk factor, IA site, and fungal co-infections. Clinicians should remain vigilant for A. flavus and consider it in the differential diagnosis for IA.

Fungal infection, especially allergic bronchopulmonary aspergillosis, is a leading cause of infection-associated morbidity and death in patients with cystic fibrosis. We have previously discovered that the new leading treatment in cystic fibrosis, CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor (ETI, Trikafta), drastically reduces the colonization and infection by Aspergillus fumigatus. However, the reasons for this decrease in patients are not known so far. In this study, we have shown, using A. fumigatus reference strains and strains isolated from patients with cystic fibrosis, that CFTR modulators have no discernible impact on initial conidia growth in vitro. However, in a condition-dependent manner, we demonstrated a decrease in the minimal effective concentration (MEC) of caspofungin when administered with ETI on conidia. By contrast, during macrophage infection, we observed that high concentrations of ETI treatment promoted fungal growth but inhibited inflammasome activation.IMPORTANCEThe advent of ETI therapy represents a pivotal moment, signaling the onset of major changes in the medical field of cystic fibrosis and its related infectious diseases. However, the impact of ETI treatment on the patient's microbiota and pathogens has to be further studied as proof arises of changes in patient colonization.

The host innate immune system provides the first line of protection against invading microbial pathogens, including fungi. Recognition of fungi by host pattern-recognition receptors (PRRs) is critical for their clearance. PRRs bind to pathogen-associated molecular patterns (PAMPs) that can be present on the fungal surface, secreted by them, or found in their genetic material, but also damage-associated molecular patterns (DAMPs) released by host cells as a result of fungal infection. These receptors can be located at the cell surface, the endosome, or in the cytosol of host cells. Depending on PRR location and the nature of the molecular patterns (PAMPs/DAMPs) they recognize, their activation induces specific signaling pathways culminating in tailored immune responses. There are two families of innate immune receptors that can principally sense fungi, namely membrane-bound Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). In addition, as phagocytosed fungal pathogens can escape the phagolysosome and reach the cytoplasm, cytosolic sensors such as Nod-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are also important in fungal sensing and play essential roles in antifungal host protection. This review summarizes the cytosolic receptors and the signaling pathways involved in antifungal innate immunity.