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The diagnosis of schistosomiasis currently relies on microscopic detection of schistosome eggs in stool or urine samples and serological assays. The poor sensitivity of standard microscopic procedures performed in routine laboratories, makes molecular detection methods of increasing interest. The aim of the study was to evaluate two in-house real-time Schistosoma PCRs, targeting respectively S. mansoni [Sm] and S. haematobium [Sh] in excreta, biopsies and sera as potential tools to diagnose active infections and to monitor treatment efficacy. Schistosoma PCRs were performed on 412 samples (124 urine, 86 stools, 8 biopsies, 194 sera) from patients with suspected schistosomiasis, before anti-parasitic treatment. Results were compared to microscopic examination and serological assays (enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination (HA) and Western Blot (WB) assay). Compared to microscopy, PCRs significantly increased the sensitivity of diagnosis, from 4% to 10.5% and from 33.7% to 48.8%, for Sh in urine and Sm in stools, respectively. The overall sensitivity of PCR on serum samples was 72.7% and reached 94.1% in patients with positive excreta (microscopy). The specificity of serum PCR was 98.9%. After treatment, serum PCR positivity rates slowly declined from 93.8% at day 30 to 8.3% at day 360, whereas antibody detection remained positive after 1 year. Schistosoma PCRs clearly outperform standard microscopy on stools and urine and could be part of reference methods combined with WB-based serology, which remains a gold standard for initial diagnosis. When serological assays are positive and microscopy is negative, serum PCRs provide species information to guide further clinical exploration. Biomarkers such as DNA and antibodies are of limited relevance for early treatment monitoring but serum PCR could be useful when performed at least 1 year after treatment to help confirm a cured infection.

Azole-resistant Aspergillus fumigatus (AR Af ) has emerged worldwide during the last decades. Drug pressure after long term treatments of chronically infected patients and the propagation of environmental clones selected under the pressure of imidazoles fungicides used in agriculture and farming both account for this emergence. The objectives of this study were to determine the rate of azole resistance in Aspergillus fumigatus during a 5-year period, taking into account (i) differences between underlying diseases of the patients treated, (ii) cross-resistance between azoles, and (iii) focusing on the 5-year evolution of our center’s cystic fibrosis cohort. Overall, the rates of voriconazole (VRC)-resistant and itraconazole (ITC)-resistant A. fumigatus isolates were 4.1% (38/927) and 14.5% (95/656), respectively, corresponding to 21/426 (4.9%) and 44/308 (14.3%) patients, respectively. Regarding cross-resistance, among VRC-R isolates tested for ITC, nearly all were R (20/21;95%), compared to only 27% (20/74) of VRC-R among ITC-R isolates. The level of azole resistance remained somewhat stable over years but greatly varied according to the azole drug, patient origin, and clinical setting. Whereas azole resistance during invasive aspergillosis was very scarce, patients with cystic fibrosis were infected with multiple strains and presented the highest rate of resistance: 5% (27/539) isolates were VRC-R and 17.9% (78/436) were ITC-R. These results underline that the interpretation of the azole resistance level in Aspergilllus fumigatus in a routine setting may consider the huge variability depending on the azole drug, the clinical setting, the patient background and the type of infection.

Filamentous fungi frequently colonize the airways of patients with cystic fibrosis and may cause severe diseases, such as the allergic bronchopulmonary aspergillosis. The most common filamentous fungi capable to chronically colonize the respiratory tract of the patients are Aspergillus fumigatus and Scedosporium species. Defining the treatment strategy may be challenging, the number of available drugs being limited and some of the causative agents being multiresistant microorganisms. The knowledge of the fungal niches in the outdoor and indoor environment is needed for understanding the origin of the contamination of the patients. In light of the abundance of some of the causative molds in compost, agricultural and flower fields, occupational activities related to such environments should be discouraged for patients with cystic fibrosis (CF). In addition, the microbiological monitoring of their indoor environment, including analysis of air and dust on surfaces, is essential to propose preventive measures aiming to reduce the exposure to environmental molds. Nevertheless, some specific niches were also identified in the indoor environment, in relation with humidity which favors the growth of thermotolerant molds. Potted plants were reported as indoor reservoirs for Scedosporium species. Likewise, Exophiala dermatitidis may be spread in the kitchen via dishwashers. However, genotype studies are still required to establish the link between dishwashers and colonization of the airways of CF patients by this black yeast. Moreover, as nothing is known regarding the other filamentous fungi associated with CF, further studies should be conducted to identify other potential specific niches in the habitat.

(1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU) remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluated Aspergillus PCR input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45 COVID-19 patients were prospectively monitored twice weekly for Aspergillus markers and anti-Aspergillus serology. We evaluated the concordance between (I) Aspergillus PCR and culture in respiratory samples, and (II) blood PCR and serum galactomannan. Patients were classified as putative/proven/colonized using AspICU algorithm and two other methods. (3) Results: The concordance of techniques applied on respiratory and blood samples was moderate (kappa = 0.58 and kappa = 0.63, respectively), with a higher sensitivity of PCR. According to AspICU, 9/45 patients were classified as putative IA. When incorporating PCR results, 15 were putative IA because they met all criteria, probably with a lack of specificity in the context of COVID-19. Using a modified AspICU algorithm, eight patients were classified as colonized and seven as putative IA. (4) Conclusion: An appreciation of the fungal burden using PCR and Aspergillus serology was added to propose a modified AspICU algorithm. This proof of concept seemed relevant, as it was in agreement with the outcome of patients, but will need validation in larger cohorts.

Schistosomiasis is a major public health issue for migrants. This study aims to describe the clinical presentation and management of imported schistosomiasis in France. We included all new cases of schistosomiasis in patients aged ≥18 years, defined by a positive specific Western blot and/or a positive parasitological analysis of urine, stool or biopsy, between January 1, 2016, and December 31, 2019, in 4 laboratories in Paris and Western France. Over the study period, 532 patients were included. Mean age was 37 years (18–91), and 461/532 (87 %) were men. Among 476/532 (89 %) patients born in an endemic area, 433 (91 %) were born in sub-Saharan Africa. Most of the patients (405/532, 76 %) had only a positive serology, and 127/532 (24 %) had ova on microscopic examination. Among 361/532 (68 %) who had at least one urine, stool or biopsy analysis, microscopic analysis was positive in 127 (35 %). Imaging showed lesions compatible with schistosomiasis in 88/164 (54 %) patients with clinical symptoms and 13/29 (45 %) patients without (p = 0.5). Patients who arrived in France less than one year before diagnosis were more likely to have clinical symptoms than those who arrived in France 1–5 years and >5 years prior to diagnosis (52 %, 41 % and 43 %, respectively, p = 0.03). Two-hundred and seventeen patients (40.8 %) were left untreated. Approximately 50 % of patients with imported chronic schistosomiasis have radiological abnormalities, whether they are symptomatic or not, and management is heterogeneous. Multidisciplinary international guidelines are requested to clarify the management of this neglected disease.

The indoor air quality of healthcare and care facilities is poorly studied. The aim of this study was to qualitatively and quantitatively describe the chemical pollution and the microbiological contaminations of the indoor environment of these facilities. Methods: A wide range of chemical compounds (39 volatile and 13 semi-volatile organic compounds, carbon dioxide, fine particulate matter) and microorganisms (fungi and bacteria) were studied. Sampling campaigns were conducted in two French cities in summer 2018 and winter 2019 in six private healthcare facilities (general practitioner’s offices, dental offices, pharmacies) and four care facilities (nursing homes). Results: The highest median concentrations of chemical compounds (μg/m3) were measured for alcohols (ethanol: 378.9 and isopropanol: 23.6), ketones (acetone: 18.8), aldehydes (formaldehyde: 11.4 and acetaldehyde: 6.5) and terpenes (limonene: 4.3). The median concentration of PM2.5 was 9.0 µg/m3. The main bacteria of these indoor environments were Staphylococcus, Micrococcus and Bacillus genera, with median bacterial concentrations in the indoor air of 14 cfu/m3. The two major fungal genera were Cladosporium and Penicillium, with median fungal concentrations of 7 cfu/m3. Conclusions: Indoor air in healthcare and care facilities contains a complex mixture of many pollutants found in higher concentrations compared to the indoor air in French hospitals in a previous study.

Humoral immune components have been individually studied in the context of interaction of host with Aspergillus fumigatus , a major airborne fungal pathogen. However, a global view of the multitude and complex nature of humoral immune components is needed to bring new insight into host- Aspergillus interaction. Therefore, we undertook comparative proteomic analysis of the bronchoalveolar lavage fluid collected from individuals infected or colonized with A. fumigatus versus controls, to identify those alveolar humoral components affected upon A. fumigatus infection. Complement proteins C1q, C8 beta-chain, factor-H, ficolin-1, ficolin-2, mannan binding lectin serine peptidase 2, pentraxin-3 and the surfactant protein-D were identified as the major humoral immune components affected by A. fumigatus infection and colonization. Based on this observation, we hypothesize that crosstalk between these humoral components is essential during host- Aspergillus interaction giving new specific leads to study for better understanding the pathogenesis. Furthermore, the affected humoral components could be potential diagnostic markers of A. fumigatus infection or colonization.

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.

The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P  = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P  = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% ( P  < 0.0001). Yeast fungemia ( n  = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia ( n  = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P  < 0.0001). Invasive aspergillosis ( n  = 1,661) and mucormycosis ( n  = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P  = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools. IMPORTANCE The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired in vitro resistance in France. Therefore, other tracks of improvement should be investigated actively.

Scedosporium apiospermum is a saprophytic filamentous fungus involved in human infections, of which the virulence factors that contribute to pathogenesis are still poorly characterized. In particular, little is known about the specific role of dihydroxynaphtalene (DHN)-melanin, located on the external layer of the conidia cell wall. We previously identified a transcription factor, PIG1, which may be involved in DHN-melanin biosynthesis. To elucidate the role of PIG1 and DHN-melanin in S. apiospermum, a CRISPR-Cas9-mediated PIG1 deletion was carried out from two parental strains to evaluate its impact on melanin biosynthesis, conidia cell-wall assembly, and resistance to stress, including the ability to survive macrophage engulfment. ΔPIG1 mutants did not produce melanin and showed a disorganized and thinner cell wall, resulting in a lower survival rate when exposed to oxidizing conditions, or high temperature. The absence of melanin increased the exposure of antigenic patterns on the conidia surface. PIG1 regulates the melanization of S. apiospermum conidia, and is involved in the survival to environmental injuries and to the host immune response, that might participate in virulence. Moreover, a transcriptomic analysis was performed to explain the observed aberrant septate conidia morphology and found differentially expressed genes, underlining the pleiotropic function of PIG1.