Les mycotoxines présentes dans les supports papiers

La présence de moisissures dans les bioaérosols est une constante, aussi bien dans les environnements professionnels que domestiques. Des toxines sont présentes au niveau des spores fongiques et peuvent atteindre directement les épithéliums respiratoires. Cependant, toutes les espèces ne produisent pas les mêmes toxines et certaines peuvent se succéder sur un support donné sans pour autant être présentes simultanément. Le projet visait à identifier et quantifier certaines mycotoxines présentes dans des supports naturellement contaminés (papiers peints de logements insalubres et manuscrits de collection), de relier leur présence à celle d’espèces fongiques et d’évaluer la cytotoxicité des mycotoxines sur des modèles in vitro d’épithélium respiratoire développés dans le cadre du projet

The geography of French creative class: An exploratory spatial data analysis

This paper analyses the creative class geography in France, in 2006. This geography is seen here through the lens of Explanatory Spatial Data Analysis (ESDA). This method brings originality to the question of creative people geography in addition to the spatial context, France, where this question hasn’t been deepened yet. Methodology allows measurement of spatial agglomeration degree and identification of creative people location patterns. First, by computing locational Gini index and Moran’s I statistic of global spatial autocorrelation. These measures provide an overview of the spatial distribution of creative people among French districts and the existence of some hotspot regions with strong dynamic of creative people accumulation. Second, Exploratory Spatial Data Analysis (ESDA) tools, such as Moran scatterplot and LISA statistics, allow to identify district clusters of creative people. It leads to evidence that creative people are unevenly geographically distributed across French districts. District clusters of creative occupations result from spreading of French largest cities influence.Creative class, ESDA, location patterns, spatial autocorrelation, French districts

Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model

International audienceBACKGROUND: The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking.METHODS: We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus.RESULTS: The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). CONCLUSIONS: The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay

Uniform distribution of three Candida albicans microsatellite markers in two French ICU populations supports a lack of nosocomial cross-contamination

BACKGROUND: The nosocomial acquisition of Candida albicans is a growing concern in intensive care units (ICUs) and understanding the route of contamination is relevant for infection control guidelines. METHODS: To analyze whether there is a specific ecology for any given hospital, we genotyped C. albicans isolates of the ICU of Versailles hospital (Hospital A) and compared the results with those previously obtained in another ICU in Henri Mondor hospital (Hospital B) using three polymorphic microsatellite markers (PMM). RESULTS: Among 36 patients with at least one positive culture for C. albicans, 26 had a specific multilocus genotype, two shared a common multilocus genotype, and 8 had the most common multilocus genotype found in the general population. The time interval between periods of hospitalization between patients with common genotypes differed by 13 to 78 days, thus supporting a lack of direct contamination. To confirm this hypothesis, the multilocus genotypic distributions of the three PMM were compared between the two hospitals. No statistically significant difference was observed. Multiple correspondences analysis did not indicate the association of a multilocus genotypic distribution with any given hospital. CONCLUSION: The present epidemiological study supports the conclusions that each patient harbours his/her own isolate, and that nosocomial transmission is not common in any given ICU. This study also supports the usefulness and practicability of PMM for studying the epidemiology of C. albicans

Continuous Decline of Toxoplasma gondii Seroprevalence in Hospital: A 1997–2014 Longitudinal Study in Paris, France

Background: The protozoan Toxoplasma gondii presents a risk for reactivation of latent cysts in immunocompromised patients. Anti-T. gondii antibodies are therefore usually screened before chemotherapy or transplantation to propose prophylactic measures against this parasite. We analyzed the results obtained in our hospital to study the epidemiological trend of T. gondii infection.Methods: We collected all the anti-Toxoplasma antibody titers from January 1, 1997 to December 31, 2013 using the Platelia IgG ELISA assay (Bio-Rad). The results were classified as positive when titers reached a concentration of ≥10 UI/ml. Only the first result obtained at entry for each patient was considered. T. gondii seroprevalence was estimated using a multivariate logistic regression model accounting for age, sex, and year in which the sample was collected.Results: A total of 21,480 patient samples were analyzed. The seroprevalence continuously decreased over time, from 64.5% in 1997 to 54.7% in 2013 (i.e., an average of 1.3% per year, p < 0.001). The decrease was 5.0% per year for patients <20 years. After 2013, the model predicts that the seroprevalence would continuously decrease. We also observed a higher proportion of seropositive men than women in the 15- to 45-year-old group (58.5% versus 52.0%, p < 10-3).Conclusion: The overall seroprevalence of toxoplasmosis at our hospital showed an accelerating downward trend over 17 years. The reason for this continuous decline is likely associated with the lower parasite presence within meat. Thus, although young immunocompromised patients are increasingly less at risk of reactivation in the near future, older immunocompromised patients will remain at high risk of reactivation. The reasons of the higher prevalence in men remain to be explored

Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro

<p>Abstract</p> <p>Background</p> <p>Invasive aspergillosis, which is mainly caused by the fungus <it>Aspergillus fumigatus</it>, is an increasing problem in immunocompromised patients. Infection occurs by inhalation of airborne conidia, which are first encountered by airway epithelial cells. Internalization of these conidia into the epithelial cells could serve as a portal of entry for this pathogenic fungus.</p> <p>Results</p> <p>We used an <it>in vitro </it>model of primary cultures of human nasal epithelial cells (HNEC) at an air-liquid interface. <it>A. fumigatus </it>conidia were compared to <it>Penicillium chrysogenum </it>conidia, a mould that is rarely responsible for invasive disease. Confocal microscopy, transmission electron microscopy, and anti-LAMP1 antibody labeling studies showed that conidia of both species were phagocytosed and trafficked into a late endosomal-lysosomal compartment as early as 4 h post-infection. In double immunolabeling experiments, the mean percentage of <it>A. fumigatus </it>conidia undergoing phagocytosis 4 h post-infection was 21.8 ± 4.5%. Using combined staining with a fluorescence brightener and propidium iodide, the mean rate of phagocytosis was 18.7 ± 9.3% and the killing rate 16.7 ± 7.5% for <it>A. fumigatus </it>after 8 h. The phagocytosis rate did not differ between the two fungal species for a given primary culture. No germination of the conidia was observed until 20 h of observation.</p> <p>Conclusion</p> <p>HNEC can phagocytose fungal conidia but killing of phagocytosed conidia is low, although the spores do not germinate. This phagocytosis does not seem to be specific to <it>A. fumigatus</it>. Other immune cells or mechanisms are required to kill <it>A. fumigatus </it>conidia and to avoid further invasion.</p

Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells

BACKGROUND: The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds. RESULTS: We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10(-8 )M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts. CONCLUSION: Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined