Landscape Diversity Related to Buruli Ulcer Disease in Côte d'Ivoire

Buruli ulcer (BU) is one of the most neglected but treatable tropical diseases. The causative organism, Mycobacterium ulcerans, is from the family of bacteria that causes tuberculosis and leprosy. This severe skin disease leads to long-term functional disability if not treated. BU has been reported in over 30 countries mainly with tropical and subtropical climates, but Côte d'Ivoire is one of the most affected countries. M. ulcerans is an environmental bacterium and its mode of transmission to humans is still unclear, such that the disease is often referred to as the “mysterious disease” or the “new leprosy”. Here, we explored the relationship between environmental and socioeconomic factors and BU cases on a nationwide scale. We found that irrigated rice field cultures areas, and, to a lesser extent, banana fields as well as areas in the vicinity of dams used for irrigation and aquaculture purposes, represent high risk zones for the human population to contract BU in Côte d'Ivoire. This work identifies high-risk areas for BU in Côte d'Ivoire and deserves to be extended to different countries. We need now to obtain a global vision and understanding of the route of transmission of M. ulcerans to humans in order to better implement control strategies

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

Facteurs de virulence de champignons filamenteux au cours de la mucoviscidose : l'exemple de la mélanine

Cystic fibrosis is an inherited genetic disorder predisposing to fungal colonization and infection, dominated by the saprophytic filamentous fungi Aspergillus fumigatus and Scedosporium apiospermum without major epidemiologic changes during the last 10 years as shown in this work. Moreover, the therapeutic management of these infections may be complicated by the increasing emergence of A. fumigatus strains resistant to triazole antifungals, the prevalence of which reached 18% in the study period (2015-2019). Besides, the ability of these fungi to establish in humans relies on a set of intrinsic properties or virulence factors that remain poorly elucidated, especially in S. apiospermum. The fungal cell wall is a crucial element in the interaction with the host, via the recognition of surface antigenic motifs, by phagocytic receptors, that initiate fungicidal mechanisms. We showed that the analysis of the transcriptomic response of human macrophages to S. apiospermum infection was a faster and more intense pro-inflammatory cytokinic storm compared to A.-fumigatus, associated to a reduction of the survival of intrama crophagic spores. DiHydroxyNaphthalene (DHN)-melanin is a conserved cell wall pigment, which is thought to be involved in fungal virulence, as initially described in phytopathogenic fungi. The rôle of melanin in S. apiospermum was explored through the phenotypic and transcriptomic characterization of mutants deleted from the PIG1 transcription factor, obtained by CRISPR-Cas9 technology. The albino phenotype of the mutants obtained demonstrated the regulatory role of PIG1 on the enzymatic cascade of DHN-melanin biosynthesis in the spores of S. apiospermum. Finally, this work highlighted the involvement of DHN-melanin in i) the masking of cell wall polysaccharides, ii) the protection of conidia against different abiotic stresses (thermal, oxidative, ionising) and iii) the escape of conidia from fungicidal mechanisms of human macrophages. In summary, fungal melanin is a virulence factor in S. apiospermum, which represents a potential therapeutic target to cure fungal infections.La mucoviscidose est une maladie génétique héréditaire prédisposant aux colonisations et infections fongiques, dominées par les champignons filamenteux saprophytes Aspergillus fumigatus et Scedosporium apiospermum sans modification épidémiologique majeure au cours des 10 dernières années comme nous le montrons dans ce travail. De plus, la prise en charge thérapeutique de ces infections peut être compliquée par l’émergence grandissante d’isolats d’A. fumigatus résistants aux antifongiques triazolés, dont la prévalence atteignait 18% dans la période étudiée (2015-2019). Par ailleurs, la capacité de ces champignons à s’établir chez l’homme repose sur un ensemble de propriétés intrinsèques ou facteurs de virulence qui restent encore peu élucidés, en particulier chez S. apiospermum. La paroi est un élément crucial de l’interaction avec l’hôte, via la reconnaissance de motifs antigéniques présents à sa surface, par les récepteurs phagocytaires, initiant des mécanismes fongicides. L’analyse de la réponse transcriptomique de macrophages humains à l’infection par S. apiospermum a révélé la mise en place d’un orage cytokinique pro-inflammatoire plus rapide et plus intense en comparaison à l’infection par A. fumigatus, associée à une réduction de la survie des spores intra-macrophagiques. La DiHydroxyNaphtalène (DHN)- mélanine est un pigment pariétal conservé, qui interviendrait dans la virulence des champignons, comme initialement décrit chez les champignons phytopathogènes. Le rôle de la mélanine chez S. apiospermum a été exploré, à travers l’étude phénotypique et transcriptomique de mutants délétés du facteur de transcription PIG1, obtenus par technologie CRISPR-Cas9. Le phénotype albinos des mutants obtenus a démontré le rôle régulateur de PIG1 sur la cascade enzymatique de biosynthèse de la DHN-mélanine dans les spores de S. apiospermum. Enfin, ce travail a mis en évidence l’implication de la DHN-mélanine dans i) le masquage des polysaccharides de paroi, ii) la protection des conidies contre différents stress abiotiques (thermique, oxydative, ionisants) et iii) l’échappement des conidies aux mécanismes fongicides de macrophages humains. En résumé, la mélanine fongique est un facteur de virulence chez S. apiospermum, qui constitue une cible thérapeutique potentielle dans la prise en charge des infections fongiques

Virulence factors of filamentous fungi isolated during cystic fibrosis : the example of melanin

La mucoviscidose est une maladie génétique héréditaire prédisposant aux colonisations et infections fongiques, dominées par les champignons filamenteux saprophytes Aspergillus fumigatus et Scedosporium apiospermum sans modification épidémiologique majeure au cours des 10 dernières années comme nous le montrons dans ce travail. De plus, la prise en charge thérapeutique de ces infections peut être compliquée par l’émergence grandissante d’isolats d’A. fumigatus résistants aux antifongiques triazolés, dont la prévalence atteignait 18% dans la période étudiée (2015-2019). Par ailleurs, la capacité de ces champignons à s’établir chez l’homme repose sur un ensemble de propriétés intrinsèques ou facteurs de virulence qui restent encore peu élucidés, en particulier chez S. apiospermum. La paroi est un élément crucial de l’interaction avec l’hôte, via la reconnaissance de motifs antigéniques présents à sa surface, par les récepteurs phagocytaires, initiant des mécanismes fongicides. L’analyse de la réponse transcriptomique de macrophages humains à l’infection par S. apiospermum a révélé la mise en place d’un orage cytokinique pro-inflammatoire plus rapide et plus intense en comparaison à l’infection par A. fumigatus, associée à une réduction de la survie des spores intra-macrophagiques. La DiHydroxyNaphtalène (DHN)- mélanine est un pigment pariétal conservé, qui interviendrait dans la virulence des champignons, comme initialement décrit chez les champignons phytopathogènes. Le rôle de la mélanine chez S. apiospermum a été exploré, à travers l’étude phénotypique et transcriptomique de mutants délétés du facteur de transcription PIG1, obtenus par technologie CRISPR-Cas9. Le phénotype albinos des mutants obtenus a démontré le rôle régulateur de PIG1 sur la cascade enzymatique de biosynthèse de la DHN-mélanine dans les spores de S. apiospermum. Enfin, ce travail a mis en évidence l’implication de la DHN-mélanine dans i) le masquage des polysaccharides de paroi, ii) la protection des conidies contre différents stress abiotiques (thermique, oxydative, ionisants) et iii) l’échappement des conidies aux mécanismes fongicides de macrophages humains. En résumé, la mélanine fongique est un facteur de virulence chez S. apiospermum, qui constitue une cible thérapeutique potentielle dans la prise en charge des infections fongiques.Cystic fibrosis is an inherited genetic disorder predisposing to fungal colonization and infection, dominated by the saprophytic filamentous fungi Aspergillus fumigatus and Scedosporium apiospermum without major epidemiologic changes during the last 10 years as shown in this work. Moreover, the therapeutic management of these infections may be complicated by the increasing emergence of A. fumigatus strains resistant to triazole antifungals, the prevalence of which reached 18% in the study period (2015-2019). Besides, the ability of these fungi to establish in humans relies on a set of intrinsic properties or virulence factors that remain poorly elucidated, especially in S. apiospermum. The fungal cell wall is a crucial element in the interaction with the host, via the recognition of surface antigenic motifs, by phagocytic receptors, that initiate fungicidal mechanisms. We showed that the analysis of the transcriptomic response of human macrophages to S. apiospermum infection was a faster and more intense pro-inflammatory cytokinic storm compared to A.-fumigatus, associated to a reduction of the survival of intrama crophagic spores. DiHydroxyNaphthalene (DHN)-melanin is a conserved cell wall pigment, which is thought to be involved in fungal virulence, as initially described in phytopathogenic fungi. The rôle of melanin in S. apiospermum was explored through the phenotypic and transcriptomic characterization of mutants deleted from the PIG1 transcription factor, obtained by CRISPR-Cas9 technology. The albino phenotype of the mutants obtained demonstrated the regulatory role of PIG1 on the enzymatic cascade of DHN-melanin biosynthesis in the spores of S. apiospermum. Finally, this work highlighted the involvement of DHN-melanin in i) the masking of cell wall polysaccharides, ii) the protection of conidia against different abiotic stresses (thermal, oxidative, ionising) and iii) the escape of conidia from fungicidal mechanisms of human macrophages. In summary, fungal melanin is a virulence factor in S. apiospermum, which represents a potential therapeutic target to cure fungal infections

Molecular diagnosis of Pneumocystis pneumonia in immunocompromised patients

International audiencePurpose of review: Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised patients, who present with severe respiratory distress with low fungal loads. Molecular detection of Pneumocystis in broncho-alveolar lavage (BAL) has become an important diagnostic tool, but quantitative PCR (qPCR) needs standardization.Recent findings: Despite a high negative predictive value, the positive predictive value of qPCR is moderate, as it also detects colonized patients. Attempts are made to set a cut-off value of qPCR to discriminate between PCP and colonization, or to use noninvasive samples or combined strategies to increase specificity.Summary: It is easy to set a qPCR cut-off for HIV-infected patients. In non-HIV IC patients, a gain in specificity could be obtained by combining strategies, that is, qPCR on BAL and a noninvasive sample, or qPCR and serum beta-1,3-D-glucan dosage

Crèche collective ou crèche familiale ? (comparaison des absences des enfants pour cause infectieuse)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Anti-Toxoplasma IgG assays: What performances for what purpose? A systematic review

International audienceChronic infection with Toxoplasma gondii is attested by the detection of specific anti-Toxoplasma IgG. A wide panel of serologic methods is currently marketed, and the most suitable method should be chosen according to the laboratory resources and the screened population. This systematic review of evaluation studies aimed at establishing an overview of the performances, i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of marketed anti-Toxoplasma IgG assays, and discussing their technical characteristics to guide further choice for routine diagnostic use. According to PRISMA guidelines, the search performed in PubMed and Web of Science databases recovered 826 studies, of which 17 were ultimately included. Twenty commercial anti-Toxoplasma IgG assays were evaluated, in comparison with an accepted reference method. Most of them were enzyme-immunoassays (EIAs, n = 12), followed by agglutination tests (n = 4), immunochromatographic tests (n = 3), and a Western-Blot assay (WB, n = 1). The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The PPV was not a discriminant indicator among methods, whereas significant disparities (87.5%–100%) were reported among NPVs, a key-parameter assessing the ability to definitively rule out a Toxoplasma infection in patients at-risk for opportunistic infections

Qu’est-ce que la roue de Sainte Catherine ? Donnez-vous votre langue au chat ?

National audienc

Moisissures dans l’environnement et impacts sur la santé humaine

National audienceExposure to ubiquitous molds in our environment is inevitable in many circumstances: at hospital, at work, at home… and can be responsible for infection and allergy depending on different underlying risk factors.In hospitals, exposure of immunosuppressed patients to filamentous micromycetes such as Aspergillus and mucorales can result in lifethreatening invasive aspergillosis and mucormycosis. Prevention of these infections relies on two possible strategies: chemoprophylaxis and environmental prevention with air treatment and associated measures that allow a « protected area ». At work and at home, recurrent exposure to molds can result in chronic infection or immunoallergic disease. Beside molds, combination of exposure to other microorganisms (such as yeasts, Pneumocystis, bacteria and viruses) as well as to chemical compounds, what we call the exposome, can induce synergistic effects on health (or cocktail effects).Monitoring of the environmental fungal biocontamination is an essential tool for protected areas in hospitals and is also pertinent, using different techniques, to evaluate the fungal risk at home and at work.L’exposition aux moisissures, qui sont ubiquitaires dans notre environnement, est inévitable dans de nombreuses circonstances : à l’hôpital, sur le lieu du travail, au domicile… et peut induire un risque infectieux ou allergique en fonction de différents facteurs prédisposants.À l’hôpital, l’exposition de patients immunodéprimés aux micromycètes filamenteux tels qu’Aspergillus ou les mucorales peut se compliquer d’infections graves telles que les aspergilloses ou les mucormycoses invasives. La prévention de ces infections liées aux soins repose sur deux stratégies possibles : la chimioprophylaxie et la maîtrise du risque environnemental dans des secteurs « protégés » avec traitement de l’air et mesures annexes. Dans le cadre professionnel ou au domicile, l’exposition récurrente et prolongée aux moisissures de l’environnement peut induire des tableaux d’infections chroniques ou immuno-allergiques, en fonction de différents facteurs de susceptibilité de l’hôte. Aux moisissures s’ajoute généralement une exposition plus globale, microbiologique (avec les levures Pneumocystis, les bactéries et les virus) et chimique, constituant l’exposome dans son ensemble avec des risques d’effets synergiques (ou effets cocktails). La surveillance de la biocontamination fongique environnementale est un outil désormais indispensable dans les secteurs dits « protégés » des établissements de santé et peut se révéler pertinente, mais selon des modalités différentes, pour analyser le risque domiciliaire ou professionnel

Un « Eczéma » d’Origine Fongique

International audienc