Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
The sources of exposure during diseases due to Aspergillus fungi in cystic fibrosis patients are still poorly explored. We assessed home fungal exposure in patients suffering from cystic fibrosis and analysed its impact on the presence of Aspergillus biological markers, the colonisation of airways, as well as the sensitization and Aspergillus serology. Between March 2012 and August 2012, 34 patients benefited from a visit performed by a home environment medical adviser including sampling for mycological analysis. The number of colonies of Aspergillus was not significantly different in the various sampling sites (P = 0.251), but the number of non-Aspergillus colonies was much higher in the kitchen (P = 0.0045). Subsequently, home fungal exposure was compared between the groups “absence of Aspergillus-related markers” and “presence of Aspergillus-related markers”. Home exposure to Aspergillus (P = 0.453) and non-Aspergillus (P = 0.972) flora was not significant between the 2 groups. Within this series of 34 patients that should be expanded, we note an absence of clear relationship between home exposure and the Aspergillus-linked markers in patients suffering from cystic fibrosis. This result should be taken into account regarding too restrictive hygiene advices provided to families, given the fact that fungal exposure can also results from activities performed away from home.
La source d’exposition au cours des pathologies aspergillaires du patient atteint de mucoviscidose reste encore peu explorée. Nous avons évalué l’exposition fongique domiciliaire chez des patients atteints de mucoviscidose, et analysé son impact sur la présence de marqueurs biologiques aspergillaires, colonisation des voies aériennes, ainsi que sensibilisation et sérologie anti-aspergillaire. Trente-quatre patients ont bénéficié d’une visite par un conseiller médical en environnement intérieur entre mars et août 2012, comprenant des prélèvements à visée mycologique. Le nombre de colonies aspergillaires ne différait pas significativement d’un site de prélèvement à l’autre (p = 0,251), mais le nombre de colonies non aspergillaires était significativement plus important dans la cuisine (p = 0,0045). L’exposition fongique domiciliaire a ensuite été comparée entre les groupes « marqueurs aspergillaires absents » et « marqueurs aspergillaires présents ». L’exposition domiciliaire à une flore aspergillaire (p = 0,453) et non aspergillaire (p = 0,972) ne différait pas significativement entre les 2 groupes. Sur cette série de 34 patients qui mérite d’être élargie, on note une absence de lien évident entre l’exposition domiciliaire et la pathologie aspergillaire. Ce résultat doit rendre prudent sur des conseils d’hygiène parfois très contraignants donnés aux familles, l’exposition fongique étant également importante dans le cadre des activités extra-domiciliaires.
ISSN: 1156-5233

hal-01158660
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660/file/Exposition%20domiciliaire%20aux%20moisissures%20postprint%20MYCMED-S-14-00173.pdf
DOI : 10.1016/j.mycmed.2015.03.005

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial EIA (Bordier Affinity Products) with those of the Bio-Rad and VirionSerion EIAs. This assay is novel in the association of two recombinant antigens with somatic and metabolic antigens of A. fumigatus. In a prospective multicentre study, 436 serum samples from 147 patients diagnosed with CPA (136 sera/104 patients) or ABPA (94 sera/43 patients) and from 205 controls (206 sera) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad and VirionSerion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (p < 0.01), which was itself more sensitive than the VirionSerion kit (p=0.04). The Bordier and Bio-Rad kits had similar specificities (p=0.8), both higher than that of the VirionSerion kit (p=0.02). The areas under the ROC curves confirmed the superiority of the Bordier kit over the Bio-Rad and the VirionSerion kits (0.977, 0.951 and 0.897, respectively; p < 0.01 for each comparison). In a subset analysis of 279 sera tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; p=0.10).The use of recombinant, somatic and metabolic antigens in a single EIA improved the balance between sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
ISSN: 0095-1137

hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/file/Prospective%20evaluation%20of%20a%20new%20Aspergillus.pdf
DOI : 10.1128/JCM.03261-15

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
La détection d’Aspergillus dans le liquide bronchiolo-alvéolaire (LBA) est un des critères du diagnostic probable ou prouvé de l’aspergillose invasive (AI). Parallèlement à l’examen mycologique (ED et/ou culture) et à la détection de l’antigène galactomannane (GM) identifiés comme critères EORTC/MSG du diagnostic d’AI probable (de Pauw 2008), la PCR sur prélèvements pulmonaires est devenue un argument majeur du diagnostic de routine. Plusieurs méthodes d’amplification ont été publiées et l’objectif de ce travail était d’évaluer les performances de 2 cibles d’amplification : le gène mitochondrial d’A. fumigatus (AFmito) et l’ARN ribosomal 28S. Entre 01/2012 et 10/2015, 324 LBA ont été prospectivement collectés et analysés sur le plan mycologique (ED et culture) et ont bénéficié d’une détermination du GM (EIA Platelia assay Biorad, seuil à 1,0 si mesure isolée dans le LBA, ou 0,8 si associée à une mesure dans le sérum > 0,5) et d’une PCR AFmito. Puis rétrospectivement, un test PCR 28S a été effectué sur les ADN extraits disponibles (312/324). Selon les critères EORTC/MSG modifiés de 2008, les patients testés étaient classés comme suit : 1 AI prouvée, 47 AI probables et 11 AI possibles. Les autres patients étaient considérés comme 11 colonisés, et 256 non infectés. Les sensibilités du GM dans le LBA, de la PCR 28S et de la PCR AFmito étaient de 58 %, 61 % et 50 %, respectivement. La sensibilité de l’examen mycologique (ED ± culture) était de 33 %. La spécificité du GM dans le LBA, des PCR 28S et AFmito PCR et de la culture étaient de 94 %, 97 %, 97 % et 98 %, respectivement. Les valeurs prédictives négatives étaient de 93 %, 95 %, 92 % et 89 %, respectivement. La concordance entre les 2 PCR était de 97 % (cœfficient kappa 0,84), alors qu’elle était de 88 % (kappa 0,40) entre la PCR 28S et le GM dans le LBA, et de 88 % (kappa 0,43) entre la PCR AFmito PCR et le GM dans le LBA. En conclusion, la PCR 28S a présenté la meilleure performance pour la détection moléculaire d’Aspergillus dans le LBA comparativement à la PCR AFmito. La combinaison de la PCR 28S et de la détection du GM dans le LBA permet d’atteindre une sensibilité de 80 % tout en conservant une excellente spécificité (91 %)
ISSN: 1156-5233

hal-01334068
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334068
DOI : 10.1016/j.mycmed.2016.04.048

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Molds and allergens are common indoor biocontaminants. The aims of this study were to assess the concentrations of common molds in indoor air and floor dust and the concentrations of house dust mite, cat and dog allergens in mattress dust in French dwellings, and to assess predictors of these concentrations. A sample of 150 houses in Brittany (western France) was investigated. Airborne Cladosporium and Penicillium were detected in more than 90% of the dwellings, Aspergillus in 46% and Alternaria in only 6% of the housings. Regarding floor dust samples, Cladosporium and Penicillium were detected in 92 and 80% of the housings respectively, Aspergillus in 49% and Alternaria in 14%. House dust mite allergens Der p1 and Der f1 were detected in 90% and 77% of the mattress dust samples respectively and Can f1 and Fel d1 in 37% and 89% of the homes. Airborne and dustborne mold concentrations, although not statistically correlated (except for Aspergillus) shared most of their predictors. Multivariate linear models for mold levels, explaining up to 62% of the variability, showed an influence of the season, of the age of the dwelling, of aeration habits, presence of pets, smoking, signals of dampness, temperature and relative humidity. Allergens in the dust of the mattress were strongly related to the presence of pets and cleaning practices of bedsheets, these factors accounting for 60% of the variability. This study highlights ubiquitous contamination by molds and underlines complex interaction between outdoor and indoor sources and factors
ISSN: 0048-9697

hal-01165440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165440/file/Molds%20and%20allergens%20in%20French%20dwellings%20rev2_clean%20version.pdf
DOI : 10.1016/j.scitotenv.2015.06.039
PUBMED : 26094801

Éditeur(s) : HAL CCSD
Résumé : International audience
Early antifungal therapeutic strategies are proposed during invasive fungal infection (IFI), but antifungal stewardship programs should institute a systematic reevaluation of prescriptions, particularly in the context of empirical treatment. Here, we aimed to evaluate the performances and particularly the negative predictive value (NPV) of diagnostic strategies, including a whole blood panfungal quantitative PCR assay (PF-qPCR) in a high risk population for IFI. The first step was to standardize and optimize a new PF- rtPCR targeting ITS2 region. Then, this method was evaluated in a multicenter prospective study including 313 patients with suspected IFI for whom an early antifungal treatment was prescribed. All patients enrolled at day 0 of their treatment benefited from serum Aspergillus galactomannan (GM) antigen detection twice a week, weekly PF-qPCR assay, and when indicated and feasible, CT-scan and mycological sampling. In total, 125 of 313 patients were diagnosed with IFI: 68 invasive aspergillosis (eight proven, 48 probable and 12 possible), one fusariosis, 47 candidemia, three disseminated candidiasis and six cryptococcosis. Globally, the sensitivity of the PF-qPCR assay was only 40%, but the specificity, PPV and NPV were 96%, 88% and 69%, respectively. In the population of patients at high risk for invasive aspergillosis who also benefited from Aspergillus GM detection, the sensitivity and the NPV of the combined detection reached to 78% and 84%, respectively. Even higher NPV were obtained when combining negative PF-qPCR and CT scan (95%) as well as negative GM and CT scan (93%), thus allowing to rationalize and re-evaluate the prescription of empirical treatment in such highly selected population.
The Journal of Infection

hal-01146845
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146845
DOI : 10.1016/j.jinf.2015.04.005
PUBMED : 25896093

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Marine ecosystems cover about 70% of the planet surface and are still an underexploited source of useful metabolites. Among microbes, filamentous fungi are captivating organisms used for the production of many chemical classes of secondary metabolites bound to be used in various fields of industrial application. The present study was focused on the collection, isolation, screening and genotyping of pigmented filamentous fungi isolated from tropical marine environments around La Réunion Island, Indian Ocean. About 150 micromycetes were revived and isolated from 14 marine samples (sediments, living corals, coral rubble, sea water and hard substrates) collected in four different locations. Forty-two colored fungal isolates belonging to 16 families, 25 genera and 31 species were further studied depending on their ability to produce pigments and thus subjected to molecular identification. From gene sequence analysis, the most frequently identified colored fungi belong to the widespread Penicillium, Talaromyces and Aspergillus genera in the family Trichocomaceae (11 species), then followed by the family Hypocreaceae (three species). This study demonstrates that marine biotopes in La Réunion Island, Indian Ocean, from coral reefs to underwater slopes of this volcanic island, shelter numerous species of micromycetes, from common or uncommon genera. This unstudied biodiversity comes along with the ability for some fungal marine inhabitants, to produce a range of pigments and hues.
ISSN: 2309-608X

hal-01657071
http://hal.univ-reunion.fr/hal-01657071
http://hal.univ-reunion.fr/hal-01657071/document
http://hal.univ-reunion.fr/hal-01657071/file/14-%20Fouillaud%20et%20al.%2C%20J.%20of%20Fungi%202017.pdf
DOI : 10.3390/jof3030036

Éditeur(s) : HAL CCSD
Résumé : National audience
Introduction Une exposition domiciliaire fongique élevée quantifiée par l’index environnemental moléculaire Environmental Relative Moldiness Index (ERMI) est associée au développement de l’asthme dans l’enfance. Dans ce travail, nous avons utilisé cette technique basée sur la quantification moléculaire de 36 champignons dans les poussières pour comparer sa valeur dans l’air à la détection par séquençage haut-débit NGS. Matériels et méthodes Des prélèvements de poussière et d’air ont été collectés dans 20 logements étiquetés « moisis » et 20 logements « non moisis » par les méthodes suivantes : 2 m2 de poussières prélevées à l’aide d’un embout Mitest™ positionné sur un aspirateur ; 3 m3 d’air prélevés par le collecteur cyclonique Coriolis® (Bertin Technologies, France). Tout d’abord, nous avons validé l’ERMI dans l’air versus les poussières, puis comparé dans les prélèvements d’air l’ERMI le séquençage NGS (10 échantillons « moisis » versus 10 échantillons « non moisis »). La cible était le gène 18S séquencé par pyroséquençage à l’aide du système Roche 454. Résultats et discussion Une corrélation entre l’ERMI « poussières » et l’ERMI « air » a été observée avec une valeur significative du test Kendall's tau. Les moisissures intérieures les plus identifiées étaient Aspergillus restrictus, A. fumigatus, A. versicolor, Aureobasidium pullulans Penicillium crustosum, Wallemia sebi, auxquelles s’associaient des moisissures classiquement d’extérieur, Cladosporium cladosporoides, Cladosporium herbarum. L’analyse des séquences obtenues par pyroséquençage était superposable à l’observation par ERMI. Les 3 genres les plus représentés dans l’air intérieur étaient Aspergillus, Penicillium et Cladosporium. Toutefois, quelques genres non inclus dans le panel ont pu être détectés en quantité non négligeable, à l’image des levures notamment du genre Cryptococcus. L’ERMI et le NGS apparaissent donc utiles et corrélés pour la quantification de la charge fongique environnementale dans l’air. L’ERMI a l’avantage d’être une technique rapide, mais sa limite est de cibler a priori 36 genres fongiques (définis initialement aux États-Unis). L’analyse NGS permet d’identifier d’autres genres potentiellement pertinents et donc d’adapter les cibles pour un ERMI « français »
Congrès de la SFMM
Talence-Bordeaux, France

hal-01198651
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01198651
DOI : 10.1016/j.mycmed.2015.06.013

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Abstract Indoor fungal contamination has been associated with a wide range of adverse health effects, including infectious diseases, toxic effects and allergies. The diversity of fungi contributes to the complex role that they play in indoor environments and human diseases. Molds have a major impact on public health, and can cause different consequences in hospitals, homes and workplaces. This review presents the methods used to assess fungal contamination in these various environments, and discusses advantages and disadvantages for each method in consideration with different health risks. Air, dust and surface sampling strategies are compared, as well as the limits of various methods are used to detect and quantify fungal particles and fungal compounds. In addition to conventional microscopic and culture approaches, more recent chemical, immunoassay and polymerase chain reaction (PCR)-based methods are described. This article also identifies common needs for future multidisciplinary research and development projects in this field, with specific interests on viable fungi and fungal fragment detections. The determination of fungal load and the detection of species in environmental samples greatly depend on the strategy of sampling and analysis. Quantitative PCR was found useful to identify associations between specific fungi and common diseases. The next-generation sequencing methods may afford new perspectives in this area.
ISSN: 1040-841X

hal-00874670
https://hal.archives-ouvertes.fr/hal-00874670
DOI : 10.3109/1040841X.2013.777687
PUBMED : 23586944

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent. Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population. A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS. Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population.
ISSN: 0761-8425

hal-01118185
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118185
DOI : 10.1016/j.rmr.2010.01.004
PUBMED : 20965392

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used.
ISSN: 1156-5233

hal-00759179
https://hal.archives-ouvertes.fr/hal-00759179
DOI : 10.1016/j.mycmed.2012.01.003
PUBMED : 23177816

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Our goal was to determine if the US Environmental Relative Moldiness Index (ERMI) scale might have application in France. Twenty homes in Brittany, north western region of France were classified by inspection as "Moldy" or "Non-Moldy". Dust and air samples were collected (MiTest sampler or Coriolis sampler, respectively) from each home and analyzed by quantitative polymerase chain reaction (QPCR) for the 36 fungi that make-up the ERMI. Inspection and ERMI values provided a consistent assessment for 90% of the homes. Two homes originally classified as "Non-Moldy" were found to fit better into the "Moldy" category based on the QPCR analysis and the ERMI. Dust and air samples analyzed by QPCR provided similar fungal contamination assessments. In conclusion, a metric like the ERMI describes mold burdens in homes on a continuum, as opposed to the frequently used dichotomous approach (moldy vs. non-moldy). Although a larger, random national sampling of French homes is needed, these results suggest that these same 36 fungi may be useful in creating an ERMI for France.
ISSN: 1438-4639

inserm-00817898
http://www.hal.inserm.fr/inserm-00817898
http://www.hal.inserm.fr/inserm-00817898/document
http://www.hal.inserm.fr/inserm-00817898/file/Gangneux-Possible-Application-accepted.pdf
DOI : 10.1016/j.ijheh.2012.06.004

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
Chronic rhinosinusitis (CRS) rank second at chronic inflammatory diseases in industrialized countries and are an important public health concern. Diagnosis relies on a set of arguments including clinical signs, imaging, histopathologic and mycological analyses of sinus specimens, collected during nasal endoscopy. The sensitivity of fungal cultures is reported to be poor, even when direct examination is positive, thus the epidemiology of fungal chronic sinusitis is ill-known. This study evaluated the sensitivity of molecular diagnosis in 70 consecutive samples (61 patients with CRS) analysed at the University Hospital of Rennes during a 3-year period. DNA detection was performed using a conventional PCR method targeting the ITS1/ITS2 sequence and the resulting amplification products were sequenced. Fungal CRS was proven in 42 patients (69%), of which only 20 (48%) had a positive culture. 37/42 (88%) patients were diagnosed with a fungus ball, 3 with allergic fungal CRS and 2 with undetermined fungal CRS. PCR was positive in all 42 cases and direct sequencing allowed to identify fungi in all cases but one, and detected multiple infection in 3. Aspergillus fumigatus was present in 69% of patients; Cladosporium cladosporoides in 9.5%, Scedosporium sp., A. nidulans and A. flavus in 7% each. In 2/19 patients with negative direct examination, sequencing analysis revealed the presence of Capnobotryella sp. and C. cladosporoides, in clinical settings compatible with fungal sinusitis. In conclusion, ITS1/ITS2 PCR had a twice better sensitivity than culture, and combined sequencing provides accurate epidemiological data on fungal CRS.
ISSN: 1369-3786

hal-01383632
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01383632
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01383632/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01383632/file/Contribution%20of%20molecular%20tools%20for%20the%20diagnosis.pdf
DOI : 10.1093/mmy/myw041