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
Résumé : National audience
Objective of the study An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. Materials and methods A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. Results The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Conclusion Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year. © 2016 Elsevier Masson SAS
Journal de Mycologie Medicale

hal-01467554
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467554
DOI : 10.1016/j.mycmed.2016.11.001
PUBMED : 27887809

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
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 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 Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. METHODS: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. CONCLUSIONS: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.
ISSN: 0305-7453

hal-00874741
https://hal.archives-ouvertes.fr/hal-00874741
DOI : 10.1093/jac/dks266
PUBMED : 22850692

Éditeur(s) : HAL CCSD
Résumé : National audience
Objectifs La recherche d’anticorps anti-aspergillaires est une analyse essentielle au diagnostic des formes chroniques d’aspergilloses. De nombreuses techniques sont disponibles, commerciales ou non, regroupées par la nomenclature française en méthodes de dépistage et de confirmation. La SFMM a mené en janvier–février 2015 une étude de type « avis d’expert » sur les performances de ces techniques et leur stratégie de mise en œuvre. Méthodes Quarante experts ont été sollicités pour répondre à un questionnaire en ligne comprenant 37 questions. Les réponses, obligatoires pour tous les items, devaient être cotées de 1 à 9 selon l’accord total (9) ou le désaccord total (1) de l’expert. L’analyse a été faite sur la valeur de la cote médiane et les coefficients de variation (écart-type/moyenne) pour juger de la variabilité des réponses. Résultats Trente-six questionnaires ont été complétés. Les CV des réponses allaient de 10 % à 75 %, seuls 38 % d’entre eux étant supérieurs à 50 %. La distinction entre méthode de dépistage et méthode de confirmation est globalement jugée comme pertinente (médiane = 7) mais un positionnement clair des techniques en dépistage ou confirmation n’est obtenu avec un CV inférieur à 30 % que pour l’Elisa en dépistage et l’immunoélectrophorèse et le western blot en confirmation. La pratique d’une technique de confirmation est essentiellement recommandée en cas de positivité de la méthode de dépistage (médiane = 9 ; CV = 14 %), en fonction du contexte clinique (8 ; 31 %) ou lors d’un suivi (8 ; 33 %). En cas de discordance entre méthode de dépistage et de confirmation, les experts recommandent une interprétation directe des résultats en donnant priorité aux résultats de la méthode de confirmation (en fonction du dossier du patient) (8 ; 28 %). Conclusion Cette enquête montre l’absence de consensus sur la stratégie de détection des anticorps anti-aspergillaires et doit inciter les mycologues français à harmoniser au mieux leurs pratiques, afin de répondre à la demande des cliniciens
Congrès de la SFMM
Talence-Bordeaux, France

hal-01198639
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01198639
DOI : 10.1016/j.mycmed.2015.06.012

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 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 Elsevier
Résumé : International audience
: In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.
ISSN: 1438-4221

inserm-01065096
http://www.hal.inserm.fr/inserm-01065096
http://www.hal.inserm.fr/inserm-01065096/document
http://www.hal.inserm.fr/inserm-01065096/file/2014_Iriart_-_Complementary_tool_for_managementsur histo_infections_in_AID.pdf
DOI : 10.1016/j.ijmm.2014.07.016