Pneumocystis jirovecii colonization among cystic fibrosis patients: A French prospective multicenter study

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of P. aeruginosa colonization and better FEV1 values. Results are discussed considering the natural history of CF

Fungal colonization in Cystic Fibrosis (CF): Epidemiology and antifungal resistance in a French cohort of CF patients – Focused on Aspergillus fumigatus colonization

Introduction: Cystic fibrosis (CF) is the major genetic inherited disease in the European Caucasian population, with an average of 1 in 3000 living births in France. Prognostic depend essentially on the lung impairments. While considerable attention therefore has been paid over recent decades to prevent and treat bacterial respiratory infections, we observed emergence of fungi colonization in CF respiratory tract. In particular, Aspergillus fumigatus represents the most common causative agent colonizing the airways of CF patients; it can be responsible for Allergic Bronchopulmonary Aspergillosis (ABPA). Since oral corticosteroids and itraconazole represent the mainstay of ABPA treatment, long-term therapy may increase the risk of acquired resistance to azoles that is mainly associated with amino acid substitutions in the CYP51A gene of A. fumigatus. Objective: First, we managed to have exhaustive epidemiological data on species of filamentous fungi able to colonize the airway tract of 300 CF patients followed-up in our national prospective study ("MucoFong" study – PHRC1902). Second, CF patients being chronically exposed to azole (especially to itraconazole), our study aimed to evaluate the prevalence of azole resistance in isolates prospectively collected from CF patients followed-up in seven French hospitals involved in our national prospective study. Third, we focused on the most prevalent species: Aspergillus fumigatus, studying the azole resistance at molecular level. To our knowledge, it is the first multicenter study focused on azole resistance of A. fumigatus in CF. Methods: A total of 243 sputa were analyzed using the same protocol in each centre. The MICs of antifungal drugs were evaluated for each isolate using the E-test ® strips. Focusing on A. fumigatus, a total of 87 isolates was collected in 85 patients. These isolates were characterized at the molecular level by targeting ITS, ß-tubulin and MAT-A/α genes. The CYP51A gene as well as its promoter was sequenced; a 3D Cyp51A protein homology model was built. Results and discussion: 300 patients were enrolled in this study. At inclusion time, most of them were adults colonized with A. fumigatus (about 35% of the patients). Scedosporium was isolated in 5%, and Exophiala in about 2%. Regarding antifungal susceptibility, isolates of Scedosporium and Exophiala exhibited antifungal resistance comparable with published data. Regarding A. fumigatus, a majority of isolates (88.1%) were found sensitive to itraconazole (MIC≤ 2μg/ml), and 2 new mutations were identified and localized within 3-dimensional Cyp51A protein model. To obtain insight into azole resistance of A. fumigatus, the results are analyzed taking into account clinical data, itraconazole exposition, and the potential correlation between the identified CYP5IA mutations and azole resistance is discussed based on the Cyp51A protein homology model

Molecular diagnosis of Pseudoterranova decipiens s.s in human, France

Background: Anisakis and Pseudoterranova are the main genera involved in human infections caused by nematodes of the Anisakidae family. Species identification is complicated due to the lack of differential morphological characteristics at the larval stage, thus requiring molecular differentiation. Pseudoterranova larvae ingested through raw fish are spontaneously eliminated in most cases, but mechanical removal by means of endoscopy might be required. To date, only very few cases of Pseudoterranova infection have been reported in France. Case presentation: A 19-year-old woman from Northeastern France detected, while brushing her teeth, a larva exiting through her mouth. The patient who presented with headache, diarrhea, and abdominal cramps reported having eaten baked cod. The worm was a fourth-stage larva with a size of 22 × 0.9 mm, and molecular biology identified it as Pseudoterranova decipiens sensu stricto (s. s.). In a second P. decipiens infection case, occurring a few months later, a worm exited through the patient’s nose after she had eaten raw sea bream. Conclusion: These two cases demonstrate that Pseudoterranova infection is not uncommon among French patients. Therefore, molecular techniques should be more widely applied for a better characterization of anisakidosis epidemiology in France

The Airway Microbiota in Cystic Fibrosis: A Complex Fungal and Bacterial Community—Implications for Therapeutic Management

International audienceBackground Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways. Methodology and Principal Findings Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus

Transmission de Pneumocystis = Pneumocystis transmission

star, openConférence présentée au Symposium « Pneumocystis et pneumocystose 100 ans après », présidence Patricia Roux et Eduardo Dei-Cas, faculté de médecine Necker, Paris le 29 novembre 2008. Congrès SFMM – 29 novembre 2008, Paris/Congress of the French Society of medical mycology – November 29, 2008, ParisInternational audienceLes microorganismes du genre Pneumocystis sont des micro-champignons cosmopolites adhérant aux cellules épithéliales alvéolaires du poumon de l'homme et d'autres mammifères. Ils déterminent des pneumonies mortelles chez les sujets traversant des situations de profonde immunodépression. L'étroite spécificité d'hôte des populations naturelles de Pneumocystis spp. suggère que les populations humaines représentent le réservoir de Pneumocystis jirovecii, seule espèce du genre identifiée chez l'homme. La transmission aérienne d'un hôte infecté à un hôte susceptible a été bien établie chez l'animal et différentes observations suggèrent l'existence d'une transmission inter-humaine du parasite. Chez la souris, un seul jour de contact suffit pour que l'infection soit transmise. Par ailleurs, l'utilisation d'un modèle expérimental murin de transmission naturelle de Pneumocystis a permis de mettre en évidence que les hôtes immunocompétents, porteurs transitoires du champignon, peuvent transmettre l'infection à des hôtes immunodéprimés ou à d'autres hôtes immunocompétents. Ainsi aujourd'hui, l'infection par Pneumocystis chez des sujets non immunocompromis prend une nouvelle dimension en santé publique. Enfin, une transmission verticale de Pneumocystis spp. par voie transplacentaire semble fréquente chez le lapin, mais absente chez les modèles rat et souris. L'hypothèse d'une transmission transplacentaire du champignon chez l'homme, longtemps suspectée, vient quant à elle d'être renforcée par une étude récente dans laquelle l'ADN de P. jirovecii a été détecté dans les poumons de fœtus et de placentas de femmes ayant subi des fausses couches. The genus Pneumocystis contains multiple species that attach specifically to type-I alveolar epithelial cells in the lungs of mammalian hosts, including humans. These fungi can cause severe pneumonitis, particularly in hosts with marked impairment of the immune system. The strong host species specificity of Pneumocystis strains suggests that Pneumocystis infection in humans is an anthroponosis, and that humans serve as reservoirs of Pneumocystis jirovecii, the sole species found in humans. Airborne transmission of Pneumocystis spp. from host to host has been demonstrated in rodent models and several observations suggest that inter-individual transmission occurs in humans in both hospitals and the community. In mice, a one-day exposure is enough for airborne transmission of the infection. An airborne transmission mouse model of Pneumocystis, which mimics the route and intensity of natural Pneumocystis infection, revealed that non-immunocompromised hosts transiently infected with Pneumocystis are able to transmit the infection to either immunocompromised or immunocompetent hosts. Consequently, Pneumocystis infection of non-immunocompromised hosts is increasingly becoming a recognized public health issue. Finally, vertical transmission of Pneumocystis via the transplacental route has been demonstrated in rabbits, but it does not appear to occur in rats or SCID mice. In humans, congenital transmission was suspected for many years, and a recent report documented the presence of Pneumocystis jirovecii DNA in foetal lung and placenta samples, recovered from non-immunodepressed pregnant women who had a miscarriage

Phylogenetic analysis of human and animal isolates of Trichophyton mentagrophytes based on MnSOD and ITS sequence comparisons

National audienc

Phylogenetic analysis of human and animal isolates of Trichophyton mentagrophytes based on MnSOD and ITS sequence comparisons

National audienc

Severe pulmonary toxoplasmosis after allo-SCT in two patients: from Toxoplasma genotyping to clinical management.

International audienc