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

Clinical and microbiological efficacy of micafungin on Geosmithia argillacea infection in a cystic fibrosis patient

Cystic fibrosis are at risk of colonization by a number of fungi, including Geosmithiaargillacea which appears to be an emerging pathogen in these patients. This pathogen has been recently reported as a cause of invasive/systemic mycosis in immunocompromized patients such as colonized patients who are immunosuppressed for lung transplantation. In this context, we report here a case of clinical and microbiological efficacy of micafungin in a French cystic fibrosis patient chronically colonized with G. argillacea. O.D., a female F508Del-CFTR homozygous patient was diagnosed at birth with cystic fibrosis in January 1996. She was found chronically colonised with multi-resistant Staphylococcus aureus (MRSA) from 1997 to 2011, and with Aspergillus fumigatus from 2001 to 2006. She was treated alternatively with oral voriconazole and itraconazole from 2004 to 2008, and with posaconazole since february 2008. Geosmithia argillacea was first diagnosed in May 2007, and chronic colonisation was persistent from this date to August 2010 with 23/28 fungus positive sputum samples, in spite of posaconazole therapy. For an isolate obtained in October 2008, minimal inhibitory/effective concentrations (MIC/MEC, mg/ml) determined using the Eucast method were 2.0, 2.0, 16.0, 2,0, 0.25 and 0.015 for amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and micafungin, respectively. The FEV1 predicted value was 73% at the time of first fungus isolation and was decreased to 47% in October 2009. She then was given caspofungin for 21 days ((70 mg/day, later reduced to 50 mg) which resulted in clinical improvement (FEV1 = 64% in January 2010) without eradication of G. argillacea. In June 2010, treatment with micafungin (75 mg, 21days) was realized owing to deterioration of the respiratory function (FEV1 = 56%),without clinical improvement ( FEV1 = 47% in August 2010). O.D. was then treated from September, 23 to November 3, 2010 with micafungin (100mg bid for 21 days and 100mg/day for the following 21 days) which resulted in clinical and microbiological improvement. FEV1 predicted ranged 67-68% in October and December 2010, and February and May 2011, and from the end of treatment to December 2010, 5/6 sputum samples were found negative for G. argillacea. The positive sample contained fungus of the same genotype as previous isolates. The present case is to our knowledge the first description of G. argillacea eradication in a chronically colonized cystic fibrosis patient. Similar to previous studies, G. argillacea colonization was detected in the presence of chronic MRSA after A. fumigatus eradication. Since no change in bacterial colonization was observed before, during, and after G. argillacea colonization, the present case is consistent with a pathogenic role of the fungus in cystic fibrosis patients. In vitro antifungal susceptibility assays suggested that echinocandins are most effective agents against this fungus with a lowest MEC for micafungin (7 isolates studied, MEC range: 0.015-0.03), although eradication could only be obtained with high dose micafungin for a long time (6 weeks)

Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference

While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a “one health” approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis

Evaluation and mangement of fungal risk in cystic fibrosis: first results of a national French study

Date du colloque&nbsp;: 06/2009</p

8th European Conference on Rare Diseases & Orphan Products (ECRD 2016)

MEETING ABSTRACTS: Open Access 8th European Conference on Rare Diseases & Orphan Products (ECRD 2016), Edinburgh, UK. 26-28 May 201

Quantifying Vegetation Biophysical Variables from Imaging Spectroscopy Data: A Review on Retrieval Methods

An unprecedented spectroscopic data stream will soon become available with forthcoming Earth-observing satellite missions equipped with imaging spectroradiometers. This data stream will open up a vast array of opportunities to quantify a diversity of biochemical and structural vegetation properties. The processing requirements for such large data streams require reliable retrieval techniques enabling the spatiotemporally explicit quantification of biophysical variables. With the aim of preparing for this new era of Earth observation, this review summarizes the state-of-the-art retrieval methods that have been applied in experimental imaging spectroscopy studies inferring all kinds of vegetation biophysical variables. Identified retrieval methods are categorized into: (1) parametric regression, including vegetation indices, shape indices and spectral transformations; (2) nonparametric regression, including linear and nonlinear machine learning regression algorithms; (3) physically based, including inversion of radiative transfer models (RTMs) using numerical optimization and look-up table approaches; and (4) hybrid regression methods, which combine RTM simulations with machine learning regression methods. For each of these categories, an overview of widely applied methods with application to mapping vegetation properties is given. In view of processing imaging spectroscopy data, a critical aspect involves the challenge of dealing with spectral multicollinearity. The ability to provide robust estimates, retrieval uncertainties and acceptable retrieval processing speed are other important aspects in view of operational processing. Recommendations towards new-generation spectroscopy-based processing chains for operational production of biophysical variables are given