Center National Of Reference

Paris, France

Center National Of Reference

Paris, France
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Lescat M.,French Institute of Health and Medical Research | Lescat M.,University of Paris Pantheon Sorbonne | Clermont O.,French Institute of Health and Medical Research | Clermont O.,University Paris Diderot | And 20 more authors.
Environmental Microbiology Reports | Year: 2013

We undertook a large-scale epidemiological survey of commensal Escherichia coli in Trois-Sauts, an isolated village located in the south of French Guiana where human population exchanges are restricted and source of antibiotics controlled. Stools from 162 Wayampi Amerindians and rectal swabs from 33 human associated and 198 wild animals were collected in the close proximity of the village. The prevalence of E.coli was decreasing from humans (100%) to human associated (64%) and wild (45%) animals. A clear genetic structure between these three E.coli populations was observed with human strains belonging very rarely to B2 phylogroup (3.7%), exhibiting few virulence genes and bacteriocins but being antibiotic resistant whereas wild animal strains were characterized by 46.1% of B2 phylogroup belonging, with very unique and infrequent sequence types, numerous extraintestinal genes and bacteriocins but no antibiotic resistance; the human-associated animal strains being intermediate. Furthermore, an unexpected genetic diversity was observed among the strains, as the housekeeping gene nucleotide diversity per site of the Trois-Sauts's strains was higher than the one of reference strains representative of the known species diversity. The existence of such E.coli structured phylogenetic diversity within various hosts of a single localization has never been reported. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.


Meunier I.,Montpellier University | Meunier I.,Center National Of Reference | Senechal A.,French Institute of Health and Medical Research | Arndt C.,Eye Clinic | And 8 more authors.
Ophthalmology | Year: 2011

Purpose To evaluate a genetic approach of BEST1 and PRPH2 screening according to age of onset, family history, and Arden ratio in patients with juvenile vitelliform macular dystrophy (VMD2) or adult-onset vitelliform macular dystrophy (AVMD), which are characterized by autofluorescent deposits. Design Clinical, electrophysiologic, and molecular retrospective study. Participants The database of a clinic specialized in genetic sensory diseases was screened for patients with macular vitelliform dystrophy. Patients with an age of onset less than 40 years were included in the VMD2 group (25 unrelated patients), and patients with an age of onset more than 40 years were included in the AVMD group (19 unrelated patients). Methods Clinical, fundus photography, and electro-oculogram (EOG) findings were reviewed. Mutation screening of BEST1 and PRPH2 genes was systematically performed. Main Outcome Measures Relevance of age of onset, family history, and Arden ratio were reviewed. Results Patients with VMD2 carried a BEST1 mutation in 60% of the cases. Seven novel mutations in BEST1 (p.V9L, p.F80V, p.I73V, p.R130S, pF298C, pD302A, and p.179delN) were found. Patients with VMD2 with a positive family history or a reduced Arden ratio carried a BEST1 mutation in 70.5% of cases and in 83% if both criteria were fulfilled. Patients with AVMD carried a PRPH2 mutation in 10.5% of cases and did not carry a BEST1 mutation. The probability of finding a PRPH2 mutation increased in the case of a family history (2/5 patients). Electro-oculogram was normal in 3 of 15 patients with BEST1 mutations and reduced in the 3 patients with PRPH2 mutations. Conclusions Age of onset is a major criterion to distinguish VMD2 from AVMD. Electro-oculogram is not as relevant because decreased or normal Arden ratios have been associated with mutations in both genes and diseases. A positive family history increased the probability of finding a mutation. BEST1 screening should be recommended to patients with an age of onset less than 40 years, and PRPH2 screening should be recommended to patients with an age of onset more than 40 years. For an onset between 30 and 40 years, PRPH2 can be screened if no mutation has been detected in BEST1. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2011 American Academy of Ophthalmology.


Trocello J.-M.,Center National Of Reference | Corbillon E.,Haute Autorite de Sante | Bourdain F.,Service de Neurologie | Xie J.,Center National Of Reference | And 2 more authors.
Pratique Neurologique - FMC | Year: 2010

The French National Diagnosis and Treatment Protocol (PNDS) for Wilson's disease was elaborated by the Wilson's disease reference center, with methodological support from the French National Health Authority (HAS), according to the measures of the 2005-2008 French National Plan for Rare Diseases. This PNDS was drafted after a critical analysis of the international literature, and its contents were discussed and validated by a multidisciplinary working group. It explains to health providers the optimum management and care pathway for a patient with Wilson's disease. This article resumes the essential matters of the PNDS concerning the management of patients with neurological symptoms. The exhaustive text of the PNDS for Wilson's disease is available online on the HAS website (http://www.has-sante.fr). © 2010 Elsevier Masson SAS. All rights reserved.


Aghokeng A.F.,Virology Laboratory | Aghokeng A.F.,Montpellier University | Monleau M.,Montpellier University | Eymard-Duvernay S.,Montpellier University | And 10 more authors.
Clinical Infectious Diseases | Year: 2014

Background. The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART.Methods. Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment.Results. Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4+ T-cell counts at ART initiation were low (99-172 cells/L). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine.Conclusions. Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries. © 2013 The Author.


Lavault S.,Groupe Hospitalier Pitie Salpetriere | Lavault S.,University Pierre and Marie Curie | Lavault S.,French Institute of Health and Medical Research | Dauvilliers Y.,French Institute of Health and Medical Research | And 15 more authors.
Sleep Medicine | Year: 2011

Background: The benefit/risk ratio of modafinil was recently re-evaluated by the European Medicines Agency and was shown to be negative for idiopathic hypersomnia (IH) because of insufficient data. Objective: To evaluate the benefit/risk ratio of modafinil in idiopathic hypersomnia (with and without long sleep time) vs. narcolepsy/cataplexy. Subjects and methods: The benefit (Epworth sleepiness score, ESS; visual analog scale, patient and clinician opinions) and risks (habituation, adverse effects) of modafinil were studied in a consecutive clinical cohort of 104 IH patients (59 with long sleep time) and 126 patients with narcolepsy/cataplexy. Results: Modafinil was the first line treatment in 96-99% of patients. It produced a similar ESS change in IH patients and in narcolepsy patients (-2.6 ± 5.1 vs. -3 ± 5.1) and a similar benefit as estimated by the patients (6.9 ± 2.7 vs. 6.5 ± 2.5 on a visual analog scale) and clinicians. The ESS change was lower in IH patients with long sleep time than in those without. Sudden loss of efficacy and habituation were rare in both groups. Patients with IH reported similar but more frequent adverse effects with modafinil than narcolepsy patients: nervousness (14%), palpitations (13%), and headache (11%). Conclusion: Modafinil has an excellent benefit/risk ratio in idiopathic hypersomnia, with or without long sleep time, similar to its effect on narcolepsy/cataplexy. © 2011 Elsevier B.V.


Aubry A.,University Pierre and Marie Curie | Aubry A.,French Institute of Health and Medical Research | Aubry A.,Center National Of Reference | Sougakoff W.,University Pierre and Marie Curie | And 15 more authors.
PLoS ONE | Year: 2014

Background: Tuberculosis (TB) is one of the major public health problems in Congo. However, data concerning Mycobacterium tuberculosis drug resistance are lacking because of the insufficient processing capacity. So, the aim of this study was to investigate for the first time the resistance patterns and the strain lineages of a sample of M. tuberculosis complex (MTBC) isolates collected in the two main cities of Congo. Methods: Over a 9-day period, 114 smear-positive sputa isolated from 114 patients attending centers for the diagnosis and treatment of TB in Brazzaville and Pointe Noire were collected for culture and drug susceptibility testing (DST). Detection of mutations conferring drug resistance was performed by using line probe assays (GenoType MTBDRplus and MTBDRsl) and DNA sequencing. Strain lineages were determined by MIRU-VNTR genotyping. Results: Of the 114 sputa, 46 were culture positive for MTBC. Twenty-one (46%) were resistant to one or more first-line antiTB drugs. Of these, 15 (71%) were multidrug resistant (MDR). The most prevalent mutations involved in rifampin and isoniazid resistance, D516V (60%) in rpoB and S315T (87%) in katG respectively, were well detected by MTBDRplus assay. All the 15 MDR strains were susceptible to fluoroquinolone and injectable second-line drug. No mutation was detected in the rrs locus involved in resistance to amikacin and capreomycin by both the MTBDRsl assay and DNA sequencing. By contrast, 9 MDR strains belonging to the same cluster related to T-family were identified as being falsely resistant to fluoroquinolone by the MTBDRsl assay due to the presence of a double substitution T80A-A90G in GyrA. Conclusions: Taken together, these data revealed a possible spread of a particular MDR clone in Congo, misidentified as fluoroquinolone resistant by MTBDRsl assay. Thus, this test cannot replace gold-standard culture method and should be interpreted carefully in view of the patient's native land. Copyright: © 2014 Reekie et al.


Tourdjman M.,Institute of Veille Sanitaire | Laurent E.,Institute of Veille Sanitaire | Leclercq A.,Center National Of Reference
Revue Francophone des Laboratoires | Year: 2014

Human listeriosis is an uncommon foodborne bacterial illness caused by ingestion of food contaminated by Listeria monocytogenes. This bacterium is widespread in nature and is a common cause of zoonosis in herd animals. Many food products might become contaminated at various stages of production. Although ingestion of L. monocytogenes is a frequent occurrence, incidence of human listeriosis in the French general population is low - approximately 5 cases per million population - but incidence rates are higher in particular at-risk groups including older adults, pregnant women and their newborns, and persons with impaired cell-immunity. Invasive clinical syndromes most frequently include bacteremia, central nervous system infection and pregnancy-related infection. Other rare invasive presentations include joint and bone infections, endocarditis, as well as foreign material-associated infections. Non-invasive illnesses are rare and include acute febrile gastroenteritis and localized cutaneous or ocular infections. Invasive listeriosis is a potential severe condition with a case fatality rate of 20-30%. Incidence of human listeriosis has dramatically declined over the past decades, primarily because of implementation of food safety measures in the food industry. By carefully following food safety precautions, risk of listeriosis can be substantially reduced. © 2014 - Elsevier Masson SAS - Tous droits réservés.

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