Agnès Gautheret-Dejean

Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix, Lutetia Parisorum, Île-de-France, France

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Publications (83)249.2 Total impact

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    ABSTRACT: We recently published a paper in the Journal of Medical Virology titled "Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections" [Gautheret-Dejean et al., 2015]. Hønge et al. followed up with a commentary on our findings, which we have read with great interest. We are grateful for this opportunity to respond to their comments and give some precisions/clarifications in this letter. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Journal of Medical Virology
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    ABSTRACT: Major differences exist between HIV-1 and HIV-2 in terms of epidemiology, pathogenicity, sensitivity to antiretrovirals. Determining the type of HIV infecting a patient is essential for management. The aim of this study was to evaluate the ability of simple/rapid tests to differentiate between HIV-1 and/or HIV-2 infections. We analyzed 116 samples from patients infected with HIV-1 (n = 61), HIV-2 (n = 47), or HIV-1+HIV-2 (n = 8) at the chronic stage of infection. Each sample was tested with SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1-HIV2, ImmunoFlow HIV1-HIV2 (WB), Genie III HIV-1/HIV-2, ImmunoComb HIV1&2 BiSpot. HIV-1, or HIV-2 single infection was identified with a sensitivity ranging from 90% to 100%. The ability to detect dual infection was less sensitive (12.5-100%). SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1-HIV2, and Genie III were unable to detect HIV-1 group O infection in one, one and two cases, respectively. The specificity of detection of HIV-1, HIV-2, or HIV-1+HIV-2 antibodies differed greatly (36-100%). ImmunoComb BiSpot had the highest sensitivity values (99-100% for HIV-1, 98% for HIV-2, and 75-87.5% for dual infection) and specificity values (94-100% for HIV-1, 100% for HIV-2, and 97-100% for dual infection). In conclusion, this study showed that no single rapid test had a perfect sensitivity/specificity ratio, particularly in the case of the double infections. J. Med. Virol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Jun 2015 · Journal of Medical Virology
  • Henri Agut · Pascale Bonnafous · Agnès Gautheret-Dejean
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    ABSTRACT: Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    No preview · Article · Apr 2015 · Clinical Microbiology Reviews
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    Preview · Article · Sep 2014 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Background: Idiopathic nephrotic syndrome (INS) is likely a primary immune disorder, but viruses might also be involved in the mechanisms of the disease. Here, we investigate the link between herpesvirus infection and the first manifestation of INS in children. Methods: A prospective, multicentre, and population-based case-control study called NEPHROVIR included 164 patients, aged 6 months to 15 years old, newly diagnosed with INS, and 233 controls matched for gender, age, and period of sample. The analysis was done on 124 patients and 196 controls. Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and human herpesvirus-7 (HHV-7) DNA prevalence at diagnosis were assessed from whole peripheral blood samples, as well as EBV and CMV viral load and seroprevalence. Results: EBV DNA was significantly more prevalent in cases than in controls (50.8 vs 29.1 %; OR = 2.6; p = 0.0002), with no difference in viral load. A significant difference was also found for CMV (11.3 vs 3.6 %; p = 0.02) and HHV-7 (83 vs 72 %; p = 0.02) DNA prevalence between cases and controls. There were significantly more EBV and CMV recent infections or reactivations based on VCA-IgM and CMV IgM in cases than controls, while there were no differences in IgG seroprevalence. Conclusion: The prevalence of positive EBV DNA detection and recent infection or reactivation is higher in children at onset of INS compared to a population matched for age, gender, and time of sampling.
    No preview · Article · Jun 2014 · Pediatric Nephrology
  • Agnès Gautheret-Dejean · Henri Agut
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    ABSTRACT: The diagnosis of HHV-6A, HHV-6B, and HHV-7 is based on both serologic and direct approaches. Serology is a classical convenient tool for the diagnosis of primary infection and epidemiologic studies; however, its use is limited by some difficulties in the interpretation of antibody serum titers and positive IgM detection in the context of a lifelong persisting infection, inability to differentiate the two HHV-6 viruses, and cross-reactivity between betaherpesviruses. Direct diagnosis was historically based on virus isolation in primary cell cultures. Molecular diagnosis, based on quantitative PCR and RT-PCR, is more sensitive and accessible than virus culture and antigen detection. It allows us to detect infection in a wide range of human specimens, to distinguish between active and latent infections as well as between HHV-6A and HHV-6B, to assess the efficacy of antiviral therapies, and to readily recognize HHV-6 chromosomal integration. Combined with PCR, nucleotide sequencing allows epidemiologic investigations as well as the recognition of resistance to antivirals. The most recent developments in molecular techniques-namely, digital PCR and next-generation sequencing-offer novel opportunities for the accurate investigation of infection pathophysiology.
    No preview · Article · Mar 2014
  • C. Méni · A. Chabrol · M. Wassef · A. Gautheret-Dejean · J.-F. Bergmann · S. Mouly
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    ABSTRACT: La lymphadénite histiocytaire nécrosante (maladie de Kikuchi-Fujimoto) est une entité clinico-pathologique rare caractérisée par l’association d’une lymphadénopathie cervicale postérieure bien limitée et d’une fièvre, touchant principalement les femmes jeunes.ObservationNous rapportons le cas d’un patient africain de 41 ans présentant une maladie de Kikuchi-Fujimoto atypique car compliquée d’un lupus cutané, d’un syndrome d’activation macrophagique et d’une méningite lymphocytaire. Une méningite tuberculeuse, initialement évoquée en raison de l’origine ethnique et de la présentation clinique, était éliminée par l’histologie ganglionnaire caractéristique de maladie de Kikuchi-Fujimoto, la négativité des prélèvements microbiologiques, l’évolution clinique et la découverte d’une intégration virale génomique d’ADN d’HHV6.ConclusionL’association d’adénopathies cervicales, d’un syndrome d’hémophagocytose, d’une méningite lymphocytaire et d’une intégration génomique d’HHV-6 doit faire évoquer une maladie de Kikuchi.
    No preview · Article · Jun 2013 · La Revue de Médecine Interne
  • A. Gautheret-Dejean
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    ABSTRACT: En 2010, la législation française du diagnostic de l’infection par le virus de l’immunodéficience humaine a changé avec la parution des arrêtés des 28 mai et 9 novembre. Les tests rapides d’orientation diagnostique (TROD) peuvent désormais être utilisés lors de contexte d’urgence mais également dans un but d’élargissement de l’offre de dépistage en dehors d’un laboratoire d’analyse (établissement et services de santé, cabinet médical de ville, structure de prévention ou associative). Les principaux avantages des TROD VIH sont : réalisation sur le terrain au plus près des personnes, rapidité, simplicité, stockage à température ambiante, différenciation VIH-1/VIH-2 pour certains. Cependant, ils ont un certain nombre d’inconvénients : performances analytiques (sensibilité et spécificité) inférieures à celles des tests Elisa combinés, subjectivité de lecture, manque de traçabilité, exploration du VIH uniquement, contrôles de production et distribution variables et coût élevé. Les objectifs de cette revue sont de présenter le cadre législatif de l’utilisation des TROD VIH en France, leurs performances, avantages et inconvénients.
    No preview · Article · Feb 2013 · Immuno-analyse & Biologie Spécialisée
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    Dataset: Table S1
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    ABSTRACT: Results of a 12 month routine HIV screening program with a rapid test after written inform consent in non eligible patients at 6 university hospital emergency departments (EDs) in Paris area (2009–2011). (DOC)
    Preview · Dataset · Oct 2012
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    ABSTRACT: In October 2009 the French National Authority for Health recommended that HIV testing be proposed at least once to all persons aged 15 to 70 years in all healthcare settings. We examined whether routine HIV screening with a rapid test in emergency departments (EDs) was feasible without dedicated staff, and whether newly diagnosed persons could be linked to care. This one-year study started in December 2009 in 6 EDs in the Paris area, using the INSTI™ test. Eligible individuals were persons 18 to 70 years old who did not present for a vital emergency, for blood or sexual HIV exposure, or for HIV screening. Written informed consent was required. Among 183 957 eligible persons, 11 401 were offered HIV testing (6.2%), of whom 7936 accepted (69.6%) and 7215 (90.9%) were tested (overall screening rate 3.9%); 1857 non eligible persons were also tested. Fifty-five new diagnoses of HIV infection were confirmed by Western blot (0.61% (95% CI 0.46-0.79). There was one false-positive rapid test result. Among the newly diagnosed persons, 48 (87%) were linked to care, of whom 36 were not lost to follow-up at month 6 (75%); median CD4 cell count was 241/mm(3) (IQR: 52-423/mm(3)). Screening rates were similar to those reported in opt-in studies with no dedicated staff. The rate of new diagnoses was similar to that observed in free anonymous test centres in the Paris area, and well above the prevalence (0.1%) at which testing has been shown to be cost-effective.
    Full-text · Article · Oct 2012 · PLoS ONE
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    ABSTRACT: Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease.
    Full-text · Article · May 2012 · Reviews in Medical Virology
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    ABSTRACT: Human herpesvirus-6 and -7 (HHV-6 and HHV-7) may lead to pathological manifestations in renal transplant recipients. The aim of this study was to investigate beta-herpesvirus infections in 50 adult kidney transplant recipients after transplantation to examine the effect, interactions, and pathogenic consequences of infection and the effect of immunosuppressive regimens and Human cytomegalovirus (HCMV) prophylaxis with VACV. Beta-herpesviruses loads in the blood of 50 adult kidney transplant recipients over a 6-month period after transplantation and 198 blood donors were determined using polymerase chain reaction. The rate of HHV-6 detection in peripheral mononuclear cells (PBMCs) was higher in patients with end-stage renal disease and during the post-transplantation follow-up than in healthy subjects (33% and 68% vs. 12%, respectively). The detection rate of HHV-7 in PBMCs was similar between patients, both before grafting and during the follow-up for transplant recipients (69% and 88%, respectively), and healthy subjects (78%), and correlated with the number of lymphocytes. HCMV in plasma was detected only in patients during the post-transplant period (24%). VACV prophylaxis had no negative effect on the replication of HHV-6 or HHV-7, and univariate analyses demonstrated associations between HHV-6 infection and acute graft rejection [Odds ratio (OR) = 2.94, 95% confidence interval (CI), 1.05-8.2, P = 0.04], and between HHV-7 infection and cholestasis [OR = 2.61 (95% CI, 1.08-6.3), P = 0.03]. Immunosuppressive regimens had no effect on beta-herpesviruses infections. This study revealed the differing behavior of HCMV, HHV-6, and HHV-7 in kidney transplant recipients, and confirmed the association of HHV-6 with graft rejection.
    Full-text · Article · Mar 2012 · Journal of Medical Virology
  • P. Bonnafous · A. Gautheret-Dejean · H. Agut
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    ABSTRACT: The human herpesvirus 6 (HHV-6) is an opportunistic agent like the genetically related human cytomegalovirus (HCMV). After primary infection usually occurring in childhood, it may reactivate during immunosuppression, leading to symptoms of varying severity, such as encephalitis. If no antiviral regimen has been formally approved yet, the anti-HCMV drugs, ganciclovir (GCV), cidofovir (CDV) and foscarnet (PFA), are also active in vitro and in vivo against HHV-6. However, prolonged treatment may lead to the selection of mutants resistant to these drugs. In recent years, resistant clinical or laboratory HHV-6 strains have emerged and have been studied. The involvement of various viral genomic mutations in the resistance has been addressed by different genetic, functional or structural approaches, enabling to understand the underlying molecular mechanisms. Until now, the evidence of the role of a mutation in GCV resistance has only been obtained for the M318V substitution of the viral phosphotransferase, enzyme involved in metabolism of GCV, by means of phenotype restoration tests. This technique remains to be developed to study mutations in the gene of the final target of antiviral drugs, the viral DNA polymerase.
    No preview · Article · Jan 2012 · Virologie
  • A. Gautheret-Dejean · P. Bonnafous · H. Agut
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    ABSTRACT: Le sixième herpesvirus humain est un Betaherpesvirus proche du cytomégalovirus infectant plus de 90 % de la population générale adulte. Agent de l’exanthème subit lors de la primo-infection, il est responsable de pathologies graves chez le sujet immunodéprimé pouvant conduire au décès des patients et nécessitant une prise en charge thérapeutique. À ce jour, seule la multiplication active du virus a été associée à des manifestations pathologiques. Or, le phénomène d’intégration du génome viral au génome cellulaire récemment mis en évidence soulève de nombreuses questions en termes de pathogénicité, réactivation et diagnostic. Lors d’une immunodépression, les marqueurs virologiques directs sont à privilégier pour le diagnostic et le suivi des infections avec, en premier lieu, la mesure de la charge virale dans le sang et les liquides biologiques. L’arsenal thérapeutique comporte des molécules agissant sur la synthèse du génome viral et s’enrichit peu à peu avec de nouvelles molécules. Cependant, aucun schéma thérapeutique standardisé n’a été établi jusqu’à présent et nous devons continuer nos recherches pour améliorer la connaissance de ce virus et de la prise en charge de ses infections.
    No preview · Article · Dec 2011 · Journal des Anti-Infectieux
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    ABSTRACT: Diagnosis of human herpesvirus-6A (HHV-6A), -6B (HHV-6B) or -7 (HHV-7) infections is often based on the measure of viral load in blood. The aim of this study was to define usual values of HHV-6A, HHV-6B and HHV-7 loads in blood fractions (whole blood [WB], mononuclear cells [PBMCs], polymorphonuclear leukocytes [PMNLs]) of blood donors. HHV-6A, HHV-6B and -7 DNAs were quantitated using real-time PCR assays in WB, PBMCs and PMNLs separated on Ficoll or dextran gradients, respectively, for 200 blood donors. Viral loads were expressed as the number of viral genomic copies per million cells (Cop/M) for all fractions, and also per milliliter for WB. HHV-6B DNA was rarely detected in WB (8%), PBMCs (16.5%), and PMNLs (10.5%), HHV-6A was never detected, whereas HHV-7 DNA was often present in WB (51.5%), PBMCs (62%) and PMNLs (51.5%). Median loads were low with 81 Cop/M in WB, 62 Cop/M in PBMCs and 34.5 Cop/M in PMNLs for HHV-6B, and 129 Cop/M in WB, 225 Cop/M in PBMCs and 62 Cop/M in PMNLs for HHV-7. Viral load expression per million cells and per mL were equivalent. One subject had chromosomally integrated HHV-6 with high viral loads ranging from 2.23×10(6) to 3.21×10(6) Cop/M in all compartments and plasma. These results allow to propose viral load in WB as a sensitive and suitable marker, with values for healthy subjects at approximately 100 Cop/M for both viruses. The prevalence of chromosomally integrated HHV-6 was 0.5%.
    No preview · Article · Nov 2011 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    ABSTRACT: The replication of human herpesvirus-6 (HHV-6) DNA is catalyzed by the viral DNA polymerase pU38 and the processivity factor pU27 which stabilizes the enzyme on the DNA template. The genetic polymorphism of pU27 among 46 clinical strains of HHV-6 variant A or B and four strains resistant to antivirals was investigated. Overall, 28 amino acid changes (7.6%) and a two-amino acid deletion were identified among the 368 residues of pU27, when using the U1102 (variant A) sequence as the reference. Eleven amino acid changes (3.0%) specifically differentiated both variants. The median intravariant amino acid variability was 1.2% and 0.3% for A and B, respectively. Except for a single change, the pU27 sequence of multi-drug resistant HHV-6 strains was also conserved. Structural models of pU27 for variants A and B were derived from that of the human cytomegalovirus homologue pUL44, and showed either identical or very similar residues in the regions interacting with viral DNA polymerase and viral DNA molecule. As pU27 is both highly conserved and essential for viral replication, it might constitute an interesting target for antiviral chemotherapy.
    Full-text · Article · Mar 2010 · Antiviral research
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    D Boutolleau · C Deback · J Géli · Z Aït-Arkoub · F Angleraud · A Gautheret-Dejean · H Agut
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    ABSTRACT: The Roche LightCycler 480 (LC480) system was evaluated for quantitative molecular diagnosis of opportunistic viral infections caused by human cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and BK virus (BKV), in comparison with "in-house" real-time PCR assays. A total of 253 whole blood specimens obtained from transplant recipients were tested. Both the "in-house" and the LC480 methods were highly correlated (Spearman correlation coefficient Rho> or =0.85; p<0.0001) with an excellent overall qualitative agreement (90.5%) and no significant quantitative difference between both techniques for the four viruses tested. The accuracy of the LC480 protocols were confirmed further by the results obtained with the 44 samples from the Quality Control for Molecular Diagnosis (QCMD) 2008 proficiency panel. The LC480 system constitutes a suitable and versatile real-time PCR platform in a routine laboratory setting for the diagnosis and monitoring of opportunistic viral infections in transplant recipients, by measuring HCMV, EBV, HHV-6, and BKV loads in whole blood samples.
    Full-text · Article · Nov 2009 · Pathologie Biologie
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    Henri Agut · David Boutolleau · Claire Deback · Pascale Bonnafous · Agnès Gautheret-Dejean
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    ABSTRACT: Herpesviruses cause chronic lifelong infections in humans and may cause life-threatening diseases in immunosuppressed patients. Antiviral drugs targeted to viral DNA polymerase, such as acyclovir, penciclovir, ganciclovir, foscarnet and cidofovir, are currently available and have been proven to be efficient against clinical symptoms of herpesvirus infections. The resistance of herpesviruses to these drugs is associated with specific mutations of viral genes encoding either DNA polymerase or enzymes phosphorylating nucleoside analogs. Resistance is detected and characterized by means of specific susceptibility assays, which can be classified as phenotypic, genetic and functional. These tests are used both to investigate novel antiviral compounds and look for the emergence of resistant viruses in treated patients in case of clinical failure. Although susceptibility assays are often time consuming and present some limitations regarding the interpretation of their results, their use in the monitoring of antiherpetic treatments should be promoted and improved, in parallel to the development of novel efficient drugs.
    Full-text · Article · Nov 2009 · Future Microbiology
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    ABSTRACT: Human immunodeficiency viruses (HIV) have a high level of genetic diversity. The outlier variants of HIV type 1 (HIV-1) group O are distantly related to HIV-1 group M. Their divergence has an impact on serological diagnosis, with a risk of false-negative results. In this study, we report 20 failure cases, involving patients with primary or chronic infection, in France and Cameroon between 2001 and 2008. Our results indicate that some assays detected group O infection much less efficiently than others. Two major reasons for these false-negative results were identified: the presence or absence of a group O-specific antigen (and the designed sequence) for the detection of antibodies and the greater envelope variability of group O than of group M strains. This study highlights the complexity of screening for these divergent variants and the need to evaluate test performance with a large panel of strains, due to the extensive diversity of group O variants.
    Full-text · Article · Aug 2009 · Journal of clinical microbiology
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    ABSTRACT: The Roche LightCycler 480 (LC480) system was evaluated for quantitative molecular diagnosis of opportunistic viral infections caused by human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and BK virus (BKV), in comparison with "in-house" real-time PCR assays. A total of 253 whole blood specimens obtained from transplant recipients were tested. Both the "in-house" and the LC480 methods were highly correlated (Spearman correlation coefficient Rho>or=0.85; p<0.0001) with an excellent overall qualitative agreement (90.5%) and no significant quantitative difference between both techniques for the four viruses tested. The accuracy of the LC480 protocols were confirmed further by the results obtained with the 44 samples from the Quality Control for Molecular Diagnosis (QCMD) 2008 proficiency panel. The LC480 system constitutes a suitable and versatile real-time PCR platform in a routine laboratory setting for the diagnosis and monitoring of opportunistic viral infections in transplant recipients, by measuring HCMV, EBV, HHV-6, and BKV loads in whole blood samples.
    Full-text · Article · Aug 2009 · Journal of virological methods

Publication Stats

1k Citations
249.20 Total Impact Points


  • 2006-2015
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • University of Nantes
      Naoned, Pays de la Loire, France
    • University of Leuven
      Louvain, Flemish, Belgium
  • 2003-2015
    • Université René Descartes - Paris 5
      • Faculté des Sciences Pharmaceutiques et Biologiques de Paris
      Lutetia Parisorum, Île-de-France, France
    • Laboratoire des Sciences du Climat et l'Environnement
      Gif, Île-de-France, France
  • 2009-2014
    • UPMC
      Pittsburgh, Pennsylvania, United States
    • University of Tours
      Tours, Centre, France
  • 1999-2014
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service de Virologie
      Lutetia Parisorum, Île-de-France, France
  • 2009-2010
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2006-2009
    • Pierre and Marie Curie University - Paris 6
      • Dynamique, épidémiologie et traitement des infections virales (ER 1)
      Lutetia Parisorum, Île-de-France, France