Laboratoire Of Microbiologie Clinique

Paris, France

Laboratoire Of Microbiologie Clinique

Paris, France

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Chaillon A.,University of California at San Diego | Essat A.,University Paris - Sud | Frange P.,University of Paris Descartes | Frange P.,Laboratoire Of Microbiologie Clinique | And 22 more authors.
Retrovirology | Year: 2017

Background: Characterizing HIV-1 transmission networks can be important in understanding the evolutionary patterns and geospatial spread of the epidemic. We reconstructed the broad molecular epidemiology of HIV from individuals with primary HIV-1 infection (PHI) enrolled in France in the ANRS PRIMO C06 cohort over 15 years. Results: Sociodemographic, geographic, clinical, biological and pol sequence data from 1356 patients were collected between 1999 and 2014. Network analysis was performed to infer genetic relationships, i.e. clusters of transmission, between HIV-1 sequences. Bayesian coalescent-based methods were used to examine the temporal and spatial dynamics of identified clusters from different regions in France. We also evaluated the use of network information to target prevention efforts. Participants were mostly Caucasian (85.9%) and men (86.7%) who reported sex with men (MSM, 71.4%). Overall, 387 individuals (28.5%) were involved in clusters: 156 patients (11.5%) in 78 dyads and 231 participants (17%) in 42 larger clusters (median size: 4, range 3-41). Compared to individuals with single PHI (n = 969), those in clusters were more frequently men (95.9 vs 83%, p < 0.01), MSM (85.8 vs 65.6%, p < 0.01) and infected with CRF02_AG (20.4 vs 13.4%, p < 0.01). Reconstruction of viral migrations across time suggests that Paris area was the major hub of dissemination of both subtype B and CRF02_AG epidemics. By targeting clustering individuals belonging to the identified active transmission network before 2010, 60 of the 143 onward transmissions could have been prevented. Conclusion: These analyses support the hypothesis of a recent and rapid rise of CRF02_AG within the French HIV-1 epidemic among MSM. Combined with a short turnaround time for sample processing, targeting prevention efforts based on phylogenetic monitoring may be an efficient way to deliver prevention interventions but would require near real time targeted interventions on the identified index cases and their partners. © 2017 The Author(s).


Avettand-Fenoe V.,University of Paris Descartes | Avettand-Fenoe V.,Laboratoire Of Virologie | Hocqueloux L.,CHR dOrleans | Ghosn J.,University of Paris Descartes | And 7 more authors.
Clinical Microbiology Reviews | Year: 2016

HIV-1DNApersists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIVDNAload in blood is also predictive of the presenceandseverity ofsomeHIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replicationcompetent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis. © 2016, American Society for Microbiology. All Rights Reserved.


Frange P.,Laboratoire Of Microbiologie Clinique | Frange P.,University of Paris Descartes | Faye A.,Service de Pediatrie Generale | Faye A.,University Paris Diderot | And 16 more authors.
The Lancet HIV | Year: 2016

Background: Durable HIV-1 remission after interruption of combined antiretroviral therapy (ART) has been reported in some adults who started treatment during primary infection; however, whether long-term remission in vertically infected children is possible was unknown. We report a case of a young adult perinatally infected with HIV-1 with viral remission despite long-term treatment interruption. Methods: The patient was identified in the ANRS EPF-CO10 paediatric cohort among 100 children infected with HIV perinatally who started ART before 6 months of age. HIV RNA viral load and CD4 cell counts were monitored from birth. Ultrasensitive HIV RNA, peripheral blood mononuclear cell (PBMC)-associated HIV DNA, HIV-specific T-cell responses (ie, production of cytokines and capacity to suppress HIV infection), reactivation of the CD4 cell reservoir (measured by p24 ELISA and HIV RNA in supernatants upon phytohaemagglutinin activation of purified CD4 cells), and plasma concentrations of antiretroviral drugs were assessed after 10 years of documented control offtherapy. Findings: The infant was born in 1996 to a woman with uncontrolled HIV-1 viraemia and received zidovudine-based prophylaxis for 6 weeks. HIV RNA and DNA were not detected 3 days and 14 days after birth. HIV DNA was detected at 4 weeks of age. HIV RNA reached 2·17× 106 copies per mL at 3 months of age and ART was started. HIV RNA was undetectable 1 month later. ART was discontinued by the family at some point between 5·8 and 6·8 years of age. HIV RNA was undetectable at 6·8 years of age and ART was not resumed. HIV RNA has remained below 50 copies per mL and CD4 cell counts stable through to 18·6 years of age. After 11·5 years of control offtreatment, HIV RNA was below 4 copies per mL and HIV DNA was 2·2 log10 copies per 106 PBMCs. The HLA genotype showed homozygosity at several loci (A*2301-, B*1503/4101, C*0210/0802, DRB1*1101-, and DQB1*0602-). HIV-specific CD8 T-cell responses and T-cell activation were weak. Interpretation: Findings from this case suggest that long-term HIV-1 remission is possible in perinatally infected children who receive treatment early, with characteristics similar to those reported in adult HIV post-treatment controllers. Further studies are needed to understand the mechanisms associated with HIV remission and whether early treatment of infected children might favour the conditions needed to achieve HIV control after treatment discontinuation. Funding: Agence de recherche ANRS (France Recherche Nord & Sud Sida-HIV Hépatites). © 2016 Elsevier Ltd.


Leruez-Ville M.,University of Paris Descartes | Leruez-Ville M.,Laboratoire Of Microbiologie Clinique | Leruez-Ville M.,Center National Of Reference Cytomegalovirus Laboratoire Associe | Stirnemann J.,University of Paris Descartes | And 9 more authors.
American Journal of Obstetrics and Gynecology | Year: 2016

Background: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. Objective: We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. Study Design: We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. Results: In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm3, and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. Conclusion: Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling. © 2016 Elsevier Inc.


PubMed | CNR Institute of Neuroscience, Laboratoire Of Microbiologie Clinique, Hopitaux Universitaires Paris Nord Val Of Seine, Unite de Bacteriologie Hygiene and 9 more.
Type: Journal Article | Journal: The Journal of hospital infection | Year: 2015

The impact of Clostridium difficile infection (CDI) on healthcare costs is significant due to the extra costs of associated inpatient care. However, the specific contribution of recurrences has rarely been studied.The aim of this study was to estimate the hospital costs of CDI and the fraction attributable to recurrences in French acute-care hospitals.A retrospective study was performed for 2011 on a sample of 12 large acute-care hospitals. CDI costs were estimated from both hospital and public insurance perspectives. For each stay, CDI additional costs were estimated by comparison to controls without CDI extracted from the national DRG (diagnosis-related group) database and matched on DRG, age and sex. When CDI was the primary diagnosis, the full cost of stay was used.A total of 1067 bacteriological cases of CDI were identified corresponding to 979 stays involving 906 different patients. Recurrence(s) were identified in 118 (12%) of these stays with 51.7% of them having occurred within the same stay as the index episode. Their mean length of stay was 63.8 days compared to 25.1 days for stays with an index case only. The mean extra cost per stay with CDI was estimated at 9,575 (median: 7,514). The extra cost of CDI in public acute-care hospitals was extrapolated to 163.1 million at the national level, of which 12.5% was attributable to recurrences.The economic burden of CDI is substantial and directly impacts healthcare systems in France.


PubMed | Institute Pasteur Paris, Laboratoire Of Microbiologie Clinique, University of Paris Descartes and Paris-Sorbonne University
Type: Journal Article | Journal: Medecine et maladies infectieuses | Year: 2015

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised adults and children, the number of which has been continuously increasing in the last decades. The purpose of our review was to provide epidemiological, clinical, and biological data and antifungal treatment options in the pediatric population. Several biological assays (galactomannan enzyme immunoassay, -D-glucan, detection of Aspergillus spp. DNA) have proven useful adjuncts for the diagnosis of IA in adult studies. However, data on these assays in children is limited by small sample sizes and sometimes conflicting results concerning their sensitivity/specificity. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. It is thus necessary to develop new antifungal formulations specifically adapted to the pediatric population and to evaluate their pharmacokinetic/pharmacodynamic profile, their safety, and their effectiveness in infants and children.


Camelena F.,Laboratoire Of Microbiologie Clinique | Pilmis B.,Equipe mobile de microbiologie clinique | Mollo B.,Equipe mobile de microbiologie clinique | Hadj A.,Service de chirurgie orthopedique | And 2 more authors.
Anaerobe | Year: 2016

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T. praeacuta. The patient was successfully treated by piperacillin - tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole. © 2016 Elsevier Ltd.


Cassir N.,Aix - Marseille University | Hraiech S.,Aix - Marseille University | Nougairede A.,Aix - Marseille University | Nougairede A.,Laboratoire Of Microbiologie Clinique | And 3 more authors.
Eurosurveillance | Year: 2014

We herein describe and analyse the first outbreak of severe pneumonia caused by human adenovirus type 1 (HAdV C type 1), which included immunocompetent patients in an intensive care unit (ICU) of Marseille, France, and occurred between September and October 2012. Seven successive patients were diagnosed by HAdV specific real-time polymerase chain reaction with a positive bronchoalveolar lavage. After the collection of nasopharyngeal swabs from healthcare workers, three nurses working night shifts tested positive for HAdV C including one that had exhibited respiratory signs while working one week before the outbreak. She was the most likely source of the outbreak. Our findings suggest that HAdV-1 could be considered as a possible cause of severe pneumonia even in immunocompetent patients with a potential to cause outbreaks in ICUs. HAdV rapid identification and typing is needed to curtail the spread of this pathogen. Reinforcing hand hygiene with antiseptics with demonstrated activity against non-enveloped viruses and ensuring that HCWs with febrile respiratory symptoms avoid direct patient contact are critical measures to prevent transmission of HAdV in healthcare settings. ©2007-2013. All rights reserved.


PubMed | Service de chirurgie orthopedique, Equipe mobile de microbiologie clinique and Laboratoire Of Microbiologie Clinique
Type: | Journal: Anaerobe | Year: 2016

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T.praeacuta. The patient was successfully treated by piperacillin - tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole.


Frange P.,Laboratoire Of Microbiologie Clinique | Frange P.,University of Paris Descartes | Frange P.,CNR Institute of Neuroscience | Leruez-Ville M.,Laboratoire Of Microbiologie Clinique | And 2 more authors.
Reanimation | Year: 2016

Cytomegalovirus (CMV) infection is a common complication in immunodeficient patients, especially after haematopoietic stem cell or solid organ transplantation, and it is associated with multiple direct and indirect effects. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. However, therapeutic options ([val]ganciclovir, foscarnet, cidofovir) are still limited and could expose to severe toxicities. Moreover, drug-resistant CMV infection is now increasing in incidence. After many years during which we have seen few tangible advances in terms of new antiviral drugs, we are now experiencing an exciting period of late-stage drug development, characterized by a series of phase III trials incorporating a variety of novel agents (especially letermovirir and brincidofovir).This article reviews the current state of treatment of severe CMV infections and summarizes the data on investigational drugs in clinical development. © 2015, Société de réanimation de langue française (SRLF) and Springer-Verlag France.

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