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Patients with chronic obstructive pulmonary disease (COPD) exhibit frequent acute exacerbations (AE). The objectives of this study were first to evaluate the prevalence of pathogens associated to these episodes by combining conventional bacteriology and multiplex viral and bacterial PCR assays in sputum specimens, and second to determine whether C-reactive protein (CRP) value and clinical outcome could be influenced by the type of microbial agent(s) recovered from these samples. A cohort of 84 Tunisian patients hospitalized at the emergency room for AECOPD was investigated prospectively for the semi-quantitative detection of bacteria by conventional culture (the threshold of positivity was of 10

This article reports the observed rate of infection with severe acute respiratory syndrome coronavirus-2 in healthcare workers (HCWs) who worked on wards dedicated to care of patients with coronavirus disease 2019 (COVID-19) compared with HCWs who worked on non-COVID-19 wards. The infection rate was significantly higher among HCWs who worked on non-COVID-19 wards (odds ratio 2.3, P=0.005), illustrating the need to strengthen social distancing measures and training.

Objectives This prospective study performed in the paediatric emergency department of the University Hospital of Saint-Etienne aimed to measure the impact of the 24/7 bedside use of the Veritor™ System (Becton Dickinson) on the reduction of supplementary investigations, hospital stay and antimicrobial use. Methods Influenza virus A and B antigens were detected with a rapid influenza digital immunoassay (DIA) on nasopharyngeal aspirates (NPAs) sampled from the children consulting at the paediatric emergency department between January and March 2016 for influenza-like illness. The same NPA was tested by immunofluorescence and/or molecular routine assays. Before performing the DIA, the clinician filled in a questionnaire listing the tests that he/she would have prescribed in the absence of the rapid testing. The prescription of complementary investigations, antimicrobial treatments and hospital stay were also compared to those of the 3 previous years. Results A total of 514 children with flu-like symptoms were included. The use of the DIA at bedside decreased the prescription of blood puncture by 47.9% (21.2% to 6.6%), of chest X-rays by 69.0% (33.3% to 10.3%), of lumbar puncture by 77.8% (7.0% to 1.6%), of urine culture by 79.2% (23.3% to 4.9%), of antibiotic treatments by 70.1% (16.9% to 5.1%), and of hospital stay by 25.0% (27.2% to 20.4%), resulting in a reduction of medical costs estimated to more than €69 000 in a season. Conclusions In addition to delivering a rapid aetiological diagnosis, this strategy saves medical costs and favours an antimicrobial stewardship strategy. However, further prospective studies are needed to confirm our findings.

BackgroundSARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. In this study, we wanted to assess the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralisation test.MethodsSera samples were collected from different populations: two-dose vaccinated COVID-19-naïve healthcare workers (HCWs; Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. We tested various clades such as 19A (initial one), 20B (B.1.1.241 lineage), 20I/501Y.V1 (B.1.1.7 lineage), and 20H/501Y.V2 (B.1.351 lineage).ResultsNo significant difference was observed between the 20B and 19A isolates for HCWs with mild COVID-19 and critical patients. However, a significant decrease in neutralisation ability was found for 20I/501Y.V1 in comparison with 19A isolate for critical patients and HCWs 6-months post infection. Concerning 20H/501Y.V2, all populations had a significant reduction in neutralising antibody titres in comparison with the 19A isolate. Interestingly, a significant difference in neutralisation capacity was observed for vaccinated HCWs between the two variants whereas it was not significant for the convalescent groups.ConclusionNeutralisation capacity was slightly reduced for critical patients and HCWs 6-months post infection. No neutralisation escape could be feared concerning the two variants of concern in both populations. The reduced neutralising response observed towards the 20H/501Y.V2 in comparison with the 19A and 20I/501Y.V1 isolates in fully immunized subjects with the BNT162b2 vaccine is a striking finding of the study.

This study assessed the diagnostic performance of the new coronavirus disease 2019 (COVID-19) SEROSpeed IgM/IgG Rapid Test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders)., This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen’s kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.

Background Oseltamivir shows effectiveness in reducing influenza-related symptoms, morbidity and mortality. Its prescription remains suboptimal. Objectives We aim to describe oseltamivir prescription in confirmed cases of influenza and to identify associated factors. Methods A prospective monocentric observational study was conducted between 1 December 2018 and 30 April 2019. All patients with a virologically confirmed influenza diagnosis were included. Factors associated with oseltamivir prescription were studied. Results Influenza was confirmed in 755 patients (483 children and 272 adults), of which 188 (25.1%) were hospitalized and 86 (11.4%) had signs of severity. Oseltamivir was prescribed for 452 patients (59.9%), more frequently in children than in adults [329/483 (68.1%) versus 123/272 (45.2%), P Conclusions Oseltamivir should be administered as early as possible, preferably within 24–48 h after illness onset, for the best benefits. It is, however, very important to promote the use of neuraminidase inhibitor (‘NAI’) treatment beyond 48 h in some specific patient populations.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection from re-infection and, thus, for public health policy and for vaccine development against the COVID-19. Here, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum specimens from a cohort of 140 SARS-CoV-2 qPCR-confirmed patients, including patient with mild symptoms but also more severe form including those that require intensive care. We show that nAb titers were strongly correlated with disease severity and with anti-Spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers, whereas patients with milder disease symptoms displayed heterogenous nAb titers and asymptomatic or exclusive outpatient care patients had no or poor nAb levels. We found that the nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery, as compared to individuals infected with alternative coronaviruses. We show the absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAb against SARS-CoV-2 infection. Finally, we found that the D614G mutation in the Spike protein, which has recently been identified as the major variant now found in Europe, does not allow neutralization escape. Altogether, our results contribute to the understanding of the immune correlate of SARS-CoV-2 induced disease and claim for a rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2.

Objectives: Our aim is to compare the course of the disease between healthcare workers (HCWs) and non-HCWs suffering from covid-19 and eligible for outpatient management. Methods: Single-center prospective cohort of outpatients with covid-19, diagnosed between the 10th March and the 2nd April, 2020 with a daily collection of symptoms by an on-line auto-questionnaire. Results: A total of 186 patients were included (median age, 41 years [interquartile range, 19-78 years]; 74.2% female), of whom 132 (71 %) were HCWs. The median follow-up after symptom onset was 14 (min 4 - max 24) days. HCWs were significantly younger than non HCWs (median age 40.3 years vs. 47.2 years [p

International audience; Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.

Background Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. Method A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016–2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. Results Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%–27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%–9.2%), 13.7% (95% CI: 9.9%–18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%–5.5%) for symptomatic influenza. Conclusions Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. Clinical Trials Registration NCT02868658.

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Introduction Une grande partie des connaissances en cours concernant la COVID-19 est basée sur les données des patients hospitalisés. Notre objectif est de décrire l’évolution au jour le jour de la COVID-19 dans les cas admissibles à une prise en charge ambulatoire. Matériels et méthodes Cohorte prospective monocentrique de patients présentant une infection par le SARS-CoV-2 confirmée virologiquement et présentant des symptômes modérés, admissibles à une prise en charge ambulatoire, entre le 10 mars et le 2 avril 2020. Les symptômes quotidiens ont été recueillis au moyen d’un auto-questionnaire en ligne. Nous avons considéré qu’un patient était guéri lorsqu’aucun des trois symptômes principaux (fièvre, dyspnée et douleur thoracique) n’était signalé après les derniers symptômes connus via l’application en ligne. Résultats Un total de 186 patients ont été inclus (âge médian, 41 ans [intervalle interquartile, 19–78 ans] ; 74,2 % de femmes), dont 132 (71 %) étaient des professionnels de santé. Treize patients (7 %) souffraient d’hypertension artérielle (la comorbidité la plus courante) et le suivi médian après l’apparition des symptômes était de 14 jours (min 4–max 24). Les professionnels de santé étaient significativement plus jeunes que les autres (âge médian de 40,3 ans contre 47,2 ans [p

to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients.HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads.from July 2012 to February 2015, 196 adult patients undergoing ASCT were enrolled. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19% at 40 days after transplantation. The onset of active HHV-6 infection occurred with a median of 13 days after stem cell re-infusion. HHV-6 infection was associated with an increased frequency of non-infectious complications (OR = 5.05; 95%CI 1.78-14.32; P 0.001). Moreover, the severity of these non-infectious complications was higher in recipients exhibiting HHV-6 infection (OR = 4.62; 95%CI 1.32-16.2; p 0.01). Delayed neutrophils 10 (IQR: 8-14) vs 8 (IQR: 6-11) days and platelets recoveries 15 (IQR: 11.8-18.5) vs 8 (IQR: 4-14) days were observed in patients with active HHV-6 infection compared to non-infected ones.in this study, 11.2% ASCT recipients presented active HHV-6 infection associated with significantly delayed hematologic reconstitution.

Mobile phones (MPs) of healthcare workers (HCWs) may represent an important source of transmission of infectious agents. This longitudinal study documents the contamination of these tools. Ten MPs handled by senior pediatricians were sampled once a week during 23 weeks in three pediatric wards of the University Hospital of Saint-Etienne, France. Cultures were performed for bacteria and multiplex PCR assays for a panel of respiratory and enteric viruses. A questionnaire on hygiene habits regarding phoning and care was filled-in by pediatricians before and after the study. From a total of 230 samples, 145 (63%) were contaminated by at least one pathogen. The MPs from emergency departments were the most impacted. Viruses were detected in 179 samples, bacteria were isolated in 59 samples. Contamination increased during the winter epidemic peak. A cross-contamination by Paracoccus yeei between hands and MPs of different HCWs was demonstrated. The communication of the study results influenced the hygiene behaviors. This study highlights the contamination of MPs by pathogens that are resistant in the environment, and its sustainability along the winter season. The role of MPs as vectors of nosocomial infection needs to be better investigated.

Emergency Departments (ED) of hospitals are greatly impacted by winter epidemics of respiratory diseases. To detect the underlying overcrowding, it is essential to study patient flow. In this paper we propose to model the admission flow corresponding to clinical diagnoses encoded with ICD-10 which are more likely linked with respiratory diseases. To achieve this, clustering algorithms are applied on time evolving diagnoses in the adult ED of Saint-Etienne and benchmarked regarding a time series of laboratory-confirmed influenza data. For both K-Means and Hierarchical algorithms, the cluster containing the laboratory-confirmed series is composed of ICD-10 codes of diagnoses representing respiratory diseases and diseases linked with cardiac disorders, showing that these diseases present similar variations overtime. The information contained in such a cluster makes it possible to plot the average number of arrivals of these diagnoses overtime and the average length of stay of the patients in the ED who only have one or several of these diagnoses. Such an acknowlegdement about its patient flow will allow an ED staff to detect the underlying overcrowding.

Background To achieve the 90-90-90 targets assigned by UNAIDS, it is crucial to monitor ART in HIV-1-infected patients, especially in resource-limited countries. Objectives To evaluate the immunovirological response after 12 months of ART in newly HIV-1-diagnosed people in Bamako, Mali; to determine primary and acquired resistance rates to antiretroviral drugs; and to evaluate the impact of primary resistance on the efficacy of ART. Patients and methods One hundred and nineteen HIV-1-infected people (88.2% women; median age 34 years) were enrolled between January and June 2014. HIV-1 RNA loads (Abbott RealTime HIV-1 assay) were tested in the blood before and at months 3, 6 and 12 after initiation of ART. Primary and acquired resistances to ART were evaluated by the Viroseq™ HIV-1 genotyping assay. Results During the study, 8.4% of people died and 37% were lost to follow-up. After 1 year of ART, an undetectable HIV-1 RNA viral load was found in 87.7% of cases. The overall rate of primary drug resistance mutations was 17.5% (3.2%, 15.9% and 0% for NRTIs, NNRTIs and PIs, respectively). These mutations were not associated with either higher mortality rates or larger numbers of virological failures. The acquired resistance rate was estimated at 3.1%. Conclusions Our study showed a high primary resistance level and a huge proportion of people non-adherent to the treatment programme. Reassuringly, almost 90% virological success and a low level of acquired mutations were observed in adherent people at month 12. Reinforced education, regular virological monitoring and early HIV-1 diagnosis may help to improve retention in the care system.

Seven commercial immunochromatographic assays intended for the detection of group A rotavirus antigens in human stool samples were evaluated. These assays showed similar levels of diagnostic accuracy and were suitable for the detection of rotavirus in patients with acute gastroenteritis but missed some asymptomatic rotavirus shedding identified by real-time reverse transcription-PCR.

Highlights • Systematic antimicrobials are recommended in community-acquired pneumonia of child. • A large panel of bacteria and viruses was detected in 85 children exhibiting CAP. • More than 60% of children with CAP exhibited an exclusive viral infection. • A co-infection with at least 2 viruses was observed in >40% of the children. • Data suggest that the use of antimicrobials in child's CAP should be revisited., Background The management of children with community-acquired pneumonia (CAP) is largely influenced by the development of new molecular diagnostic tests that allow the simultaneous detection of a wide range of pathogens. Objectives Evaluation of a diagnostic approach including multiplex PCR assays for revisiting the epidemiology and etiology of CAP in children at hospital. Study design Children of all ages consulting at the Emergency Department of the University hospital of Saint-Etienne, France, during the 2012–2013 winter period were included. In addition to bacterial cultures, the following pathogens were detected using biplex commercially-available rt-PCR tests: adenovirus, respiratory syncytial virus, human metapneumovirus, bocavirus, rhinovirus/enterovirus, coronavirus, influenza viruses A and B, parainfluenza viruses, Mycoplasma pneumoniae and Chlamydophila pneumonia. Results From 85 patients with CAP, at least one pathogen was identified in 81 cases (95.3%), including 4 bacterial exclusive infections (4.7%), 53 viral exclusive infections (62.4%) and 24 mixed infections (28.2%). Coinfection by at least two viruses was observed in 37 cases (43.5%). Mean age was higher in the case of documented bacterial infection (P

International audience; Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients. METHODS: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection. RESULTS: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR. CONCLUSIONS: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.

Morbidity and mortality of Herpes simplex virus encephalitis (HSE) remain high. Relapses of neurological signs may occur after initial clinical improvement under acyclovir treatment. We report here a case of post-HSE anti-N-methyl-d-aspartate receptor-mediated encephalitis in an adult and perform a systematic search on PubMed to identify other cases in adults. We identified 11 previously published cases, to discuss diagnostic and therapeutic management. Symptoms in adults are often inappropriate behaviors, confusion and agitation. Diagnosis of anti-NMDA-R encephalitis after HSE is often delayed. Treatment consists in steroids, plasma exchange, and rituximab. Prognosis is often favorable. Anti-NMDA-R antibodies should be searched in cerebrospinal fluid of patients with unexpected evolution of HSE. This emerging entity reopens the hot debate about steroids in HSE.

International audience; Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children

Distribution of Cytomegalovirus DNA Load in the Inflamed Colon of Ulcerative Colitis Patients

Resume Contexte En France, les infections a Rotavirus sont responsables chaque annee d’environ 300 000 episodes de gastroenterite aigue (GEA) chez les enfants de moins de cinq ans. Elles sont egalement a l’origine de 138 000 consultations en ville et de 18 000 hospitalisations. L’etude Surveillance for Hospitalized Rotavirus Infections in Kids (SHRIK) est une etude prospective observationnelle europeenne realisee afin d’evaluer le fardeau des gastroenterites a Rotavirus (GERV) chez ces enfants. Methode L’etude SHRIK se deroulait sur une periode d’un an et s’adressait aux patients de moins de cinq ans ayant consulte le service des urgences pour une gastroenterite aigue (GE-U), ayant ete hospitalises pour une gastroenterite aigue (GE-H) ou ayant developpe une GERV 48 heures apres leur hospitalisation (GE-N). Un echantillon de selles etait preleve pour chacun des enfants inclus et analyse par methode Elisa. Resultats Les resultats presentes concernent les patients inclus en France. Un total de 755 patients atteints de GEA et âges de moins de cinq ans a ete inclus (357 pour une GE-U, 372 pour une GE-H et 26 pour une GE-N). Parmi ces patients, la proportion de GERV etait de 49,1 % pour les GE-U (n = 114) et de 64,4 % pour les GE-H (n = 186). La majorite (89 %) des GERV concernait des enfants de moins de deux ans. Selon l’echelle de Vesikari, la GEA des patients GERV etait plus frequemment qualifiee de « severe » que celle des patients atteints de gastroenterite non a Rotavirus (GENRV) (68,4 % contre 41,9 %, p Conclusion L’etude SHRIK montre que le fardeau des infections a Rotavirus est eleve ; elles representent plus de 70 % des GEA traitees a l’hopital au cours du pic hivernal.

F. Forest, S. Duband, S. Pillet, M.-L. Stachowicz, J. Cornillon, J.-M. Dumollard, M. Peoc'h. Lethal human herpesvirus-6 encephalitis after cord blood transplant. Transpl Infect Dis 2011: 13: 646–649. All rights reserved Abstract: Clinical, biological, pathological, and imaging findings were all suggestive of lethal human herpesvirus-6-associated encephalitis in a 61-year-old man who had undergone a cord blood transplant. The neuropathological findings of this unusual autopsy case and the pathogenesis of this infection in immunocompromised patients are discussed.

We described two cases of acalculous cholecystitis (AAC), due to EBV primary infection in two young Caucasian women and we reviewed other reported cases. In contrast with AAC of other etiologies, antibiotics and surgery are not useful in the management of AAC secondary to EBV.

BACKGROUND Immunosuppressive therapies used for treating ulcerative colitis are known to favor chronic and latent viral diseases. This study aimed at evaluating prospectively the association between colonic cytomegalovirus (CMV) reactivation and anti-tumor necrosis factor (TNF) monoclonal antibodies (mabs) by comparison to azathioprine (AZA) in a series of flare-ups occurring in consecutive ulcerative colitis patients. METHODS A total of 109 flare-ups were recorded in 73 patients receiving a maintenance therapy by anti-TNF mabs (n = 69) or AZA (n = 40). The CMV DNA load in colonic tissue was determined by reverse transcription polymerase chain reaction on a pair of biopsies. RESULTS The number of CMV reactivation was of 35% and 38% in patients receiving anti-TNF mabs and AZA, respectively. The median of CMV DNA load was 378 [10-29,800] and 8300 [10-3,25,000] copies/mg of tissue in patients treated by anti-TNF mabs and AZA, respectively (P = 0.11 by Mann-Whitney U test). In a subgroup of 45 patients under anti-TNF mabs requiring an optimized treatment by infliximab, clinical remission (partial Mayo score

The evaluation of the fully automated BD MAX Cdiff assay on a panel of 100 stool samples characterized by the Xpert C. difficile assay reported a high concordance between the two molecular assays (kappa coefficient of 0.96), which makes this new assay suitable for routine detection of toxigenic Clostridium difficile.

Introduction Human Herpes Virus 6 (HHV-6) is an opportunistic and potentially life-threatening infectious agent frequently identified after allogeneic hematopoietic cell transplantation (allo-SCT). In autologous hematopoietic stem cell transplantation (ASCT) setting, although the immune system recovery is rapid and the risk of infection lower in ASCT recipients than allo-SCT ones, cell immunity is impaired and some recipients may develop prolonged myelosuppression, delayed platelet recovery, diarrhea, skin rashes compatible with HHV-6 infection. The primary objective was to evaluate the incidence of HHV-6 infection in ASCT recipients; secondary objectives were to analyze the clinical relevance of this infection on hematopoietic reconstitution, CMV co-infections and other infectious and non-infectious complications. Patients and methods From July 2012 to February 2015, 196 patients undergoing ASCT were enrolled in the prospective multicentric VIRAUTO6 study (NCT02090803). HHV-6 DNA load was measured by quantitative PCR in whole blood specimens once during the 7 days before transplantation and prospectively once a week after transplantation until hematopoietic recovery defined as ANC > 1 x 109/L and platelets > 50 x 109/L with transfusion support cessation. Active HHV-6 and CMV infections were defined as 2 consecutive blood HHV-6/CMV DNAemias ≥ 450 copies/mL, one week apart. Chemotherapy related toxicities were assessed according to the WHO classification. Results The median age of this cohort (127 male, 64.8%) was 59.4 (52.5; 64.8) years. Underlying hematological diseases were lymphoma (108, 55.1%), myeloma (86, 43.9%) and leukemia (1, 0.5%). At transplantation, complete remission or very good partial remission were observed in 125 patients (63.8%), and partial response or refractory disease for others (71, 36.2%). Bicnu-Etoposide-Aracytine-Melphalan (BEAM) conditioning regimen was used in 93 patients (47.4%) and melphalan alone conditioning regimen in 87 patients (44.4%). The median follow-up was 16 (14; 20) days. The median ANC and platelets recovery was 9 (7; 12) days and 15 (10; 25) days, respectively. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19.2% at 40 days after transplantation. Among them, only one patient had CMV infection in the same period. The onset of active HHV-6 infection occurred with a median of 13 (12; 15.8) days after transplantation and with a median blood HHV-6 DNAemia of 7,035 (1,192; 19,875) copies/mL. HHV-6 infection occurred less frequently in patients with Melphalan conditioning regimen compared to BEAM alone (OR 0.11; 95%CI 0.02-0.47; p HHV-6 disease occurred in 3 patients (1.5% of the cohort): 2 patients had skin rash with positive skin biopsy for HHV-6 DNA and one patient had fever with no other cause than HHV-6 infection. For 2 patients, ganciclovir treatment was introduced for a median of 11.5 (9.8; 13.2) days. Delayed neutrophils and platelets engraftments were noted with an increased median duration of ANC: 11 (9; 16) vs 9 (7; 12) days; p=0.004) and platelets: 25 (14; 29) vs 15 (10; 24) days; p=0.011 recovery in recipients with HHV-6 infection compared to those without HHV-6 infection. The kinetics of platelets recovery according to HHV-6 infection are shown in figure 1. Conclusion This work relates the first prospective multicentric study assessing incidence and clinical impact of HHV-6 infection in ASCT recipients. Our study supports that 11.2% patients undergoing ASCT had HHV-6 Infection with significantly different outcomes, especially delayed hematopoietic reconstitution. Figure 1. platelets recovery > 20 x 109/L ; p-value = 0.009 Figure 1. platelets recovery > 20 x 109/L ; p-value = 0.009 Figure 2. platelets recovery > 50 x 109/L ; p-value = 0.007 Figure 2. platelets recovery > 50 x 109/L ; p-value = 0.007 Disclosures Augeul-Meunier: janssen: Consultancy; gilead: Consultancy. Salles:Novartis: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Mundipharma: Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.

Summary Background Consequences of latent cytomegalovirus (CMV) infection reactivation on inflammatory bowel disease (IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. Aim To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. Methods First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment (n = 26), were compared to matched patients with negative blood CMV PCR in a case–control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. Results In the case–control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. Conclusions CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively.

Cytomegalovirus is a deoxyribonucleic acid virus that infects a large part of the human population; after primary infection, it develops a latent state and can be reactivated, notably after a decrease in host immune defences. In patients with inflammatory bowel diseases, cytomegalovirus is frequently involved, either as an agent of colitis or through local asymptomatic reactivation. Due to the immune context of inflammatory bowel diseases and to the immunosuppressive therapies that are used to treat them, cytomegalovirus entertains complex relationships with these diseases. Whereas Crohn's disease seems little impacted by cytomegalovirus, this agent interferes strongly with the natural progression of ulcerative colitis. While immune treatments have a clear influence on the occurrence of cytomegalovirus colitis in ulcerative colitis (favourable for steroids and cyclosporine and rather inhibitory for infliximab), the role of cytomegalovirus infection on ulcerative colitis is more debated with roles ranging from innocent bystander to key pathogen suggested. There is however growing evidence for a participation of intestinal cytomegalovirus infection in the resistance of ulcerative colitis to steroids and the investigation of cytomegalovirus infection in intestinal biopsies by immunohistochemistry or quantitative polymerase chain reaction assay is strongly recommended. In several studies, treatment of cytomegalovirus infection by ganciclovir was shown to restore the response to immunomodulatory therapies and even to prevent the need for colectomy. All of these recently acquired data need to be validated by randomised clinical trials conducted on a large panel of ulcerative colitis patients.

Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-ups of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy was evaluated in intestinal tissue.Forty-two consecutive patients (sex ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were included prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines.Sixteen patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue; all of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7; 95% confidence interval: 1.2-22.5). A CMV DNA load above 250 copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+=4.33; area under the receiver-operating characteristic curve=0.85). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir; a clinical remission was observed in seven cases, with a sustained response in five of them.The CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC. Initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.

International audience; Objectives Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540). Patients and methods Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected. Results Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance. Conclusions These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.

Relationship between respiratory morbidity and influenza virus has been well-documented in infants, whatever their age. However, in spite of severe cardiac and respiratory events of central origin, autonomic dysfunction potentially induced by this virus is poorly understood. We thus explored the autonomic nervous system (ANS) profile of infected infants during the 2009 pandemic influenza disease.A group of 10 consecutive infants (51 year and 51 year) presenting with nvH1N1 infection was evaluated with heart rate variability (HRV) and spontaneous baroreflex (SBR) through a recording during a 15-minute period of quiet sleep as well as 24h holter monitoring. The same recordings were performed in 10 control subjects, paired for gestational and postnatal age. HRV sympathetic and parasympathetic (VLF, LF and HF) indices were obtained using spectral-domain analysis, and spontaneous baroreflex sensitivity (SBR) using simultaneous non-invasive continuous measure of arterial pressure and heart rate.The group of infants less than 1 year had similar value as control group. Conversely, the group of infants more than 1 year showed significant lower spectral total power values (Ptot: 3347 vs. 5926 ms(2)/Hz, p0.1) and significant lower VLF, LF and HF indices (all p0.05) than the control group.nvH1N1 infection in child could be associated with severe central autonomic dysfunction. Due to potential severe consequences, a systematic evaluation of autonomic regulation should be performed in order to avoid dramatic events.

Resume Introduction La rupture de rate est une complication exceptionnelle de la primo-infection a cytomegalovirus (CMV). Observations Nous rapportons 2 cas de rupture spontanee de rate au cours d'une primo-infection a CMV chez des sujets immunocompetents. Dans un cas une profonde anemie par carence martiale etait presente, et dans le second, un deficit en pyruvate kinase a ete mis en evidence. Les 2 cas furent traites de facon conservatrice avec succes. Discussion Neuf autres cas publies dans la litterature medicale sont egalement revus. Ils ne permettent pas de mettre en evidence de facteurs de risque particuliers pour cette complication.

The aim of the study was to evaluate the performance of the combined antigen and antibody HIV screening assay VIDAS HIV DUO Ultra (BioMerieux, Marcy l'Etoile, France) in comparison with two other combined tests: the former version of the same test (VIDAS HIV DUO, BioMerieux) and the AxSYM HIV Ag/Ab Combo assay (Abbott Laboratories, Rungis, France). A prospective study was performed on serum specimens received on a routine basis for HIV testing: 1443 blood samples were tested with the three assays. Sensitivity was 100% for the three tests. Specificity assessed on repeated false-positive samples was 99.86, 99.03 and 99.65% for VIDAS HIV DUO Ultra, VIDAS HIV DUO and AxSYM HIV Ag/Ab Combo, respectively. In addition, 14 seroconversion panels were tested with the VIDAS DUO Ultra and AxSYM HIV Ag/Ab Combo assays. For four of these panels, a positive signal was detected one blood sampling point earlier with the VIDAS DUO Ultra assay, corresponding to a higher sensitivity of the HIV antigen test. These results indicate that the VIDAS HIV DUO Ultra exhibits an improved specificity with comparison to the former version of this assay and an excellent sensitivity for early detection of HIV seroconversion.

In 1967 Andre Lwoff published in Nature, “Principles of Classification and Nomenclature of Viruses” (Nature 215:13–14). Such a classification rested on cryptogram with morphological and molecular characters. This classification, in addition to its heuristic value, was very useful notably for teaching.

Since the declaration of the novel influenza A (H1N1) pandemic by the World Health Organization in June 2009, several neurologic complications have been reported including encephalitis, encephalopathy, seizures, and neuropsychiatric perturbations [1, 2]. Most of the cases concerned children [1] and had a benign course with early and appropriate management. When performed, brain magnetic resonance imaging (MRI) was normal. We report the first case of H1N1 virus related to acute hemorrhagic leukoencephalopathy. A 56-year-old Caucasian woman without past medical history consulted her general practitioner 24 h after the onset of an influenza syndrome. She received imipenem per os 2 g per day for 10 days. On the fifth day, the patient was referred for permanent dyspnea, headache, and 38.5 C fever. No cognitive changes were observed. Pulmonary auscultation found crackles. A chest X-ray showed features of acute respiratory distress syndrome with bilateral infiltrative opacities. At admission, H1N1 was isolated from nasopharyngeal specimens by reverse-transcription polymerase chain reaction (RT-PCR) [3]. The virus could not be isolated by cell culture for sequencing. One hundred fifty milligrams oseltamivir and 40 mg methylprednisolone intravenous per day were administered over 5 days while imipenem was continued. On the sixth day, massive oxygen desaturation occurred despite noninvasive oxygenotherapy. The patient became comatose. She was transferred to the intensive care unit. Mechanical ventilation was then performed after intubation. Brain MRI with T2-, T2*-, and T1-weighted sequences with and without gadolinium infusion showed extensive bilateral hemispheric leukoencephalopathy predominating in the subcortical regions and extending in the right striatum. Several microbleeds were present in the same territories (Fig. 1a–g). MRI angiography was normal. Electroencephalography recorded bilateral slow waves. Cerebrospinal fluid (CSF) was xanthochromic and contained 0.51 g/L protein in a polyclonal pattern with 90 red blood cells and 8 lymphocytes/ mm. PCR was negative for cytomegalovirus, herpes simplex, Epstein–Barr, and H1N1 viruses. Specific antiH1N1 antibody titer determined by hemagglutination inhibition against the A/California/7/2009 strain was 10 in CSF and more than 1,280 in serum. Culture for bacteria and mycosis remained sterile. Neither antinuclear nor onconeural antibodies were noted. On the tenth day, the patient awoke but was deeply confused. The Mini-Mental State Examination (MMSE) score was 19/30 with deficit in time and space orientation and calculation errors. Neurological examination found a left pyramidal syndrome with 4/5 Medical Research Council score on limb muscle testing. Diagnosis of acute partially hemorrhagic leukoencephalopathy linked to the H1N1 virus was reached, and steroid therapy started with methylprednisolone 500 mg daily for 3 days. On the 40th day, muscle strength was normal. The MMSE was 29/30. An extensive neuropsychological expertise showed minor abnormalities with normal memory, verbal comprehension, and executive F. A. Cisse J.-C. Antoine G. Jousserand J.-P. Camdessanche (&) Department of Neurology, University Hospital, 42055 Saint-Etienne Cedex 02, France e-mail: j.philippe.camdessanche@chu-st-etienne.fr

M. Delvincourt1, A. Lopez2, S. Pillet2, A. Bourrier1, P. Seksik1, J. Cosnes1, F. Carrat3, J. Gozlan4, L. Beaugerie1, X. Roblin5, L. Peyrin-Biroulet2, H. Sokol1 *. 1APHP St Antoine Hospital, Gastroenterology, Paris, France, 2Nancy Hospital, Gastroenterology, Nancy, France, 3APHP St Antoine Hospital, Public health, Paris, France, 4APHP St Antoine Hospital, Virology, Paris, France, 5Saint Etienne Hospital, Gastroenterology, France