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Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

Influenza viruses and severe acute respiratory syndrome coronavirus 2 are respiratory viruses with a high potential for evolution. Their circulation must be carefully monitored.. The development of diagnostic tools, as well as the search for universal vaccines and new treatments, are strategic tools in public health that allow us to be ready to face future emergencies.

After the huge decrease of measles thanks to vaccination, measles reappeared in 2008, with 604 cases reported at the Institut national de veille sanitaire (InVS), then 1,544 cases in 2009 and 2,605 cases up to 2010, June. At the same time, 86 viral strains were detected from saliva samples at the Centre national de référence de la rougeole et des Paramyxoviridae respiratoires (CNR) in 2008, 316 in 2009 and 946 up to August 2010. The reality of the outbreak was confirmed by the increase of the endemic cases: 0.0009% cases in 2008 and 0.004% in 2010, the diffusion to all parts of France, and the more specific attack of infants: 4% in 2008 and 9% in 2010, and of young adults: 17% in 2008 and 38% in 2010. Most of the cases (82%) occurred in non-vaccinated people. The number of hospitalised cases has increased as well, going from 18% in 2008 to 34% in 2010. The strain of this outbreak is a genotype D4. It appeared in 2008 then it spread in 2009 and 2010, representing 19, 75 and 99% of the strains, respectively. All the viruses in this genotype belonged to the Montreal-like cluster described in 1989: Montréal.CAN/89xD4. At the beginning of the outbreak some were closed to a variant which appeared in England in 2007 MVs/Enfield.GBR/14.07(D4), but most of them (95%) are nowidentical to a strain which caused a small focus of measles in the region Vendee at the last trimester 2008: MVs/Montaigu.FRA/43.08(D4). The salivary diagnosis of measles, which was introduced in France in 2005, in parallel to the obligation of reporting measles cases, has been proved very efficient: 75% of saliva are collected in the first four days, and viral RNA was detected in 536 (81%) out the 660 samples received at the CNR up to now in 2010; 136 (21%) saliva had IgM specific antibodies and 18% had neither RNA, nor IgM.

Les virus grippaux et le severe acute respiratory syndrome coronavirus 2 sont des virus respiratoires dont le potentiel évolutif est important. Leur circulation doit être surveillée attentivement. Le développement des moyens de diagnostic, ainsi que la recherche de vaccins universels et de nouveaux traitements sont des outils stratégiques en santé publique permettant de se tenir prêts pour faire face à de futures émergences.

Background Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). Several cohorts reported that people treated by tenofovir disoproxil fumarate and emtricitabine are less likely to develop SARS CoV-2 infection and related severe COVID-19. Methods We conducted a pilot randomized, open-label, controlled, phase 2 trial at two hospitals in France. Eligible patients were consecutive outpatients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and an interval from symptom onset to enrolment of 7 days or less. Patients were randomly assigned in a 1:1 ratio to receive oral tenofovir disoproxil fumarate and emtricitabine (2 pills on day 1 followed by 1 pill per day on days 2–7) or the standard of care. The primary and secondary endpoints were SARS-CoV-2 viral clearance from baseline assessed by cycle threshold (Ct) RT-PCR on nasopharyngeal swab collected at day 4 and day 7, respectively. A higher Ct corresponds to a lower SARS CoV-2 viral burden. Other endpoints were the time to recovery and the number of adverse events. This trial is registered with ClinicalTrials.gov, NCT04685512. Findings From November, 20th 2020 to March, 19th 2021, 60 patients were enrolled and randomly assigned to a treatment group (30 to tenofovir disoproxil fumarate and emtricitabine and 30 to standard of care). The median number of days from symptom onset to inclusion was 4 days (IQR 3–5) in both groups. Amongst patients who received tenofovir disoproxil fumarate, the difference from standard of care in the increase in Ct RT-PCR from baseline was 2.3 (95% confidence interval [-0.6 to 5.2], p = 0.13) at day 4 and 2.9 (95% CI [0.1 to 5.2], p = 0.044) at day 7. At day 7, 6/30 in the tenofovir disoproxil fumarate and emtricitabine group and 3/30 in the standard of care group reported no COVID-related symptoms. Adverse events included 11 cases of gastrointestinal side effects (grade ≤ 2), three of which leaded to drug discontinuation. Three patients had COVID-19 related hospitalisation, no participant died. Interpretation In this pilot study of outpatients adult with recent non-severe COVID-19, tenofovir disoproxil fumarate plus emtricitabine appeared to accelerate the natural clearance of nasopharyngeal SARS-CoV-2 viral burden. These findings support the conduct of larger trials of tenofovir-based therapies for the prevention and early treatment of COVID-19. Funding No external funding.

Background Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. Materials and methods A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. Results Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0–0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. Conclusions This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.

Background Measles remains endemic worldwide, despite current vaccination recommendations, and is associated with high morbidity and mortality rates. We describe all cases hospitalized in Bordeaux University Hospital (BUH), the starting point of a national significant measles outbreak in 2017–2018. Methods In this retrospective study, we included all patients hospitalized in BUH from September 1, 2017, to May 31, 2018. Inclusion criteria were age >1 year, clinical symptoms, and biological confirmation by measles immunoglobulin M or measles reverse transcription polymerase chain reaction positivity. Results We included 171 patients. Most patients were immunocompetent; only 19% had preexisting medical histories. Most patients had rash and fever (97%), but some cases were atypical and difficult to diagnose. Köplik’s spots were reported in 66 cases (38%). The most frequent biological markers were blood inflammation markers (96%) and lymphopenia (81%). Unexpectedly, we found hyponatremia ( Conclusions During the BUH outbreak, measles was often complicated and sometimes atypical. Vaccination coverage was dramatically insufficient. We also describe vaccination failure cases that must be better investigated.

Prolonged measles virus detection in maternal saliva and blood was evidenced in 6 pregnant women. Maternal-fetal transmission was evidenced in 2 of 4 infants who were asymptomatic at birth, 21–24 weeks after maternal infection. Whereas peripartum congenital measles is severe, asymptomatic measles virus vertical transmission can occur earlier in pregnancy.

Hundred viruses can be isolated in patients suffering from respiratory virus infections and hospitalised in intensive care unit (ICU): influenza virus, respiratory syncytial virus, para-influenza virus, adenovirus, coronavirus, rhinovirus, enterovirus, human metapneumovirus, bocavirus… Nasal or tracheobronchial specimens, which contain many epithelial cells will be used to isolate these common viruses. In immunocompromised patients a bronchoalveolar lavage has to be added to these specimens in order to detect cytomegalovirus and some adenovirus. The immunofluorescence or immunoenzymatic assays, which detect viral antigens in the infected cells are the easiest and fastest diagnostic methods, theoretically. As with other techniques, specimen quality is a major determinant of their performance. Unfortunately, the sensitivity of the antigen detection assays is low in respiratory infections in adults. Then the virus recovery by cell culture, which is usually more sensitive than the antigen detection assays, can be helpful. Many studies have reported more respiratory virus detections using nucleic acid testing such as PCR. They detect viruses, which are missed by conventional methods and increase the detection of common respiratory virus. Multiplex PCR assays have been developed, and these can simultaneously detect several viruses directly in clinical specimens. Nucleic acid testing can subtype viruses using subtype-specific primers, and analyse strain variation through genetic. It can be used also to quantify the viral load in clinical specimens. More recently real-time RT-PCR assays have been developed to get more rapidly the results of the nucleic acids assays. Specimen quality, timing and transportation conditions may be less critical for nucleic acid testing than for culture or antigen detection, as viable virus and intact infected cells need not to be preserved. Moreover, viral nucleic acids are detectable for several days longer into the clinical course than is cultivable virus, potentially allowing a diagnosis to be made in late-presenting patients. However, in a clinical virology laboratory, where the speed, low cost, and high sensitivity of the methods are required, the sequential use of antigen detection tests and multiplex PCR could be the best choice, particularly in the clinical setting of respiratory virus infections in adults hospitalised in ICU. In the future, the development of real-time multiplex PCR is likely to be top-priority.

Once very common in children, mumps virus infection is now much rarer thanks to vaccination, recommended in the majority of countries in the world. This virus of the family Paramyxoviridae has a marked tropism for glandular tissues which explains the great diversity of pathologies related to this virus, including parotitis, orchitis or meningitis. Due to the lower circulation of the virus, the proportion of infected adults increases. A surveillance system for mumps virus infections at the national and international levels is organized, particularly at the molecular level. In France, it is provided by the national reference center for Measles, Mumps and Rubella. Although it has led to a significant reduction in the number of cases, the long-term effectiveness of mumps vaccination is questionable. The nature of the vaccine strains and the lack of regular stimulation of populations by circulating wild viruses may explain, in part, the decrease in immunity over time. Thus, the vaccination recommandations could evolve in the future to reach eradication in a medium or long term.

International audience; Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.

Resume Position du probleme La France est confrontee a une nouvelle resurgence de la rougeole. Depuis le mois de novembre 2017, le nombre de cas est en forte augmentation. La couverture vaccinale dans la population generale, tous les âges confondus, se situe en dessous du seuil requis pour esperer l’arret rapide de la circulation du virus. Concernant les professionnels de sante, le taux d’immunisation contre cette maladie est peu connu. Dans ce contexte, le service de sante au travail du CHU de Caen a effectue un etat des lieux de la connaissance de l’immunisation contre la rougeole des personnels de sante au sein des services a risques. Methodes L’etat des lieux concernant la connaissance de l’immunisation contre la rougeole a ete effectue au sein des services de pediatrie, d’imagerie, des urgences pediatriques et adultes du CHU de Caen, et de l’institut d’hematologie de Basse-Normandie (IHBN). L’analyse inclut tous les professionnels de sante presents au sein de ces services sur la periode de mars et avril 2018. Le recueil de donnees a ete effectue par consultation des dossiers medicaux des services de sante au travail, et en prenant en compte l’ensemble des reponses aux courriers envoyes aux personnels. Resultats Les donnees recueillies concernant l’etat d’immunisation contre la rougeole se rapportent a 1017 professionnels de sante. En se basant sur les criteres propres aux recommandations, 234 (50,6 %) sur les 462 professionnels nes avant 1980 et 437 (78,7 %) sur les 555 professionnels nes a compter de 1980 ont pu etre consideres comme immunises. Sur l’ensemble de l’echantillon, 115 (11,3 %) ont beneficie d’une serologie rougeole positive. Parmi ces 1017 professionnels, nous manquons d’information sur l’etat d’immunisation contre la rougeole pour 174 (17,1 %). Conclusion L’etat d’immunisation du personnel soignant reste insuffisant pour eviter la survenue de cas de rougeole et est egalement insuffisamment renseigne. Il est essentiel de disposer de la connaissance de l’etat d’immunisation de cette population, de proceder au rattrapage de la vaccination des personnels non immunises, au sein des services de sante au travail, afin de prevenir l’apparition de nouveaux cas de rougeole et de renforcer l’information concernant l’importance des precautions air, liees a la transmission aeroportee, en cas de contage rougeole.

Wie kaum ein anderer Kunstler des vergangenen Jahrhunderts hat John Cage die Grenzen seiner eigenen Disziplin in Frage gestellt und Inspirationen aus unterschiedlichen Bereichen der Kunst und des Lebens in seine Kompositionen einfliesen lassen.

Background HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). Objectives The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. Study design The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. Results We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. Conclusions These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.

International audience

BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.

On 30 October 2017, an outbreak of measles started in the Nouvelle-Aquitaine (NA) region in France among Bordeaux University students before spreading to other regions. Until 1 July 2018, 1,101 cases were reported in NA, including 98 complications and two deaths. Cases were related to clusters (e.g. students, healthcare workers) in 16%; 81% of cases were not vaccinated against measles as recommended. Vaccination coverage above herd immunity threshold remains the main preventative outbreak measure.

International audience; ObjectivesTo assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.MethodsThis was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.ResultsPrevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL

Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.

International audience; Background: Human respiratory syncytial virus (HRSV) is the main viral cause of severe lower respiratory tract disease in infants and young children. The aim of this study was to describe for the first time the genetic variability of HRSV in Cameroonian patients living in Yaounde for three consecutive epidemic seasons.Methods: HRSV-positive nasopharyngeal samples detected in children less than 15 years in Yaounde were collected from September 2011 to December 2013. Semi-nested RT-PCR, sequencing, and phylogenetic analyses of the second hypervariable region of the G gene were performed.Results: A total of 57 HRSV-positive samples were collected during the study period. Among these, 46 (80.7%) could be amplified in the G gene. HRSV group A (HRSV-A) and group B (HRSV-B) co-circulated in this population at 17.4 and 82.6%, respectively. HRSV-A strains clustered in the NA-1 genotype while HRSV-B strains clustered in the BA-9 genotype. HRSV-A strains accounted for 33.3% (2/6), 4.3% (1/23), and 29.4% (5/17) of the viruses isolated in 2011, 2012, and 2013, respectively.Conclusions: This study reports molecular epidemiology data of HRSV in Cameroon for the first time. Additional studies are required to clarify evolutionary patterns of HRSV throughout sub-Saharan Africa to support antiviral and vaccine development.

International audience; `Objectives: To analyse a measles outbreak in a Roma community. Methods: We describe a community-wide outbreak of genotype D8 measles that took place in southeastern France, between May and July 2017, along with the control measures adopted. Results: We identified a total of eighteen cases, between six months and 24 years old. All cases were unvaccinated or incompletely vaccinated and belonged to a sedentary French Roma community. Most of them (67%) were hospitalised, with three cases (17%) of severe measles including one death of a 16-year-old girl who had previously received oral corticosteroids. The latter was the only lethal case notified in France during theyear 2017. Control measures included intensification of surveillance, isolation of cases, and a large vaccination campaignin this Romacommunity. During the outbreak period, there was no caseof healthcareassociated measles transmission. A broad adherence to vaccination through the mediating role of both the chief of the community and the pastor allowed reaching completed vaccination coverage of 90%. Conclusions: Efforts should be concentrated to enhance access to health services for minorities such as the Roma community characterized by low vaccination coverage. A trustful relationship with leaders of the community is essential to ensure adherence to vaccination. In France, attributable mortality to measles is low and concerns mainly unvaccinated and immunodepressed patients. (c) 2018 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Introduction La rougeole reste une infection virale potentiellement severe, endemique dans le monde malgre les campagnes de vaccination. Nous decrivons les cas hospitalises au CHU de Bordeaux, point de depart d’une nouvelle epidemie de grande ampleur en 2017–2018 en France. Materiels et methodes De facon retrospective, nous avons inclus tous les patients hospitalises au CHU de Bordeaux du 1er septembre 2017 au 31 mai 2018. Les criteres d’inclusion etaient un âge superieur a 1 an, des signes cliniques compatibles avec la rougeole et une confirmation biologique du diagnostic par serologie (IgM positives) et/ou par PCR. Les virus etaient ensuite sequences pour genotypage (centre de reference). Resultats Cent-soixante et onze patients ont ete inclus, dont 125 adultes et 46 enfants. L’âge moyen etait de 22,7 ans et le sex-ratio 1/1. La duree moyenne d’hospitalisation etait de 4,9 jours. La plupart des patients (98,5 %) presentaient une eruption cutanee febrile, avec pourtant une errance diagnostique au debut de l’epidemie. Une toux etait presente dans 88 % des cas (151) avec une catarrhe oculo-nasale dans 65 % des cas (112). Le signe de Koplik etait probablement sous-diagnostique avec une frequence rapportee de 38,5 % (soit 66 patients). Les signes biologiques les plus frequents etaient un syndrome inflammatoire biologique (73 %), une lymphopenie (65 %) et une thrombopenie (32 %). De facon inhabituelle, une hyponatremie ( Soixante-cinq patients (38 %) ont presente une forme jugee grave : 47 pneumopathies, 54 hepatites, 7 keratites bilaterales et 10 formes neurologiques, dont un syndrome de Guillain Barre et une encephalite a inclusions chez une adolescente immunodeprimee, decedee dans les suites. Au total, 8 patients ont ainsi necessite une hospitalisation prolongee en soins intensifs. Sur ces cas hospitalises potentiellement severes, 136 patients (80 %) n’etaient pas correctement vaccines (moins de deux injections), parmi lesquels 28 soignants. A noter, 49 patients ont developpe une authentique infection rougeoleuse malgre des IgG positives (vaccination prealable ou antecedent viral). Conclusion La rougeole reste actuellement frequente dans le monde et les formes graves ne sont pas rares, y compris en France : 171 hospitalisations dont 65 pour formes graves sont decrites dans cette epidemie bordelaise. La population francaise reste sous-vaccinee ; neanmoins, cette vaccination pourrait etre insuffisante dans certains cas (IgG + ) qui seront detailles dans un autre travail.

Background: Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Methods: Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in 4 samples (QCMD). Results: Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log10 copies/106PBMC) for the three positive QC that were correctly classified by each laboratory (QC1

Measles outbreaks are regularly reported in European countries despite efforts to improve vaccination coverage. In January 2016, an outbreak occurred in a refugee settlement in Calais, France. We report here the complete genome sequence of a wild-type measles virus isolated from a health care worker (MVi/Calais. FRA/01.16) infected during this outbreak.

Viral respiratory infections are common in children, most of which are due to a virus. They can lead to serious infections, and these children may require treatment in a pediatric intensive care unit (PICU). This prospective study evaluated the epidemiology of respiratory viruses and associated illnesses among children hospitalized in a PICU during the three winter months of 2012-2013.All the children admitted to the PICU, University Hospital of Caen, France, were included. Nasal swabs were collected and specimens were tested using a single real-time PCR (polymerase chain reaction).Of the 105 patients admitted to the PICU during the study period, 84 fulfilled the inclusion criteria. The "respiratory group" included 37 patients with respiratory symptoms at admission while the "nonrespiratory group" included 47 patients with no respiratory symptoms. The 84 nasal swabs collected included 54 that were considered positive (64.3%) and 70 viruses were detected. The most commonly detected virus was RSV (n=28; 40.0% positive samples), followed by HRV (n=24; 34.3%). Viruses were more frequently detected in the respiratory (86.5%) than in the nonrespiratory (42.6%) group (P0.001). Statistical analysis by subgroups revealed that RSV infections were significantly more frequent in the respiratory group (54.1%) than in the nonrespiratory group (6.4%) (P0.001). There was no difference for HRV (32.4% and 27.7%) or for the other viruses. No difference in duration of hospitalization or duration of mechanical ventilation was demonstrated depending on the virus detected.The use of the very sensitive multiplex PCR technique increased virus detection rates in both symptomatic and asymptomatic subjects.We have confirmed the frequency of RSV infections in a PICU and found that many patients without respiratory symptoms have respiratory infections caused by viruses. The impact of these infections on patient outcome should now be analyzed in order to demonstrate the role played by respiratory viruses.

The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI)0.3 and a strong avidity as an AI0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects.

Background Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored. Methods Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species. Results Among the factors influencing the cellularity were the type of sample (p

Measles is one of the most contagious diseases implicated in an outbreak in Western Europe for a few years. In France, the outbreak began in 2008, especially in the southern regions. Most of the cases are mild but deleterious effects can occur in infants, during the pregnancy, or in immunosuppressive patients. Pneumonia and encephalitis are the major complications in these patients. Measles illness during pregnancy results in a higher risk of premature labor, spontaneous abortion, and low-birthweight infants. Death from measles was reported in approximately 0.3% of cases. The National Reference Center for measles and paramyxoviridae is implicated in biological confirmation of cases and epidemiologic surveillance. Virologic diagnosis consists in a direct detection of viral RNA (real time PCR), or indirect detection of the immune response (IgM and IgG) in saliva samples. The measles genotype is determined by sequencing a 450 nucleotids fragment of the N gene, as the World Health Organization (WHO) recommendation. This molecular analysis helps determine the geographic origin of the virus and the viral strains circulating in the country. In 2011, 3105 specimens were received. PCR was positive for 1990 patients (64%), with a large majority of children younger than 2 years of age and young adults. The most important cause of measles resurgence is low vaccination coverage. The role of pediatricians is important in order to achieve the goal of 95% of vaccination coverage established by the WHO.

Viral respiratory infections are common in infants and can be severe. The new pandemic influenza virus H1N1v2009 was feared to cause particularly severe outcomes.This study aimed at evaluating the impact of H1N1v2009 on the viral epidemiology, the clinical presentation and the severity of respiratory infections in infants.This prospective epidemiologic study included all infants2 years of age, both inpatients and outpatients, presenting with respiratory symptoms, from November 2009 through April 2010, at the pediatric emergency department of the University Hospital of Caen, France. A nasal swab was taken for viral detection and analyzed by immunofluorescence and, if negative, polymerase chain reaction. Severe respiratory infection was defined by a score of respiratory severity.One thousand twenty-one infectious episodes with a respiratory sample met inclusion criteria. Eight hundred thirty-four samples (81.7%) were positive. The viruses with the highest incidence were the respiratory syncytial virus (34.2%), the rhinoviruses (23.9%), the coronaviruses (9.3%) and H1N1v2009 (7.7%). Of all infections, 28.6% were severe and more frequent in infants with risk factors. H1N1v2009 infections had a low risk of severe respiratory disease (odds ratios = 0.15) and hospitalization (odds ratios = 0.40) compared with the other viruses. Respiratory syncytial virus infections had a high risk of respiratory severity (odds ratios = 7.85) and were responsible for 71.4% of admissions to the intensive care unit.Despite the modest impact of H1N1v2009 observed in this study, further surveillance is needed to detect virological factors that may increase its severity.

Resume Alors que la place de la PCR est bien reconnue pour le diagnostic des infections neuromeningees a enterovirus (EV), l’utilisation des techniques de biologie moleculaire dans les infections respiratoires a EV est encore mal definie. Objectifs Definir les apports des outils moleculaires (PCR et genotypage) dans le diagnostic et l’epidemiologie des infections respiratoires a EV. Methodes Au cours de l’annee 2008, 3612 secretions nasales ont eu une recherche virale par IFD et culture MRC5. Dans un second temps, sont realises une recherche virale sur culture HuH7 (SN negative en IF) et une PCR duplex enterorhinovirus (PEVRV) sur 816 surnageants de culture HuH7 presentant un ECP. De plus, 327 SN de nouveau-nes ont eu une recherche systematique par la PCR EV temps reel « maison » (PEV) utilisee pour le diagnostic des infections meningees. Un genotypage a ete realise chez 68 patients presentant une identification d’EV sur surnageants de cultures MRC5 ou HuH7. Resultats Trente-cinq EV ont ete isoles en culture (0,97 %) ; la combinaison des deux PCR, PEVRV et PEV, a permis d’identifier respectivement, 41 EV, 8 EV-RV et 12 RV supplementaires, portant le nombre de positif a 96 (2,6 %). Chez les NN, 32 (11,3 %) SN sont positives avec la PEV. Parmi les 98 SN testees par PEV et PEVRV, 27 etaient positives et nous avons detecte dix EV, cinq EV-RV et 12 RV. De janvier a decembre 2008, la distribution saisonniere montre le pic estival habituel d’infections meningees et un pic automnal correspondant d’infections respiratoires. Cinq serotypes predominent : 19 EV68 (29,7 %), 12 CB3 (18,7 %), neuf E3 (14,1 %), six CA9 (9,4 %) et six CB1 (9,4 %). Les EV68 sont tous isoles en octobre a novembre et 17/19 (89,5 %) des patients positifs ont ete hospitalises avec des signes d’insuffisance respiratoire aigue. Conclusion Les methodes de diagnostic moleculaires des infections respiratoires a EV (PCR et genotypage) permettent d’identifier precisement les souches circulantes dans un temps relativement court, apportant un benefice epidemiologique, clinique et economique de sante.

Resume En Normandie, le virus respiratoire syncytial (hRSV) est trouve dans 64,1 % des cas de bronchiolites aigues chez l’enfant hospitalise, les rhinovirus dans 26,8 %, le metapneumovirus humain (hMPV) dans 7,6 % et les virus para-influenza (PIV) dans 3,4 %. Dans les bronchiolites aigues communautaires, on a une repartition differente : hRSV : 42 %, rhinovirus : 19,5 %, coronavirus : 8 %, PIV : 3,5 %, hMPV : 2,5 %. Le hRSV infecte les nourrissons (86,9 %), dont 53,7 % ont moins de 6 mois et 48,2 % des hRSV sont detectes en novembre et decembre, et 44,5 % en janvier et fevrier. L’epidemie debute la 1re ou 2e semaine d’octobre, mais elle varie d’une annee a l’autre et d’une region a l’autre. A l’hopital, les bronchiolites a hRSV sont passees de 261 cas par epidemies de 1999 a 2003, a 341 cas de 2004 a 2009. Les rhinovirus sont associes a des bronchiolites aigues dans 38,4 % des cas ; 54,6 % des souches etant identifiees en septembre et octobre, et 38,5 % en mars et avril ; 34,2 % infectent des nourrissons de moins de 6 mois, 37,8 % entre 6 mois et 2 ans, et 19,5 % des enfants entre 2 et 5 ans. Les epidemies a hMPV coincident avec celles du hRSV mais ont 6 fois moins de cas hospitalises. Le hMPV infecte les nourrissons (74 %) mais plus âges que ceux infectes par le hRSV. Il entraine une bronchiolite aigue dans 59 % des cas, une pneumonie dans 17 %. Les infections a PIV (environ 100 cas hospitalises par an) se repartissent en PIV3 : 62,7 %, PIV1 : 25,3 % et PIV2 : 7,3 %. Les PIV1 apparaissent tous les 2 ans, a l’automne. Les infections a PIV3 sont automnales et hivernales, avec des infections au printemps les annees sans PIV1. Il y a des bronchiolites aigues dans 29,8 % des infections a PIV3 et 18,3 % a PIV1.

Resume La grippe saisonniere est due aux virus influenza A et B. Il s’agit de virus enveloppes dont le genome est constitue de sept a huit fragments d’ARN. Les differents sous-types sont determines par la nature des deux glycoproteines de surface HA et NA. La grippe saisonniere est une maladie epidemique et hivernale dans les zones a climat tempere. Son epidemiologie est liee a la grande variabilite du virus au cours du temps, necessitant la mise en place d’un systeme d’alerte detectant chaque annee les variants circulants dominant et determinant la composition vaccinale. Les symptomes cliniques de la grippe ne sont pas suffisamment specifiques pour permettre le diagnostic sans examen virologique. Cela est particulierement vrai en periode non epidemique, chez les sujets de plus de 65 ans et chez les enfants de moins de cinq ans. L’enfant represente une cible privilegiee des infections a virus influenza. Le recours a l’hospitalisation est d’autant plus eleve que l’enfant est jeune. Chez le nourrisson, l’infection peut etre paucisymptomatique et s’accompagner de manifestations non respiratoires (lethargie, convulsions, malaises). Le diagnostic virologique de la grippe est justifie chez tous les sujets hospitalises pour un syndrome respiratoire compatible avec une infection a virus influenza. Il existe plusieurs outils permettant une recherche directe du virus dans les secretions respiratoires : isolement du virus en culture, detection d’antigenes, detection moleculaire de l’ARN. Le choix de la methode se fait selon les caracteristiques du test : sensibilite, specificite, rapidite et simplicite de realisation, cout.

A method was developed for the detection and quantitation of HAdV (human adenovirus) and HBoV (human bocavirus) based on a duplex real-time PCR, the AB PCR, using a Smartcycler instrument. A control real-time PCR was carried out on albumin DNA to standardise the non-homogenous respiratory samples. No cross-reactivity was observed with viruses or bacteria that could be found in the respiratory tract. The diagnosis rate using the AB PCR on clinical samples was 10.7%: 3.4% for HBoV detection, 6.9% for HAdV detection and 0.3% double detection HBoV–HAdV. The clinical and epidemiological characteristics of the HAdV- and HBoV-infected patients were evaluated. In the HAdV-positive group and the HBoV-positive group the samples were classified according to the severity of the disease. The HAdV viral load did not appear to be linked to the severity of the disease. Conversely, the difference between the two HBoV groups, severe and non-severe, was significant statistically when the comparison was based on the viral load (P = 0.006) or after adjustment of the viral load to the number of cells in the samples (P = 0.02).

Resume Les coronavirus forment un grand groupe de virus infectant les mammiferes et les oiseaux ; cinq d’entre eux infectent l’homme : HCoV 229E et OC43, connus depuis les annees 1960, SARS-CoV identifie en mars 2003 lors de l’epidemie de syndrome de detresse respiratoire aigu severe, NL63 et HKU1, identifies respectivement en 2004 et 2005. Ce sont des virus enveloppes dont le genome est une molecule d’ARN de polarite positive de tres grande taille. Leur mode evolutif fait intervenir plusieurs parametres : la generation de nombreux mutants lors de la replication, responsable d’une distribution en quasi-especes de la population virale, la capacite a etablir des infections persistantes, la possibilite de deletions importantes, la grande flexibilite du genome due a un fort taux de recombinaisons homologues et heterologues, la capacite a franchir les barrieres d’especes et a s’adapter au nouvel environnement. Les coronavirus (hors SARS-CoV) sont ubiquitaires et circulent sous forme epidemique. Les differents HCoV co-circulent avec une distribution entre les types qui est variable selon les annees et les regions geographiques. Ce sont essentiellement des virus responsables d’infections respiratoires hautes et basses. Le SARS-CoV est, lui, un virus emergent responsable de l’epidemie de pneumopathies atypiques entre novembre 2002 et juillet 2003. Sa circulation a ete interrompue grâce a la mise en place de mesures sanitaires drastiques. L’implication des HCoV dans des pathologies digestives et neurologiques reste a preciser. La detection des coronavirus est difficile, et fait appel surtout a des techniques moleculaires. Il n’existe actuellement aucun traitement specifique des infections a HCoV.