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Segmental vitiligo (SV) is a unilateral subtype of vitiligo which is clinically characterized by a cutaneous depigmentation and histologically by a melanocyte loss from the epidermis and hair follicle reservoirs. To date, its pathogenesis remains a mystery. In many cases, this skin depigmentation shares several clinical features and dysfunctions with herpes zoster (HZ). So, for the first time, we examined whether any nucleus and cell fusion associated with a positive immunolabelling of varicella-zoster virus (VZV) and VZV mature virions could be found in SV skin samples as in herpes zoster (HZ). A total of 40 SV samples were used for histological and immunochemical studies. Control samples were obtained from three HZ, and 10 generalized vitiligo lesions. For ultrastructural study, three recent SV and one HZ as controls were recruited. Here, we report that nuclear fusion in epidermal cells were statistically associated with recent SV (p .001), whereas syncytia formation was associated with long-lasting SV (p = .001). A positive detection of VZV antigen was statistically associated in the epidermis with recent SV and in the dermis with long-lasting SV (p = .001). Finally, the discovery of mature virions in 3/3 recent SV samples provides additional arguments for our viral hypothesis.

International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.

International audience; OBJECTIVE: To describe COVID-19 breakthrough infections in two nursing homes (NHs) sites of active COVID-19 clusters despite optimal vaccination coverage.METHODS: A cross-sectional study was conducted in two NHs of south-western France, following the investigation of COVID-19 clusters (February-March 2021). SARS-CoV-2-confirmed infection was defined by positive RT-PCR. Antibodies neutralization capacities were tested in a subgroup of fully-vaccinated and seropositive-residents. RESULTS: Of the 152 residents, 66% were female with median age 87 years (IQR: 80.0-90.2). Overall, 132 (87%) residents received 2 doses of vaccine, 14 (9%) one dose and 6 (4%) were unvaccinated. Forty-seven (31%) residents had confirmed infection (45 (98%) with variant 20I/501Y.V1). All 6 non-vaccinated residents, 4 /14 who had one dose and 37/132 that had two doses, were infected. Of the 39 residents reporting symptoms, 12 and 3 presented severe and critical disease, respectively. One resident with a confirmed infection died. Infected-residents had a median anti-S IgG titre of 19 116.0 (IQR: 3 028.0-39 681.8 AU/mL), 19 times higher than that of non-infected vaccinated persons (1,207.0; IQR: 494.0-2,782.0). In the subgroup of 19 residents tested for neutralizing antibodies, the neutralizing titre (50%) was strongly positively correlated with the anti-S IgG titre (correlation coefficient = 0.83), and 1.5 times higher for the infected than non-infected residents [5.9 (IQR: 5.3-6.9) vs. 3.6 (2.9-3.8)].CONCLUSION: Institutionalized elderly persons who undergo breakthrough infection develop higher titres of anti-S IgGs, which are strongly correlated with the neutralizing capacity of the antibodies. These results advocate for additional vaccine doses in this population.

International audience; Objectives: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.Methods: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here.Results: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.Discussion: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases’ fatality is linked to age.Significance StatementBronchial epithelia are the primary target for SARS-CoV-2 infections. Our work uses reconstituted bronchial epithelia from adults and children. We show that infection of adult epithelia with SARS-CoV-2 is rapid and results in the synchronized release of large clusters of infected cells and syncytia into the apical lumen contributing to the released infectious virus dose. Infection of children derived bronchial epithelia revealed an intrinsic resistance to infection and virus spread, probably as a result of a faster onset of interferon secretion. Thus, our data provide direct evidence for the epidemiological observation that children are less susceptible to SARS-CoV-2.

International audience; Since the beginning of the pandemic, a race has been underway to detect SARS-CoV-2 virus infection (PCR screening, serological diagnostic kits), treat patients (drug repurposing, standard care) and develop a vaccine. After almost a year of active circulation worldwide, SARS-CoV-2 variants have appeared in different countries. Those variants include mutations in multiple regions of the genome, particularly in the spike gene. Because this surface protein is a key player in both the spread of the virus and the efficacy of vaccine strategies, the challenge is to efficiently monitor the appearance of spike mutations in the population. The present work describes a procedure based on the widely available Sanger technology to produce a full-length sequence of the spike gene from patient-derived samples.

International audience; This study aims to assess the efficacy and safety of convalescent plasma therapy (CPT) in COVID-19 critically ill patients with protracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia. A retrospective cohort study was conducted in intensive care unit (ICU). All patients with severe COVID-19 pneumonia for whom RNAemia remained positive more than 14 days after onset of the infection were included and given CPT. The primary objective was to evaluate SARS-CoV-2 RNAemia 7 days (D7) after CPT. A total of 14 patients were included and they received a median CPT volume of 828 ml (range: 817-960). CPT was administered in a median time of 14 days after ICU admission. At D7, 13/14 patients had negative SARS-CoV-2 blood PCR and one patient had negative blood PCR 11 days after CPT. At D7 and at D14, the clinical status was improved in 7/14 and 11/14 patients, respectively. The 28-day mortality rate was 14%. No CPT-related adverse effects had been reported. CPT is safe and may be efficient in patients with protracted RNAemia admitted in ICU for severe COVID-19 pneumonia. Randomized controlled trials are needed to confirm these results.

OBJECTIVE: In March 2020, we implemented screening of the contacts of a COVID-19 cluster having occurred in the Lot-et-Garonne department, the first department of the Nouvelle-Aquitaine region to be affected by the active circulation of SARS-CoV-2. We aimed to describe the impact of this screening on the local SARS-CoV-2 outbreak. METHODS: All high-risk contacts, as well as the individuals living in their households, were screened. We detailed the evolution of the number of confirmed COVID-19 cases in the Lot-et-Garonne department and the rest of the Nouvelle-Aquitaine region. RESULTS: Among the 89 screened individuals, 10 new cases were confirmed, including 4 asymptomatic persons. In Lot-et-Garonne, the number of confirmed COVID-19 cases immediately decreased after this screening and no epidemic peak occurred, contrary to what was observed in the rest of the region. CONCLUSION: The early screening of high-risk contacts of COVID-19 cases and members of their household implemented a few days before the first lockdown probably helped to prevent the spread of the virus in the department.

Contexte La transfusion de plasma de donneurs convalescents (PDC) au cours de la COVID-19 est controversée. En France, hors essai clinique, elle est encadrée par un protocole à usage thérapeutique soumis à un avis multidisciplinaire (RCP) préalable. L’expérience de ce traitement en réanimation n’est pas décrite. Méthode Tous les patients admis dans une unité de réanimation d’un CHU pour un SDRA COVID-19 et ayant une PCR plasmatique SARS-CoV-2 positive au moins 10 jours après le début des symptômes ont reçu une transfusion de PDC après validation en RCP. L’objectif principal était d’évaluer la tolérance et la virémie 7 j après la transfusion (J7). Résultats Entre mai 2020 et avril 2021, 31 patients (27 hommes et 4 femmes, âge moyen = 69 ans) ont été inclus et ont reçu un volume médian de 836 mL de PDC sur 2 jours consécutifs. Tous présentaient au moins un facteur de risque de forme grave dont 15 une affection maligne évolutive et 14 avaient une sérologie SARS-CoV-2 négative à l’admission en réanimation. Les PDC ont été transfusés en moyenne 18 j après le début des symptômes et 8 j après l’admission en réanimation. À J7, 22/31 patients avaient une PCR plasmatique négative. Le délai médian de négativation de la PCR plasmatique était de 8 j. À J 7, le score de sévérité clinique OMS était stable pour 12/31 (39 %), en amélioration pour 14/31 (45 %) et détérioré pour 5/31 (16 %) patients. La mortalité à 28 jours était de 26 % (8/31 dont 3 dans les sept jours après PDC). Aucun évènement indésirable significatif lié à la transfusion n’a été rapporté. Conclusion Notre étude confirme la faisabilité de la transfusion de PDC en réanimation, notamment en cas d’immunodépression humorale.

International audience; OBJECTIVE: There is a lack of data evaluating performance of antigenic test (AT) for SARS-CoV-2 diagnosis (Ag-RDT) in clinical practice, especially in asymptomatic subjects. The main objective of this study was to evaluate the diagnostic performance of AT compared to Reverse Transcription Polymerase Chain Reaction (RT-PCR) for SARS-CoV-2 diagnosis. METHODS: StudyCov is a monocentric cross-sectional study. A SARS-CoV-2 screening facility was set up in the Bordeaux University health campus from October 28th to November 20th 2020. Students willing to have a RT-PCR test (ARGENE SARS-CoV-2 R-GENE, BioMerieux, France) for SARS-CoV-2 diagnosis were also offered the Abbott Panbio SARS-CoV-2 antigenic rapid test. All participants attending the screening facility with an AT in addition to RT-PCR and having signed an informed consent were included in the study. The main objective was to assess performance of AT as compared with RT-PCR in the recruited population. Secondary objectives dealt with the analysis of the main objective stratified by current symptoms and risk exposure. A sensitivity analysis with different RT-PCR cycle thresholds was included. RESULTS: RT-PCR and AT results were available for 692 subjects. Overall sensitivity and specificity of AT tests were respectively 63.5% (95% confidence interval (CI): 49.0 - 76.4) and 100% (95% CI: 99.4 - 100). In the asymptomatic sub-group, they were respectively 35.0% (95% CI: 15.4% - 59.2%) and 100% (95% CI: 99.3 - 100). CONCLUSIONS: This study shows the poor sensitivity of AT in asymptomatic subjects, specificity being however excellent. The performance results fall below the World Health Organization recommendation of 80% sensitivity and question using AT in general population, especially when asymptomatic.

Recently an increasing number of new adenovirus types associated with type-dependent pathogenicity have been identified. However, identification of these clinical isolates represents the very first step to characterize novel pathogens. For deeper analyses, these adenoviruses need to be further characterized in basic virology experiments or they could be applied in translational research. To achieve this goal, it is essential to get genetic access and to enable genetic modification of these novel adenovirus genomes (deletion, insertion, and mutation). Here we demonstrate a high-throughput approach to get genetic access to new adenoviruses via homologous recombination. We first defined the cloning conditions regarding homology arm-length and input adenoviral genome amounts. Then we cloned four naturally occurring adenoviruses (Ad70, Ad73, Ad74, and Ad75) into easy-to-manipulate plasmids and genetically modified them by reporter gene insertion. Three recombinant adenoviruses (Ad70, Ad73, and Ad74) containing a reporter cassette were successfully reconstituted. These novel reporter-labeled adenoviruses were further characterized using the inserted luciferase reporter with respect to receptor usage, presence of anti-adenovirus antibodies, and tropism in vitro. The identified receptor usage, the relatively low prevalence of anti-adenovirus antibodies, and the various cancer cell line transduction pattern are important features of these new pathogens providing essential information for their therapeutic application.

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.

Background Enterovirus (EV) meningitis is the most common form of meningitis. Clinical and biological manifestations may be non-specific, leading to prolonged and costly investigations. Objectives To determine the different aspects of EV meningitis and the variables associated with length of stay (LOS) in hospital independently of patients’ age. Study design Single center retrospective study of all EV PCR positive CSF samples during 3.5 years in Bordeaux University Hospital, France. Results 172 patients were included. 65 were under 3 years old and 49 over 18 years old. 10% of patients had severe forms of the disease. 47 patients (27.3%) had normal CSF count and in 63 patients (36.6%) polynuclear cells predominated in CSF. Procalcitonin, Hoens’ score or PCR in stool samples appeared as good markers for enteroviral diagnosis. Time elapsed before PCR results was associated with LOS (p = .002) and should help in limiting investigations in case of aseptic meningitis. Conclusion Rapid availability of EV PCR reduces LOS for patients and contributes to diminish unnecessary procedures and further tests.

Nuclear import of viral genomes is an important step during the life cycle of adenoviruses (AdV), requiring soluble cellular factors as well as proteins of the nuclear pore complex (NPC). We addressed the role of the cytoplasmic nucleoporin Nup358 during adenoviral genome delivery by performing depletion/reconstitution experiments and time-resolved quantification of adenoviral genome import. Nup358-depleted cells displayed reduced efficiencies of nuclear import of adenoviral genomes, and the nuclear import receptor transportin 1 became rate limiting under these conditions. Furthermore, we identified a minimal N-terminal region of Nup358 that was sufficient to compensate for the import defect. Our data support a model where Nup358 functions as an assembly platform that promotes the formation of transport complexes, allowing AdV to exploit a physiological protein import pathway for accelerated transport of its DNA. IMPORTANCE Nuclear import of viral genomes is an essential step to initiate productive infection for several nuclear replicating DNA viruses. On the other hand, DNA is not a physiological nuclear import substrate; consequently, viruses have to exploit existing physiological transport routes. Here, we show that adenoviruses use the nucleoporin Nup358 to increase the efficiency of adenoviral genome import. In its absence, genome import efficiency is reduced and the transport receptor transportin 1 becomes rate limiting. We show that the N-terminal half of Nup358 is sufficient to drive genome import and identify a transportin 1 binding region. In our model, adenovirus genome import exploits an existing protein import pathway and Nup358 serves as an assembly platform for transport complexes.

Objectives To analyse functional outcome parameters according to antimicrobial treatments after respiratory syncytial virus (RSV)-confirmed infection in adult lung transplant recipients. Methods A 9-year retrospective multicentre cohort study (2011–19) included adult lung transplant recipients with RSV-confirmed infection. The first endpoint determined new allograft dysfunction (acute graft rejection and chronic lung allograft dysfunction (CLAD)) 3 months after infection. Then baseline and 3 months' postinfection forced expiratory volume in 1 second (FEV1) values were compared according to antimicrobial treatment. Univariate logistic regression analysis was performed. Results RSV infection was confirmed in 77 of 424 lung transplant recipients (estimated incidence of 0.025 per patient per year; 95% confidence interval 0.018–0.036). At 3 months, 22 recipients (28.8%) developed allograft dysfunction: ten (13%) possible CLAD, six (7.9%) acute rejection and six (7.9%) CLAD. Recipients with the lowest preinfection FEV1 had a greater risk of developing pneumonia (median (interquartile range) 1.5 (1.1–1.9) vs. 2.2 (1.5–2.4) L/s, p 0.003) and a higher odds of receiving antibiotics (1.6 (1.3–2.3) vs. 2.3 (1.9–2.5) L/s, p 0.017; odds ratio 0.52, 95% confidence interval 0.27–0.99). Compared to tracheobronchitis/bronchiolitis, RSV-induced pneumonia led more frequently to hospitalization (91.7%, 22 vs. 58.0%, 29, p 0.003) and intensive care unit admission (33.3%, 8 vs. 0, p Conclusions At 3 months after RSV-confirmed infection, 22 recipients (28.8%) had new allograft dysfunction. Ribavirin treatment and azithromycin prophylaxis did not prevent FEV1 decline.

Background Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor (PI) indicated for the treatment of naïve and pretreated HIV-infected patients since 2007. Our study aims to describe DRV/r-treated patients experiencing virological failure (VF) documented with HIV resistance testing. Methods Data from patients belonging to the ANRS CO3 Aquitaine Cohort treated with a regimen including DRV/r between February 2007 and December 2015 were analyzed. Baseline characteristics of patients experiencing VF (defined by 2 consecutive plasma viral loads >50 copies/mL) were compared with those without VF. We then described factors associated with VF as emergence of IAS DRV resistance–associated mutations (RAMs). Results Among the 1458 patients treated at least once with a DRV/r-based regimen, 270 (18.5%) patients experienced VF during follow-up, including 240 with at least 1 genotype resistance test (GRT). DRV RAMs were detected in 29 patients (12%). Among them, 25/29 patients had ≥2 DRV RAMs before DRV/r initiation, all of whom had experienced VF during previous PI treatments. For 18/29, DRV/r was maintained after VF, and controlled viremia was restored after modification of DRV-associated antiretroviral molecules or increased DRV dose. Finally, only 6/29 patients selected new DRV RAMs after DRV/r initiation. All of these experienced previous VFs while on other PIs. Conclusions These results highlight the efficacy and robustness of DRV/r, as the emergence of DRV RAMs appeared in, A low level of darunavir resistance-associated mutation emergence in patients with virological failure during long term use of boosted darunavir. Confirmation of the robustness of this protease inhibitor in the ANRS CO3 Aquitaine cohort in a real life setting.

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.

Introduction Une epidemie de ZIKV a sevi en 2016 en Amerique latine et dans les Caraibes (A/C), en particulier, dans le cadre des JO de Rio en aout 2016. Trois cohortes dont deux dediees aux JO n’ont signale aucun cas confirme apres depistage Elisa (EuroImmun®) et une a presente des resultats incomplets en 2017. Notre objectif etait d’estimer l’incidence ZIKV et les performances diagnostiques chez des voyageurs francais sejournant en A/C a l’ete 2016. Materiels et methodes Cohorte de voyageurs adultes ayant consulte entre juin et septembre 2016 dans un grand CVI francais pour un sejour prevu en A/C de duree maximale de 3 mois. Exclusion des voyageurs ayant 1 antecedent ZKV ou un voyage en A/C de 2015 a l’inclusion. Tous les participants ont consenti un questionnaire et une ponction veineuse 4 et 6 semaines apres le retour. Le depistage a ete realise par ELISA EuroImmun (EI) IgM/IgG et « Elisa maison » du CNR dont IgM Antibody Capture (MAC) et test indirect IgG sur lysat de virus complet (INDG). Une seroneutralisation virale (VNT) a ete realisee en cas d’Elisa positifs/equivoques, de fievre ou de symptome(s) zika-like. Resultats Sur 324 voyageurs eligibles, 75 ont accepte de participer. Parmi eux, 42 (56 %) de femmes, un âge median de 34 ans [IQR 29–55], 65 (87 %) de touristes et 10 (13 %) de professionnels. La duree mediane du sejour etait de 20 jours [IQR 15–33]. L’Amerique du Sud represente 63 (84 %) destinations, l’Amerique centrale plus Mexique 6 (8 %) et les Caraibes 6 (8 %). Seulement 7 (9 %) ont signale une visite a Rio pendant les JO. La moitie (38) ont signale au moins un evenement de sante dont 7 (9 %) fievre et 12 (16 %) symptomes Zika-like (7 rashs, 5 prurits). Les Elisa EI IgM et MAC etaient tous negatifs. Les tests EI IgG et INDG etaient positifs pour 4 et 1 voyageurs. Quatre (5 %) cas de ZIKV ont ete retrospectivement confirmes par VNT : 1 femme febrile en Guadeloupe [EI IgG (+) ; MAC (−) et INDG (+)] et 3 femmes au tableau dermatologique zika-like non febrile dont 2 au Nicaragua (rash et prurit) et 1 en Martinique (rash) – avec respectivement les ELISA suivants [EI IgG (+), INDG (−)], [EI IgG initial (−), EI IgG tardif equivoque, INDG (−)] et [EI IgG(−) et INDG(−)]. Le taux d’incidence ZKV etait de 5,9 cas/100 personnes-mois [IC 95 1,9 – 14,3]. Conclusion Cette etude est la 1ere a rapporter une incidence ZKV significative parmi des voyageurs exposes a une epidemie. Les 3 cas de ZIKV avec symptome(s) zika-like sans fievre, ont ete confirmes par l’insistance des cliniciens a obtenir une VNT. Ce defaut des tests Elisa soulignent l’importance de promouvoir de nouveaux tests fiables.

Introduction Les deux Herpes simplex virus (HSV) sont responsables d’infections neuro-meningees de severite variable. Les encephalites herpetiques, habituellement associees a HSV-1 sont potentiellement mortelles, tandis que les meningites herpetiques, liees le plus souvent a HSV-2 sont benignes. La prise en charge des meningites a HSV n’est pas codifiee et un traitement antiviral serait benefique uniquement chez les patients immunodeprimes. Materiels et methodes Analyse retrospective (2010–2018) des meningites a HSV dans un CHU. Les patients avec un prelevement de liquide cerebro-spinal (LCS) positif a HSV sans signe d’encephalite ont ete inclus. Resultats Du 1er janvier 2010 au 1er octobre 2018, 36 patients (10 hommes, 26 femmes, âge moyen 35 ans) ont presente 38 episodes de meningite a HSV. Le suivi median etait de 479 jours (0-2941 jours), un patient etait decede a la derniere visite (deces non lie a la meningite a HSV). Neuf presentaient des lesions cutaneo-muqueuses d’allure herpetiques (2 confirmees par PCR). L’analyse du LCR montrait en moyenne une cellularite a 852 elements/mm3 avec 83 % de lymphocytes et une proteinorachie a 1,55 g/L. La PCR HSV etait positive pour HSV-2 (n = 35), pour HSV-1 (n = 1 avec PCR enterovirus egalement positive) ou HSV non typable (n = 2). La CRP moyenne etait a 11 mg/L, la PCT toujours Conclusion Les meningites a HSV-2 sont des meningites virales benignes de presentation typique et de prise en charge tres heterogene. En l’absence de signe encephalitique, l’imagerie cerebrale est normale et ne semble donc pas necessaire. Le traitement antiviral ne modifie probablement pas l’evolution clinique toujours favorable de la maladie. Une etude prospective permettrait de valider cette hypothese.

Background CMV reactivation, which enhances immune senescence, could be associated with a higher risk of cancer. Objectives We compared the prevalence of positive CMV DNAemia in HIV-infected patients with and without cancer. Study design This case–control study, nested in the ANRS-CO3 Aquitaine Cohort, included patients with a first diagnosis of cancer (2002–2007) as cases. Two controls were matched per case. Cancer risk was estimated using conditional logistic regression models, an Odds Ratio (OR) of 2 could be detected with 80% power. The variables considered were: ≥1 positive CMV DNAemia, CD4+ and CD8+ counts, HIV plasma load. Plasma CMV DNA was retrospectively quantified within the 3-year period preceding the endpoint. Results The 143 cases (93 non-AIDS-related and 50 AIDS-related cancers) and 284 controls had a median age of 47 years (IQR: 41–56). At the time of diagnosis or censorship, for cases and controls, median values were respectively, for CD4+ count: 327cells/mm 3 (IQR: 164–514) and 416 (IQR: 275–582), and for HIV plasma load: 2.6log 10 copies/mL (IQR: 1.7–4.7) and 1.7log 10 copies/mL (IQR: 1.7–3.3). We performed 2056 CMV PCR; 14 cases (9.8% [95% CI: 4.9–14.7]) and 19 controls (6.7% [CI: 3.8–9.6]) presented ≥1 positive PCR. CMV DNAemia was not associated with the risk of cancer (unadjusted and adjusted p -values=0.19 and 0.54, respectively). HIV load >500copies/mL was independently associated with a higher risk of cancer (OR=2.02; p =0.002; 95% CI: 1.29–3.17). Conclusion This large case–control study did not show any differential exposure to positive CMV plasma DNAemia between cancer cases and controls.

Lymphoepithelioma-like carcinoma (LELC), which is commonly reported in the nasopharynx and occasionally in other organs, remains a rare condition in gynecology. It is morphologically defined as a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltrate. We present a case of an 82-year-old woman with a 10 cm LELC of the ovary shown by inguinal lymph nodes. There was no peritoneal carcinomatosis. Cytoreductive surgery was performed to remove a left ovarian neoplasm and multiple involved lymph nodes. Cytoreduction was complete. The tumor was a mixed poorly undifferentiated ovarian carcinoma consisting of 95% LELC and 5% moderately differentiated serous adenocarcinoma. Immunohistochemistry showed a large infiltration of T lymphocytes and plasma cells. Epstein-Barr virus was not detected by immunolabeling and polymerase chain reaction. The patient was still alive at 24 months of follow-up. To our knowledge, this is the second case of ovarian LELC and the first description of the native tumor before chemotherapy. In conclusion, this rare tumor of the ovary is difficult to diagnose both preoperatively and perioperatively. However, clinicians and pathologists should be aware that ovarian tumors with massive involvement of lymph nodes and no peritoneal carcinomatosis are suggestive of such a diagnosis and that prognosis is relatively good.

Background Kidney transplant recipients infected with cytomegalovirus (CMV) undergo a persistent gammadelta T cell expansion in their peripheral blood. The anti-CMV function of these cells was previously demonstrated by their ability to kill CMV-infected cells in vitro. Methods To gain insight into the role of gammadelta T cells within the antiviral immune network, we compared the expansion kinetics of these T cells with that of CMV pp65-specific CD8(+) alphabeta T cells in the peripheral blood of twenty-one kidney transplant recipients. Results Both the percentage and the absolute number of pp65-specific CD8(+) T cells and gammadelta T cells showed a concomitant increase and persistence in most of the kidney transplant recipients with CMV infection. Both cell subsets exhibited an effector/memory phenotype (CD28(-), CD27(-), and CD45RA(+)) that predominated for the entire follow-up period. Conclusions In conclusion, CMV-specific CD8(+) alphabeta T cells and gammadelta T cells share common expansion kinetics and a common effector phenotype, suggesting that these cell types act similarly in response to CMV infection.

The ability of human γδ T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vδ2− γδ T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vδ2− γδ T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vδ2− γδ T cells were found as naive cells in CMV− patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vδ2− γδ T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster γδ T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vδ2− γδ T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.

In a prospective cohort of 82 renal transplant recipients, we evaluated the capacity of the cytomegalovirus (CMV) load in whole blood (WB) to predict the plasma CMV load, aiming to identify active CMV infections by using WB samples only and to deduce a WB threshold. Using quantitative real-time PCR, a total of 1,474 WB samples were assayed, of which 279 were positive for CMV, and 140 out of the 276 paired plasma samples tested positive. Thirty (36.6%) patients presented with at least one positive plasma PCR result, and 21 infection episodes (19 patients) required curative treatment (median follow-up time, 12 months). When the plasma CMV load was >500 copies/ml ( n = 70), more than 94% (95% confidence interval, 86.0%, 98.4%) of WB samples had >500 copies/ml. Two prediction models were built: log 10 plasma viral load (VL) was calculated as −0.3777 + 0.9342 × log 10 WB VL and as −0.3777 + 0.8563 × log 10 WB VL for patients with and without treatment, respectively. In the validation sample (578 routine samples), 77.2% of the observed and expected plasma viral loads were concordant (95% confidence intervals, 73.5 and 80.5%). According to the model, the plasma viral load was >500 copies/ml when the WB load was >3,170 or >4,000 copies/ml in patients with or without treatment, respectively. WB seems to be an appropriate candidate for routine CMV monitoring of transplant recipients by using a single assay.

Background Variability of human cytomegalovirus (HCMV) genes counteracting immune responses is poorly investigated in non-cultured clinical strains. Objectives In HCMV-infected renal graft recipients, we aimed to (i) investigate the variability of four HCMV immunomodulatory genes, without any culture-related viral selection, (ii) provide evolutionary sequence data, and (iii) study co-existing HCMV variants and their evolution. Study design UL18, UL40, UL111a and US3 were sequenced in 31 blood samples from 17 patients (8 with sequential samples). Cloning of UL40 PCR products was performed in one donor-positive/recipient-positive (D+/R+) patient's samples. Results Each patient harboured a unique strain (combination of four genes), however single identical genes were demonstrated among various patients, suggesting recombination events. Sequencing showed in D+/R− recipients, either complete gene stability (four patients) or significant variability (one patient); in three D+/R+ patients, multiple gene variations, possibly linked to super- or co-infections. Cloning evidenced different variants at each time point with an increasing variability over time, illustrating possibly viral reactivations and the subsequent evolution of the variants mixture. Conclusion A noticeable HCMV natural polymorphism was shown, with different evolutive patterns. Moreover, we described the co-evolution of variants mixtures in one patient. Consequences on HCMV infection and graft function deserve further studying.

Hepatic steatosis is a common feature in liver biopsies from patients with chronic hepatitis C and is associated with fibrosis progression. Patients with HIV infection and hepatitis C virus (HCV) coinfection have more rapid progression of liver fibrosis than patients with HCV infection alone. The prevalence and factors associated with hepatic steatosis are not well defined in HCV-HIV-coinfected patients.Steatosis was assessed among 148 HCV-HIV-coinfected patients of the Aquitaine Cohort. Steatosis was graded as follows: none, mild (1%-10% of hepatocytes), moderate (11%-30%), severe (31%-60%), and massive (more than 60%). Epidemiologic, clinical, biologic, and therapeutic data were retrieved from the cohort database to investigate the risk factors.Steatosis was present in 67% of patients (95% confidence interval [CI]: 59% to 74%) and was at least moderate in 30% (95% CI: 23% to 38%). Steatosis was macrovesicular or mixed (macro- and microvesicular) in 40.5% and 52.8% of patients, respectively. Necroinflammatory activity was the only factor independent of steatosis (adjusted odds ratio = 5.3, 95% CI: 1.6 to 17.9). When necroinflammatory activity was removed from the model, HCV genotype 3 and body mass index (BMI) were significantly associated with steatosis.Liver inflammation, HCV genotype 3, and BMI are associated with steatosis, a common finding in HCV-HIV-coinfected patients.

Background Cytomegalovirus (CMV) remains a major opportunistic agent among transplant recipients. While detection of CMV pp65-lower matrix protein (pp65Ag) is still widely used for monitoring CMV infection, real-time PCR assays have been recently developed for routine quantitation of CMV DNA. However, correlations are lacking between results of pp65Ag and quantitative PCR assays and there is no consensus yet as to the more appropriate blood compartment (whole blood (WB), leukocytes, plasma) to be tested with PCR assays. Objectives The aims of the study were to determine, in a population of transplant recipients: (i) the correlation between pp65Ag and CMV quantitative real-time PCR in our setting and (ii) the utility of plasma CMV DNA quantitation in comparison to WB quantitation. Methods In 170 blood samples (from 61 solid organ or bone marrow transplant recipients) with pp65Ag results, CMV quantitation was performed in WB and plasma using an in-house real-time quantitative PCR. Results Real-time PCR and pp65Ag results in WB were correlated: thresholds of 10 and 50(+) cells/200,000 cells were equivalent to 3.3 log10 copies/mL (2000 copies/mL) and 3.8 log10 copies/mL (6300 copies/mL), respectively. When WB viral load was ≥3.6 log10 copies/mL, the risk to have a negative plasma CMV DNA result was ≤2.5%. Conclusions For the routine exploration of a single compartment, whole blood would represent a suitable compromise: easy processing for a sensitive assay. The 3.6 log10 copies/mL threshold, which could help in identifying active CMV infection, deserves further evaluation.

We prospectively assessed the prevalence of occult hepatitis B virus (HBV) infection by investigating HBV replication in 160 human immunodeficiency virus (HIV)-infected patients with isolated antibodies to hepatitis B core antigen. This prevalence was 0.6% (1 case/160 patients; 95% confidence interval, 0%-3.4%). A second serum sample was collected later from 52 of the patients. HBV DNA was once again undetectable in all patients, except for the sole patient who had previously been found to be HBV DNA positive.

The HTLV-I envelope plays a major role in the process of target cell infection. It is implied in the recognition of the viral receptor(s), penetration of the viral genetic material, and induction of host immunity to the virus. It is thus important to study the genetic variability of the viral env gene as well as its variation in terms of evolution. In a new approach to these features, we sequenced the entire env gene of 65 HTLV-I isolates originating from Gabon, French Guiana, West Indies, and Iran, such isolates representing all major HTLVI phylums but the Australo-Melanesian one. The sequences obtained and all PTLV-I (HTLV-I and STLV-I) env sequences available in the literature were analyzed. Phylogenetic studies using different algorithms (minimum evolution, neighbor joining, maximum parsimony, and maximum likelihood) gave the same clear-cut results. Newly sequenced HTLV-I isolates described in this report allocated in three well-defined subtypes: Cosmopolitan, Central African, and a new distinct one that we termed "Maroni" subtype (present in the Maroni Basin, French Guiana, and West Indies). Clearly, the most divergent PTLV-I strains present in Asia- Australo-Melanesia as well as African and Asian STLV-I derived from the same node in the phylogenetic tree as isolates of the Central African subtype. In addition, we showed that within each PTLV-I subtype, groups of isolates may be characterized by nonrandom and systematically associated mutations.

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating infectious disease, caused by the human polyomavirus JC (JCV), that usually occurs in immunocompromised patients. In this setting, PML has been observed in increasing numbers of patients with hematological malignancies, mostly lymphoproliferative B-cell disorders. Despite attempts with various drugs, PML has generally remained unresponsive to treatment. We report the successful use of cidofovir in a patient who developed PML 6 months before angioimmunoblastic T-cell lymphoma (AITL) was diagnosed. To the best of our knowledge, this is the first case of PML in AITL. Our case demonstrates the expanding clinical importance of PML in hematological conditions, and neurological symptoms and/or white matter changes on central nervous system imaging should arouse the suspicion of PML and lead to rapid cidofovir introduction. Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating infectious disease, caused by the human polyomavirus JC (JCV), that usually occurs in immunocompromised patients. In this setting, PML has been observed in increasing numbers of patients with hematological malignancies, mostly lymphoproliferative B-cell disorders. Despite attempts with various drugs, PML has generally remained unresponsive to treatment. We report the successful use of cidofovir in a patient who developed PML 6 months before angioimmunoblastic T-cell lymphoma (AITL) was diagnosed. To the best of our knowledge, this is the first case of PML in AITL. Our case demonstrates the expanding clinical importance of PML in hematological conditions, and neurological symptoms and/or white matter changes on central nervous system imaging should arouse the suspicion of PML and lead to rapid cidofovir introduction.

To the Editor: Enterovirus 71 (EV-71) causes primarily asymptomatic or benign infections in children

The molecular characterization of HIV-1 isolates in drug-naive cases in the early stages of HIV disease was studied in 128 cases from Mumbai (Bombay), India. Subtype C was largely predominant followed by A-C intersubtype recombinants, one subtype A and one CRF01 AE. Compared to subtype B, subtype C exhibited an important polymorphism; the percentages of substitutions could reach more than 90%. Two isolates showed M184V substitution the reverse transcriptase indicating resistance to 3TC.

Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range. Human infections, although controversial, have been described in Europe, Asia, and the United States. The present study investigated the existence of BDV infections in immunocompromised human beings, namely, 82 human immunodeficiency virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40 RNAs were detected in peripheral white blood cells with reverse transcription-nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the two groups of patients. BDV p24 RNAs were identified in only one of those. BDV RNA was detected in the absence of any neuropsychiatrical illness, suggesting that BDV infections may occur in asymptomatic carriers. The severity and particularity of cellular immunosuppression could explain the significantly increased detection of BDV RNA in HIV-infected patients.

A total of 107 HIV-1 isolates from untreated adult patients recruited in Abidjan, CMte d'Ivoire, in 2001 and 2002 were sequenced in the env, reverse transcriptase (RT), and protease genes. The results show that CRF02_AG is still predominant in this west African population; key mutations of resistance to antiretroviral drugs (NRTI, NNRTI, and PIs) were detected in 5.6% of the patients. We hypothesize that these resistant mutants have been acquired through horizontal transmission. Compared to a previous study carried out by our group in 1997-2000 in a similar population of Abidjan, it seems that there is a dynamic process of resistance and that a survey will be necessary.

The aim of this study was to examine whether hepatitis C virus (HCV) pretreatment quasispecies complexity was linked to virological response or other clinical and biological parameters, in human immunodeficiency virus (HIV)-coinfected patients undergoing anti-HCV treatment. In addition, HCV quasispecies composition is described longitudinally in these patients before, during, and after treatment. The 52 HIV-coinfected patients were included in a randomized therapeutic trial. At inclusion, they had CD4+ counts of >250/μl, HIV plasma load of

An open-label, randomized trial was conducted to compare the efficacy and safety of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN-alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks, followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31 patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22 weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients). Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week 12. Sustained virological response was achieved in 10 patients (15%; 6 in group A and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3 log(10) copies/mL between inclusion and week 4 were associated with virological response. In conclusion, the combination of conventional IFN-alpha-2a and ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.

We describe an acromegalic patient who developed a parvovirus B19 (PVB19) infection concomitantly with sarcoidosis, which was complicated by chronic red blood cell aplasia and severe thrombocytopenia, despite disappearance of the virus from serum and the production of high levels of specific polyclonal antibodies to PVB19. Mitogen stimulation of the patient's peripheral blood mononuclear cells induced oversecretion of interferon-gamma (IFN-gamma). Because hematopoietic suppression by IFN-gamma has been reported, a possible mechanism underlying reticulocytopenia and thrombocytopenia could involve IFN-gamma.

The aims of this study were to assess the sociodemographic, epidemiological, clinical, and biological characteristics of French patients co-infected with human immunodeficiency virus-hepatitis C virus (HIV-HCV), as well as the management of their HCV infection. Data on 509 HIV-HCV co-infected patients, followed up at six French University Hospitals, were collected using a questionnaire. Student's t-test, Pearson's chi-square, Fisher's exact, and Fisher-Freeman-Halton's exact tests were used. The mean age of the patients was 38.3 years, and the male to female sex ratio 2.08; 88% of patients were born in Metropolitan France, and 20% were dependent on health benefits; 74% were intravenous drug users and 14% blood or blood product recipients. Forty-seven percent were in CDC classification stage A, 18% had a CD4+ count of200, and 79% were undergoing current antiretroviral treatment. HCV RNA was positive in 84% (50% type 1, 13% untypable). Forty-four percent had normal alanine aminotransferase (ALT) levels, 24% alcohol consumption15 g/day, and 51% had undergone liver biopsy (10% of which had cirrhosis). Histological grade was not related to ALT level or CD4+ count. Overall, 40% of patients had been treated for HCV infection. HCV treatment was significantly associated with performance of liver biopsy, histological grade, ALT level, CD4+ count, Centers for Disease Control (CDC) classification, but not with age or alcohol consumption. Rate of early response to treatment was fifty percent among patients treated with bitherapy. Eighty-nine percent of all patients with previous or current anti-HCV treatment had undergone liver biopsy. In conclusion, despite the difficulties in managing hepatitis C in HIV-infected patients, almost one-half of all patients in this study had received anti-HCV treatment.

CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens were evaluated before and during an anti-HCV regimen (interferon-alpha2a and ribavirin) in 36 patients coinfected with HCV and human immunodeficiency virus (HIV), to determine whether immune responses against HCV antigens are present in such patients, whether these responses are modified by anti-HCV treatment, and whether they are correlated with treatment efficacy. The CD4 responses against HCV antigens (primarily core antigens) detected at study entry in one-half of the patients did not correlate with anti-HCV treatment efficacy. Of 36 patients, 8 had patterns of persistent immune response to infection by genotypes 3 or 4 that were significantly correlated with sustained virologic response. Persistent immunologic reactivity and sustained virologic response coexisted only in patients infected with genotype 3. These findings suggest that HCV genotype may influence specific immune response, which, in turn, is implicated in virologic control.

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.

International audience; Objective. - We report the features and diagnosis of complicated mumps in previously vaccinated young adults. Patients and methods. - We retrospectively studied 7 cases of complicated mumps managed during 1 year at the Bordeaux University Hospital. The diagnosis was suggested by the clinical presentation and confirmed using specific RT-PCR. Results. - Five cases of meningitis, 1 of orchitis, and 1 of unilateral hearing impairment were identified. Each of the 7 patients had been previously vaccinated with MMR, 4 had received 2 doses of this vaccine. Blood tests revealed high rates of IgG antibbdies, Usually considered as sufficient for immunological protection, arid every patient had at least 1 positive RT-PCR test for mumps. Conclusion. - Outbreaks of complicated mumps may still occur despite abroad coverage of MMR vaccination. The clinical presentation suggested mumps but the final diagnosis could only be confirmed by genomic detection of the virus. Unusual viral strains with increased neurovirulence, insufficient population coverage associated with immunity decrease over time may explain outbreaks of complicated mumps. A full vaccine scheme of contact people or a third injection of vaccine for previously vaccinated people who are at risk of developing mumps are required to prevent further spreading of the disease during the outbreak. (C) 2014 Elsevier Masson SAS. All rights reserved.; Objectifs : Description et diagnostic de formes compliquées d’oreillons chez de jeunes adultes préalablement vaccinés. Patients et méthodes : Étude rétrospective de 7 cas de formes compliquées d’oreillons survenues au CHU de Bordeaux sur une période de 12 mois. Le diagnostic est évoqué sur la présentation clinique et la confirmation est obtenue par réalisation d’une RT-PCR spécifique. Résultats : Cinq méningites, 1 orchite et 1 épisode de surdité brusque unilatérale ont été identifiés. Tous les patients avaient été préalablement vaccinés et 4 patients avaient même reçu 2 injections du vaccin ROR. Le bilan sérologique révélait la présence d’IgG à taux élevé généralement considéré comme protecteur, tous les patients avaient une PCR positive sur au moins un prélèvement. Conclusions : Le risque de survenue d’épidémie de formes rares et compliquées par le virus des oreillons persiste malgré l’implémentation à large échelle de la vaccination grâce au ROR. Les manifestations cliniques sont évocatrices, mais le diagnostic est réalisé par mise en évidence du génome viral. L’émergence de souches virales neurovirulentes mal couvertes par les vaccins existants, associée à une couverture vaccinale en population générale insuffisante et à la diminution progressive de l’efficacité avec le temps, semblent être les raisons les plus probables à la survenue de ces épidémies. En contexte de foyers épidémiques survenant en collectivité, un rappel vaccinal par une 3ème injection chez les personnes préalablement vaccinées par 2 injections remontant à plus de 10 ans et la réalisation d’un schéma vaccinal complet pour les autres pourraient limiter l’extension de l’épidémie.

Env C2/V3, gag p17/p24, pol protease, and RT regions of HIV-1 isolates recently obtained from 25 HIV-1 seropositive individuals from Ho Chi Minh City (Vietnam) were studied, and genes subtypes were determined by DNA sequence analyses. Twenty-three isolates out of 25 were identified as belonging to subtype E, now recognized as circulating recombinant form 1 (CRF01_AE). The motif at the top of the V3 loop (generally GPGQ) was then preceded by an isoleucine or a methionine (M) residue; the M residue might be a local signature of Vietnamese E isolates compared to Thai E viruses. Two isolates (8%) were shown to be intersubtype recombinants: one E/B and one CRF02_AG(IBNG)/D. The polymorphism of pol protease was considered only for CRF01_AE isolates and is clearly different from that recorded for B viruses with substitutions at positions 13, 35, 36, 41, 69, and 89.

Pathogenic enteric viruses can be introduced into the environment as a result of human activities. Enteroviruses are regularly detected in environmental waters or shellfish and can provoke potentially serious diseases. Some authors believe that enteroviruses could represent an interesting indicator of viral contamination in the environment. Since molecular approaches seem to be promising for the detection of these viruses, we developed a simple qualitative RT-PCR procedure for enteroviruses, together with a quantitative RT-PCR assay using RNA internal standard. After one-tube-RT-PCR, this standard and wild enterovirus RNA were detected by differential hybridization with specific probes and a fluorimetric reaction. The quantification of enteroviruses, conducted in a sewage treatment plant, showed a decreasing number of genomic copies from the entrance to the exit (from 3.8 x 10(5) to 5.4 x 10(4) RNA copies/mL) but indicated the presence of enterovirus RNA in the neighboring river (2.2 x 10(3) RNA copies/mL). In bathing areas, enterovirus RNA was detected in 16 out of 226 samples, with copies numbers ranging from 3.7 x 10(2) RNA copies/mL to 7 x 10(4) RNA copies/mL.