HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients.

The objective of this study was to determine how clinicians make use of the modern multiplex PCR assays (MPAs) to manage patients hospitalized for community-acquired pneumonia (CAP). We studied the use of MPAs in 1648 patients hospitalized for CAP over a 3-year period at the moment of the setup of the new PCR assay. We observed that the use of MPAs for the identification of multiple respiratory pathogens marks a radical change in the investigation of CAP etiology. Surprisingly, the contribution of MPAs to the medical decision-making process varies drastically according to the units of care.

Purpose. Bartonella is an increasingly isolated emerging pathogen that can cause severe illness in humans, including cat scratch disease (CSD). The bacteria are difficult to grow and thus many detection methods have been developed, especially molecular. We previously developed a PCR method targeting ribC to identify Bartonella sp. A manufactured kit (RealCycler BART, Progenie Molecular) was commercialised shortly thereafter for the detection of Bartonella infection, including Bartonella henselae. Methodology. We performed a comparison between this test and our in-house PCR assay on 73 lymphadenopathy samples sent to the laboratory for suspicion of CSD. Results/Key findings. Among the 28 positive samples for Bartonella, 21 were identified by the two PCR assays, and seven by the commercial kit only. Conclusion. The performance of this commercial kit suggests that it could be a suitable alternative to our in-house PCR assay, highlighting the importance of the molecular methods used to diagnose CSD.

Investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. In a routine care setting, we assessed the diagnostic performance of a multiplex PCR assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. We enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at Tours University Hospital during the winter of 2011-2012. Respiratory samples (mostly nasopharyngeal aspirates) were studied prospectively by indirect immunofluorescence assay and multiplex PCR, that enable detection of 8 viruses and 21 respiratory pathogens respectively. In total, 255 of the 279 (91.4%) samples had interpretable results by both methods. At least one respiratory pathogen was detected by multiplex PCR in 171 specimens (65%). Overall, 130 (76%) of the 171 positive samples were positive for only one respiratory pathogen, 37 (22%) samples were positive for two pathogens and four (2%) were positive for three pathogens. With indirect immunofluorescence assay, a respiratory virus was detected in 27 of the 255 (11%) specimens. Indirect immunofluorescence assay detected some of the influenza virus A (15/51, 29%) infections identified by multiplex PCR and some (7/15, 47%) human metapneumovirus and (5/12, 42%) respiratory syncytial virus infections, but it did not detect all the adenovirus infections. Thus, access to multiplex molecular assays improves the diagnostic spectrum and accuracy over conventional methods, increasing the frequency of identification of the respiratory pathogens involved in community-acquired acute respiratory illness.

Des outils de détection rapide des bactéries et des virus impliqués dans les infections pulmonaires ont été développés pour pallier les difficultés rencontrées au cours de la pandémie grippale à virus A(H1N1)pdm2009. L'absence de diagnostic avait rendu difficiles la mise en place de mesures préventives et l'utilisation ciblée des antiviraux. Depuis les techniques de PCR multiplex qui ciblent 15 à 20 pathogènes sur un prélèvement unique se sont établies dans la routine. Les objectifs de ce travail étaient d'évaluer l'utilisation de la PCR multiplex comme outil diagnostique des pneumopathies aiguës communautaires (PAC) et de tester un outil PMSI de mesure d'impact médical et économique de son utilisation. Les patients avec PAC hospitalisés en pneumologie et en réanimation polyvalente au CHRU de Tours ont été sélectionnés à partir d'un algorithme PMSI sur trois hivers (semaine 38 à semaine 18 de l'année suivante) : avant l'utilisation de la PCR multiplex (2008–2009), en utilisation hebdomadaire (2010–2011) et en routine quotidienne (2011–2012). Un retour aux dossiers sur un échantillon aléatoire de 570 patients a permis la validation de l'algorithme PMSI. Un recueil de variables d'intérêt (durée de séjour, durée d'antibiothérapie, prescription d'antiviraux, nombre et type de prélèvements à visée microbiologique, ventilation mécanique, ECMO) a été mené pour mesurer l'impact de l'utilisation de cette innovation sur la prise en charge et évaluer l'impact économique (estimation des coûts). Il y avait 1349 patients hospitalisés pour PAC sur la période. Les paramètres de performance du PMSI étaient : sensibilité 94 %, spécificité 85 %, valeur prédictive positive 83 %, valeur prédictive négative 95 %. En 2010–2011, 27 % [IC95 % 25,6–27,6 %] des PAC hospitalisées avaient bénéficié d'une PCR, dont 18,2 % [IC95 % 17,5–19 %] en pneumologie et 37,2 % [IC95 % 35,7–38,8 %] en réanimation, et 33,5 % [IC95 % 32,2–34,9 %] en 2012–2013, dont 13,0 %[IC95 % 12,5–18,4 %] en pneumologie et 66,9 % [IC 95 % 64,3–69,8 %] en réanimation. En 2010–2011, 58 % des PCR étaient positives et 67 % en 2011–2012. Les analyses de l'impact médico-économiques sont en cours. La PCR multiplex n'est pas un outil diagnostique systématique de patients hospitalisés pour PAC, y compris pour les PAC sévères.

Des outils de détection rapide des bactéries et des virus impliqués dans les infections pulmonaires ont été développés pour pallier les difficultés rencontrées au cours de la pandémie grippale à virus A(H1N1)pdm2009. L'absence de diagnostic avait rendu très difficiles la mise en place de mesures préventives et l'utilisation ciblée des antiviraux. Depuis les techniques de PCR multiplex qui ciblent 15 à 20 pathogènes sur un prélèvement unique se sont établies dans la routine. Les objectifs de ce travail étaient de faire une évaluation précoce de l'impact médical et économique de l'utilisation de la PCR multiplex dans la prise en charge des pneumopathies aiguës communautaires (PAC). Les patients avec PAC hospitalisés en pneumologie, en réanimation médicale au CHRU de Tours ont été sélectionnés à partir d'un algorithme PMSI sur trois hivers : – avant l'utilisation de la PCR multiplex (2008–2009); – en utilisation hebdomadaire (2010–2011); – en routine quotidienne (2011–2012). Un retour aux dossiers sur un échantillon aléatoire de 570 patients a permis la validation de l'algorithme PMSI. Un recueil de variables d'intérêt (durée de séjour, durée d'antibiothérapie…) a été mené pour mesurer l'impact de l'utilisation de cette innovation sur la prise en charge et évaluer l'impact économique (estimation des coûts). Les paramètres de performance du PMSI étaient : sensibilité 94 %, spécificité 85 %, valeur prédictive positive 83 %, valeur prédictive négative 95 % ; 22 % des PAC hospitalisées en 2010–2011 avaient bénéficié d'une PCR, dont 15 % en pneumologie et 31 % en réanimation, et 28 % en 2012–2013, dont 16 % en pneumologie et 56 % en réanimation. En 2010–2011, 58 % des PCR étaient positives et 67 % en 2011–2012. Les analyses de l'impact médico-économiques sont en cours. Le premier constat est que le recours à la PCR multiplex n'est pas systématique face à une PAC hospitalisée, même en période hivernale.

Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening. In March 2012, 6000 unscreened women aged 30–65 years, living in a French region covered by a screening programme, who had not responded to an initial invitation to have a Pap smear were equally randomised to three groups: ‘no intervention’; ‘recall’, women received a letter to have a Pap smear; and ‘self-sampling’, women received a self-sampling kit to return to a centralised virology laboratory for PCR-based HPV testing. Participation was higher in the ‘self-sampling’ than in the ‘no intervention’ group (22.5% vs 9.9%, P<0.0001; OR 2.64) and ‘recall’ group (11.7%, P<0.0001; OR 2.20). In the ‘self-sampling’ group, 320 used the self-sampling kit; for 44 of these women with positive HR-HPV test results, 40 had the recommended triage Pap smear. The ICER per extra screened woman was 77.8€ and 63.2€ for the ‘recall’ and ‘self-sampling’ groups, respectively, relative to the ‘no intervention’ group. Offering an in-home, return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening.

L'identification des agents pathogènes est importante pour la mise en œuvre d'un traitement adapté des infections respiratoires basses (IRB) mais les méthodes diagnostic classiques sont souvent mises en défaut. Nous rapportons l'impact sur la pratique clinique de l'utilisation de la PCR multiplex pour la détection de 18 virus et 4 bactéries. Entre janvier 2012 et avril 2014, une PCR multiplex a été réalisée sur aspiration nasopharyngée chez tous les patients adultes hospitalisés pour une IRB dans le service de maladies infectieuses du CHU de Tours. Sur 133 patients testés, un pathogène a été identifié chez 72 patients (54 %) dont 4 cas avec un Mycoplasma pneumoniae. Les 68 autres identifications étaient des virus avec Myxovirus influenzae A (22 patients), Rhino/entérovirus (16), Coronavirus (11), Bocavirus (11), Metapneumovirus (6), virus syncitial respiratoire (4), Adénovirus (4), Myxovirus influenzae B (3) et Paramyxovirus influenzae (2). Avec les méthodes classiques, un agent pathogène a été identifié dans 6 cas : 3 Streptococcus pneumoniae et 3 Mycoplasma pneumoniae. Lorsqu'un virus a été identifié comme cause de l'IRB, la radiographie pulmonaire montrait un syndrome alvéolaire dans 21 cas. L'identification d'un agent viral par PCR multiplex a permis un arrêt anticipé de l'antibiothérapie chez 14 patients et l'absence d'initiation d'un antibiotique chez 6 autres patients. La PCR multiplex est utile pour l'identification microbiologique des infections respiratoires virales (54 %) et pour la prise en charge des patients en limitant la prescription inappropriée d'antibiotique (15 % d'arrêt ou de non prescription).

Objective. Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (VSC-DRY) or swab in liquid medium (VSC-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (CCC-LIQ).Methods. Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV + with detection of at least one HR-HPV or probable HR-HPV type.Results. Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of CCC-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in VSC-DRY samples were 88.7% and 92.5%, respectively, and in VSC-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV+ in VSC-DRY, VSC-LIQ and CCC-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV+ in VSC-DRY samples, 1 was HR-HPV in VSC-LIQ samples and 1 was HR-HPV in CCC-LIQ samples.Conclusions. Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program. (C) 2014 Elsevier Inc. All rights reserved.

Despite a large body of literature, the impact of chronic cytomegalovirus (CMV) infection in donor on long-term graft survival remains unclear, and factors modulating the effect of CMV infection on graft survival are presently unknown. In this retrospective study of 1279 kidney transplant patients, we analyzed long-term graft survival and evolution of CD8+ cell population in donors and recipients by CMV serology and antigenemia status. A positive CMV serology in the donor was an independent risk factor for graft loss, especially among CMV-positive recipients (R+). Antigenemia was not a risk factor for graft loss and kidneys from CMV-positive donors remained associated with poor graft survival among antigenemia-free recipients. Detrimental impact of donor’s CMV seropositivity on graft survival was restricted to patients with full HLA-I mismatch, suggesting a role of CD8+ cells. In R+ patients with positive CMV antigenemia during the first year, CD8+ cell count did not increase at 2 years posttransplantation, in contrast to R− recipients. In addition, marked CD8+-cell decrease was a risk factor of graft failure in these patients. This study identifies HLA-I full mismatch and a decrease of CD8+ cell count at 2 years as important determinants of CMV-associated graft loss.

Introduction : Les méningites à Pneumocoque sont les plus fréquentes des méningites bactériennes de l'adulte [1].Elles sont graves du fait de la sévérité de leur pronostic et des séquelles qu'elles engendrent.Le but du travail est d'analyser leurs facteurs pronostiques.Patients et méthodes : Il s'agit d'une étude prospective étalée sur une période de 4 ans et demi allant de janvier 2007 à septembre 2011.Étaient inclus, les patients adultes hospitalisés au service d'accueil des urgences du CHU IBN ROCHD de Casablanca pour méningite et chez qui l'étude cytobactériologique du LCR a mis en évidence le Streptococcus pneumoniae.Les paramètres étudiés étaient les données démographiques, cliniques, radiologiques et évolutives.Deux

BACKGROUND:Streptococcus pneumoniae is a significant cause of morbidity-mortality: leading agent of community-acquired pneumonia and the first cause of death due to infectious diseases in France. Vaccines are available for children and adults, avoiding serious complications. We studied hospitalizations for pneumococcal pneumonia in Centre region in 2004-2008, using the 2004-2008 national hospital discharges database and assessed vaccine coverage of a sample population. METHODS:Hospital discharges with diagnosis of pneumococcal pneumonia were selected, using the corresponding code (J13) in the French Diagnosis-Related Group coding system. We analysed hospitalization and patient data using linkage of the inpatient stays with their anonymous identification number. We analysed hospitalization and patient data: number and length of stay/patient, co-morbid factors and pneumococcal immunisation status. RESULTS:One thousand five hundred and forty-one hospitalisations were found for pneumococcal pneumonia in Centre Region, in 2004-2008. The time pattern showed an annual increase in hospital stays: winter hospitalisations were most frequent. The median age was 58 years, range: 2 months-106 years. The sex ratio M/F of the 1417 distinct inpatients was 1.43. The hospital impact was substantial, with prolonged length of stay (mean=9.9 days), frequent stays in intensive care unit (20%) and high death rate (6%). The vaccine coverage of the population with pneumococcal pneumonia was only 23%. CONCLUSION:Using the national hospital discharges database, this study presents a snapshot of pneumococcal pneumonia in one French region and demonstrates the local major clinical impact, as found in France. It shows that the hospital discharge database is a potential tool for epidemiology despite its possible bias. This type of study could be useful for organizing a regional vaccination campaing due to the better knowledge of the disease.

Regional pneumococcal observatories in region Centre, created in 1997, participate with the others pneumococcal observatories alongside the National Reference Center for Pneumococci and the Institut de Veille Sanitaire at the monitoring of the evolution of resistance of pneumococci to antibiotics in France. Between 1997 and 2007, 2427 strains of Streptococcus pneumoniae were isolated in part from cerebrospinal fluids, blood and middle ear fluid, from children and adults. The prevalence of pneumococci with a decreased susceptibility to penicillin (PDSP) decreased strongly in region Centre: 56.8 % in 2001, 39.6 % en 2007. These data are similar to the French national data over the same period.