This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Staphylococcus aureus is the main pathogen responsible for bone and joint infections worldwide and is also capable of causing pneumonia and other invasive severe diseases. Panton-Valentine leukocidin (PVL) and methicillin-resistant S. aureus (MRSA) have been studied as factors related with severity in these infections. The aims of this study were to describe invasive community-acquired S. aureus (CA-SA) infections and to analyse factors related to severity of disease. Paediatric patients (aged 0-16 years) who had a CA-SA invasive infection were prospectively recruited from 13 centres in 7 European countries. Demographic, clinical and microbiological data were collected. Severe infection was defined as invasive infection leading to death or admission to intensive care due to haemodynamic instability or respiratory failure. A total of 152 children (88 boys) were included. The median age was 7.2 years (interquartile range, 1.3-11.9). Twenty-six (17%) of the 152 patients had a severe infection, including 3 deaths (2%). Prevalence of PVL-positive CA-SA infections was 18.6%, and 7.8% of the isolates were MRSA. The multivariate analysis identified pneumonia (adjusted odds ratio (aOR) 13.39 (95% confidence interval (CI) 4.11-43.56); p 0.008), leukopenia at admission (<3000/mm(3)) (aOR 18.3 (95% CI 1.3-259.9); p 0.03) and PVL-positive infections (aOR 4.69 (95% CI 1.39-15.81); p 0.01) as the only factors independently associated with severe outcome. There were no differences in MRSA prevalence between severe and nonsevere cases (aOR 4.30 (95% CI 0.68- 28.95); p 0.13). Our results show that in European children, PVL is associated with more severe infections, regardless of methicillin resistance.

No abstract

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections (ALRI) and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants below 6 months of age. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among the elderly. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations to develop a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance, and passive laboratory surveillance, using the EU acute respiratory infection (ARI) and WHO extended severe acute respiratory infection (SARI) case definitions. Furthermore, we recommend the use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for a good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and estimation of the RSV burden and impact of the future immunisation programmes.

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.