Prevalence of Aeromonas spp. Infection in Pediatric Patients Hospitalized with Gastroenteritis in Latvia between 2020 and 2021

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Genomic investigations of unexplained acute hepatitis in children

Funding Information: UKHSA funded the metagenomics and HAdV sequencing. We thank A. Nathwani for helpful discussions. We acknowledge the considerable contribution from the GOSH microbiology laboratory. We thank the medical students who contributed to the DIAMOND consortium. All research at GOSH and UCL GOSH Institute of Child Health is made possible by the NIHR GOSH Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research (NIHR), the UKRI or the Department of Health and Social Care. The work was part funded by the NIHR Blood and Transplant Research Unit in Genomics to Enhance Microbiology Screening (GEMS), the National Institute for Health and Care Research (CO-CIN-01) or jointly by NIHR and UK Research and Innovation (CV220-169, MC_PC_19059). S. Morfopoulou is funded by a W.T. Henry Wellcome fellowship (206478/Z/17/Z). S.B. and O.E.T.M. are funded by the NIHR Blood and Transplant Research Unit (GEMS). M.M.M. and M.L. are supported in part by the NIHR Biomedical Research Centre of Imperial College NHS Trust. J.B. receives NIHR Senior Investigator Funding. M.N. and J.B. are supported by the Wellcome Trust (207511/Z/17/Z and 203268/Z/16/Z). M.N., J.B. and G.P. are supported by the NIHR University College London Hospitals Biomedical Research Centre. P. Simmonds is supported by the NIHR (NIHR203338). T.S.J. is grateful for funding from the Brain Tumour Charity, Children with Cancer UK, GOSH Children’s Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the NIHR. DIAMONDS is funded by the European Union (Horizon 2020; grant 848196). PERFORM was funded by the European Union (Horizon 2020; grant 668303). Publisher Copyright: © 2023, The Author(s).Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the 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-mediated 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.publishersversionPeer reviewe

Which low urgent triaged febrile children are suitable for a fast track? An observational European study.

The number of paediatric patients visiting the ED with non-urgent problems is increasing, leading to poor patient flow and ED crowding. Fast track aims to improve the efficiency of evaluation and discharge of low acuity patients. We aimed to identify which febrile children are suitable for a fast track based on presenting symptoms and management. This study is part of the Management and Outcome of Fever in children in Europe study, which is an observational study including routine data of febrile children <18 years attending 12 European EDs. We included febrile, low urgent children (those assigned a triage acuity of either 'standard' or 'non-urgent' using the Manchester Triage System) and defined children as suitable for fast track when they have minimal resource use and are discharged home. Presenting symptoms consisted of neurological (n=237), respiratory (n=8476), gastrointestinal (n=1953) and others (n=3473, reference group). Multivariable logistic regression analyses regarding presenting symptoms and management (laboratory blood testing, imaging and admission) were performed with adjustment for covariates: patient characteristics, referral status, previous medical care, previous antibiotic use, visiting hours and ED setting. We included 14 139 children with a median age of 2.7 years (IQR 1.3-5.2). The majority had respiratory symptoms (60%), viral infections (50%) and consisted of self-referrals (69%). The neurological group received imaging more often (adjusted OR (aOR) 1.8, 95% CI 1.1 to 2.9) and were admitted more frequently (aOR 1.9, 95% CI 1.4 to 2.7). The respiratory group had fewer laboratory blood tests performed (aOR 0.6, 95% CI 0.5 to 0.7), were less frequently admitted (aOR 0.6, 95% CI 0.5 to 0.7), but received imaging more often (aOR 1.8, 95% CI 1.6 to 2.0). Lastly, the gastrointestinal group had more laboratory blood tests performed (aOR 1.2. 95% CI 1.1 to 1.4) and were admitted more frequently (aOR 1.4, 95% CI 1.2 to 1.6). We determined that febrile children triaged as low urgent with respiratory symptoms were most suitable for a fast track. This study provides evidence for which children could be triaged to a fast track, potentially improving overall patient flow at the ED