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.
Purpose: Aeromonas species are emerging human enteric pathogens. However, there is no systematic analysis of Aeromonas infection in the pediatric population in Latvia. The aim of the study was to describe potential sources, prevalence of infection, associated virulence factors and antimicrobial resistance of Aeromonas spp. isolated from fecal samples. Methods: Stool samples (n = 1360) were obtained from the Children’s Clinical University Hospital between 2020 and 2021. The target population was pediatric patients, 0 to 18 years of age, with a preliminary diagnosis of gastroenteritis. Identification was performed by Maldi-TOF, antimicrobial resistance by Vitek2 and 9 virulence factors by polymerase chain reaction (PCR). Results: Aeromonas spp. were isolated in 50 stool samples; positive findings made up 3.6% of all study cases and included four species: A. hydrophila, A. caviae, A. veronii, and A. eucrenophila. In 42% of the samples, Aeromonas spp. appeared alongside the other significant pathogens: Campylobacter jejuni, Salmonella Enteritidis, Salmonella Typhimurium, Yersinia enterocolitica, norovirus, adenovirus, and rotavirus. The study population positive for Aeromonas spp. infection contained 28 male (56%) and 22 female (44%) patients; median age was 4.56 years. The most common symptoms were: diarrhea, blood in stool, vomiting, abdominal pain, and fever. Aside from expected natural resistance, no significant antibacterial resistance was detected. The presence of multiple virulence genes was noticed in all isolates. No statistically significant correlation was found between the virulence patterns, bacterial species, and the intensity of clinical symptoms. Discussion: According to the clinical data and the results of this study Aeromonas spp. has an important role in pediatric practice and requires appropriate attention and monitoring.
Background Biobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people’s (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures. Methods We designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated via the Young Person’s Advisory Group North England (YPAGne) and participating CYP’s secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer. Results One hundred two CYP completed the survey. Most were between 16–18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73). Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: ‘altruism’, ‘potential benefits outweigh individual risk’, 'frugality', and ‘(in)convenience’. Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: ‘altruism’, ‘body integrity’ and ‘sample frugality’. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80). Conclusion Prospective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity should be part of the consenting procedure, if possible.
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