Browsing by Author "Barzdina, Arta"
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Item Adeno-associated virus 2 infection in children with non-A–E hepatitis(2023-05-18) Ho, Antonia; Orton, Richard; Tayler, Rachel; Thomson, Emma C.; DIAMONDS Consortium; ISARIC4C Investigators; Zavadska, Dace; Laivacuma, Sniedze; Rudzate, Aleksandra; Stoldere, Diāna; Barzdina, Arta; Barzdina, Elza; Madelane, Monta; Grāvele, Dagne; Rīga Stradiņš UniversityAn outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland 1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case–control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10−12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a ‘helper virus’ to support AAV2 replication) and disease susceptibility related to HLA class II status.Item Biobanking and consenting to research : a qualitative thematic analysis of young people’s perspectives in the North East of England(2023-12) van der Velden, Fabian J.S.; Lim, Emma; Gills, Lily; DIAMONDS Consortium; Zavadska, Dace; Laivacuma, Sniedze; Rudzate, Aleksandra; Barzdina, Arta; Madelane, Monta; Stoldere, Diāna; Barzdina, Elza; Grāvele, Dagne; Rīga Stradiņš UniversityBackground: 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.Item Genomic investigations of unexplained acute hepatitis in children(2023-03-30) Morfopoulou, Sofia; Buddle, Sarah; Torres Montaguth, Oscar Enrique; Breuer, Judith; DIAMONDS Consortium; PERFORM consortium; Zavadska, Dace; Laivacuma, Sniedze; Rudzāte, Aleksandra; Barzdina, Arta; Madelane, Monta; Grāvele, Dagne; Balode, Anda; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavare, Jana; Pucuka, Zanda; Urbane, Urzula Nora; Selecka, Katrina; Deksne, Dārta; Rīga Stradiņš UniversitySince 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.Item GFAP and NF expression in brain tissue in children and adults after fatal traumatic brain injury(2011) Barzdina, Arta; Pilmane, Māra; Pētersons, Aigars; Department of Anaesthesiology, Intensive Care and Clinical simulations; Institute of Anatomy and Anthropology; Department of Paediatric SurgeryBackground and objectives. Still, there is almost no information about the role of biomarkers in the pathological processes of the brain in those patients, which die immediately after the injury, and those, which die several hours after the trauma. Design and Settings. A retrospective study. The human brain tissue material from the archive of the Institute of Anatomy and Anthropology in Riga Stradins University (RSU). Methods. We used the brain tissue material from the trauma and counterstroke spots of 28 patients. Brain tissue specimens were routinely fixed, embedded into paraffin, cut in 5 μm thick slides. For immuno-histochemistry we used monoclonal antibodies against NF proteins to detect axonal injury and monoclonal antibodies against GFAP to detect astrocytes. Results. Statistical correlation was seen between the lethal cases and survived in the brain tissue in the areas of counterstroke between lethal cases and survived for NF and GFAP presence (p=0.017) The data was compared, by dividing patients into groups of children and adults. Each of these groups was divided into 2 sub-groups. Statistically significant differences were noted between the lethal and the survived cases in the group of children for GFAP (Mann-Whitney U Test, p = 0.015) and in the group of adults for NF in the area of the counterstroke (Mann-Whitney U Test, p = 0.019). Conclusions. Higher quantities of intermediated filaments such as GFAP and NF are characteristic in the patients who survived after a head trauma in comparison to those, who died on the spot of the accident. Children under 2 years of age with severe head trauma have more dynamic glial cell reaction than other patients.