Browsing by Author "Madelane, Monta"
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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 Association of non-invasive markers of liver fibrosis with HCV coinfection and antiretroviral therapy in patients with HIV(2019-08-01) Koļesova, Oksana; Eglite, Jeļena; Koļesovs, Aleksandrs; Krumiņa, Angelika; Ekšteina, Ilze; Madelane, Monta; Viksna, Ludmila; Klīniskās imunoloģijas un imunoģenētikas starpkatedru laboratorija; Department of InfectologyThe aim of this study was to assess the main effects and interaction between viral hepatitis C (HCV) coinfection and antiretroviral therapy (ART) by using a nonparametric ANOVA on direct and indirect markers of liver fibrosis in HIV-infected patients. The sample included 178 HIV patients aged from 23 to 65 (36% females). The following parameters were determined in blood of patients: hyaluronic acid, pro-matrix metalloproteinase-1, alanine aminotransferase, aspartate aminotransferase, and platelet count. The FIB-4 index was also calculated. The nonparametric ANOVA revealed no significant interaction between HCV coinfection and ART. This provides evidence for an independent contribution of each factor on promotion of the pathology. The results also demonstrated that the direct and indirect indicators of liver fibrosis are associated differently with the studied factors. Therefore, a combination of markers should be used for monitoring of liver fibrosis in HIV-infected patients.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 Difference in markers of microbial translocation and cell apoptosis in HIV monoinfected and HIV/HCV coinfected patients(2019-08-01) Madelane, Monta; Krumiņa, Angelika; Simanis, Raimonds; Šķenders, Ģirts; Ivanovs, Andrejs; Sture, Gunta; Viksna, Ludmila; Department of InfectologyImmune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were measured. No significant difference in LPS, EndoCAb, Cyt-c levels between HIV and HIV/HCV patients was found. The CK18 level was higher in the HIV/HCV group. Correlation between CD4+ cell count and EndoCAb antibodies was found in HCV positive patients. There was a significant effect of ART on markers for EndoCAb IgA and EndoCAb IgM antibodies in the HIV monoinfected group. Correlation between CD4+ cell count and EndoCAb antibodies and LPS was found in HIV/HCV patients on ART. Coinfection with HCV can lead to more pronounced response in EndoCAb antibody production and higher levels of cell apoptosis markers, despite similar LPS levels. ART has a positive effect on immune activation.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.