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1.
  • Abou Ghayda, Ramy, et al. (author)
  • The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis
  • 2022
  • In: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:6, s. 2402-2413
  • Journal article (peer-reviewed)abstract
    • The aim of this study is to provide a more accurate representation of COVID-19s case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
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  • Alestig, Erik, 1973, et al. (author)
  • Genetic diversity of genotype D3 in acute hepatitis B
  • 2013
  • In: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 85:7, s. 1148-1154
  • Journal article (peer-reviewed)abstract
    • Acute hepatitis B related to injection drug use is often caused by HBV-D3, a subgenotype that probably was introduced in Western Europe in the 1960s. The aim of this study was to describe genetic change over time in injection drug use-related HBV-D3 in one geographic area. Fourteen complete genomes and partial genomic regions of 17 HBV strains of subgenotype D3 causing acute (n=30) or chronic (n=1) hepatitis B at different time points between 1975 and 2009 were investigated. The 14 complete genomes clustered in phylogenetic trees on a sub-branch of HBV-D3 along with a few published sequences with high bootstrap values. In contrast, the phylogenetic tree topology based on nucleotides coding for surface antigen or core was uncertain with bootstrap values below 70% or lower. Variation of nucleotides coding for amino acids 125, 136, and 143 in the a determinant of HBsAg was however linked to complete genome phylogeny, indicating that these codons might be useful as markers for clades. The results show that knowledge about circulating strains is critical for the interpretation of molecular epidemiology investigations. The low degree of genetic change over time of HBV-D3 in the studied groups suggests that outbreaks of acute hepatitis B in injection drug users might originate from a limited number of individuals with chronic infection. Classification based on core or S region phylogeny obtained poor support from bootstrap values, but the presence of clade-specific amino acid substitutions suggests that the S region may be useful for subgenomic molecular epidemiology of HBV.
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  • Almroth, Gabriel, et al. (author)
  • Monitoring Hepatitis C Infection in a Major Swedish Nephrology Unit and Molecular Resolution of a New Case of Nosocomial Transmission
  • 2010
  • In: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 82:2, s. 249-256
  • Journal article (peer-reviewed)abstract
    • Hepatitis C virus (HCV) infection is a frequent problem in hemodialysis units. The prevalence and incidence of HCV infection over a decade were studied in a nephrology unit affected by previous nosocomial HCV transmission. The HCV non-structural 5B protein gene was sequenced to achieve phylogenetic analysis of a new (incident) case of infection. Proportions of patients who were and were not infected with HCV remained similar over the period, as did the inflow and outflow of patients infected previously. In 1997, 12/157 (8%) of patients at the unit (treatment: hemodialysis, peritoneal dialysis, and renal transplant recipients) were positive in HCV RNA, whereas in 2007 the overall number was 9/239 (4%). One patient acquired an HCV infection, and the NS5B sequence in that case clustered with genotype 2b sequences found in patients from an earlier outbreak. Comparing the HCV from the incident patient with several stored longitudinal samples and cloned PCR products from the most likely source patient revealed close phylogenetic relationship with an HCV quasispecies member from the possible source. The source patient and the incident newly infected patient were not scheduled on the same dialysis shift, although the records showed that simultaneous treatment occurred on two occasions during the months preceding transmission. In conclusion, over the 10-year period, the proportion of HCV-infected patients at the unit was unchanged. Only one new infection occurred, which originated from a fellow patient's quasispecies. This establishes phylogenetic analysis as a valuable tool for tracing patient sources of HCV transmission. J. Med. Virol. 82:249-256, 2010. (C) 2009 Wiley-Liss, Inc.
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  • Anagandula, Mahesh, et al. (author)
  • Infection of Human Islets of Langerhans With Two Strains of Coxsackie B Virus Serotype 1 : Assessment of Virus Replication, Degree of Cell Death and Induction of Genes Involved in the Innate Immunity Pathway
  • 2014
  • In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 86:8, s. 1402-1411
  • Journal article (peer-reviewed)abstract
    • Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1. Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFN beta, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFN beta, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential beta-cell tropism of the virus.
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  • Ayukekbong, James, et al. (author)
  • Enteric viruses in healthy children in Cameroon: viral load and genotyping of norovirus strains.
  • 2011
  • In: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 83:12, s. 2135-42
  • Journal article (peer-reviewed)abstract
    • Data regarding prevalence of noroviruses (NoVs) among asymptomatic persons are scarce. The current study carried out on samples from Cameroon describes the asymptomatic shedding of NoVs and other enteric viruses in healthy children and in adults infected with HIV but lacking symptoms of gastroenteritis. Enteric viruses were common with a prevalence of 53.7% in the children, and 35.5% in the adult participants. Multiple enteric viruses (2-5 agents) were detected in fecal samples from 65% of the children, and co-infection with NoV was demonstrated in almost all cases of multiple infections. NoV viral loads in the healthy children were within disease causing range and significantly higher than those observed in the adults (P<0.01). Sequencing and genotyping of NoV strains by phylogeny showed a marked diversity within two distinct genogroups, GI and GII, and strains clustered with genotypes GI.3, GII.17, GII.8, and GII.4. Genetic similarities to recent outbreak strains from other continents suggest a rapid circulation of NoVs that includes healthy children, who may constitute a reservoir for pathogenic NoVs.
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  • Ayukekbong, James, et al. (author)
  • Molecular Analysis of Enterovirus in Cameroon by Partial 50UTR-VP4 Gene Sequencing Reveals a High Genetic Diversity and Frequency of Infections
  • 2014
  • In: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 86:12, s. 2092-2101
  • Journal article (peer-reviewed)abstract
    • Enteroviruses (EVs) often infect humans, presenting as endemic or epidemic infections. In this study, the diversity of infecting EVs was studied among 146 children and 137 adults in a small community in Cameroon. The participants provided 2,458 fecal samples during 1-year monthly collection; 10 or more samples were obtained from 55%. Partial 5UTR-VP4 region could be sequenced in 393/547 PCR positive samples obtained from 119 children and 85 adults. EV-RNA was detected in at least one sample from 235 participants (83%) during the study period. A total of 121 different strains were identified, 66 infected only children, 29 only adults, and 26 infected both children and adults. There were children with up to five episodes with different strains, and adults with up to four such episodes. Infants aged <5 years were significantly more often EV infected compared to older participants. Infections with species EV-C constituted two third of all cases, and overall EV infections were more common during the rainy season. Species EV-B more often infected children than adults. Most strains were detected only for certain months of the year; however five strains were observed during the time spans of 5-10 months. Two strains were excreted up to eight months in three children and one adult. In 11 of the 128 families with paired samples the child and the adult were infected simultaneously by the same strain, indicating common source of infection. The study revealed a surprising complexity of EV ecosystem in a single community. J. Med. Virol. 86:2092-2101, 2014. (c) 2014 Wiley Periodicals, Inc.
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  • Berg, Anna-Karin, et al. (author)
  • Enterovirus Markers and Serum CXCL10 in Children With Type 1 Diabetes
  • 2010
  • In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 82:9, s. 1594-1599
  • Journal article (peer-reviewed)abstract
    • Most patients with type 1 diabetes are considered to have a T-cell mediated autoimmune disease. The chemokine CXCL10 promotes the migration of activated T-cells. Virus infections might contribute to the pathogenesis of type 1 diabetes and enterovirus protein and/or genome have been detected in beta-cells from a majority of tested newly diagnosed children with type 1 diabetes. The chemokine CXCL10 is induced in human islet cells by enterovirus infections in vivo and in vitro, but is not expressed in islets from normal organ donors. Since CXCL10 is a chemokine known to be induced by virus infections and/or cellular damage, our aim was to study if levels of CXCL10 are elevated in serum from children with type 1 diabetes and whether it correlates to the presence of enterovirus markers. CXCL10, neutralizing antibody titer rises against certain enterovirus, and antibodies against GAD65 were measured in serum, and enterovirus PCR was performed on whole blood from 83 type 1 diabetes patients at onset, 48 siblings and 69 controls. CXCL10 was also measured in serum from 46 patients with proven enterovirus infection and in serum from 46 patients with other proven virus infections. The CXCL10 serum levels were not elevated in children at onset of type 1 diabetes and there was a considerable overlap between the groups with 99(8-498) pg/ml in serum from children with type 1 diabetes, 120 (17-538) pg/ml in serum from controls, and 117 (7-448) pg/ml in siblings of the children with type 1 diabetes. The CXCL10 serum levels in patients with proven enterovirus infection were slightly increased compared to the levels in the other groups, 172 (0-585) pg/ml but there was no statistically significant difference. In contrast, CXCL10 serum levels in patients with other proven virus infections were clearly elevated 418 (34-611) pg/ml. Despite that elevated CXCL10 levels have been demonstrated in some groups of patients with type 1 diabetes, in this study the mean CXCL10 serum levels were not elevated in patients with type 1 diabetes neither in patients with proven enterovirus infection. In contrast, in patients with other virus infections the CXCL10 levels were elevated, presumably reflecting the severity or the site of infection. This suggests that local production of CXCL10 in the affected organ cannot be measured reproducible in serum and that its potential use in clinical practice is limited.
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  • Berggren, Malin, 1975, et al. (author)
  • Alternative EBNA1 expression in organ transplant patients.
  • 2005
  • In: Journal of medical virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 76:3, s. 378-85
  • Journal article (peer-reviewed)abstract
    • In order to identify patients at risk for developing post-transplant lymphoproliferative disease (PTLD), a sensitive nested RT-PCR method for detection of EBNA1 gene expression in peripheral blood cells was used. EBNA1 expression in peripheral blood samples from 60 organ recipients was analyzed and compared with 24 healthy controls in a retrospective study. Overall, EBNA1-positive samples were detected at least once in 43% of the transplant patients with post-transplant lymphoproliferative disease, in 18% of the other transplant patients and in none of the healthy controls. The odds ratio for EBNA1 expression in patients with post-transplant lymphoproliferative disease was 3.42 (95% CI=1.02-11.54) compared to other transplant recipients. Together with normal EBV Q promoter initiated EBNA1 transcripts, an alternatively spliced form was expressed in peripheral blood cells in the above-mentioned transplant patients. This transcript lacks the U leader exon in the 5'-untranslated region (UTR). We have previously identified and characterized a functional internal ribosome entry site, the EBNA IRES, in the untranslated U leader exon of EBNA1. Transfection experiments with EBNA1 coding plasmids followed by Western blot showed that the EBNA IRES promotes cap-independent translation and increases the EBNA1 protein level. The alternative EBNA1 transcript lacking this function is expressed in the majority of the investigated EBNA1-positive patient samples as well as in some EBV-positive B-cell lines. Alternative splicing in this form gives EBV potential to regulate the translation of EBNA1 by modifying the 5' UTR. These findings indicate a new mechanism for EBNA1 expression in vivo.
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  • Bergroth, T., et al. (author)
  • Selection of drug-resistant HIV-1 during the early phase of viral decay is uncommon in treatment-naive patients initiated on a three- or four-drug antiretroviral regimen including lamivudine
  • 2009
  • In: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 81:1, s. 1-8
  • Journal article (peer-reviewed)abstract
    • Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naive HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naive patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four-drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment-naive adherent patients is potent enough to prevent development of resistance during the first months of therapy.
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  • Bonkoungou, Isidore Juste O., et al. (author)
  • Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction
  • 2018
  • In: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 90:9, s. 1453-1460
  • Journal article (peer-reviewed)abstract
    • Burkina Faso introduced rotavirus vaccine (RotaTeq) to the national immunization program in November 2013. This study describes the detection rates, clinical profiles, and molecular epidemiology of rotavirus and norovirus (NoV) infections among children amp;lt;5 years hospitalized (n=154) because of acute diarrhea in Ouagadougou, Burkina Faso, from December 2012 to November 2013, just before the start of vaccination. Overall, 44% and 23% of fecal samples were positive for rotavirus and NoV, respectively, most of them detected during the cold dry season (December-March). The predominant G/P combinations were G12P[8] (47%) and G6P[6] (30%). G2P[4] (n=3), G12P[6] (n=3), and G6P[8] (n=1) werealso detected. Nearly all (94%) successfully genotyped NoV strains belonged to genotype GII.4. The predominance of rotavirus and NoV was noteworthy in the age group 6 months, with 67% rotavirus and 22% NoV, respectively. Vomiting was significantly more common among rotavirus-infected children. To conclude, this study shows high detection rates of both rotavirus and NoV in children with severe diarrhea in Burkina Faso just before the introduction of rotavirus group A vaccination. The results can be used for estimating the impact of rotavirus group A vaccination, which started in the end of 2013. Furthermore, this study shows that the G6P[6] rotavirus strains emerging in Burkina Faso in 2010 is now established as a regionally important genotype.
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  • Bucardo, Filemon, et al. (author)
  • Genetic susceptibility to symptomatic norovirus infection in Nicaragua. : norovirus susceptibility in Nicaragua
  • 2009
  • In: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 81:4, s. 728-35
  • Journal article (peer-reviewed)abstract
    • Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.
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