Objectives. To evaluate the influence of low-dose MTX and etanercept treatment on efficacy of measles, mumps and rubella (MMR) revaccination in children with juvenile idiopathic arthritis. Methods. A ...prospective nested case–control study was performed to investigate markers of MMR revaccination induced humoral and cell-mediated immunity in 15 patients with juvenile idiopathic arthritis (ages 6–17 yrs), treated with either low-dose MTX therapy alone or in combination with etanercept. The control group consisted of 22 healthy children. Production of IFN-γ by T memory cells upon in vitro stimulation with measles, mumps and rubella antigens and seroprevalence of virus-specific IgG antibodies were assessed. Medication use, disease activity and patients' comments on side-effects were observed during the period of 6 months before and after revaccination. Results. Low-dose MTX therapy following MMR vaccination proved not to hamper T-cell mediated immunity in vitro. Neither low-dose MTX nor etanercept treatment, given simultaneously with revaccination, markedly interfered with generation of long-lived virus-restricted T cells and protective levels of virus-specific IgG antibodies. No increase in disease activity or medication use was seen within 6 months after MMR revaccination, including JIA patients using etanercept. No overt measles, mumps, rubella or secondary severe infections were noted. Conclusions. Low-dose MTX and etanercept treatment do not seem to interfere with intended outcome of MMR revaccination in children with JIA.
Mitochondria fulfil several key functions within cellular metabolic and antiviral signalling pathways, including their central role in ATP generation. Viruses, as intracellular parasites, require ...from their cellular host the building blocks for generation of their viral progeny and the energy that drives viral replication and assembly. While some viruses have adopted ways to manipulate the infected cell such that cellular metabolism supports optimal virus production, other viruses simply exhaust cellular resources. The association of viruses with mitochondria is influenced by several important factors such as speed of the viral replication cycle and viral dependence on cellular enzymes and metabolites. This review will highlight the complex interconnectivity of viral life cycles with the three main mitochondrial metabolic pathways, namely β-oxidation, the tricarboxylic (TCA) cycle, and oxidative phosphorylation. This interconnectivity has the potential to reveal interesting points for antiviral therapy with either prometabolites or antimetabolites and highlights the importance of the viral association with mitochondrial metabolism.
Rotavirus infections are common causes of infant hospitalization. The present study examined the effectiveness of anti-rotavirus vaccination in preventing rotavirus-related hospitalizations in ...Germany, following its state and nationwide introductions in 2008 and 2013, respectively.
During 15 consecutive seasons 9557 stool samples of hospitalized children of 5 years and younger with acute gastroenteritis were screened for rotavirus A. Rotavirus G and P genotypes were assessed after vaccine introduction. Vaccine effectiveness was determined by comparison of rotavirus incidence in pre-vaccine and post-vaccine cohorts. The herd effect was calculated as the difference between the observed reduction of rotavirus-related hospitalizations and the expected direct vaccine effect.
The number of rotavirus-related hospitalizations declined after vaccine introduction. Approximately 26% (503/1955) of prevented cases could be attributed to the herd effect. Human rotaviruses of genotypes G3P8, G1P8, G9P8, G4P8, G2P4 and G12P8 were most frequent. Uncommon genotypes remained rare. The direct, indirect, total and overall vaccine effectiveness was 86% (95% confidence interval (CI) 83.2–89.1%), 48% (95% CI 42.8–52.6%), 93% (95% CI 91.3–94.3%) and 69% (95% CI 66.5–72.0%), respectively. There was no significant difference in vaccine-type or in genotype-specific vaccine effectiveness.
Anti-rotavirus vaccination efficiently reduced rotavirus-related hospitalizations in Germany in the past decade. The vaccines analysed in this article provide a broadly heterologous and long-lasting protection. The herd effect substantially contributed to the observed drop in the number of incidences of severe rotavirus infections. Presumably, constant high vaccine coverage will lead to a continued upward trend in the overall vaccine efficiency.
Childhood morbidity and mortality of diarrhoeal diseases are high, particularly in low-income countries and noroviruses and sapoviruses are among the most frequent causes worldwide. Their ...epidemiology and diversity remain not well studied in many African countries. To assess the positivity rate and the diversity of sapoviruses and noroviruses in Northwest Ethiopia, during November 2015 and April 2016, a total of 450 faecal samples were collected from outpatient children aged <5 years who presented with diarrhoea. Samples were screened for noroviruses and sapoviruses by real-time RT-PCR. Partial VP1 genes were sequenced, genotyped and phylogenetically analysed. Norovirus and sapovirus stool positivity rate was 13.3% and 10.0%, respectively. Noroviruses included GII.4 (35%), GII.6 (20%), GII.17 (13.3%), GII.10 (10%), GII.2 (6.7%), GII.16 (5%), GII.7 (3.3%), GII.9, GII.13, GII.20 and GI.3 (1.7% each) strains. For sapoviruses, GI.1, GII.1 (20.0% each), GII.6 (13.3%), GI.2 (8.9%), GII.2 (11.1%), GV.1 (8.9%), GIV.1 (6.7%), GI.3 and GII.4 (2.2% each) genotypes were detected. This study demonstrates a high genetic diversity of noroviruses and sapoviruses in Northwest Ethiopia. The positivity rate in stool samples from young children with diarrhoea was high for both caliciviruses. Continued monitoring is recommended to identify trends in genetic diversity and seasonal variations.
AbstractBackgroundThe impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza ...B strain (trivalent vaccine). AimThe aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. MethodsPartial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts. FindingsDuring the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza. InterpretationPhylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar. ConclusionWorld Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines. FundingThis research was partially supported by the Association of Sponsors and Friends of Leipzig University.
Abstract Background Efforts to reduce the impact of group A rotaviruses on human morbidity and mortality rely on oral immunisation with live attenuated or recombinant vaccines. A major challenge in ...immunisation is the vast inter- and intragenotypic diversity accomplished by circulating rotaviruses. Objectives To monitor rotavirus inter- and intragenotypic diversity in hospitalised children. Study design From January 2008 to December 2009 stool samples from 1994 paediatric in-patients suffering from diarrhoea were screened for rotavirus. Rotavirus G- and P-genotypes were determined by nucleotide sequencing and phylogenetic analysis was performed. Results Rotavirus A was detected in stool samples of 341 children, comprising G1P8, G2P4, G3P8, G4P8, G9P8, as well as uncommon G12P6 genotypes and mixed infections. Predominant strains shifted from G1P8 and G9P8 genotypes in the first season to G3P8 and G4P8 genotypes in the second season. The highest intragenotypic diversity was detected in G1 strains and consisted of co-circulating G1-Ic, G1-Id, G1-Ie and G1-II rotaviruses. The G2 analysis revealed different intragenotypic lineages: G2-IIa, G2-IIb and G2-IIc. Interestingly, the circulating G4-Ib rotaviruses were characterised by insertions of 3 or 6 additional coding nucleotides within variable region 4 of VP7. Whereas different G9-III VP7 gene segments were detected G3-Ia sequences were highly homologous. In the VP4 analysis P8-III gene segment predominated over P4-Vb, P8-I, P8-IV and P6-I. Conclusions A remarkable rotavirus heterogeneity was detected in the limited local setting and time span. Continued monitoring and nucleotide sequencing is necessary to document possible effects of rising immunisation levels on intragenotypic rotavirus diversity.
Although teratogenic rubella virus (RV) causes a vaccine-preventable disease, it is still endemic in several countries worldwide. Thus, there is a constant risk of RV importation into non-endemic ...areas. RV monitoring, especially during measles and Zika virus outbreaks, requires reliable diagnostic tools. For this study, a TaqMan-based one-step reverse transcription-quantitative PCR (RT
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qPCR) assay, with the p90 gene as a novel and so far unexplored target for detection of clade I and II genotypes, was developed and evaluated. Automated nucleic acid extraction was carried out. Performance characteristics of the TaqMan RT
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qPCR assay were determined for a RV plasmid standard and RNA extracted from virus-infected cell culture supernatants representing clade I and II genotypes. Diagnostic specificity and sensitivity were validated against other RNA and DNA viruses, relevant for RV diagnostic approaches and for RV-positive clinical samples, respectively. The assay is specific and highly sensitive with a limit of detection as low as five to one copies per reaction or 200 infectious virus particles per ml. The coefficients of variation (CV) were specified as intra- (within one run) and inter- (between different runs) assay variation, and calculated based on the standard deviations for the obtained Ct values of the respective samples. Intra- and inter-assay CV values were low, with a maximum of 3.4% and 2.4%, respectively. The assay was shown to be suitable and specific for the analysis of clinical samples. With p90 as a novel target, the highly sensitive and specific TaqMan assay outlined in this study is suitable for RV diagnosis worldwide.
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