10 research outputs found
Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe
Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by ana
Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2
Stability and Feasibility of Dried Blood Spots for Hepatitis E Virus Serology in a Rural Setting
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. In many low-income countries it causes large outbreaks and disproportionally affects pregnant women and their offspring. Surveillance studies to find effective preventive interventions are needed but are hampered by the lack of funding and infrastructure. Dried blood spots (DBS) offer an easier and more robust way to collect, transport, and store blood samples compared to plasma/serum samples, and could ease some of the barriers for such studies. In this study we optimize an HEV IgG ELISA for DBS samples and validate it on 300 paired DBS and plasma samples collected in rural areas of Bangladesh from participants in a HEV vaccine study. We demonstrate that HEV IgG in blood stored as DBS is stable for two months at up to 40 °C, and for five freeze-thaw cycles. The specificity was 97% and the overall sensitivity of the DBS assay was 81%. The sensitivity was higher in samples from vaccinated participants (100%) compared to previously infected participants (59%), reflecting a positive correlation between IgG titer and sensitivity. We found a strong correlation between DBS and plasma samples with an r2 of 0.90, but with a higher degree of difference between individual paired samples. Our study shows that DBS offers a stable alternative to plasma/serum for HEV IgG measurements and can facilitate serological studies, particularly in resource limited areas
Ongoing multi-strain food-borne hepatitis A outbreak with frozen berries as suspected vehicle: four Nordic countries affected, October 2012 to April 2013
Increase in hepatitis A in tourists from Denmark, England, Germany, the Netherlands, Norway and Sweden returning from Egypt, November 2012 to March 2013
HEV study protocol : design of a cluster- randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh
Introduction Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in the developing world and is a public health problem, in particular among pregnant women, where it may lead to severe or fatal complications. A recombinant HEV vaccine, 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China), is licensed in China, but WHO calls for further studies to evaluate the safety and immunogenicity of this vaccine in vulnerable populations, and to evaluate protection in pregnancy. We are therefore conducting a phase IV trial to assess the effectiveness, safety and immunogenicity of the HEV 239 vaccine when given in women of childbearing age in rural Bangladesh, where HEV infection is endemic.
Methods and analysis Enrolment of a target of approximately 20 000 non-pregnant women, aged 16–39 years, started on 2 October 2017 in Matlab, Bangladesh. Sixty-seven villages were randomised by village at a 1:1 ratio to receive either the HEV vaccine or the control vaccine (hepatitis B vaccine). A 3-dose vaccination series at 0, 1 and 6 months is ongoing, and women are followed up for 24 months. The primary outcome is confirmed HEV disease among pregnant women. After vaccination, participants are requested to report information about clinical hepatitis symptoms. Participants who become pregnant are visited at their homes every 2 weeks to collect information about pregnancy outcome and to screen for clinical hepatitis. All suspected hepatitis cases undergo laboratory testing for diagnostic evaluation. The incidence of confirmed HEV disease among pregnant and non-pregnant women will be compared between the HEV vaccinated and control groups, safety and immunogenicity of the vaccine will also be evaluated.
Ethics and dissemination The protocol was reviewed and approved by the International Centre for Diarrhoeal Disease Research, Bangladesh Research Review Committee and Ethical Review Committee, and the Directorate General of Drug Administration in Bangladesh, and by the Regional Ethics Committee in Norway. This article is based on the protocol version 2.2 dated 29 June 2017. We will present the results through peer-reviewed publications and at international conferences.
Trial registration number The trial is registered at clinicaltrials.gov with the registry name “Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh” and the identifier NCT02759991