Summary Background The prevalence of hepatitis E virus (HEV) genotype 3 infections in the English population (including blood donors) is unknown, but is probably widespread, and the virus has been ...detected in pooled plasma products. HEV-infected donors have been retrospectively identified through investigation of reported cases of possible transfusion-transmitted hepatitis E. The frequency of HEV transmission by transfusion and its outcome remains unknown. We report the prevalence of HEV RNA in blood donations, the transmission of the virus through a range of blood components, and describe the resulting morbidity in the recipients. Methods From Oct 8, 2012, to Sept 30, 2013, 225 000 blood donations that were collected in southeast England were screened retrospectively for HEV RNA. Donations containing HEV were characterised by use of serology and genomic phylogeny. Recipients, who received any blood components from these donations, were identified and the outcome of exposure was ascertained. Findings 79 donors were viraemic with genotype 3 HEV, giving an RNA prevalence of one in 2848. Most viraemic donors were seronegative at the time of donation. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused before identification of the infected donation. Follow-up of 43 recipients showed 18 (42%) had evidence of infection. Absence of detectable antibody and high viral load in the donation rendered infection more likely. Recipient immunosuppression delayed or prevented seroconversion and extended the duration of viraemia. Three recipients cleared longstanding infection after intervention with ribavirin or alteration in immunosuppressive therapy. Ten recipients developed prolonged or persistent infection. Transaminitis was common, but short-term morbidity was rare; only one recipient developed apparent but clinically mild post-transfusion hepatitis. Interpretation Our findings suggest that HEV genotype 3 infections are widespread in the English population and in blood donors. Transfusion-transmitted infections rarely caused acute morbidity, but in some immunosuppressed patients became persistent. Although at present blood donations are not screened, an agreed policy is needed for the identification of patients with persistent HEV infection, irrespective of origin, so that they can be offered antiviral therapy. Funding Public Health England and National Health Service Blood and Transplant.
Background. Enhanced surveillance and molecular characterisation studies of hepatitis E virus (HEV) in England and Wales have been undertaken since 2003. The dynamics of hepatitis E have changed ...recently with an increase in the number of indigenous cases and an observed viral shift. Methods. HEV antibody and RNA data were analysed to ascertain the annual number of acute infections, the HEV genotype disposition and viral phylogeny. These data were investigated in the context of collected travel history and demographic data. Results. In total, 2713 acute hepatitis E cases were diagnosed, of which 1376 were indigenous infections. Travel associated cases remained steady and mainly associated with Genotype 1 infections. In contrast, major fluctuations were noted in indigenously-acquired cases with a dramatic year on year increase during 2010-2012. Molecular characterisation demonstrated indigenous infections to cluster into two distinct phylogenetic groups with the emergence of a novel group of Genotype 3 viruses coinciding with the recent increase in cases. Conclusions. HEV infection rates are dynamic in England and Wales, influenced by changing trends in indigenously-acquired cases. The recent increase in indigenous cases and the emergence of indigenous viruses not commonly circulating prior to 2010 suggest that the risk of acquiring HEV has changed.
Since 2010, reports of infection with hepatitis E virus (HEV) have increased in England and Wales. Despite mounting evidence regarding the zoonotic potential of porcine HEV, there are limited data on ...its prevalence in pigs in the United Kingdom. We investigated antibody prevalence, active infection, and virus variation in serum and cecal content samples from 629 pigs at slaughter. Prevalence of antibodies to HEV was 92.8% (584/629), and HEV RNA was detected in 15% of cecal contents (93/629), 3% of plasma samples (22/629), and 2% of both (14/629). However, although HEV is prevalent in pigs in the United Kingdom and viremic pigs are entering the food chain, most (22/23) viral sequences clustered separately from the dominant type seen in humans. Thus, pigs raised in the United Kingdom are unlikely to be the main source of human HEV infections in the United Kingdom. Further research is needed to identify the source of these infections.
Summary Background The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute ...to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact. Methods We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies. Findings The assay had a specificity of 100% (95% CI 98·9–100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8–98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1–20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2–4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level. Interpretation This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions. Funding Wellcome Trust ERAES Programme, Save the Children.
Abstract
It is currently unknown how post-COVID-19 syndrome (PCS) may affect those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This longitudinal study includes ...healthcare staff who tested positive for SARS-CoV-2 between March and April 2020, with follow-up of their antibody titers and symptoms. More than half (21 of 38) had PCS after 7–8 months. There was no statistically significant difference between initial reverse-transcription polymerase chain reaction titers or serial antibody levels between those who did and those who did not develop PCS. This study highlights the relative commonality of PCS in healthcare workers and this should be considered in vaccination scheduling and workforce planning to allow adequate frontline staffing numbers.
In this study, 55% of healthcare workers with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had Post-COVID-19 Syndrome at 7-8 months following symptom onset. Developing the syndrome had no association with antibodies against the receptor binding domain of SARS-CoV-2.
Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may ...reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype.
•Allele-specific PCR for identification of the SARS-CoV-2 Delta variant is described.•The method is a simple, rapid and inexpensive alternative to genome sequencing.•Genotyping results by ...allele-specific PCR were entirely concordant with sequencing.•Sensitivity of allele-specific PCR matched that of the SARS-CoV-2 diagnostic PCR.•Samples with insufficient virus for sequencing were successfully genotyped.
The highly transmissible Delta variant of SARS-CoV-2 (B.1.617.2), first identified in India, is currently replacing pre-existing variants in many parts of the world. To help guide public health policies it is important to monitor efficiently its spread. Genome sequencing is the gold standard for identification of Delta, but is time-consuming, expensive, and unavailable in many regions.
To develop and evaluate a rapid, simple and inexpensive alternative to sequencing for Delta identification.
A double-mismatch allele-specific RT-PCR (DMAS-RT-PCR) was developed. The technique exploits allele-specific primers, targeting two spike gene mutations, L452R and T478K, within the same amplicon. The discriminatory power of each primer was enhanced by an additional mismatch located at the fourth nucleotide from the 3′ end. Specificity was assessed by testing well characterised cell culture-derived viral isolates and clinical samples, most of which had previously been fully sequenced.
In all cases the results of viral genotyping by DMAS-RT-PCR were entirely concordant with the results of sequencing, and the assay was shown to discriminate reliably between the Delta variant and other variants (Alpha and Beta), and ‘wild-type’ SARS-CoV-2. Influenza A and RSV were non-reactive in the assay. The sensitivity of DMAS-RT-PCR matched that of the diagnostic SARS-CoV-2 RT-qPCR screening assay. Several samples that could not be sequenced due to insufficient virus were successfully genotyped by DMAS-RT-PCR.
The method we describe would be simple to establish in any laboratory that can conduct PCR assays and should greatly facilitate monitoring of the spread of the Delta variant globally.
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