BACKGROUND AND AIMS:An estimated 270 000 people in the UK live with hepatitis B infection, the leading global cause of liver cancer. In 2022, opt-out hepatitis B testing was introduced in emergency departments (ED) in London. We conducted a 2-year multicentre evaluation of this programme across seven sites. METHODS:Adults testing positive for hepatitis B surface antigen (HBsAg) through ED opt-out testing (n = 983) were compared with those referred via non-ED pathways (n = 416) over at least 12 months in the same regions with a six-month follow-up period. Demographics, clinical characteristics and factors influencing time to assessment were analysed. RESULTS:ED testing led to a 107% increase in HBV assessments. Of 983 HBsAg-positive individuals, 90.2% (887/983) were contactable and 97% (660/679) of those requiring assessment were linked to care. 35% were aware of their diagnosis but not under specialist care. Among ED-diagnosed individuals, 16.37% had significant fibrosis and 20.45% had viral loads > 2000 IU/mL. ED referrals were older (mean age 51 vs. 47 years, p < 0.001) and had lower viral loads (mean log10 HBV DNA 2.08 vs. 2.78, p < 0.001). Mean time to assessment in the ED group was 90 days. CONCLUSIONS:ED opt-out testing has doubled new assessments of hepatitis B cases, identifying individuals who would benefit from surveillance and/or treatment. Linkage-to-care rates were very high, though time to assessment was prolonged by service factors. A significant proportion were aware of their diagnosis but lost to care, underscoring the need for services which can maintain engagement.

Abstract Background and Aims Human Cytomegalovirus (CMV) can cause significant morbidity in transplant recipients. Primary CMV infection in CMV seronegative recipients (R−) and reactivation of CMV in seropositive recipients (R+) post-transplant can lead to CMV end organ disease (EOD). At Royal Free Hospital (RFH), London, United Kingdom, CMV EOD is prevented through pre-emptive therapy (PET), which utilises quantitative real-time PCR (qPCR) in whole blood to monitor all transplant patients and guide therapeutic interventions (1). PET is started in D+R− transplant patients following the first detectable CMV DNA (≥200 copies/ml) in blood (2). For CMV seropositive patients, PET is started when CMV DNA is ≥3000 copies/ml. This differs from many transplant centres which provide CMV anti-viral prophylaxis for the first 3-6 months post-transplant to patients at high risk of developing CMV EOD. In this observational study, the effectiveness of our PET approach and differences in CMV viral replication kinetics was retrospectively analysed in renal transplant recipients of differing CMV serostatus. Method A retrospective review of results from electronic patient records and laboratory information management system for patients who underwent renal transplantation from April 2021 to January 2023 was conducted. Patients were divided into four groups based on organ donor and recipient CMV IgG serostatus (D+R−, D+R+, D−R+, D−R−). Those who were followed up for less than 90 days or had unknown donor serostatuses were excluded. Results A total of 227 patients who received renal transplantation between April 2021 to January 2023 were identified. Of which, 11% (25/227) were D+R−, 42.3% (96/227) were D+R+, 33% (75/227) were D−R+ and 13.7% (31/227) were D−R−. Within each group, 60% (15/25) of D+R−, 61.5% (59/96) of D+R+ and 48% (36/75) of D−R+ patients developed CMV viraemia during the monitoring period. Of CMV viraemic patients, all D+R− (15/15), 54.2% (32/59) of D+R+ and 27.8% (10/36) of D−R+ patients were treated with valganciclovir as per our PET protocol. None of the D−R− patients developed any CMV viraemia. The mean peak viral load for patients with viraemia requiring treatment with valganciclovir was 4772 copies/ml (range 210-30000 copies/ml) in D+R−, 5050 copies/ml (range 3000-30000 copies/ml) and 5050 copies/ml (range 3300-18000 copies/ml) in D+R+ and D−R+ groups respectively. The mean time to first viraemia was 59 days (range 15-332) for the D+R−, 40 days (range 7-177) for D+R+ and 43 days (range 15-91) for D−R+ patients. Furthermore, the mean duration of viraemia was 34 days for D+R−, 37.5 days for D+R+ and 30.5 days for D−R+ groups. 19 patients had CMV viraemia recurrence requiring re-treatment, 63%were D+R− (12/19), 32% were D+R+ (6/19) and 5% (1/19) were D−R+. Across all four groups, two patients developed CMV EOD. One D+R+ patient was found to have CMV in respiratory sample and one D−R+ patient had CMV on colon biopsy. One D+R− patient developed UL97 mutations (M460I and A594V) conferring ganciclovir resistance due to poor compliance and was treated with maribavir. Conclusion PET is a safe and effective approach which reduces the risk of CMV EOD and antiviral medication resistance in SOT patients. Our PET approach provides monitoring of all patients regardless of CMV serostatus thereby reducing the risk of CMV EOD in all patients by ensuring early treatment of viraemia.

BACKGROUND:Opt-out Emergency Department blood borne virus (EDBBV) screening was introduced at the Royal Free Hospital under the NHSEI (NHS England and NHS Improvement) programme to expand opt-out testing in local authority areas with high HIV prevalence. This initiative was part of the "Toward Zero" policy towards ending HIV transmission in England by 2030. METHODS:All patients attending the Royal Free Hospital Emergency Department (ED) aged 16 and over were screened for blood borne viruses (HIV/HBV/HCV) unless they opted out. We looked at HIV data from patients seen in ED between the initiation of EDBBV testing on the 12th of April and 12th of August 2022. Hepatitis B and C data was reviewed in a separate study. OUTCOME:A total of 12,208 samples from 10,641 patients were screened for HIV. Amongst these samples there were 88 which were positive, giving a seroprevalence of 0.84 %. There were 48 patients who were already known to local HIV services, 35 were known to HIV services outside of our Trust and 5 were new diagnoses. CONCLUSION:Our results confirmed our local HIV prevalence to be very high, as per the UK Health Security Agency and supports the need for HIV testing. Opt-out ED BBV screening has been a highly effective method for identifying people living with HIV who are unaware of their status.

Background: In 2018, BHIVA set a target to achieve 100% microelimination of hepatitis C by 2021 for people living with diagnosed HIV.This was thought feasible due to the robust infrastructure around HIV care facilitating the delivery of direct acting antivirals (DAAs) which can cure hepatitis C infection.Here we outline progress towards this ambition.Method: Data were collected from the comprehensive national HIV and AIDS reporting system (HARS) which links people living with diagnosed HIV across HIV consultations to monitor outcomes.Hepatitis C status is a mandatory field for HARS data collection, and can be completed to indicate infection status, or not having been tested.Patients were defined as cleared if reported to have no infection for a continuous 28 week period, in accordance with hepatitis C care pathway definitions.Reinfection was defined as evidence of active infection after clearance.Results: The baseline was March 2015 to March 2016, with 4.6% (3,222 of 70,539) of people seen for HIV care showing evidence of active HCV infection in this period.HCV prevalence was highest among people who inject drugs (50%, 532 of 1,062), those exposed through blood or blood products (22%, 113 of 514), and gay, bisexual and other men who have sex with men (4%, 1,063 of 23,674).Of the 3,222 with HIV/HCV at baseline, 3,080 were included (exclusion: 12 died before April 2016 and 130 were not seen for care after the baseline period).By the end of 2021, 70% (2,153/3,080) had cleared HCV infection.A further 288 individuals had no infection reported at last attendance, but insufficient followup to confirm clearance.Overall, 21% (639/2,159) of those coinfected at baseline did not clear HCV infection, including 118 individuals reinfected after clearance.Co-infection reduced from 4.6% (3,222 of 70,539) at baseline to 0.9% (639/68,329) by the end of 2021 (on average 6 years of follow up per coinfected individual).Conclusion: Overall, 70% of patients with HIV/HCV coinfection had cleared their HCV infection by the end of 2021, though given the conservative clearance definition used, this is likely an underestimate.This adds to the growing body of evidence that microelimination is feasible.

Background: The National Health Service (NHS) in England commissioned opt-out testing in London Emergency Departments (ED) in April 2022 to allow early identification and management of hepatitis B (HBV) and hepatitis C virus (HCV) infection in patients unaware of their infection status.Methods: All adults over the age of 16 undergoing blood tests in the ED at the Royal Free Hospital were tested for HBV surface antigen and anti-HCV IgG unless they opted out. Data was collected between the 12th of April and 22nd of August 2022.Outcome: Of 11,215 patients tested for HCV, 164 patients were found to be anti-HCV IgG positive, giving a seroprevalence rate of 1.46 %. 52 of the anti-HCV IgG positive patients did not have any previous HCV serology result. 23 of the anti-HCV IgG positive patients were also HCV RNA positive giving an RNA seroprevalence of 0.21 %, and 17 of those were new diagnoses of HCV viraemia. For HBV testing, 82 (0.73 %) out of 11,192 patients tested were found to be HBsAg positive, including one patient who presented acutely with a positive HBV core IgM. 39 of the HBsAg positive patients were previously unknown to us; of these, 9 had an HBV viral load of more than 2000 IU/mL, including 3 patients with positive HBV e antigen and one patient with hepatitis D virus co-infection.Conclusion: Opt-out screening of HBV and HCV in ED is effective at identifying patients with previously undiagnosed viral hepatitis infection and providing an opportunity to engage them in specialist care.

Aim In the United Kingdom, organ donors/recipients are screened for evidence of human T-cell leukaemia virus type-1 and type-2 (HTLV-1/2) infections. Since the United Kingdom is a low prevalence country for HTLV infections, a screening assay with high sensitivity and specificity is required. Samples with repeat reactivity on antibody testing are sent to a reference lab for confirmatory serological and molecular testing. In the case of donor screen, this leads to delays in the release of organs and can result in wastage. We aim to assess whether a signal/cut-off (S/CO) ratio higher than the manufacturer's recommendation of 1.0 in the Abbott Architect antibody assay is a reliable measure of HTLV-1/2 infection. Methods We conducted a 5 year retrospective analysis of 7245 patients from which 11 766 samples were tested on the Abbott Architect rHTLV I/II assay. Reactive samples (S/CO >1) were referred for confirmatory serological and molecular detection (Western Blot and proviral DNA) at UK Health Security Agency, (formerly PHE, Colindale), the national reference laboratory. Electronic, protected laboratory and hospital patient databases were employed to collate data. Results A total of 45 patients had initially reactive samples. 42.2% (n = 19/45) had an S/CO ratio > 20, with HTLV infection confirmed in n = 18/19 and indeterminate confirmatory results in n = 1/19. No samples with an S/CO ratio <4 (48.9%, n = 22/45) or 4-20 (8.9%, n = 4/45) had positive confirmatory results on subsequent confirmatory testing. Conclusion Samples with an S/CO >20 likely represent a true HTLV-1/2 infection. Reactive samples with an S/CO <4 were unlikely to confirm for HTLV infections. Interpretation of these ratios can assist clinicians in the assessment of low reactive samples and reiterates the need for faster access to confirmatory testing.

Previous vaccination with either BNT162b2 or ChAdOx1 reduces 60-day mortality from coronavirus disease 2019 from the B0.1.1.7 lineage by 69.3%. Breakthrough infections are not primarily driven by viral genomic mutations. Background Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic. Methods We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020-March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed. Results Overall, 116 of 119 cases developed COVID-19 post-first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P < .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset >= 14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (-1.89 days; 95% CI: -4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage). Conclusions Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.

The related several penetration and fusion processes of SARS-COV-2 are very outstanding to observe with some phylogenetic features and pathogenesis of this very respiratory viral disease from the perspective of virology and epidemiology. Furthermore, very interesting to look at is SARS-COV-2, the largest RNA consistent Coronavirus with a substantial classification, sometimes found symptomatic or sometimes asymptomatic. To understand better, some additional figures are included here. Surely that SARS-COV-2 has a very complicated life cycle and genetic make-up and plasma therapeutic action is one of the successful fighters with the assistance of antigen. The role of Receptor Binding Domain and primary hosts in the diffusion of this disease is eventually undeniable.

Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

Reviews in Medical VirologyVolume 29, Issue 6 e2091 EDITORIAL Management of HCV peri-transplant recapitulates management of CMV Paul Griffiths, Corresponding Author Paul Griffiths p.griffiths@ucl.ac.uk Institute of Immunity and Transplantation, University College London, London, UK Correspondence Paul Griffiths, Institute of Immunity and Transplantation, University College London, London, UK. Email: p.griffiths@ucl.ac.ukSearch for more papers by this authorTanzina Haque, Tanzina Haque Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this authorAileen Marshall, Aileen Marshall Department of Hepatology, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author Paul Griffiths, Corresponding Author Paul Griffiths p.griffiths@ucl.ac.uk Institute of Immunity and Transplantation, University College London, London, UK Correspondence Paul Griffiths, Institute of Immunity and Transplantation, University College London, London, UK. Email: p.griffiths@ucl.ac.ukSearch for more papers by this authorTanzina Haque, Tanzina Haque Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this authorAileen Marshall, Aileen Marshall Department of Hepatology, Royal Free London NHS Foundation Trust, London, UKSearch for more papers by this author First published: 11 November 2019 https://doi.org/10.1002/rmv.2091Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume29, Issue6November 2019e2091 RelatedInformation

Abstract Background 2018 to 2019 has seen a global resurgence in measles cases, with the UK seeing an over 3-fold increase in cases in 2018 compared with 2017. In this context, our center saw a cluster of geographically linked measles cases presenting in the first quarter of 2019. We present this with comparative data of confirmed measles cases from our center over the preceding 10 years. Given the growing recognition of measles “re-infection” in fully vaccinated individuals, we also present our first confirmed cases of reinfection within this cohort. Methods Retrospective analysis of confirmed measles cases (positive Measles IgM or detectable Measles RNA) between 2009 and 2019. Laboratory and demographic data were obtained from electronic patient records. Results 18 cases (of which 14 were adults) of measles (all genotype D8 of those tested) were confirmed in the first 4 months of 2019. 12 presented within a 14 day period from a geographically linked part of North London. There were 4 confirmed measles re-infections (detectable measles RNA on a buccal swab with either a high Measles IgG avidity or previous documented measles immunity). From the 10 year data, cases peaked in 2011 and 2016 consistent with national trends. Of the 89 cases identified, 60 (67%) were adults, who were over twice as likely to be admitted as children, had a longer median length of stay in hospital (2 days vs. 1.5 days) and were more likely to develop a hepatitis (1/10 pediatric cases vs. 26/48 adults, p ≤ 0.01)or other complications. The majority of adults (68%) were unsure of their vaccination status. Conclusion 4 cases of 18 in the first 4 months of 2019 were confirmed re-infections. Re-infections in fully vaccinated individuals are described in the literature, typically presenting with a milder course; however, these are the first cases we have identified at our center. Overall, adult cases were more likely to be admitted to hospital and to have a complicated course compared with children. Vaccination history in adults was of limited clinical utility due to lack of reliable documentation and the potential for reinfection. Disclosures All authors: No reported disclosures.