Pilot postal birth cohort HCV Screening in UK primary care.

BACKGROUND: Birth cohort screening has been implemented in some countries to identify the potentially 'missed population' of undiagnosed chronic Hepatitis C Virus (HCV) in people who may not be found through targeted approaches. AIM: To determine uptake of HCV antibody testing using an oral swab screening method, overall yield, whether those testing positive had risk markers in their primary care record, and cost per case detected. DESIGN AND SETTING: Pilot screening study set in general practices in the Southwest, South London and Yorkshire and Humber. METHOD: Participants consenting were sent an oral swab kit in the post and saliva samples were tested for antibody to HCV. RESULTS: 16,436/98,396 (16.7%) patients consented and were sent an oral swab kit. 12,216 (12.4%) returned a kit, with 31 participants (yield 0.03%) testing positive for HCV antibody. 45% of those positive had a risk marker for HCV on their primary care record. Two (yield 0.002%) were confirmed RNA positive and referred for treatment, both had HCV risk markers. Cost per case detected was £16,000 per HCV antibody and £247,997 per chronic HCV. CONCLUSIONS: Wide-scale screening could be delivered and identified people infected with HCV, however most of these individuals could have been detected through lower-cost targeted screening. Yield and cost per case found were substantially worse than model estimates and targeted screening studies. Birth cohort screening should not be rolled out in primary care in England.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Seroprevalence of immunity to hepatitis A and hepatitis B among gay, bisexual and other men who have sex with men (GBMSM) attending sexual health clinics in London and Leeds, England, 2017-2018.

OBJECTIVES: Although hepatitis A virus (HAV) and hepatitis B virus (HBV) immunisation is recommended in the UK for gay, bisexual and other men who have sex with men (GBMSM), data on immunisation coverage are limited. We aimed to determine the seroprevalence of HAV and HBV immunity among a sample of GBMSM attending sexual health services (SHS) in England. METHODS: Residual serum samples from HIV/syphilis testing for adult GBMSM attending eight SHS in London and one in Leeds were tested for markers of HAV immunity (HAV IgG) and HBV immunity (anti-HBs) using an unlinked anonymous approach. We estimated seroprevalence of HAV and HBV immunity overall and stratified by individuals' characteristics, which we obtained from the Genitourinary Medicine Clinic Activity Dataset Sexually Transmitted Infection (STI) Surveillance System. We used logistic regression to calculate crude and adjusted ORs between seropositivity and demographic and clinical characteristics. RESULTS: Seroprevalence of immunity to HAV (74.5% of 2577) and HBV (77.1% of 2551) was high. In adjusted analysis, HAV IgG seroprevalence varied by clinic and WHO region of birth (global p<0.001 for each), increased with older age (ORs of 1.50 (95% CI 1.18 to 1.86), 2.91 (2.17 to 3.90) and 3.40 (2.44 to 4.75) for ages 26-35, 36-45 and >46 vs 18-25 years (global p<0.001), was higher in those with an STI in the past year (1.58 (1.25 to 2.00); p<0.001) and those who were living with HIV (1.82 (1.25 to 2.64); p<0.001). Anti-HBs seroprevalence varied by clinic (global p<0.001), increased with older age (global p<0.001) and was higher in those with an STI in the past year (1.61 (1.27 to 2.05); p<0.001). CONCLUSION: Our findings provide a baseline seroprevalence from which to monitor serial levels of immunity to HBV and HAV in GBMSM accessing SHS. Levels of immunity for both viruses are high, noting samples were taken after recent widespread outbreaks and vaccination campaigns. High vaccine coverage in all GBMSM should be maintained to prevent further outbreaks.

Analysing HCV incidence trends in people who inject drugs using serial behavioural and seroprevalence data: A modelling study.

INTRODUCTION: The introduction of new direct-acting antivirals for hepatitis C virus (HCV) infection, has enabled the formulation of a HCV elimination strategy led by the World Health Organisation (WHO). Guidelines for elimination of HCV target a reduction in incidence, but this is difficult to measure and needs estimating. METHODS: Serial cross-sectional bio-behavioural sero-surveys provide information on an individual's infection status and duration of exposure and how these change over time. These data can be used to estimate the rate of first infection through appropriate statistical models. This study utilised updated HCV seroprevalence information from the Unlinked Anonymous Monitoring survey, an annual survey of England, Wales and Northern Ireland monitoring the prevalence of blood borne viruses in people who inject drugs. Flexible parametric and semiparametric approaches, including fractional polynomials and splines, for estimating incidence rates by exposure time and survey year were implemented and compared. RESULTS: Incidence rates were shown to peak in those recently initiating injecting drug use at approximately 0.20 infections per person-year followed by a rapid reduction in the subsequent few years of injecting to approximately 0.05 infections per person-year. There was evidence of a rise in incidence rates for recent initiates between 2011 and 2020 from 0.17 infections per person-year (95 % CI, 0.16-0.19) to 0.26 infections per person-year (0.23-0.30). In those injecting for longer durations, incidence rates were stable over time. CONCLUSIONS: Fractional polynomials provided an adequate fit with relatively few parameters, but splines may be preferable to ensure flexibility, in particular, to detect short-term changes in the rate of first infection over time that may be a result of treatment effects. Although chronic HCV prevalence has declined with treatment scale up over 2016-2020, there is no evidence yet of a corresponding fall in the rate of first infection. Seroprevalence and risk behaviour data can be used to estimate and monitor HCV incidence, providing insight into progress towards WHO defined elimination of HCV.

Understanding current antenatal Hepatitis C testing and care in maternity services in England.

OBJECTIVES: Universal opt-out antenatal screening for Hepatitis C virus (HCV) is not currently recommened and it is recommended that maternity services offer risk-based testing. We aimed to investigate antenatal HCV testing and adherence to testing guidance. METHODS: A cross-sectional survey was circulated to maternity service providers between November-December 2020 which included testing policy, training for healthcare staff, and management of women found to be HCV positive. Descriptive data are presented. RESULTS: A total of 75 questionnaires were returned, representing 48 % of English maternity service providers. 87 % of providers reported offering antenatal HCV risk-based testing. Risk factors used to identify pregnant women for testing varied. Less than 15 % of respondents considered women that were ever homeless or with history of incarceraton or from higher HCV prevalence areas as high risk. CONCLUSIONS: Current antenatal HCV testing practices are inadequate and HCV infection likely goes undiagnosed in pregnancy, especially among vulnerable population groups. In the absence of universal antenatal screening, re-framing antenatal HCV risk-based testing and management as a quality improvement initiative and developing HCV specific pathway guidance for maternity units is required.

Use of a meningococcal group B vaccine (4CMenB) in populations at high risk of gonorrhoea in the UK.

The meningococcal group B vaccine, 4CMenB, is a broad-spectrum, recombinant protein vaccine that is licensed for protection against meningococcal group B disease in children and adults. Over the past decade, several observational studies supported by laboratory studies have reported protection by 4CMenB against gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae. Gonorrhoea is a major global public health problem, with rising numbers of diagnoses and increasing resistance to multiple antibiotics. In England, more than 82 000 cases of gonorrhoea were diagnosed in 2022, with nearly half of the cases diagnosed among gay, bisexual, and other men who have sex with men. There are currently no licensed vaccines against gonorrhoea but 4CMenB is estimated to provide 33-47% protection against gonorrhoea. On Nov 10, 2023, the UK Joint Scientific Committee on Vaccination and Immunisation agreed that a targeted programme should be initiated using 4CMenB to prevent gonorrhoea among individuals at higher risk of infection attending sexual health services in the UK. This decision was made after reviewing evidence from retrospective and prospective observational studies, laboratory and clinical data, national surveillance reports, and health economic analyses. In this Review, we summarise the epidemiology of invasive meningococcal disease and gonorrhoea in England, the evidence supporting the use of 4CMenB for protection against gonorrhoea, and the data needed to inform long-term programme planning and extension to the wider population.

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

Identifying missed opportunities for hepatitis C virus antenatal testing and diagnosis in England.

New case-finding opportunities are needed to achieve hepatitis C virus (HCV) elimination in England by the year 2030. HCV antenatal testing is not offered universally in England but is recommended for women with risk factors for HCV (e.g. injecting drug use, being born in a high-prevalence country). The aim of this analysis was to investigate the missed opportunities for HCV antenatal testing among women who had given birth and were subsequently diagnosed with HCV at some time after childbirth. By linking data on live births (2010-2020) to laboratory reports of HCV diagnoses (1995-2021), we identified all women who were diagnosed with HCV after the date of their first childbirth. This group was considered to potentially have experienced a missed opportunity for HCV antenatal testing; HCV-RNA testing and treatment outcomes were also obtained for these women. Of the 32,295 women who gave birth between 2010 and 2020 with a linked diagnosis of HCV (median age: 34 years, 72.1% UK-born), over half (n = 17,123) were diagnosed after childbirth. In multivariable analyses, the odds of being diagnosed with HCV after childbirth were higher in those of Asian Bangladeshi, Black African or Chinese ethnicity and among those born in Africa. Over four-fifths (3510/4260) of those eligible for treatment were linked to treatment, 30.7% (747/2435) of whom had a liver scarring level of at least moderate and 9.4% (228/2435) had cirrhosis. Given the potential opportunity to identify cases of HCV with targeted case-finding through antenatal services, universal opt-out testing should be considered in these settings.

Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual, and other men who have sex with men in England: a mathematical modelling study.

BACKGROUND: The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks. METHODS: We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration. FINDINGS: Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox. INTERPRETATION: The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks. FUNDING: National Institute for Health Research (UK).

Anti-Hepatitis C (HCV) test positivity and new HCV diagnoses among women tested in antenatal services in England between 2015-2019.

OBJECTIVE: To determine associations with hepatitis C virus (HCV) positivity, new HCV diagnoses and subsequent linkage to HCV treatment services among pregnant women in England. METHOD: A retrospective cohort using routine laboratory tests for HCV-specific antibody (anti-HCV) and HCV-RNA undertaken during antenatal attendances England. All women receiving at least one anti-HCV test during an antenatal clinic attendance between 2015 and 2019 were included. Multivariable logistic regression was used to investigate sociodemographic associations with anti-HCV test positivity among pregnant women who did (PWIDs) and did not (non-PWIDs) inject drugs, as well as to identify sociodemographic factors associated with being newly diagnosed during pregnancy. Linkage to antiviral treatment services and treatment outcomes were determined for those women who tested HCV-RNA positive. RESULTS: 32,088 women (median age 32 years, 19,664 (61 %) UK-born, 337 (1.1 %) PWID) received an anti-HCV test among whom 814 (2.5 %) had a positive anti-HCV test (95 % confidence interval [2.4-2.7 %]). Anti-HCV test positivity was 2.1 % [2.0-2.3 %] among non-PWIDs and 40 % [35-46 %] among PWIDs. In multivariable analyses among non-PWIDs, anti-HCV test positivity was associated with older age, living in more deprived areas, and varied by ethnicity and country of birth. Among PWIDs, anti-HCV test positivity was associated with older age only. Three hundred and twenty (39 %) of the women testing anti-HCV positive were new diagnoses; those who were newly diagnosed were younger and lived in less deprived than those with a prior diagnosis whereas PWIDs were less likely to be newly diagnosed. HCV-RNA positivity was 52 % (n = 330/640, 95 %CI[47.6-55.5 %]) among those with an HCV-RNA test within 30 days, and 75 % (n = 220/293, 95 %CI[69.7-79.9 %]) of those eligible for treatment had engaged in HCV treatment services after antenatal testing. CONCLUSIONS: Antenatal testing for HCV provides an opportunity for new case findings and engagement with treatment services where needed. Therefore, universal opt-out testing for HCV antenatally should be reconsidered.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

A scoping review of media campaign strategies used to reach populations living with or at high risk for Hepatitis C in high income countries to inform future national campaigns in the United Kingdom.

BACKGROUND: With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. METHODS: We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. RESULTS: A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. CONCLUSION: Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs.

Retrospective cohort study assessing coverage, uptake and associations with hepatitis B vaccination among females who engage in sex work attending sexual health services in England between 2015 and 2019.

OBJECTIVES: Females who engage in sex work (FSW) are at high risk of hepatitis B virus (HBV) and are eligible for HBV vaccination. The objective of this analysis was to explore coverage, uptake and correlates of HBV vaccination among FSW who attend sexual health services (SHS) in England. METHODS: Data on all attendances at SHS in England were obtained from the GUMCAD STI Surveillance System. Attendees were eligible for inclusion if they were female, had not been previously diagnosed with HIV and sex work was recorded between 2015 and 2019. Bivariable and multivariable logistic regression models were used to investigate sociodemographic factors (age, ethnicity, region of birth and region of residence) associated with having received an HBV vaccination on or after an attendance where sex work was reported. RESULTS: There were 13 769 FSW attending SHS in England between 2015 and 2019 (median age 30 years, 71% white ethnicity). HBV vaccination coverage was 37% (n=5050/13 751, 95% CI 35.9%-37.5%). Among those that first reported sex work between 2015 and 2019, HBV vaccination uptake was 30% (n=3249/10 681, 95% CI 29.6%-31.3%). In multivariable analyses, HBV vaccination uptake was associated with younger age (5-year increase: OR=0.87, 95% CI 0.85, 0.89) and being born in South America (37%, adjusted OR (aOR)=1.40, 95% CI 1.18, 1.66) compared with being born in the UK. Being of Asian ethnicity (19%, aOR=0.63, 95% CI 0.45, 0.89) compared with white ethnicity was associated with reduced odds of HBV vaccination. Sixteen FSW were diagnosed with HBV after their first attendance where sex work was recorded. CONCLUSIONS: To achieve the WHO goals of elimination of HBV as a public health threat by the year 2030, further research is needed to understand the individual and structural barriers to the offering and uptake of HBV vaccination among FSW, as well as using health promotion methods to improve uptake.

Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara-Bavaria Nordic vaccine against mpox in children: a national outbreak response.

BACKGROUND: In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children. METHODS: This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. FINDINGS: Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. INTERPRETATION: A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. FUNDING: UK Health Security Agency.

Effectiveness of one dose of MVA-BN smallpox vaccine against mpox in England using the case-coverage method: an observational study.

BACKGROUND: The UK experienced a national outbreak of mpox (formerly known as monkeypox) disease that started in May, 2022, as did many other countries worldwide, with case numbers rising rapidly, mainly among gay, bisexual, and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN), an attenuated smallpox vaccine, was offered to at-risk GBMSM. We aimed to assess the effectiveness of a single MVA-BN dose against symptomatic mpox disease in at-risk GBMSM. METHODS: In this case-coverage study, mpox cases in England were sent questionnaires collecting information on demographics, vaccination history, symptoms, and sexual orientation. Returned questionnaires were linked to laboratory data and a public health case management system (HP Zone) to obtain additional information on symptom onset and specimen date. Cases with a rash onset date (or alternative proxy) between July 4 and Oct 9, 2022, were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method in which vaccine coverage among cases is compared with coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of at-risk GBMSM. Sensitivity analyses included an increase and decrease of 20% differences in the estimated high-risk GBMSM population size. FINDINGS: By Nov 3, 2022, 1102 people had responded to questionnaires, of which 739 were excluded (52 females or self-declared male heterosexuals, 590 with an index date outside of the study period, and 97 missing a vaccination date). 363 cases were included in the analyses. Vaccine uptake among eligible GBMSM increased steadily from July, 2022, reaching 47% by Oct 9, 2022. Of the 363 confirmed cases, eight cases either did occur or were likely to have occurred at least 14 days after vaccination, 32 within 0-13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness against symptomatic mpox at least 14 days after a single dose was 78% (95% CI 54 to 89) ranging from 71 to 85 in sensitivity analyses. Vaccine effectiveness within 0-13 days after vaccination was -4% (95% CI -50 to 29). INTERPRETATION: A single MVA-BN dose was highly protective against symptomatic mpox disease among at-risk GBMSM, making it a useful tool for mpox outbreak control when rapid protection is needed. For cases in which numbers at highest risk of infection exceed vaccine supply, there might be benefit in prioritising delivery of first doses. FUNDING: UK Health Security Agency.

Investigating rates and risk factors for hepatitis C virus reinfection in people receiving antiviral treatment in England.

England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow-up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person-years (PYs, 95% confidence interval (CI) 7.37-8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98-25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21-24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two-fifths of those with reinfection (43%, n = 329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n = 222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.

Blood-borne virus testing in emergency departments - a systematic review of seroprevalence, feasibility, acceptability and linkage to care.

BACKGROUND: Blood-borne viruses (BBVs) cause significant morbidity and mortality worldwide. Emergency departments (EDs) offer a point of contact for groups at increased risk of BBVs who may be less likely to engage with primary care. We reviewed the literature to evaluate whether BBV testing in this setting might be a viable option to increase case finding and linkage to care. METHODS: We searched PubMed database for English language articles published until June 2019 on BBV testing in EDs. Studies reporting seroprevalence surveys, feasibility, linkage to care, enablers and barriers to testing were included. Additional searches for grey literature were performed. RESULTS: Eight-nine articles met inclusion criteria, of which 14 reported BBV seroprevalence surveys in EDs, 54 investigated feasibility and acceptability, and 36 investigated linkage to care. Most studies were HIV-focused and conducted in the USA. Seroprevalence rates were in the range 1.5-17% for HCV, 0.7-1.6% for HBV, and 0.8-13% for HIV. For studies that used an opt-in study design, testing uptake ranged from 2% to 98% and for opt-out it ranged from 16% to 91%. There was a wide range of yield: 13-100% of patients received their test result, 21-100% were linked to care, and 50-91% were retained in care. Compared with individuals diagnosed with HIV, linkage to and retention in care were lower for those diagnosed with hepatitis C. Predictors of linkage to care was associated with certain patient characteristics. CONCLUSIONS: Universal opt-out BBV testing in EDs may be feasible and acceptable, but linkage to care needs to be improved by optimizing implementation. Further economic evaluations of hepatitis testing in EDs are needed.

Trends in COVID-19 hospital outcomes in England before and after vaccine introduction, a cohort study.

Widespread vaccination campaigns have changed the landscape for COVID-19, vastly altering symptoms and reducing morbidity and mortality. We estimate trends in mortality by month of admission and vaccination status among those hospitalised with COVID-19 in England between March 2020 to September 2021, controlling for demographic factors and hospital load. Among 259,727 hospitalised COVID-19 cases, 51,948 (20.0%) experienced mortality in hospital. Hospitalised fatality risk ranged from 40.3% (95% confidence interval 39.4-41.3%) in March 2020 to 8.1% (7.2-9.0%) in June 2021. Older individuals and those with multiple co-morbidities were more likely to die or else experienced longer stays prior to discharge. Compared to unvaccinated people, the hazard of hospitalised mortality was 0.71 (0.67-0.77) with a first vaccine dose, and 0.56 (0.52-0.61) with a second vaccine dose. Compared to hospital load at 0-20% of the busiest week, the hazard of hospitalised mortality during periods of peak load (90-100%), was 1.23 (1.12-1.34). The prognosis for people hospitalised with COVID-19 in England has varied substantially throughout the pandemic and according to case-mix, vaccination, and hospital load. Our estimates provide an indication for demands on hospital resources, and the relationship between hospital burden and outcomes.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks.

Background: Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks. Methods: A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated. Findings: R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination. Interpretation: Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks. Funding: NIHR.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18-3.74) and transplanted (OR = 3.36; 95% CI: 1.19-9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.