Development and evaluation of an outbreak surveillance system integrating whole genome sequencing data for non-typhoidal Salmonella in London and South East of England, 2016-17.

An outbreak surveillance system for Salmonella integrating whole genome sequencing (WGS) and epidemiological data was developed in South East and London in 2016-17 to assess local WGS clusters for triage and investigation. Cases genetically linked within a 5 single-nucleotide polymorphism (SNP) single linkage cluster were assessed using a set of locally agreed thresholds based on time, person and place, for reporting to local health protection teams (HPTs). Between September 2016 and September 2017, 230 unique 5-SNP clusters (442 weekly reports) of non-typhoidal Salmonella 5-SNP WGS clusters were identified, of which 208 unique 5-SNP clusters (316 weekly reports) were not reported to the HPTs. In the remaining 22 unique clusters (126 weekly clusters) reported to HPTs, nine were known active outbreak investigations, seven were below locally agreed thresholds and six exceeded local thresholds. A common source or vehicle was identified in four of six clusters that exceeded locally agreed thresholds. This work demonstrates that a threshold-based surveillance system, taking into account time, place and genetic relatedness, is feasible and effective in directing the use of local public health resources for risk assessment and investigation of non-typhoidal Salmonella clusters.

Acceptability and potential impact of delivering sexual health promotion information through social media and dating apps to MSM in England: a qualitative study.

BACKGROUND: Increasing rates of sexually transmitted infections (STIs) in men-who-have-sex-with-men (MSM) in England is a pressing public health concern. Interventions targeting MSM, including information provision that effectively promotes sexual health, are needed. To support such intervention development, it is necessary to understand acceptable ways of delivering sexual health information. We explored the acceptability and potential uses and impacts of delivering sexual health information to MSM through social media and geosocial networking apps or dating apps. METHODS: Semi-structured interviews were conducted in person or by telephone with 25 MSM resident in England recruited via dating apps and social media advertisements. Interviews explored sexual health information sources, perceptions and uses. Attitudes towards sexual health promotion through social media and dating apps were then discussed. The data were analysed using thematic analysis. RESULTS: Sexual health information delivery through social media and dating apps was considered acceptable. Receiving information when browsing social media was viewed positively by most, as people have time to absorb information. In contrast, concerns were expressed that sharing or commenting on social media sexual health information may lead to judgements and discrimination. While social media reaches a high proportion of the population, dating apps can easily target MSM. However, tensions exist between the ability to provide information at an opportune time through dating apps, when users are connecting with new sexual partners, with the potential to adversely affect the app user's experience. Hypothetical and actual uses and impacts of sexual health information ranged from no impact to reading information, sharing with peers, and increased awareness, to influencing healthcare-seeking, decision-making and risk-taking behaviours. Ensuring that information is engaging, positive in tone, not too clinical, focused on building social norms and delivered by trusted organisations were viewed as important for supporting its use. CONCLUSIONS: Overall, these findings support the development of new interventions that use dating apps and social media for sexual health promotion.

Prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay, England, June to August 2019.

We identified two new Chlamydia trachomatis (CT) variants escaping Aptima Combo 2 (AC2) assay detection, in clinical specimens of two patients. One had a C1514T mutation the other a G1523A mutation, both within the AC2 23S rRNA target region. The prevalence of such variants among persons tested for CT in England was estimated to be fewer than 0.003%.

Operational burden of implementing Salmonella Enteritidis and Typhimurium cluster detection using whole genome sequencing surveillance data in England: a retrospective assessment.

Since April 2014 all presumptive Salmonella isolates received by Public Health England (PHE) have been characterised using whole genome sequencing (WGS) and the genomic data generated used to identify clusters of infection. To inform the implementation and development of a national gastrointestinal infection surveillance system based on WGS we have retrospectively identified genetically related clusters of Salmonella Enteritidis and Salmonella Typhimurium infection over a one year period and determined the distribution of these clusters by PHE operational levels. Using a constrained WGS cluster definition based on single nucleotide polymorphism distance, case frequency and temporal spread we demonstrate that the majority of clusters spread to multiple PHE operational levels. The greatest investigative burden is on national level staff investigating small, geographically dispersed clusters. We also demonstrate that WGS identifies long-running, slowly developing clusters that may previously have remained undetected. This analysis also indicates likely increased workload for local health protection teams and will require an operational strategy to balance limited human resources with the public health importance of investigating small, geographically contained clusters of highly related cases. While there are operational challenges to its implementation, integrated cluster detection based on WGS from local to international level will provide further improvements in the identification of, response to and control of clusters of Salmonella spp. with public health significance.

National outbreak of Pseudomonas aeruginosa associated with an aftercare solution following piercings, July to September 2016, England.

We report a national Pseudomonas aeruginosa outbreak from a common source following piercings between July and September 2016 in England. The multi-agency outbreak investigation included active case finding, microbiological testing of environmental samples and case specimens including Variable Number Tandem Repeat (VNTR) typing and a retrospective cohort study. Overall, 162 outbreak cases (29 confirmed, 14 probable and 119 possible) and 14 non-outbreak cases were identified; all confirmed cases had ear piercings (93% cartilage). Outbreak cases were predominantly female (95%) and had a median age of 18 years (interquartile range: 13-56 years). Nineteen outbreak cases required surgery under general anaesthetic The same outbreak VNTR type (11,3,5,3,3,3,6,4,7) was isolated from bottles of an aftercare solution from a single manufacturer and in specimens from confirmed cases who attended eight different piercing studios supplied with this product. In the cohort study, use of aftercare solution was associated with becoming a case (aOR: 4.60, 95% confidence interval: 1.65-12.90). Environmental, microbiological and epidemiological investigations confirmed that contamination during production of aftercare solution was the source of this national outbreak; highlighting challenges in the regulation of a cosmetic products used in the piercing industry and that guidance on piercing aftercare may need to be reviewed.

National outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to mixed salad leaves, United Kingdom, 2016.

We investigated a large outbreak of Escherichia coli O157 in the United Kingdom (UK) with 165 cases between 31 May and 29 July 2016. No linked cases were reported in other countries. Cases were predominately female (n = 128) and adult (n = 150), 66 attended hospital and nine had features of haemorrhagic uraemic syndrome. A series of epidemiological studies (case-control, case-case, ingredients-based and venue-based studies) and supply chain investigations implicated mixed salad leaves from Supplier A as the likely outbreak vehicle. Whole genome sequencing (WGS) indicated a link with strains from the Mediterranean and informed the outbreak control team to request that Supplier A cease distributing salad leaves imported from Italy. Microbiological tests of samples of salad leaves from Supplier A were negative. We were unable to confirm the source of contamination or the contaminated constituent leaf although our evidence pointed to red batavia received from Italy as the most likely vehicle. Variations in Shiga toxin-producing E.coli surveillance and diagnosis may have prevented detection of cases outside the UK and highlights a need for greater standardisation. WGS was useful in targeting investigations, but greater coverage across Europe is needed to maximise its potential.

Lack of Secondary Transmission of Ebola Virus from Healthcare Worker to 238 Contacts, United Kingdom, December 2014.

In December 2014, Ebola virus disease (EVD) was diagnosed in a healthcare worker in the United Kingdom after the worker returned from an Ebola treatment center in Sierra Leone. The worker flew on 2 flights during the early stages of disease. Follow-up of 238 contacts showed no evidence of secondary transmission of Ebola virus.

Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017.

Between July 2016 and January 2017, 37 confirmed cases of hepatitis A with two unique IA genotype strains primarily among men who have sex with men, were reported across eight areas in England and Northern Ireland. Epidemiological and laboratory investigations indicate that these strains may have been imported several times from Spain, with secondary sexual transmission in the United Kingdom. Local and national public health services are collaborating to control this ongoing outbreak.

Initial Stability of Cemented vs Cementless Tibial Components Under Cyclic Load.

BACKGROUND: Cement fixation of total knee components remains the gold standard despite resurgence in cementless fixation with the goal of long-term durable fixation. Initial stability is paramount to achieve bony ingrowth of cementless components. METHODS: Twelve cemented and cementless tibial baseplates were implanted into sawbones and tested using a physiological medial-lateral load distribution for 10,000 cycles to represent 8 weeks of in vivo function. Micromotion was measured at 5 locations around the baseplate during loading. RESULTS: Cycling had a significant effect on the change in micromotion between maximum and minimum loads at the anterior, medial, lateral, posteromedial, and posterolateral tray edge locations. A significant effect of fixation technique was detected for the anterior (P < .001), medial (P = .002), and lateral (P = .0056) locations but not for the posteromedial (P = .36) or posterolateral (P = .82) locations. Differences in micromotion between cemented and cementless components did not exceed 150 µm at any tested location. CONCLUSION: The micromotion experienced by cementless tibial components in the present study may indicate a lower initial mechanical stability than the cemented group. However, this difference in initial stability may be subclinical because the differences between average cemented and cementless micromotion were <150 µm at all measured locations under the loading regime implemented.

ESBL-Producing and Macrolide-Resistant Shigella sonnei Infections among Men Who Have Sex with Men, England, 2015.

In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum ß-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.

London 2012 Olympic and Paralympic Games: public health surveillance and epidemiology.

Mass gatherings are regarded as potential risks for transmission of infectious diseases, and might compromise the health system of countries in which they are hosted. The evidence for increased transmission of infectious diseases at international sporting mass gatherings that attract many visitors from all over the world is not clear, and the evidence base for public health surveillance, epidemiology, and response at events such as the Olympics is small. However, infectious diseases are a recognised risk, and public health planning is, and should remain, a crucial part of the overall planning of sporting events. In this Series paper, we set out the planning and the surveillance systems that were used to monitor public health risks during the London 2012 Olympic and Paralympic Games in the summer of 2012, and draw attention to the public health issues-infectious diseases and chemical, radiation, and environmental hazards-that arose. Although the absolute risk of health-protection problems, including infectious diseases, at sporting mass gatherings is small, the need for reassurance of the absence of problems is higher than has previously been considered; this could challenge conventional public health surveillance systems. Recognition of the limitations of health-surveillance systems needs to be part of the planning for future sporting events.

Olympics and Paralympics 2012 mass gathering in London: time-series analysis shows no increase in attendances at sexual health clinics.

OBJECTIVE: To determine whether the 2012 Olympic and Paralympic Games were associated with a change in the number of patients attending or diagnosed with a new sexually transmitted infection (STI) at sexual health clinics in London and Weymouth. METHODS: We undertook an interrupted time-series analysis of surveillance data from the Genitourinary Medicine Clinic Activity Dataset (GUMCAD) collected at 33 genitourinary medicine (GUM) clinics in London and Weymouth (where Games events were concentrated) between 2009 and 2012. Mixed-effects linear regression models of weekly attendance and diagnoses, incorporating temporal trends, bank holidays, categorical month and clinic closures, were used to test for the effect of the 'Olympic-Paralympic' period. We subdivided the 9-week 'Olympic-Paralympic' period (16 July 2012 to 17 September 2012) into five periods, including three Olympic weeks, two Paralympic weeks, pre-, post- and inter-Games weeks. We also compared characteristics of patients attending during the Olympic-Paralympic period and those attending during the same period in 2011. RESULTS: During the 3 weeks of the Olympics, there was a significant reduction in the number of new episode attendances (2020 fewer, 5.6% reduction (95% CI -8.2 to -2.9)) and the number of patients diagnosed with an STI (267 fewer, 4.8% reduction (95% CI -8.6 to -0.9)) compared to expected. There were no important differences in the profile of patients attending during the 2012 Olympic-Paralympic period and those attending during the same period in 2011. CONCLUSIONS: We conclude that a 'business-as-usual' approach to managing local sexual health clinics during the 2012 Olympic and Paralympics would have been appropriate.

Epidemiology of Sexually Transmitted Infections in Visitors for the London 2012 Olympic Games: A Review of Attendees at Sexual Health Services.

BACKGROUND: Mass gatherings and large sporting events, such as the Olympics, may potentially pose a risk of increased sexually transmitted infection (STI) transmission and increase burden on local STI services. The objectives of this analysis were to assess whether the STI profile of Olympic visitors differed from that of the local STI clinic population and to investigate what impact these visitors had on local STI services. METHODS: Self-administered questionnaires (completed by 29,292 patients) were used to determine the visitor status of patients attending 20 STI clinics, between July 20, 2012, and September 16, 2012, in the host cities, London and Weymouth. Using routine surveillance data from the Genitourinary Medicine Clinic Activity Dataset version 2, Olympic visitors were compared with usual attendees (local residents and non-Olympic visitors) in terms of their demographic characteristics, services utilized, and STIs diagnosed using univariate and multivariate methods. RESULTS: Compared with usual attendees, Olympic visitors were more likely to be heterosexual males (56.0% vs. 34.9%, P = 0.001), aged between 15 and 24 years of age (47.1% vs. 34.0%, P = 0.001), of white ethnicity (81.9% vs. 66.4%, P = 0.001), and born in Australasia, Asia, North America, or South America (18.8% vs. 12.0%, P = 0.006). Olympic visitors constituted 1% of new clinic attendances and were less likely to be diagnosed as having a new STI (adjusted odds ratio, 0.69; 95% confidence interval, 0.48-0.98; P = 0.040). CONCLUSIONS: In this first multisite study to examine the effect of Olympic visitors on local sexual health services, the 2012 Olympic Games was found to have minimal impact. This suggests that a "business as usual" approach would have been sufficient.

Enhanced surveillance of syphilis cases among men who have sex with men in London, October 2016-January 2017.

Syphilis rates have been increasing in men who have sex with men (MSM) in London. To describe risk behaviour and refine public health interventions, we conducted prospective enhanced surveillance of new syphilis cases in MSM attending selected London sexual health clinics (SHCs) between October 2016 and January 2017. Sexual health advisors (SHAs) completed 107 questionnaires. Eighteen per cent of respondents reported always using condoms, with lower use in HIV-positive (8%, 4/53) than HIV-negative men (33%, 14/52). Almost half of respondents reported condomless sero-discordant sex (46%, 33/72). The most frequent means of meeting new partners reported were venues (80%, 76/95), particularly bars or clubs (34%, 32/95), and apps or websites (79%, 75/95). Nearly a third of respondents reported engaging in group sex (32%, 30/95). Almost half reported drug use during sex (47%, 46/98), with HIV-positive men more likely to report use of the three main 'chemsex' drugs. The majority of respondents preferred health promotion information from SHAs (63%, 58/92) compared to other sources such as Google/Wikipedia and apps. Prevention activity should continue to focus on condomless sex, serosorting, multiple and overlapping partners, and chemsex. SHCs, particularly those serving HIV-positive men, are important sources for sexual health promotion advice.

Genomic approaches used to investigate an atypical outbreak of Salmonella Adjame.

In 2017, an outbreak of gastroenteritis in England attributed to Salmonella Adjame was detected and investigated. With the introduction of whole genome sequencing (WGS) for microbial typing, methods for comparing international outbreak data require evaluation. A case was defined as a person resident in England with a clinical sample from 1 June 2017 to 27 July 2017 from whom S. Adjame was isolated. Cases were interviewed and exposures analysed. Backward tracing of food provenance was undertaken. WGS was performed on isolates from cases and historical isolates and compared using Public Health England's SnapperDB high-quality SNP pipeline and Enterobase's Salmonella core genome multi-locus sequence typing (cgMLST) scheme. In total, 14 cases were identified. The majority were vegetarian, probably of South Asian descent, with a median age of 66.5 years with no recent international travel reported. Cases consumed a range of fresh food products including herbs and spices bought from South Asian grocers. Backward tracing did not identify a common source. WGS typing showed sub-clustering and considerable genetic variation across human samples. cgMLST allele-based analysis was comparable to SNP-derived phylogenetic analysis and clusters were defined using each method. Imported herbs or spices were suspected vehicles. The cases were linked in time and place but WGS showed marked heterogeneity, atypical of a point source Salmonella outbreak. The application of incorporating SNP or allelic differences into the case definition may not always be appropriate. With further validation, cgMLST could be used for international outbreak alerts when WGS analysis is being undertaken to facilitate comparison.

Comparison of 90-Day Perioperative Outcomes in Shoulder Arthroplasty Between the Elderly and Nonelderly Patients.

INTRODUCTION: As life expectancy increases, the incidence of shoulder arthroplasty continues to increase as well. There are few shoulder arthroplasty studies investigating perioperative complication, readmission, and mortality. Furthermore, with bundled payments on the horizon, the cost of shoulder arthroplasty has become a significant issue. Clarifying risk factors for the need for postdischarge acute care will be critical information due to the high cost of such care. The goal of this study was to compare discharge disposition, length of stay (LOS), perioperative complications, readmission, and mortality in elderly and nonelderly cohorts to determine whether age is a risk factor for shoulder arthroplasty. MATERIALS AND METHODS: We retrospectively compared 89 elderly patients (80 years or older) and 86 nonelderly patients (79 years or younger) who underwent hemiarthroplasty, total shoulder arthroplasty, reverse total shoulder arthroplasty, or revision shoulder arthroplasty from 2007 to 2015. Baseline characteristics were compared between the 2 cohorts. We then compared discharge disposition, LOS, 90-day complication rate, readmission, and mortality between the 2 cohorts. RESULTS: Average length of hospitalization and percentage of patients with greater than 2 days of hospitalization were significantly higher in the elderly cohorts. Forty-four percent of the elderly cohorts were discharged to a skilled nursing facility compared to 6% in the nonelderly cohorts (P < .0001). There were no significant differences found in 90-day major complication rate, readmission, or mortality. DISCUSSION: Shoulder arthroplasty is a valuable surgery for various indications in the elderly population. However, the likelihood of a patient to need a prolonged hospitalization or skilled nursing facility care after surgery are important questions that need to be answered. Our study shows that age over 80 years is a risk factor for prolonged hospitalization and need for skilled nursing facility care after shoulder arthroplasty. CONCLUSION: We conclude that elderly patients who undergo shoulder arthroplasty are significantly more likely to have extended hospitalizations and to be discharged to skilled nursing facilities compared to nonelderly patients.

Whole-genome sequencing revealed concurrent outbreaks of shigellosis in the English Orthodox Jewish Community caused by multiple importations of Shigella sonnei from Israel.

In December 2013, Public Health England (PHE) observed an increase in the number of cases of Shigella sonnei linked to the Orthodox Jewish Community (OJC). Ultimately, 52 cases of S. sonnei phage type (PT) P and PT7 were notified between November 2013 and July 2014. Whole-genome sequencing (WGS) was performed on a HiSeq 2500 platform (Illumina) on isolates of S. sonnei submitted to PHE during the investigation. Quality trimmed sequence reads were mapped to a reference genome using BWA-MEM, and single-nucleotide polymorphisms (SNPs) were identified using GATK2. Analysis of the core genome SNP positions (>90 % consensus, minimum depth 10×, MQ≥30) revealed that isolates linked to the outbreak could be categorized as members of distinct monophyletic clusters (MPCs) representing concurrent regional outbreaks occurring in the OJCs across the United Kingdom. A dated phylogeny predicted the date of the most recent common ancestor of the MPCs to be approximately 3.1 years previously [95 % highest posterior density (HPD), 2.4-3.4]. Isolates of S. sonnei from cases from the OJCs in Israel included in the phylogeny, branched from nodes basal to the UK OJC outbreak clusters, indicating they were ancestral to the UK OJC isolates, and that the UK isolates represented multiple importations of S. sonnei into the UK population from Israel. The level of discrimination exhibited by WGS facilitated the identification of clusters of isolates within the closely related bacterial populations circulating in the OJC that may be linked to a unique point sources or transmission routes, thus enabling a more appropriate public health response and targeted interventions.

Taste and Safety: Is the Exceptional Cuisine Offered by High End Restaurants Paralleled by High Standards of Food Safety?

INTRODUCTION: Restaurant guides such as the Good Food Guide Top 50 create a hierarchy focussing on taste and sophistication. Safety is not explicitly included. We used restaurant associated outbreaks to assess evidence for safety. METHODS: All foodborne disease outbreaks in England reported to the national database from 2000 to 2014 were used to compare the Top 50 restaurants (2015) to other registered food businesses using the Public Health England (PHE) outbreak database. Health Protection Teams were also contacted to identify any outbreaks not reported to the national database. Among Good Food Guide Top 50 restaurants, regression analysis estimated the association between outbreak occurrence and position on the list. RESULTS: Four outbreaks were reported to the PHE national outbreak database among the Top 50 giving a rate 39 times higher (95% CI 14.5-103.2) than other registered food businesses. Eight outbreaks among the 44 English restaurants in the Top 50 were identified by direct contact with local Health Protection Teams. For every ten places higher ranked, Top 50 restaurants were 66% more likely to have an outbreak (Odds Ratio 1.66, 95% CI 0.89-3.13). DISCUSSION: Top 50 restaurants were substantially more likely to have had reported outbreaks from 2000-2014 than other food premises, and there was a trend for higher rating position to be associated with higher probability of reported outbreaks. Our findings, that eating at some of these restaurants may pose an increased risk to health compared to other dining out, raises the question of whether food guides should consider aspects of food safety alongside the clearly important complementary focus on taste and other aspects of the dining experience.

Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study.

BACKGROUND: Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. METHODS: We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. FINDINGS: We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection). INTERPRETATION: We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. FUNDING: Wellcome Trust (grant number 098051).

Mortality of hepatitis B surface antigen-positive blood donors in England and Wales.

BACKGROUND: Large population-based cohort studies in areas of high hepatitis B virus (HBV) prevalence have provided the evidence establishing hepatitis B surface antigen (HBsAg) carriage as a risk factor for hepatocellular carcinoma (HCC) and liver disease. Fewer studies have examined this in Western countries, where both HBV infection and carriage are less common and transmission patterns differ. This is the only prospective population-based study to examine this relationship in Europe. METHODS: In all, 2681 male and 977 female blood donors in England and Wales, found to be HBsAg positive during routine blood-donation screening, were followed up from recruitment in 1970-1982 to December 1999 and their cause-specific mortality was analysed. This was compared with that of the general population of England and Wales. RESULTS: During a mean of 22 years of follow-up, 17.4% of the 420 deaths were due to HCC or liver disease. There were 20 deaths from HCC in male HBsAg carriers, representing a significantly high standardized mortality ratio (SMR) compared to the male population of England and Wales of 26 (SMR = 26.26; 95% CI: 16.04- 40.54). The HCC incidence rate in males was 33.5 per 100 000 person years and 4.4 per 100 000 person years in females. Men had 8.5 (SMR = 8.50; 95% CI: 6.25- 11.31) and women had 3.9 times the risk of death from liver disease (SMR = 3.89; 95% CI: 1.26-9.09). The risk of circulatory disease deaths was reduced in both males and females. There was a significant increased risk of non-Hodgkins lymphoma that was not apparent in the first decade of follow-up. The increased risk of HCC and liver disease in men fell with follow-up. CONCLUSION: Hepatitis B surface antigen carriage is a significant risk factor in England and Wales for both liver disease and HCC mortality. However, this risk has declined with duration of follow-up. This could be due to natural reversion to HBsAg negativity or as a result of treatment and avoidance of other risk factors. The increased risk of non-Hodgkins lymphoma seen in longer follow-up is likely to be related to HIV infection acquired subsequent to recruitment.