Representativeness of whole-genome sequencing approaches in England: the importance for understanding inequalities associated with SARS-CoV-2 infection.

Whole-genome sequencing (WGS) information has played a crucial role in the SARS-CoV-2 (COVID-19) pandemic by providing evidence about variants to inform public health policy. The purpose of this study was to assess the representativeness of sequenced cases compared with all COVID-19 cases in England, between March 2020 and August 2021, by demographic and socio-economic characteristics, to evaluate the representativeness and utility of these data in epidemiological analyses. To achieve this, polymerase chain reaction (PCR)-confirmed COVID-19 cases were extracted from the national laboratory system and linked with WGS data. During the study period, over 10% of COVID-19 cases in England had WGS data available for epidemiological analysis. With sequencing capacity increasing throughout the period, sequencing representativeness compared to all reported COVID-19 cases increased over time, allowing for valuable epidemiological analyses using demographic and socio-economic characteristics, particularly during periods with emerging novel SARS-CoV-2 variants. This study demonstrates the comprehensiveness of England's sequencing throughout the COVID-19 pandemic, rapidly detecting variants of concern, and enabling representative epidemiological analyses to inform policy.

Human Exposures to H5N6 Avian Influenza, England, 2018.

The human risk following exposure to the European reassortant avian influenza A(H5N6) is unknown. We used routine data collected as part of public health follow-up to assess outcomes of individuals exposed to H5N6-infected wild birds in England. There were 19 separate incidents of confirmed H5N6 among wild birds in the first quarter of 2018 in England and 69 individuals exposed to infected birds during these incidents. Five exposed individuals developed respiratory symptoms. However, no H5N6 infection was detected among those individuals with respiratory symptoms who underwent diagnostic testing, indicating that the human risk from this strain remains low.

Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study.

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C: an observational cohort study.

This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode.

Can Hepatitis C Virus (HCV) Direct-Acting Antiviral Treatment as Prevention Reverse the HCV Epidemic Among Men Who Have Sex With Men in the United Kingdom? Epidemiological and Modeling Insights.

BACKGROUND: We report on the hepatitis C virus (HCV) epidemic among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in the United Kingdom and model its trajectory with or without scaled-up HCV direct-acting antivirals (DAAs). METHODS: A dynamic HCV transmission model among HIV-diagnosed MSM in the United Kingdom was calibrated to HCV prevalence (antibody [Ab] or RNA positive), incidence, and treatment from 2004 to 2011 among HIV-diagnosed MSM in the UK Collaborative HIV Cohort (UK CHIC). The epidemic was projected with current or scaled-up HCV treatment, with or without a 20% behavioral risk reduction. RESULTS: HCV prevalence among HIV-positive MSM in UK CHIC increased from 7.3% in 2004 to 9.9% in 2011, whereas primary incidence was flat (1.02-1.38 per 100 person-years). Over the next decade, modeling suggests 94% of infections are attributable to high-risk individuals, comprising 7% of the population. Without treatment, HCV chronic prevalence could have been 38% higher in 2015 (11.9% vs 8.6%). With current treatment and sustained virological response rates (status quo), chronic prevalence is likely to increase to 11% by 2025, but stabilize with DAA introduction in 2015. With DAA scale-up to 80% within 1 year of diagnosis (regardless of disease stage), and 20% per year thereafter, chronic prevalence could decline by 71% (to 3.2%) compared to status quo in 2025. With additional behavioral interventions, chronic prevalence could decline further to <2.5% by 2025. CONCLUSIONS: Epidemiological data and modeling suggest a continuing HCV epidemic among HIV-diagnosed MSM in the United Kingdom driven by high-risk individuals, despite high treatment rates. Substantial reductions in HCV transmission could be achieved through scale-up of DAAs and moderately effective behavioral interventions.

Current concepts in vulvodynia with a focus on pathogenesis and pain mechanisms.

Vulvodynia is a common and debilitating chronic pain syndrome characterised by neuropathic-type pain. Localised provoked vulvodynia is the most common type, followed by generalised unprovoked vulvodynia. Vulvodynia is a diagnosis of exclusion. The cause is unknown but current research suggests an underlying predisposition to increased sensitivity to pain and peripheral and central neural sensitisation. Musculoskeletal factors also play an important role. Vulvodynia has a significant impact on the quality of life, mood, functional ability and relationships of patients and their partners. It is highly associated with anxiety and depression. Treatment needs to follow a biopsychosocial model and be tailored to the patient. A multimodal and multidisciplinary approach is often most effective. We have suggested a therapeutic ladder.

Exploring staff attitudes to routine HIV testing in non-traditional settings: a qualitative study in four healthcare facilities.

OBJECTIVES: To explore staff attitudes towards and experiences of the implementation of routine HIV testing in four healthcare settings in areas of high diagnosed HIV prevalence. METHODS: As part of the HINTS (HIV Testing in Non-traditional Settings) Study, routine offer of an HIV test to all 16-65-year-old patients was conducted for 3 months in an emergency department, an acute admissions unit, a dermatology outpatients department and a primary care practice. The authors conducted focus groups with staff at these sites before and after the implementation of testing. Transcriptions of focus groups were subject to thematic analysis. RESULTS: Four major themes were identified: the stigma of HIV and exceptionalisation of HIV testing as a condition; the use of routine testing compared with a targeted strategy as a means of improving the acceptability of testing; the need for an additional skill set to conduct HIV testing; and the existence within these particular settings of operational barriers to the implementation of HIV testing. Specifically, the time taken to conduct testing and management of results were seen by staff as barriers. There was a clear change in staff perception before and after implementation of testing as staff became aware of the high level of patient acceptability. CONCLUSIONS: The routine offer of HIV testing in general medical services is feasible, but implementation requires training and support for staff, which may be best provided by the local sexual health service.

Changing patterns of sexual risk behavior among London gay men: 1998-2008.

OBJECTIVES: To examine changes in the sexual behavior of London gay men between 1998 and 2008. METHODS: Gay men using London gyms were surveyed annually between 1998 and 2005, and again in 2008 (n=6064; range, 482-834 per year). Information was collected on human immunodeficiency virus (HIV) status of the respondent, unprotected anal intercourse (UAI) in the previous 3 months, type (main or casual) and HIV status of partner for UAI. Nonconcordant UAI (ncUAI) was defined as UAI with a partner of unknown or discordant HIV status. Concordant UAI (cUAI) was defined as UAI with a partner of the same HIV status ("serosorting"). RESULTS: Between 1998 and 2008, the percentage of men reporting UAI increased from 24.3% to 36.6% (P=0.07). This overall increase concealed important differences between nonconcordant and concordant UAI. While the percentage of men engaging in cUAI increased steadily between 1998 and 2008 (9.8%, 20.8%; P=0.01), the percentage reporting ncUAI increased between 1998 and 2001 (14.5%, 23.7%; P<0.001), decreased between 2001 and 2005 (23.7%, 15.6%; P<0.001), and then leveled off between 2005 and 2008 (15.6%, 15.7%; P=0.2). However, the percentage of men reporting ncUAI with a main partner increased between 2005 and 2008 for HIV-positive men (2.5%, 8.1%; P<0.05) and HIV negative men (2.1%, 5.5%; P=0.06). While the percentage of HIV negative men who reported cUAI with a main partner (i.e., serosorting) increased between 1998 and 2008 (12.4%, 21.1%; P<0.05), less than half established seroconcordance by testing together. CONCLUSIONS: The patterns of sexual behavior among London's gay men between 1998 and 2008 were dynamic and complex. Our data suggest that HIV risk with a main partner and HIV testing among couples should be given greater priority by health promotion programmes.

Circumcision among men who have sex with men in London, United Kingdom: an unlikely strategy for HIV prevention.

OBJECTIVES: To explore attitudes toward circumcision among men who have sex with men (MSM) in London and the feasibility of conducting research into circumcision and HIV prevention in this population. METHODS: A convenience sample of MSM visiting central London gyms completed a confidential, self-administered questionnaire between May and June 2008. Information was collected on participants' demographic characteristics, self-reported HIV status, sexual behavior, circumcision status, attitudes toward circumcision, and willingness to participate in research on circumcision and HIV prevention. RESULTS: Of 653 MSM, 29.0% reported that they were circumcised. Overall, HIV prevalence was 23.3%; this did not differ significantly between circumcised and uncircumcised men (18.6% vs. 25.2%, respectively; adjusted odds ratio 0.79, 95% confidence interval: 0.50-1.26). A similar proportion of circumcised and uncircumcised men reported unprotected anal intercourse in the previous 3 months (38.8% vs. 36.7%, adjusted odds ratio 1.06, 95% confidence interval: 0.72-1.55). Uncircumcised men were less likely to think that there were benefits of circumcision than circumcised men (31.2% vs. 65.4, P < 0.001). Only 10.3% of uncircumcised men said that they would be willing to participate in research on circumcision as an HIV prevention strategy. CONCLUSIONS: Most uncircumcised MSM in this London survey were unwilling to participate in research on circumcision and HIV prevention. Only a minority of uncircumcised men thought that there were benefits of circumcision. It is unlikely that circumcision would be a feasible strategy for HIV prevention among MSM in London.

Hepatitis B, hepatitis C, and mortality among HIV-positive individuals.

OBJECTIVES: To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses. DESIGN: An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom. METHODS: Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates (all cause, liver related, and AIDS related) were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort. RESULTS: Among 25 486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28-2.00) and 10.42 (5.78-18.80), respectively. HCV coinfection was significantly associated with increased all-cause (ARR 1.43, 95% CI 1.15-1.76) and liver-related mortality (ARR 6.20, 95% CI 3.31-11.60). Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63-1.83) and 0.40 (0.20-0.81), respectively. CONCLUSION: The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals.

Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV-diagnosed men who have sex with men in the United Kingdom: results from the ASTRA study.

INTRODUCTION: Transmission of Hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) in the United Kingdom is ongoing. We explore associations between self-reported sexual behaviours and drug use with cumulative HCV prevalence, as well as new HCV diagnosis. METHODS: ASTRA is a cross-sectional questionnaire study including 2,248 HIV-diagnosed MSM under care in the United Kingdom during 2011-2012. Socio-demographic, lifestyle, HIV-related and sexual behaviour data were collected during the study. One thousand seven hundred and fifty two (≥70%) of the MSM who consented to linkage of ASTRA and clinical information (prior to and post questionnaire) were included. Cumulative prevalence of HCV was defined as any positive anti-HCV or HCV-RNA test result at any point prior to questionnaire completion. We excluded 536 participants with clinical records only after questionnaire completion. Among the remaining 1,216 MSM, we describe associations of self-reported sexual behaviours and recreational drug use in the three months prior to ASTRA with cumulative HCV prevalence, using modified Poisson regression with robust error variances. New HCV was defined as any positive anti-HCV or HCV-RNA after questionnaire completion. We excluded 591 MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV result prior to questionnaire or did not have any HCV tests after the questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV diagnosis during follow-up according to self-reported sexual behaviours and recreational drug use three months prior to questionnaire (Fisher's exact test). RESULTS: Cumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI 11.5-15.4). Clinic- and age-adjusted prevalence ratios (95% CI) for cumulative HCV prevalence were 4.6 (3.1-6.7) for methamphetamine, 6.5 (3.5-12.1) for injection drugs, 2.3 (1.6-3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3-2.0) for nitrites, 1.7 (1.5-2.0) for all condom-less sex (CLS), 2.1 (1.7-2.5) for CLS-HIV-seroconcordant, 1.3 (0.9-1.9) for CLS-HIV-serodiscordant, 2.0 (1.6-2.5) for group sex, 1.5 (1.2-1.9) for more than 10 new sexual partners in the past year. Among 1,195 MSM with 2.2 years [IQR 1.5-2.4] median follow-up, there were 7 new HCV cases during 2,033 person-years at risk. Incidence was 3.5 per 1,000 person-years (95% CI 1.6-7.2). New HCV was recorded in 1.3% MSM who used methamphetamine versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM having CLS-HIV-serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who had CLS-HIV-seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new sexual partners in the previous year versus 0.2% MSM with no or up to 9 new partners (p=0.015). CONCLUSIONS: Self-reported recent use of recreational and injection drugs, condom-less sex and multiple new sexual partners are associated with pre-existing HCV infection and, with the exception of injection drugs, appear to be predictive of new HCV co-infection among HIV-diagnosed MSM.

HIV testing in non-traditional settings--the HINTS study: a multi-centre observational study of feasibility and acceptability.

BACKGROUND: UK guidelines recommend routine HIV testing in healthcare settings if the local diagnosed HIV prevalence >2/1000 persons. This prospective study assessed the feasibility and acceptability, to patients and staff, of routinely offering HIV tests in four settings: Emergency Department, Acute Care Unit, Dermatology Outpatients and Primary Care. Modelling suggested the estimated prevalence of undiagnosed HIV infection in attendees would exceed 1/1000 persons. The prevalence identified prospectively was not a primary outcome. METHODS: Permanent staff completed questionnaires assessing attitudes towards routine HIV testing in their workplace before testing began. Subsequently, over a three-month period, patients aged 16-65 were offered an HIV test by study staff. Demographics, uptake, results, and departmental activity were collected. Subsets of patients completed questionnaires. Analyses were conducted to identify factors associated with test uptake. FINDINGS: Questionnaires were received from 144 staff. 96% supported the expansion of HIV testing, but only 54% stated that they would feel comfortable delivering testing themselves, with 72% identifying a need for training. Of 6194 patients offered a test, 4105 (66·8%) accepted (61·8-75·4% across sites). Eight individuals were diagnosed with HIV (0-10/1000 across sites) and all transferred to care. Younger people, and males, were more likely to accept an HIV test. No significant associations were found between uptake and ethnicity, or clinical site. Questionnaires were returned from 1003 patients. The offer of an HIV test was acceptable to 92%. Of respondents, individuals who had never tested for HIV before were more likely to accept a test, but no association was found between test uptake and sexual orientation. CONCLUSIONS: HIV testing in these settings is acceptable, and operationally feasible. The strategy successfully identified, and transferred to care, HIV-positive individuals. However, if HIV testing is to be included as a routine part of patients' care, additional staff training and infrastructural resources will be required.

Monitoring the emergence of community transmission of influenza A/H1N1 2009 in England: a cross sectional opportunistic survey of self sampled telephone callers to NHS Direct.

OBJECTIVE: To evaluate ascertainment of the onset of community transmission of influenza A/H1N1 2009 (swine flu) in England during the earliest phase of the epidemic through comparing data from two surveillance systems. DESIGN: Cross sectional opportunistic survey. STUDY SAMPLES: Results from self samples by consenting patients who had called the NHS Direct telephone health line with cold or flu symptoms, or both, and results from Health Protection Agency (HPA) regional microbiology laboratories on patients tested according to the clinical algorithm for the management of suspected cases of swine flu. SETTING: Six regions of England between 24 May and 30 June 2009. MAIN OUTCOME MEASURE: Proportion of specimens with laboratory evidence of influenza A/H1N1 2009. RESULTS: Influenza A/H1N1 2009 infections were detected in 91 (7%) of the 1385 self sampled specimens tested. In addition, eight instances of influenza A/H3 infection and two cases of influenza B infection were detected. The weekly rate of change in the proportions of infected individuals according to self obtained samples closely matched the rate of increase in the proportions of infected people reported by HPA regional laboratories. Comparing the data from both systems showed that local community transmission was occurring in London and the West Midlands once HPA regional laboratories began detecting 100 or more influenza A/H1N1 2009 infections, or a proportion positive of over 20% of those tested, each week. CONCLUSIONS: Trends in the proportion of patients with influenza A/H1N1 2009 across regions detected through clinical management were mirrored by the proportion of NHS Direct callers with laboratory confirmed infection. The initial concern that information from HPA regional laboratory reports would be too limited because it was based on testing patients with either travel associated risk or who were contacts of other influenza cases was unfounded. Reports from HPA regional laboratories could be used to recognise the extent to which local community transmission was occurring.

Update on lymphogranuloma venereum in the United Kingdom.

OBJECTIVES: This report updates the UK epidemiology of lymphogranuloma venereum (LGV) to the end of April 2007. METHODS: The Health Protection Agency's Centre for Infections undertakes laboratory testing for LGV and subsequent epidemiological investigation of cases after laboratory confirmation of the LGV serovars (L1-3). Data analysis of enhanced surveillance and laboratory reports was undertaken. RESULTS: From October 2004 to end April 2007, 492 cases of LGV have been diagnosed and enhanced surveillance forms have been returned for 423. Cases peaked in the third quarter of 2005 with an average of 32 cases per month, while in 2006 this fell to 12 cases per month. Nationally, the outbreak is focused in London, Brighton and the North West. All cases are in men, 99% of whom are MSM, with a median age of 40 and predominantly white ethnicity (91%). Co-infection remains considerable: HIV (74%); hepatitis C (14%); syphilis (5%); and other STIs including gonorrhoea, genital herpes and hepatitis B. The number of men reporting greater than 10 sexual contacts in the previous 3 months has reduced from 23% (47) to 13% (15) from 2005-2006. DISCUSSION: The epidemic continues in the mostly white MSM population of the UK. The demographics of LGV remain similar to those previously described and high levels of HIV co-infection continue. Reduced numbers of sexual contacts might be contributing to the reduced numbers of LGV seen in 2006 but could simply mean that LGV is moving out of the highest risk groups.