Hepatitis C virus genotype 4 in England: diversity and demographic associations.

HCV strains belonging to genotype 4 may be gaining endemicity across Continental Europe but the extent of their spread in the United Kingdom is unknown. Sera referred from patients attending hospitals in England between 2004 through 2008 were characterised. A total of 243 sera carried HCV genotype 4. The most common subtypes were 4a (33%) and 4d (35%). Compared to patients infected by 4d, those infected by 4a were 20 times more likely to be Middle Eastern than English, and those infected by non-4a/4d were older, tended to be female, and 50 or 12 times more likely to be Middle Eastern or South Asian, respectively, than English. Persons infected by 4d tended to be English rather than Middle Eastern or South Asian. One group of 4d strains clustered with strains reported from persons in Europe engaged in male homosexual activity. Surveillance of trends in the importation and subsequent spread of HCV genotype 4 and its subtypes is advocated.

Hepatitis C prevalence in England remains low and varies by ethnicity: an updated evidence synthesis.

BACKGROUND: Previous evidence synthesis estimates of Hepatitis C Virus (HCV) in England did not consider excess HCV risk in ethnic minority populations. We incorporate new information on HCV risk among non-injectors by ethnic group, and additional information on injecting prevalence in order to generate new and updated estimates of HCV prevalence risk in England for 2005. METHODS: Bayesian evidence synthesis was used to combine multiple sources of data that directly or indirectly provide information on the populations at risk, or prevalence of HCV infection. HCV data were modelled by region, age group and sex as well as ethnicity for never-injectors and by injecting status (ex and current). RESULTS: Overall HCV antibody prevalence in England was estimated at 0.67% [95% credible interval (95% CrI): 0.50-0.94] of those aged 15-59 years, or 203 000 (153 000, 286 000) individuals. HCV prevalence in never-injectors remains low, even after accounting for ethnicity, with a prevalence of 0.05% (95% CrI 0.03-0.10) in those of white/other ethnicity and 0.76% (0.48-1.23) in South Asians. Estimates are similar to 2003, although patterns of injecting drug use are different, with an older population of current injecting drug users and lower estimated numbers of ex-injectors, but higher HCV prevalence. CONCLUSIONS: Incorporating updated information, including data on ethnicity and improved data on injectors, gave similar overall estimates of HCV prevalence in England. Further information on HCV in South Asians and natural history of injecting are required to reduce uncertainty of estimates. This method may be applied to other countries and settings.

Transfusion-transmitted human immunodeficiency virus (HIV) from seroconverting donors is rare in England and Wales: results from HIV lookback, October 1995 through December 2008.

BACKGROUND: Lookback is considered when human immunodeficiency virus (HIV) is detected in a repeat blood donor in case the immediately previous negative donation was donated in the infectious window period (IWP) or the assay(s) produced a false-negative result. HIV lookback investigations undertaken by NHS Blood and Transplant and the Welsh Blood Service between October 1995 and December 2008 are described. STUDY DESIGN AND METHODS: Investigations were undertaken into the previous negative donations of 113 HIV-infected donors, including retrospective testing of archive samples, tracing of components, and identification of recipients who were offered HIV testing when appropriate. Data were collated on HIV seroconverters and outcome of the lookback was summarized. RESULTS: Two previous negative donations given before the introduction of minipool nucleic acid testing (MP-NAT) screening were confirmed positive by individual retrospective polymerase chain reaction (PCR) testing of the archive specimen. Red blood cell components had been transfused from both donations. One recipient died after transfusion, and the other was alive and tested HIV positive. All 23 (20%) donations previously testing negative by MP-NAT were confirmed to be PCR negative on individual testing of an archive specimen and none of the tested recipients of these donations had evidence of transfusion-transmitted HIV. CONCLUSION: The yield of lookback was low with one positive recipient identified over 13 years of surveillance: HIV transmission occurred from a window period donation given before the introduction of MP-NAT screening and would have been detected using current testing methods. Current residual risk estimates for the United Kingdom predict that HIV lookback will be of limited benefit, as demonstrated by our data.

Hepatitis B and residual risk of infection in English and Welsh blood donors, 1996 through 2008.

BACKGROUND: Globally, of all infections that donations are tested for, hepatitis B has the highest residual risk of transfusion transmission, despite donor selection criteria and advances in testing. Every blood donation in England and Wales is tested for hepatitis B surface antigen. Knowledge of infections being detected can inform donor selection and testing strategies. STUDY DESIGN AND METHODS: Data on donation testing and infections detected are collated by the NHS Blood and Transplant and Health Protection Agency Epidemiology Unit. Infected donors are classified as having acute or chronic hepatitis B virus (HBV) by a clinician; their demographic characteristics were described. The prevalence (by acute or chronic HBV status, ethnicity, and geography) and incidence of infection were calculated between 1996 and 2008. The residual risk was calculated for four periods using a modification of the incidence and window period model; the effects of modifying variables were investigated. RESULTS: Most infections (1047/1155) detected were chronic and seen in new donors. People with acute infections were more likely to be white and/or born in Western Europe. Prevalence was highest in donors from minority ethnic communities and in London. Incidence in repeat donors has halved in recent years. The estimated frequency of an infectious donation being missed was 1.37 per million donations (2006-2008), the lowest since surveillance began or three per year. CONCLUSION: Many HBV infections in England and Wales were detected among new donors, who had chronic infection and were born overseas. The residual risk of infection declined over the 13 study years, but is still higher for HBV than other viral infections for which testing is undertaken.

Hepatitis C and B testing in English prisons is low but increasing.

BACKGROUND: Prisons are important settings for blood-borne virus control because of the high prevalence of hepatitis C and B viral infections (HCV and HBV), and behaviours associated with transmission among prisoners. METHODS: Data from sentinel laboratories in England were used to identify testing for hepatitis C (anti-HCV) and hepatitis B [hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antigen (HBc)] among male and female prisoners between 2005 and 2008. RESULTS: Between 2005 and 2008, 10 723 prisoners from 39 prisons in England were tested for anti-HCV, anti-HBc and/or HBsAg. Overall, 24.2% prisoners tested positive for anti-HCV. Anti-HCV testing increased 47% over 4 years (P < 0.001), whilst the proportion testing positive decreased significantly from 26% in 2005 to 23% in 2008 (χ(2)= 10.0, df = 3, P = 0.030). In total, 13.9% people tested positive for anti-HBc. Of 5151 people tested for anti-HBc, 4433 were also tested for HBsAg; of these 2.4% were HBsAg positive. HBsAg testing increased 35% between 2005 and 2008, with no significant change in the proportion testing positive. Between 2005 and 2008, 2.4% (CI: 2.32-2.43%) of the prison population (24 prisons) were estimated to have been tested for anti-HCV. CONCLUSIONS: Although hepatitis testing has increased, only a small proportion of the prison population were tested. More testing is required to identify infected prisoners and refer them for appropriate treatment.

Hepatitis C testing in sexual health services in England, 2002-7: results from sentinel surveillance.

OBJECTIVES: To describe testing for hepatitis C virus (HCV) in sexual health services in England between 2002 and 2007, using data from a sentinel surveillance study of hepatitis testing. METHODS: Data on all anti-HCV tests carried out between 2002 and 2007 were collected from 20 participating laboratories. Test requests originating in sexual health services were identified, allowing analysis of the demographic and clinical characteristics of individuals tested in this setting. KC60 statutory returns data were used to estimate the proportion of new genitourinary medicine clinic attendees tested for hepatitis C each year. RESULTS: 90 424 individuals were tested for anti-HCV in 100 sexual health clinics; 3.2% (n=2858) were found to be positive. Multivariable analysis showed anti-HCV status to be associated with male sex and a reported history of injecting drug use. In those clinics for which data on trends were available, testing for anti-HCV increased over the study period and the percentage testing positive decreased. KC60 data suggested that most clinics tested less than 20% of new patients for anti-HCV, although the proportion of patients tested increased over time. CONCLUSIONS: Sexual health services have become increasingly important locations for hepatitis C testing in England, although the proportion of patients testing positive is low compared with other settings. We suggest that testing in this setting could be better targeted to those most at risk of infection by thorough investigation of risk factors among service users.

Monitoring HIV testing in diverse healthcare settings: results from a sentinel surveillance pilot study.

OBJECTIVES: To assess the feasibility and utility of sentinel laboratory surveillance of HIV testing as a tool for understanding patterns and trends in HIV testing in a range of healthcare services. METHODS: Data on all anti-HIV antibody tests carried out by the Leeds Teaching Hospital Trust laboratory over a 12-month period were collated and analysed by demographic information and place of test. Individuals who tested positive were matched to the national database of HIV diagnoses to identify the proportion newly diagnosed with HIV. RESULTS: 41,013 individuals over 1 year of age were tested at least once for HIV during the study period, of whom 0.8% (n=312) were positive. The majority of individuals (77%) were tested in a genitourinary medicine (GUM) clinic or as part of antenatal care, while routine testing of people undergoing haemodialysis, fertility treatment or occupational health screening accounted for a further 13% of those tested. Few individuals (<4%) were tested in general practice. Of the 312 people testing positive, 286 could be matched to the HIV national database and 173/286 (60%) were identified as newly diagnosed. CONCLUSIONS: Little HIV testing is currently performed outside GUM and antenatal settings. Monitoring of HIV testing is essential given new guidelines recommending the expansion of testing in a wide range of settings. Sentinel laboratory surveillance can provide useful demographic data on people tested for HIV and can assess trends in testing over time. Data on HIV testing could be incorporated into existing hepatitis sentinel surveillance, allowing rapid scale-up of this surveillance scheme with minimal effort.

Can current national surveillance systems in England and Wales monitor sexual transmission of hepatitis C among HIV-infected men who have sex with men?

BACKGROUND: Recent reports suggest an increase in sexually-transmitted hepatitis C infection among HIV-infected men who have sex with men (MSM) in European cities. We investigated whether current national surveillance systems in England and Wales (E&W) are able to monitor sexual transmission of hepatitis C infection among HIV-infected MSM. METHODS: Routine laboratory reports of hepatitis C diagnoses and data from sentinel hepatitis C testing surveillance were matched to HIV diagnosis reports to determine: (i) the number of MSM diagnosed with HIV and hepatitis C (1996-2003); (ii) the number of HIV-diagnosed MSM tested for hepatitis C and found to be positive at sentinel sites (2003). RESULTS: (i) Between 1996-2003, 38,027 hepatitis C diagnoses were reported; 25,938 (68%) were eligible for matching with HIV diagnoses. Thirty-one men (four in London) had both a HIV and hepatitis C diagnosis where the only risk was sex with another man. Numbers of "co-diagnosed" MSM increased from 0 in 1996 to 14 in 2003. The majority of MSM (22/31) tested hepatitis C positive after HIV diagnosis. (ii) Of 78,058 test results from sentinel hepatitis C testing sites in 2003, 67,712 (87%) were eligible for matching with HIV diagnoses. We identified 242 HIV-diagnosed MSM who did not inject drugs who tested for hepatitis C in 2003; 11 (4.5%) tested hepatitis C positive (95% CI: 2.3%-8.0%). Applying this percentage to all MSM seen for HIV-related care in E&W in 2003, an estimated 680 MSM living with diagnosed HIV would have tested positive for sexually-transmitted hepatitis C (95% CI: 346-1208). CONCLUSION: Matching routine laboratory reports of hepatitis C diagnoses with HIV diagnoses only identified 31 HIV infected MSM with sexually-transmitted hepatitis C infection. Clinical studies suggest that this is an underestimate. On the other hand, matching sentinel surveillance reports with HIV diagnoses revealed that in E&W in 2003 nearly 5% of HIV-diagnosed MSM tested hepatitis C positive where the only risk was sex with another man. Reports of sexually-transmitted hepatitis C infection were not confined to London. Enhanced surveillance is needed to monitor sexually-transmitted hepatitis C among HIV-infected MSM in E&W.

Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment.

OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS: After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION: Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.

Serious hazards of transfusion: a decade of hemovigilance in the UK.

The Serious Hazards of Transfusion (SHOT) scheme is a UK-wide, independent, professionally led hemovigilance system focused on learning from adverse events. SHOT was established in 1996 as a confidential reporting system for significant transfusion-related events, building an evidence base to support blood safety policy decisions, clinical guidelines, clinician education, and improvements in transfusion practice. Recommendations are formulated by an independent steering group drawn from medical royal colleges and professional bodies. Ten years after its inception, SHOT has analyzed 2630 transfusion safety events, published 8 annual reports with recommendations, and presented data nationally and internationally. These recommendations have underpinned key initiatives, in particular the UK Department of Health "Better Blood Transfusion" strategy. SHOT has encouraged open reporting of adverse events and "near-misses" in a supportive, learning culture, vigilance in hospital transfusion practice, and evaluation of information technology to support this process. The importance of education and training has been emphasized. Detailed analysis of events has identified weaknesses in the transfusion chain. A collaborative initiative between SHOT, the Chief Medical Officer for England's National Blood Transfusion Committee, and the National Patient Safety Agency aims to reduce ABO-incompatible transfusions by improving bedside practice. Cumulative SHOT data have documented the decline in transfusion-related graft vs host disease after implementation of leucodepletion and have highlighted transfusion-related acute lung injury and bacterial contamination of platelets as important causes of death and morbidity. The UK blood services have developed strategies to reduce these risks. Future SHOT data will evaluate the success of these and other blood safety improvements.

Seroprevalence of low rubella IgG antibody levels among antenatal women in England tested by NHS Blood and Transplant: 2004-2009. Is rubella susceptibility increasing?

Antenatal testing for rubella susceptibility is undertaken to identify women at risk of exposure during pregnancy and to target post-partum immunisation. To evaluate the current rubella control programme and to inform future planning, data on anti-rubella IgG levels in antenatal sera tested by NHS Blood and Transplant were reviewed. The frequency of women with anti-rubella IgG <10 IU/mL increased by 60% over the 6-year study period and rates were significantly higher among younger women. The screening cut-off level of 10 IU/mL, used to identify women at risk, was determined in 1995 on the basis of early epidemiological studies and the correlates for protection now need review to support the appropriate management of a young immunised antenatal population. Ethnic minorities continue to be at increased risk of rubella susceptibility reinforcing the need to identify and opportunistically immunise these women.

Surveillance of transfusion-transmissible infections comparison of systems in five developed countries.

Most industrialized countries maintain surveillance programs for monitoring transmissible infection in blood donations, revising approaches to methodology and risk assessment as new threats emerge. A comparison of programs in the United States, Canada, France, the UK, and Australia indicates that they have similar function, although the structure of blood programs vary as does the extent and nature of formal ties with public health. The emergence of HIV in the late 1970s and early 1980s was key in recognizing that surveillance systems specific to blood transfusion were essential. Hence, most industrialized countries monitor transfusion-transmissible infections in donors and evaluate the impact of new testing and of predonation screening strategies. Emerging infections since HIV have had different transmission pathways and challenged blood programs to draw upon resources for a rapid and effective response, with recognition that the original focus on sexual/drug-related risk of HIV and hepatitis was inadequate. The focus of surveillance programs on new and emerging pathogens fulfills a key role in risk assessment and policy formulation. The precise nature of such activities varies by country because of the structure of the blood programs and surveillance systems, the strategic focus of the blood programs, and the epidemiology of disease in each country.

Planning for the healthcare burden of hepatitis C infection: Hepatitis C genotypes identified in England, 2002-2007.

BACKGROUND: Identification of HCV genotype is a prerequisite for anti-viral treatment in England. Treatment length and sustained virological response rates vary by genotype. Therefore knowledge of circulating HCV genotypes is important for health-care providers. OBJECTIVES: To describe the HCV genotypes identified in English laboratories and to investigate changes over time; sub-analysis of young adults (15-24 years) to provide information on recently circulating genotypes. STUDY DESIGN: Data from the national reference laboratory and 19 English laboratories participating in the sentinel surveillance of hepatitis testing study were analysed. Multinomial regression was used to investigate trends in genotypes identified between 2002 and 2007. RESULTS: HCV genotypes were available for 18,031 individuals. The majority (89%) of people were genotypes 1 and 3; 3a was the single largest subtype. Half of people born between 1960 and 1989 were genotype 3a and the majority of South Asian people were genotype 3a. People born pre-1940 were nine times more likely to have genotype 1b than 3a. The proportion of 1b infections, relative to 3a, declined over time, but, after adjusting for birth cohort, this effect disappeared. There was no evidence of a relative change in 1a infections. CONCLUSIONS: This is the largest study of genotypes identified in England to date. Changes in genotypes over time were due to decreased genotyping of older individuals. As the population ages, the proportion of more difficult to treat genotypes may decline, leading to possible cost-savings for health-care providers, with a higher chance of achieving sustained virological response.