Has Chlamydia trachomatis prevalence in young women in England, Scotland and Wales changed? Evidence from national probability surveys.

We evaluate the utility of the National Surveys of Attitudes and Sexual Lifestyles (Natsal) undertaken in 2000 and 2010, before and after the introduction of the National Chlamydia Screening Programme, as an evidence source for estimating the change in prevalence of Chlamydia trachomatis (CT) in England, Scotland and Wales. Both the 2000 and 2010 surveys tested urine samples for CT by Nucleic Acid Amplification Tests (NAATs). We examined the sources of uncertainty in estimates of CT prevalence change, including sample size and adjustments for test sensitivity and specificity, survey non-response and informative non-response. In 2000, the unadjusted CT prevalence was 4.22% in women aged 18-24 years; in 2010, CT prevalence was 3.92%, a non-significant absolute difference of 0.30 percentage points (95% credible interval -2.8 to 2.0). In addition to uncertainty due to small sample size, estimates were sensitive to specificity, survey non-response or informative non-response, such that plausible changes in any one of these would be enough to either reverse or double any likely change in prevalence. Alternative ways of monitoring changes in CT incidence and prevalence over time are discussed.

Human papillomavirus DNA in men who have sex with men: type-specific prevalence, risk factors and implications for vaccination strategies.

BACKGROUND: Human papillomavirus (HPV) vaccination of girls will have relatively little effect on HPV-related disease in men who have sex with men (MSM). We determined HPV prevalence and risk factors in MSM to inform the potential effectiveness of vaccinating MSM. METHODS: Cross-sectional study of 522 MSM aged 18-40 attending a London sexual health clinic who completed a computer-assisted self-interview. Urine and two swabs (anal and penile/scrotal/perianal) were collected and tested using an in-house Luminex-based HPV genotyping system. RESULTS: Prevalence of DNA of the vaccine-preventable HPV types in ano-genital specimens of men was 87/511 (17.0%), 166/511 (32.5%) and 232/511 (45.4%) for the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine types, respectively. A total of 25.1% had one of the quadrivalent types, and 7.4% had 2+ types. Median age at first anal sex was 19 (IQR 17-23) and at first clinic attendance was 24 (IQR 20-27). The increase in the odds of any HPV infection per year of age was 4.7% (95% CI 1.2-8.4). CONCLUSIONS: On the basis of the current infection status, most MSM, even among a high-risk population attending a sexual health clinic, are not currently infected with the vaccine-type HPV. A targeted vaccination strategy for MSM in the UK could have substantial benefits.

Coverage of the English national human papillomavirus (HPV) immunisation programme among 12 to 17 year-old females by area-level deprivation score, England, 2008 to 2011.

The English national human papillomavirus (HPV) immunisation programme has offered vaccination to girls aged 12 years at the start of each school year since September 2008. A catch-up programme has offered vaccination to girls up to 18 years. Delivery is predominantly school-based, with some general practitioner (GP)-based immunisation. The relationship between HPV immunisation coverage and deprivation (index of multiple deprivation, IMD) was assessed by geographical area (N=151) for each school year offered the HPV vaccine between 2008 to 2011 using the Spearman's rank correlation coefficient, and compared to that for adequate cervical screening of women aged 25 to 49 years. Coverage at age 12 showed no significant association with IMD at the area-level (p=0.12). Within the catch-up years, there was some suggestion of higher deprivation being associated with lower coverage. This was not significant for girls offered immunisation under 16 years (in compulsory education) (p=0.09), but was more marked and statistically significant for older girls (p<0.0001). The proportion of women aged 25 to 49 years with an adequate cervical screen was negatively associated with deprivation (p<0.0001). School-based HPV immunisation delivery appears to be successfully reducing inequalities in cervical cancer control at area-level. However, the catch-up cohorts above the age of compulsory education may face increased inequality. Further investigation is needed into individual-level factors associated with coverage.

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

BACKGROUND: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. METHODS: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. RESULTS: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. CONCLUSIONS: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types.

Views and experiences of men who have sex with men on the ban on blood donation: a cross sectional survey with qualitative interviews.

OBJECTIVE: To explore compliance with the UK blood services' criterion that excludes men who have had penetrative sex with a man from donating blood, and to assess the possible effects of revising this policy. DESIGN: A random location, cross sectional survey followed by qualitative interviews. SETTING: Britain. PARTICIPANTS: 1028 of 32,373 men in the general population reporting any male sexual contact completed the survey. Additional questions were asked of a general population sample (n=3914). Thirty men who had had penetrative sex with a man participated in the qualitative interviews (19 who had complied with the blood services' exclusion criterion and 11 who had not complied). Main outcome measure Compliance with the blood services' lifetime exclusion criterion for men who have had penetrative sex with a man. RESULTS: 10.6% of men with experience of penetrative sex with a man reported having donated blood in Britain while ineligible under the exclusion criterion, and 2.5% had donated in the previous 12 months. Ineligible donation was less common among men who had had penetrative sex with a man recently (in previous 12 months) than among men for whom this last occurred longer ago. Reasons for non-compliance with the exclusion included self categorisation as low risk, discounting the sexual experience that barred donation, belief in the infallibility of blood screening, concerns about confidentiality, and misunderstanding or perceived inequity of the rule. Although blood donation was rarely viewed as a "right," potential donors were seen as entitled to a considered assessment of risk. A one year deferral since last male penetrative sex was considered by study participants to be generally feasible, equitable, and acceptable. CONCLUSIONS: A minority of men who have sex with men who are ineligible to donate blood under the current donor exclusion in Britain have nevertheless done so in the past 12 months. Many of the reasons identified for non-compliance seem amenable to intervention. A clearly rationalised and communicated one year donor deferral is likely to be welcomed by most men who have sex with men.

The impact of genital warts: loss of quality of life and cost of treatment in eight sexual health clinics in the UK.

OBJECTIVES: To estimate the loss of quality of life and cost of treatment associated with genital warts seen in sexual health clinics. METHODS: A cross-sectional questionnaire study and case note review of individuals with genital warts, carried out in eight sexual health clinics in England and Northern Ireland. Individuals with genital warts attending the participating clinics were invited to take part in the questionnaire study. 895 participants were recruited. A separate sample of 370 participants who had attended a participating clinic with a first visit for a first or recurrent episode of genital warts between April and June 2007 was included in the case note review. Quality of life was measured using the EQ-5D questionnaire and the cost of an episode of care was derived from the case note review. RESULTS: The weighted mean EQ-5D index score was 0.87 (95% CI 0.85 to 0.89). The weighted mean disutility was 0.056 (95% CI 0.038 to 0.074). The estimated mean loss of quality-adjusted life-years associated with an episode of genital warts was 0.018 (95% CI 0.0079 to 0.031), equivalent to 6.6 days of healthy life lost per episode. The weighted mean cost per episode of care was £94 (95% CI £84 to £104), not including the cost of a sexually transmitted infection screen. CONCLUSIONS: Genital warts have a substantial impact on the health service and the individual. This information can be utilised for economic evaluation of human papillomavirus vaccination.

A re-evaluation of the risk of transfusion-transmitted HIV prevented by the exclusion of men who have sex with men from blood donation in England and Wales, 2005-2007.

BACKGROUND AND OBJECTIVES One component of the rationale for lifetime exclusion of men who have sex with men (MSM) from blood donation in the UK is the probable reduction in the risk of transfusion-transmitted HIV; this exclusion has recently been questioned. MATERIALS AND METHODS Data about HIV in blood donors and MSM were analysed to estimate the risk of infectious donations entering the blood supply under different scenarios of donor selection criteria (and donor compliance) for MSM and a heterosexual group with increased risk of HIV. RESULTS In 2005-2007, a change from lifetime exclusion of MSM to 5-year deferral or no deferral increased the point estimate of HIV risk by between 0·4% and 7·4% depending on compliance with the deferral (range -4% to 15%) and 26·5% (range 18% to 43%) respectively. A change from a 12-month deferral of the high-risk heterosexual group to lifetime exclusion reduced the estimated risk by about 7·2% (range 6% to 9%). Each point estimate was within the probable range of risk under the current criteria. CONCLUSION If prevalence is the only factor affected by a reduced deferral, then the increased risk of HIV is probably negligible. However, the impact of a change depends on compliance; if this stays the same or worsens, the risk is expected to increase because of more incident infections in MSM who donate blood. The risk of transfusion-transmitted HIV could probably be reduced further by improving compliance with any exclusion, particularly after recent risk behaviours.

Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England.

BACKGROUND: Knowledge of the prevalence of type-specific human papillomavirus (HPV) infections is necessary to predict the expected, and to monitor the actual, impact of HPV immunisation and to design effective screening strategies for vaccinated populations. METHODS: Residual specimens of cervical cytology (N=4719), CIN3/CGIN and cervical cancer biopsies (N=1515) were obtained from sites throughout England, anonymised and tested for HPV DNA using the Linear Array typing system (Roche). RESULTS: The prevalence of HPV 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous cell carcinomas, 82% in adeno/adenosquamous carcinomas and 63% and 91% in CIN3 and CGIN, respectively. Of all HR HPV-infected women undergoing cytology, non-vaccine HPV types only were found in over 60% of those with mild dyskaryosis or below, and in <20% of those with cancer. In women of all ages undergoing screening, HR HPV prevalence was 16% and HPV 16 and/or 18 prevalence was 5%. CONCLUSION: Pre-immunisation, high-grade cervical disease in England was predominantly associated with HPV 16 and/or 18, which promises a high impact from HPV immunisation in due course. Second-generation vaccines and screening strategies need to consider the best ways to detect and prevent disease due to the remaining HR HPV types.

Prevalence of human papillomavirus antibodies in young female subjects in England.

Sera from 1483 female subjects in England aged 10-29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0-12.3) for human papillomavirus (HPV) 6, 2.7% (1.8-3.6) for HPV 11, 11.9% (10.2-13.6) for HPV 16, 4.7% (3.5-5.8) for HPV 18, and 20.7% (18.6-22.7) for any of the four types.

Lung fibre burden in lung cancer cases employed in the rock and slag wool industry.

OBJECTIVES: To evaluate the relationship between estimated exposure to man-made vitreous fibres (MMVF) and to asbestos fibres and their concentration in the lung tissue of lung cancer cases amongst MMVF production workers. METHODS: Retrospective retrieval of available lung tissue specimens was conducted following a case-control study that assessed estimated occupational exposures of MMVF workers. Fibre recovery and analysis by transmission electron microscopy (TEM) were conducted to determine fibre type, fibre dimension and numbers per gram of dry lung tissue. For cases with detailed exposure data, geometric mean (GM) concentrations were compared across the exposure categories, and regression models were used to investigate the relationship between the lung fibres and the variables of estimated exposure, with and without additional variables that may affect fibre retention. RESULTS: A total of 24 samples from 17 cases of lung cancer were available for analysis: MMVF were detected in all cases. Asbestos fibres were detected in 16. No difference or trend in GM MMVF concentration was observed across the estimated exposure categories. Odds ratio (OR) for MMVF g(-1) dry lung was 0.5 (95% confidence interval: 0.1-2.4) for the second, and 3.5 (0.6-18.9) for the third quartile of index of average exposure to MMVF in industry, compared with the first (lowest exposed) quartile (no cases in the highest quartile). CONCLUSIONS: No observable relationship existed between estimated exposure and directly-measured lung fibres among this sample of cases. Retrospective specimen collection, intra-individual variability in fibre concentration, effect of unknown factors on fibre retention and small sample size militated against this study providing evidence for or against a relationship between estimated exposure and lung fibre concentrations.

Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the blood supply in the United Kingdom, 1996 to 2003.

Several new tests have been recently introduced by the United Kingdom Blood Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply during 1996-2003 has been estimated. These years span the introduction of nucleic acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for HIV. The frequency of an infectious donation entering the blood supply due to i) the window period, ii) assay failures and iii) human and technical errors in testing and processing, was estimated. The window period risk was estimated using the incidence of infection in donors and the length of the window period for tests in use, with an adjustment for atypical inter-donation intervals in seroconverting donors. The estimated frequency of infectious donations entering the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV, HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted HBV, HCV and HIV infection in the UK has been lowered by several improvements to donation testing, although the absolute reduction in risk has been small. Vigilance for errors and the affects of donor selection may be as or more important than further reductions to window periods of tests for improving blood safety with respect to HBV, HCV and HIV.

Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the blood supply in the United Kingdom, 1996 to 2003.

Several new tests have been recently introduced by the United Kingdom Blood Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply during 1996-2003 has been estimated. These years span the introduction of nucleic acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for HIV. The frequency of an infectious donation entering the blood supply due to i) the window period, ii) assay failures and iii) human and technical errors in testing and processing, was estimated. The window period risk was estimated using the incidence of infection in donors and the length of the window period for tests in use, with an adjustment for atypical inter-donation intervals in seroconverting donors. The estimated frequency of infectious donations entering the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV, HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted HBV, HCV and HIV infection in the UK has been lowered by several improvements to donation testing, although the absolute reduction in risk has been small. Vigilance for errors and the affects of donor selection may be as or more important than further reductions to window periods of tests for improving blood safety with respect to HBV, HCV and HIV.

Hepatitis B incidence among South Asian children in England and Wales: implications for immunisation policy.

The incidence of acute hepatitis B virus (HBV) infection is higher among South Asian than among non-South Asian UK residents, and infections in South Asians occur more often during childhood. The UK's immunisation policy should be changed to protect ethnic minority children against HBV infection.

Evaluation of the de-selection of men who have had sex with men from blood donation in England.

BACKGROUND AND OBJECTIVES: The Blood Services of the UK permanently de-select men who have had sex with men (MSM) from donating blood. The rationale for this has been questioned. This article attempts to evaluate whether this selection criterion does contribute to blood safety. MATERIALS AND METHODS: Data about transfusion-transmissible infections, in particular about human immunodeficiency virus (HIV) infection, were used to evaluate whether de-selection of MSM meets the aims of donor selection. Models were constructed to estimate the risk of HIV-infectious donations entering the blood supply should this criterion be changed. RESULTS: Many assumptions were required to generate estimates of the risk of HIV infection entering the blood supply. The accuracy of the estimates is therefore uncertain and the probable ranges around the estimates were wide. However, by using the most probable assumptions, our models suggested that de-selection of MSM for 12 months since the last sexual contact, or complete removal of this selection criterion, would be expected to increase the risk of HIV-infectious donations entering the blood supply in England by approximately 60% (from the current risk of 0.45 per year to 0.75 per year) and 500% (to 2.5 per year), respectively. The increase in numbers of non-infected donations would be relatively small--less than 2% of donations. The probability of a relatively high frequency of other sexually transmissible blood-borne infections also currently favours maintaining permanent de-selection of MSM, irrespective of the risk of HIV-infectious donations. Current compliance with this selection criteria was estimated to be 95%. CONCLUSIONS: Based on current knowledge, accepting blood donations from MSM would probably increase the risk of transfusion-transmission of HIV and of other blood-borne infections. Good compliance with this criterion has contributed greatly to the safety of blood transfusions in England. Better communication about donor selection, to maintain and improve compliance with this and other selection criteria, is recommended. Other risk groups are gaining in relative importance for the risk of transfusion-transmitted HIV infection, and ongoing evaluation of all donor-selection criteria is also recommended.

Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993-2001.

BACKGROUND AND OBJECTIVES: The frequency of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infectious donations entering the blood supply in England is too low to monitor using observational studies. The expected frequency of infectious donations can be estimated and these estimates may be used to contribute to monitoring of blood safety and used in the design of strategies to decrease the risk of transfusion-transmitted infections. MATERIALS AND METHODS: The prevalence and incidence of hepatitis B surface antigen (HBsAg), and antibodies to HCV and HIV (anti-HCV and anti-HIV, respectively) in donors in England, between 1993 and 2001, were used together with data about the length of negative 'window-periods' of current assays for each of these markers and data about test performance, to estimate the number of infectious donations that enter the blood supply. The risks were calculated separately for donations from new donors and from repeat donors, and for the three time periods 1993-95, 1996-98 and 1999-01. RESULTS: The estimated frequency of infectious donations entering the blood supply in England, between 1993 and 2001 was 1 in 260,000 for HBV and 1 in 8 million for HIV. For HCV, the frequency of infectious donations was 1 in 520,000 during 1993-98 and fell to 1 in 30 million during 1999-2001 when all donations were tested for HCV RNA. The frequency of HBV- and HCV-infectious donations entering the blood supply fell over these 9 years: the frequency of HIV-infectious donations remained essentially unchanged. The risk from donations from new donors was found to be approximately sevenfold higher than the risk from donations from repeat donors. CONCLUSIONS: The risks of HBV-, HCV- or HIV-infectious donations entering the blood supply in England are very low, and have decreased since 1993. Although the accuracy of these estimates is imperfect, mainly owing to uncertainty in some assumptions and to small numbers of infections, they provide some quantification of the risk of HBV, HCV or HIV transmission by transfusion, and allow comparison of the magnitude of these risks for each infection and over time. The methods we have used have been developed and improved from previously published methods.

Transfusion-transmitted hepatitis B virus infection in the UK: a small and moving target.

BACKGROUND AND OBJECTIVES: Transfusion-transmitted hepatitis B virus (TT-HBV) infections, when analysed in detail provide information about the nature and relative frequency of the sources of infectious donations. These cases are therefore used to inform blood safety strategies. This study updates previous reviews of the causes of TT-HBV in order to determine whether a change may have occurred in recent years. MATERIALS AND METHODS: Cases of TT-HBV reported during 1998-2001 were reviewed and the nature of the infectious donations described. These cases were compared to a previously published case series reported during 1991-97. RESULTS: Six cases of TT-HBV have been reported in the UK between 1998 and 2001. All were the result of infectious donations collected from donors with acute HBV infection. This is in contrast to the series reported during 1991-97 when only three of 14 similar cases were caused by acute infections in donors, with the majority of incidents being the result of chronic infection in donors. CONCLUSIONS: There appears to have been a change in the relative importance of acute and chronic HBV infection in blood donors in causing TT-HBV infections. Improvements in the sensitivity of HBsAg assays and/or a decrease in the prevalence of chronic HBV infection in blood donors could explain this observation. This change may have implications for strategies to reduce the risk of TT-HBV infection.

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.

The HCV National Register: towards informing the natural history of hepatitis C infection in the UK.

The aim of this paper is to describe the development of a national hepatitis C register and the completeness of the data it contains. This is a descriptive report of the structure and function of the register, including case definitions, registration and follow-up procedures, and methods used to maximize data quality and to obtain comparative data sources. The register contains data on HCV-infected individuals who acquired their infections on a known date and by a known route; to date all are transfusion recipients identified during the UK lookback exercise, who tested positive or indeterminate for anti-HCV after receiving 'infected' blood issued before the introduction of routine testing of the blood supply for anti-HCV. By 31 December 1999, 871 (87%) of 996 eligible transfusion recipients had been registered, and 984 (99%) flagged in the NHS Central Registers. Registered patients had been infected for an average of 11.1 years (SEM 0.1); around half were being cared for by clinicians with a specialist interest in liver disease. Except for the information on tobacco use, current alcohol use, and hepatitis B status, data were more than 80% complete, and for most variables, more than 90% complete. The consistency of data abstraction was found to be 98% (SEM 0.5). In conclusion, the Register contains high quality anonymised data on one of the largest cohorts of individuals with HCV infections acquired on a known date and by a known route. It could serve as a model for other chronic disease registers; developers may find the structure, design, and methodological issues addressed useful.