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Changes in hepatitis C virus (HCV) prevalence from 1992 to 2006 were examined by using 24,311 records from unlinked anonymous surveillance of injecting drug users in England and Wales. Bayesian logistic regression was used to estimate annual prevalence, accounting for changing recruitment patterns (age, gender, injecting duration, geographic region, interactions) and the sensitivity and specificity of different oral fluid testing devices. After controlling for these differences, the authors found that the adjusted HCV prevalence decreased from 70% (95% credible interval: 62, 78) in 1992 to 47% (95% credible interval: 43, 51) in 1998 before rising again to 53% (95% credible interval: 48, 58) in 2006. Women injecting drug users had a higher HCV risk than did men (odds ratio = 1.50, 95% credible interval: 1.31, 1.73). Two regions (London and North West) had a markedly higher HCV prevalence than did the rest of England and Wales. Among individuals who had injected for less than 1 year, the adjusted HCV prevalence in 2006 was higher than that in 1992 (28% vs. 19%, respectively). HCV infection can be prevented. The public health challenge in England and Wales is to increase action in order to regain a downward trend in HCV risk and the benefit that has been lost since 1998. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study sought to establish the prevalence of hepatitis C antibodies (anti-HCV) and hepatitis B antibodies (anti-HBc) among injection drug users in England and Wales. METHODS: A voluntary cross-sectional survey collected oral fluid samples and behavioral information; 2203 injectors were recruited through drug agencies, and 758 were recruited in the community. RESULTS: Prevalence was 30% for anti-HCV, 21% for anti-HBc, and 0.9% for HIV antibodies. Anti-HCV prevalence rates were significantly greater among those with longer injecting careers, those in older age groups, those residing in London, those recruited in drug agencies, those positive for anti-HBc, and those with a previous voluntary HIV test. CONCLUSIONS: Anti-HCV prevalence rates among injectors in England and Wales, where comprehensive harm reduction programs exist, are lower than rates in other industrialized countries. [ABSTRACT FROM AUTHOR]

Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.

Sustaining the impact of hepatitis B virus (HBV) vaccination on incidence and prevalence of HBV infection requires increasing and maintaining the uptake of vaccine among those at risk. In recent years, the level of vaccine uptake among people who inject drugs (PWID) in the UK has levelled-off. Data (2015-2016) from the national unlinked-anonymous monitoring survey of PWID, an annual survey that collects data from PWID across England, Wales and Northern Ireland, were used to examine HBV vaccine uptake. Data from participants who had injected drugs during the previous year were used to investigate sources of hepatitis B vaccine doses as well as factors associated with vaccine uptake. Among the 3175 anti-HBc-negative participants, 3138 (99%) reported their vaccination status; 23% (714) reported no vaccine uptake. Among those not vaccinated, 447 (63%) reported being sexually active and 116 (16%) reported sharing needles and syringes. Majority of those not vaccinated reported accessing services in the previous year that could have provided hepatitis B vaccine doses. These missed opportunities for vaccinating of PWID indicate a need for additional targeted interventions.

BackgroundMonitoring hepatitis C virus (HCV) incidence is important for assessing intervention impact. Longitudinal studies of people who inject drugs (PWID), using repeated biological tests, are costly; alternatively, incidence can be estimated using biological markers of recent infection in cross-sectional studies.AimWe aimed to compare incidence estimates obtained from two different biological markers of recent infection in a cross-sectional study to inform monitoring approaches for HCV elimination strategies.MethodSamples from an unlinked anonymous bio-behavioural survey of PWID were tested for two recent infection markers: HCV RNA with anti-HCV negative ('RNA') and low-avidity anti-HCV with HCV RNA present ('avidity'). These two markers were used separately and in combination to estimate HCV incidence.ResultsBetween 2011 and 2013, 2,816 anti-HIV-negative PWID (25% female) who had injected during the preceding year were either HCV-negative or had one of the two markers of recent infection: 57 (2.0%) had the RNA marker and 90 (3.2%) the avidity marker. The two markers had similar distributions of risk and demographic factors. Pooled estimated incidence was 12.3 per 100 person-years (pyrs) (95% credible interval: 8.8-17.0) and not significantly different to avidity-only (p = 0.865) and RNA-only (p = 0.691) estimates. However, the RNA marker is limited by its short duration before anti-HCV seroconversion and the avidity marker by uncertainty around its duration.ConclusionBoth markers have utility in monitoring HCV incidence among PWID. When HCV transmission is high, one marker may provide an accurate estimate of incidence; when it is low or decreasing, a combination may be required.

Background: Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing., Methods: Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays., Results: Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting., Conclusions: A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay.

Introduction: People injecting image and performance enhancing drugs (IPEDs) have traditionally not been perceived as being at high risk of hepatitis C virus (HCV) infection. However, recent studies indicate the HCV antibody (anti-HCV) prevalence in this group is 10-times that in the general population. HCV testing uptake and undiagnosed infections are examined using data from a voluntary unlinked-anonymous survey., Method: People injecting IPEDs across England and Wales completed a short bio-behavioural survey (2012-15). Anti-HCV status and self-reports of HCV testing were used in the analysis., Results: The participants median age was 31 years, 98% were men, 14% had also injected psychoactive drugs and the anti-HCV prevalence was 4.8% (N=564). Among those who had never injected psychoactive drugs the anti-HCV prevalence was 1.4%; among those who had recently injected psychoactive drugs (preceding 12 months) prevalence was 39% and among those who had done this previously 14% (p<0.001). Overall, 37% had been tested for HCV: among those who had recently injected psychoactive drugs 78% had been tested, as had 56% of those who had injected psychoactive drugs previously; 33% of those never injecting psychoactive drugs were tested (p<0.001). Overall, 44% of those with anti-HCV were aware of this; however, only 14% of those who had never injected psychoactive drugs were aware., Conclusions: One-in-twenty people who inject IPEDs have anti-HCV. HCV infections among those who had never injected psychoactive drugs were mostly undiagnosed, though this group had a lower prevalence. Targeted HCV testing interventions are also needed for those injecting IPEDs., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: While people who inject drugs (PWID) typically use peripheral veins, some inject into their central veins, including the femoral and jugular veins. Injection into the jugular vein can have serious adverse health consequences, including jugular vein thrombosis, deep neck infections, pneumothorax, endocarditis and sepsis. This study examined the prevalence of, and factors associated with, jugular vein injection among a large sample of PWID in the United Kingdom., Method: Unlinked anonymous surveys (2011-14) recruited PWID from agencies providing services to this population. Self-reported demographic and injection-related data were collected from consenting respondents using a brief questionnaire and dried blood spot samples were tested for exposure to HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). Univariate and multivariable logistic regression were used to examine factors associated with jugular vein injection., Results: Among 5261 PWID, one third had injected into a central vein in the previous 28 days, including 6% (n=339) who had injected into their jugular vein and 1% (n=52) who had used this site exclusively for recent injections. Factors independently associated with recent jugular vein injection in multivariable analysis included female gender, a lifetime history of imprisonment, sharing needles and syringes, poly-drug injection and injection into multiple body sites. Jugular vein injection was also associated with experiencing injection-related injuries, although no associations were identified with respect to exposure to blood borne viral infections., Conclusion: A significant minority of PWID inject into the jugular vein in the United Kingdom. Public health responses should investigate ways to support and promote good injection site management in order to minimise vascular damage and reduce problems with peripheral venous access. Women who inject drugs, PWID with a history of imprisonment and those people who are experiencing early signs of injection-related skin and soft tissue injuries are priority sub-populations for interventions., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: Infection risks among people who inject drugs (PWID) are widely recognized, but few studies have focused on image and performance enhancing drugs (IPEDs). Globally, concern about IPED injection has increased and, in the United Kingdom, IPED injectors have become the largest group using Needle and Syringe Programmes. Blood-borne virus prevalence trends among IPED injectors are explored., Method: Data from 2 surveys of IPED injectors (2010-2011; 2012-2013) and the national bio-behavioral surveillance system for PWID (1992-1997; 1998-2003; 2004-2009) were merged. Psychoactive drug injectors and women were excluded. Logistic regression analyses explored temporal changes., Results: Between 1992 and 2009, median age increased from 25 to 29 years (N = 1296), years injecting from 2 to 4. There were 53 men who had sex with men (MSM). Overall, 0.93% had HIV, 4.4% ever had hepatitis B (HBV), and 3.9% hepatitis C (HCV, from 1998, N = 1083). In multivariable analyses, HIV increased in 2004-2009 [adjusted odds ratio (AOR) = 10 (95% confidence interval (CI): 0.94 to 106) vs. 1992-2003], and remained elevated (AOR = 4.12, 95% CI: 0.31 to 54, 2012-2013); HBV also increased in 2004-2009 (AOR = 3.98, 95% CI: 1.59 to 9.97). HCV prevalence increase was only borderline significant (AOR = 2.47, 95% CI: 0.90 to 6.77, 2010-2011). HIV and HBV were associated with MSM and HCV with sharing needles/syringes. Uptake of diagnostic testing for HIV and HCV, and HBV vaccination increased (to 43%, 32% and 44% respectively). Condom use was consistently poor; needle/syringe sharing occurred., Conclusion: Blood-borne virus prevalences among IPED injectors have increased and for HIV, is now similar to that among psychoactive drug injectors. Targeted interventions to reduce risks are indicated.

Background: The extent of intentional or accidental subcutaneous and intramuscular injections and the factors associated with these have rarely been studied among people who inject drugs, yet these may play an important role in the acquisition bacterial infections. This study describes the extent of these, and in particular the factors and harms associated with accidental subcutaneous and intramuscular injections (i.e. 'missed hits')., Methods: People who inject drugs were recruited using respondent driven sampling. Weighted data was examined using bivariate analyses and logistic regression., Results: The participants mean age was 33 years (31% aged under 30-years), 28% were women, and the mean time since first injection was 12 years (N=329). During the preceding three months, 97% had injected heroin, 71% crack-cocaine, and 16% amphetamines; 36% injected daily. Overall, 99% (325) reported that they aimed to inject intravenously; only three aimed to inject subcutaneously and one intramuscularly. Of those that aimed to inject intravenously, 56% (181) reported ever missing a vein (for 51 this occurred more than four times month on average). Factors associated with 'missed hits' suggested that these were the consequence of poor vascular access, injection technique and/or hygiene. 'Missed hits' were twice as common among those reporting sores/open wounds, abscesses, or redness, swelling and tenderness at injection sites., Conclusion: Intentional subcutaneous and intramuscular injections are rare in this sample. 'Missed hits' are common and appear to be associated with poor injection practice. Interventions are required to reduce risk through improving injecting practice and hygiene., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Background: There have been increasing concerns about injection into the femoral vein - groin injecting - among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined., Method: Participants were recruited using respondent driven sampling (2006-2009). Weighted data was examined using bivariate analyses and logistic regression., Results: The mean age was 32 years; 25% were women (N=855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: "Can't get a vein elsewhere" (68%); "It is discreet" (18%); and "It is quicker" (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these "It is discreet" was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia., Conclusions: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice., (Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.)

Monitoring infections and risk in people who inject drugs (PWID) is important for informing public health responses. In 2011, a novel hepatitis C antibody (anti-HCV) avidity-testing algorithm to identify samples compatible with recent primary infection was introduced into a national surveillance survey. PWID are recruited annually, through >60 needle-and-syringe programmes and prescribing services. Of the 980 individuals that could have been at risk of HCV infection, there were 20 (2%) samples that were compatible with recent primary infection. These were more common among: those imprisoned ⩾5 times [8/213; adjusted odds ratio (aOR) 8·7, 95% confidence interval (CI) 2·04-37·03]; women (8/230; aOR 3·8, 95% CI 1·41-10·38); and those ever-infected with hepatitis B (5/56; aOR 6·25, 95% CI 2·12-18·43). This study is the first to apply this algorithm and to examine the risk factors associated with recently acquired HCV infection in a national sample of PWID in the UK. These findings highlight underlying risks and suggest targeted interventions are needed.

To determine uptake of home sampling kit (HSK) for STI/HIV compared to clinic-based testing, whether the availability of HSK would increase STI testing rates amongst HIV infected MSM, and those attending a community-based HIV testing clinic compared to historical control. Prospective observational study in three facilities providing STI/HIV testing services in Brighton, UK was conducted. Adult MSM attending/contacting a GUM clinic requesting an STI screen (group 1), HIV infected MSM attending routine outpatient clinic (group 2), and MSM attending a community-based rapid HIV testing service (group 3) were eligible. Participants were required to have no symptomatology consistent with STI and known to be immune to hepatitis A and B (group 1). Eligible men were offered a HSK to obtain self-collected specimens as an alternative to routine testing. HSK uptake compared to conventional clinic-based STI/HIV testing in group 1, increase in STI testing rates due to availability of HSK compared to historical controls in group 2 and 3, and HSK return rates in all settings were calculated. Among the 128 eligible men in group 1, HSK acceptance was higher (62.5% (95% CI: 53.5-70.9)) compared to GUM clinic-based testing (37.5% (95% CI: 29.1-46.5)), (p = 0.0004). Two thirds of eligible MSM offered an HSK in all three groups accepted it, but HSK return rates varied (highest in group 1, 77.5%, lowest in group 3, 16%). HSK for HIV testing was acceptable to 81% of men in group 1. Compared to historical controls, availability of HSK increased the proportion of MSM testing for STIs in group 2 but not in group 3. HSK for STI/HIV offers an alternative to conventional clinic-based testing for MSM seeking STI screening. It significantly increases STI testing uptake in HIV infected MSM. HSK could be considered as an adjunct to clinic-based services to further improve STI/HIV testing in MSM.

People who inject drugs are vulnerable to infections and injuries at injection sites, but these have rarely been studied in those injecting image- and performance-enhancing drugs (IPEDs). This study examined the factors associated with reported symptoms of injection site infections and injuries in IPED injectors. Of the 366 male IPED injectors surveyed, 42% reported ever having redness, swelling and tenderness (36% in the preceding year), and 6·8% had ever had an abscess or open wound at an injection site. Having these symptoms was associated with a range of factors related to drug use and healthcare utilization. One sixth (17%) of those reporting redness, tenderness and swelling had ever sought treatment, as had the majority (76%) of those reporting an abscess, sore or open wound. Most common sources of advice were emergency clinics and General Practitioners. Interventions are needed to support access to appropriate injecting equipment and provide targeted harm reduction advice.

People who inject drugs (PWID) are vulnerable to infections and injuries at injection sites. The factors associated with reporting symptoms of these, seeking related advice, and hospital admission are examined. PWID were recruited in Birmingham, Bristol and Leeds using respondent-driven sampling (N = 855). During the preceding year, 48% reported having redness, swelling and tenderness (RST), 19% an abscess, and 10% an open wound at an injection site. Overall, 54% reported ⩾1 symptoms, with 45% of these seeking medical advice (main sources emergency departments and General Practitioners). Advice was often sought ⩾5 days after the symptom first appeared (44% of those seeking advice about an abscess, 45% about an open wound, and 35% for RST); the majority received antibiotics. Overall, 9·5% reported hospital admission during the preceding year. Ever being diagnosed with septicaemia and endocarditis were reported by 8·8% and 2·9%, respectively. Interventions are needed to reduce morbidity, healthcare burden and delays in accessing treatment.

Objective: Certain intra-type variants of HPV16 have been shown to be associated with an increased risk of developing high grade cervical disease, but their potential association is confounded by apparent geographic and phylogenetic lineage dependency. The objective of this study was to evaluate the relationship between HPV16 sequence variants and cervical disease stage in monospecific infection samples from a single lineage (European, EUR) in England., Methods: One hundred and twelve women singly infected with HPV16 and displaying normal and abnormal cytology grades were selected. An 1187 bp fragment encompassing the entire LCR and a portion of the E6 open reading frame was sequenced to identify intra-type variants. Intra-type diversity was estimated using Shannon entropy., Results: Almost all samples (110/112; 98%) were assigned to the EUR lineage, one sample was classified as European-Asian (EAS) and another African (Afr1a). The mean pairwise distance of the EUR sequences in this study was low (0.29%; 95%CI 0.13-0.45%) but there were nevertheless several sites in the LCR (n=5) and E6 (n=2) that exhibited a high degree of entropy. None of these sites, however, including the T350G non-synonymous (L83V) substitution in E6, alone or in combination, were found to be associated with cervical disease stage., Conclusions: Despite using single infection samples and samples from a single variant lineage, intra-type variants of HPV16 were not differentially associated with cervical disease. Monitoring intra-lineage, site-specific variants, such as T350G, is unlikely to be of diagnostic value., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Background: Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45., Methods: Samples singly infected with HPV16 (n=226), HPV18 (n=32), HPV31 (n=75) or HPV45 (n=29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3'L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample., Results: Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2-26.1; p<0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p=0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8-18.0; p<0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31., Conclusions: This study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease.

Responses to injecting drug use have changed focus over the last 20 years. Prevalence and incidence of human immunodeficiency virus (HIV) among people who inject drugs (PWID) in England and Wales were examined in relation to these changes. A voluntary unlinked-anonymous surveillance study obtained a biological sample and questionnaire data from PWID through annual surveys since 1990. Prevalence and incidence trends were estimated via generalised linear models, and compared with a policy time-line. Overall HIV prevalence among 38,539 participations was 1.15%. Prevalence was highest among those who started injecting before 1985; throughout the 1990s, prevalence fell in this group and was stable among those who started injecting later. Prevalence was higher in 2005 than 2000 (odds ratio: 3.56 (95% confidence interval (CI) 1.40–9.03) in London, 3.40 (95% CI 2.31–5.02) elsewhere). Estimated HIV incidence peaked twice, around 1983 and 2005. HIV was an important focus of policy concerning PWID from 1984 until 1998. This focus shifted at a time when drug use and risk were changing. The increased incidence in 2005 cannot be ascribed to the policy changes, but these appeared to be temporally aligned. Policy related to PWID should be continually reviewed to ensure rapid responses to increased risk.

Background: People who inject drugs (PWID) are at risk of injection site infections and injuries. The factors associated with recent symptoms of these problems are examined., Method: PWID recruited using respondent driven sampling, underwent a computer-assisted interview and provided a dried-blood spot sample. Weight data were examined using logistic regression., Results: The mean age of the 855 participants was 32 years, and 25% were women. During the preceding 28 days, 94% had injected heroin and 50% crack-cocaine; with 41% injecting into their arms and 47% their groin. The passing on of used needles/syringes was reported by 9.7% and receiving by 8.0%. During the preceding 28 days, 21% reported having redness, swelling and tenderness, 6.1% an abscess, and 5.2% a sore/open wound at an injection site; with a quarter (24%) reporting one or more of these. A range of factors were associated with these symptoms; all three symptoms were associated with more frequent injection and the use of multiple injection sites; two of the symptoms were also associated with having recently overdosed and the use of particular injection sites., Conclusions: Injection site infections and injuries are common among PWID and targeted interventions are needed to reduce risk., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Objective: To describe drug use, sexual risks and the prevalence of blood-borne viral infections among men who inject image and performance enhancing drugs (IPEDs)., Design: A voluntary unlinked-anonymous cross-sectional biobehavioural survey., Setting: 19 needle and syringe programmes across England and Wales., Participants: 395 men who had injected IPEDs., Results: Of the participants (median age 28 years), 36% had used IPEDs for <5 years. Anabolic steroids (86%), growth hormone (32%) and human chorionic gonadotropin (16%) were most frequently injected, with 88% injecting intramuscularly and 39% subcutaneously. Two-thirds also used IPEDs orally. Recent psychoactive drug use was common (46% cocaine, 12% amphetamine), 5% had ever injected a psychoactive drug and 9% had shared injecting equipment. 'Viagra/Cialis' was used by 7%, with 89% reporting anal/vaginal sex in the preceding year (20% had 5+ female-partners, 3% male-partners) and 13% always using condoms. Overall, 1.5% had HIV, 9% had antibodies to the hepatitis B core antigen (anti-HBc) and 5% to hepatitis C (anti-HCV). In multivariate analysis, having HIV was associated with: seeking advice from a sexual health clinic; having had an injection site abscess/wound; and having male partners. After excluding those reporting male partners or injecting psychoactive drugs, 0.8% had HIV, 8% anti-HBc and 5% anti-HCV. Only 23% reported uptake of the hepatitis B vaccine, and diagnostic testing uptake was poor (31% for HIV, 22% for hepatitis C)., Conclusions: Previous prevalence studies had not found HIV among IPED injectors. HIV prevalence in this, the largest study of blood-borne viruses among IPED injectors, was similar to that among injectors of psychoactive drugs. Findings indicate a need for targeted interventions.

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Objectives: In the UK, although transmission of HIV among injecting drug user (IDUs) has been limited since the 1980s, IDUs and men who have sex with men (MSM) have higher HIV and hepatitis C virus (HCV) prevalences than the general population. MSM who are also IDUs (MSM-IDUs) may therefore have a higher risk of infection than male IDUs who only have sex with women., Methods: Analysis of data from a national survey of IDUs attending services (England, Wales and Northern Ireland) between 1998 and 2007, which collected demographic and behavioural data and oral fluid samples for HIV and HCV antibody testing., Results: Of the 8671 men who reported injecting drugs and having sex during the preceding year, 96% (8354) were men who only had sex with women (MSW). MSM-IDUs and MSW-IDUs had similar age and number of years of injecting. MSM-IDUs had a higher prevalence of HIV (adjusted OR=4.08, 95% CI 1.9 to 8.5) and of HCV (adjusted OR =1.34, 95% CI 1.1 to 1.8) and were about four times (adjusted OR =3.78, 95% CI 2.9 to 4.9) more likely to have unprotected sex with multiple partners. Among those who injected in the 4 weeks prior to participation, the MSM-IDUs had a higher level of needle/syringe sharing (adjusted OR =1.72, 95% CI 1.3 to 2.2)., Discussion: MSM-IDUs have a fourfold higher risk of HIV; HCV prevalence in MSM-IDUs is a third higher than among MSW-IDUs, suggesting elevated risk from injecting and possibly sexual transmission. These findings emphasise the need for public health interventions specifically targeted at MSM-IDUs.

Around 80% of hepatitis C virus (HCV) infections in England are among injecting drug users (IDUs). The HCV Action Plan launched in 2004 includes targets to reduce HCV prevalence in recent initiates (those starting injecting in the preceding 3 years), and to increase HCV voluntary confidential testing (VCT). The Action Plan's impact is examined using surveillance data from recent initiates participating in an annual survey of IDUs in contact with specialist services across England, 2000-2008. Participants provided an oral fluid sample (tested for anti-HCV) and completed a short questionnaire (including HCV VCT and result of last test). Overall, anti-HCV prevalence among the recent initiates was 18% (619/3463); in 2004, it was 20% (59/291), other than being lower in 2000 [11%, 73/672, adjusted odds ratio (AOR) = 0.63 95%CI 0.42-0.93] there was no change over time. Prevalence increased with age; was higher among those ever imprisoned, using a needle exchange, and having a HCV VCT; and varied by region. Overall, 42% (1460) had ever had a HCV VCT; in 2004 uptake was 45% (130/291) having increased from 26% (175/672, AOR = 0.57 95%CI 0.42-0.77) in 2000, and it rose to 62% (197/320, AOR = 2.12 95%CI 1.50-2.99) in 2008. The proportion of anti-HCV-positive IDUs aware of their infection was higher in 2006-2008 than in earlier years. The HCV Action Plan has probably helped increase recent initiates' uptake of HCV VCT and the proportion of those diagnosed with HCV infection. However, its impact on HCV transmission is unclear. There is a need to reinvigorate, and improve coverage of, interventions to prevent HCV transmission., (© 2011 Blackwell Publishing Ltd.)

The ability to detect type-specific high risk HPV (HR-HPV) infections in samples from females and males is important for monitoring the epidemiology of HPV and the impact of vaccination. Type-specific detection concordance between paired urine and genital samples from females (n = 264) undergoing routine colposcopy and males (n = 88) attending a genito-urinary medicine clinic was evaluated using an in-house genotyping assay. The overall inter-rater agreement (κ) was 0.781 for female pairs and 0.346 for male pairs. Female urine had sensitivity for detection of HPV16/18 and HR-HPV of 75% and 84%, respectively, while male urine had sensitivities of 13% and 28%, respectively. Genital samples had a higher HPV DNA copy number than urine although a small proportion (10%) of urine samples had a higher copy number than the corresponding genital sample. The proportion of females with normal cytology positive for HPV16/18 was 19%, increasing to 57% in moderate or severely dyskaryotic samples. The same trend was seen in the corresponding urine (19-43%) compounded by the reduced sensitivity of this sample type. The HPV16 viral load in female genital samples, but not in urine, was weakly associated with cervical disease stage. Despite reduced sensitivity, urine appears to be an appropriate surrogate sample for type-specific HPV detection in females for epidemiological objectives. The lower sensitivity and lack of association between viral load and disease stage in urine suggest that urine may not be useful for clinical management of HPV infection. The utility of urine for type-specific detection in males is less certain., (Copyright © 2011 Wiley-Liss, Inc.)

An unlinked anonymous survey was conducted to measure the prevalence of selected markers for HIV, hepatitis B and C infection in recruits to the UK Armed Forces to inform future screening and hepatitis B vaccination policies. During 2007, nearly 14 000 left-over samples taken from new recruits for blood typing were collected, unlinked from identifiers and anonymously tested for HIV, hepatitis C and current and past cleared hepatitis B infection. Overall, serological evidence of HIV and hepatitis C was found in 0·06% and 0·06% of recruits, respectively. Evidence of past cleared and current hepatitis B infection was found in 3·63% and 0·37% of recruits, respectively. Overall, prevalence rates were broadly consistent with UK population estimates of infection. However, HIV and hepatitis B prevalence was higher in recruits of African origin than in those from the UK (P<0·0001). Screening for these infections is an option that could be considered for those entering Services from high-prevalence countries.

Objectives: The aim of the study was to estimate the levels of transmitted drug resistance (TDR) in HIV-1 using very sensitive assays to detect minority drug-resistant populations., Methods: We tested unlinked anonymous serum specimens from sexual health clinic attendees, who had not received an HIV diagnosis at the time of sampling, by both standard genotyping and using minority detection assays., Results: By standard genotyping, 21 of 165 specimens (12.7%) showed evidence of drug resistance, while, using a combination of standard genotyping and minority mutation assays targeting three commonly observed drug resistance mutations which cause high-level resistance to commonly prescribed first-line antiretroviral therapy (ART), this rose to 32 of 165 (19.4%). This increase of 45% in drug resistance levels [95% confidence interval (CI) 15.2-83.7%; P=0.002] was statistically significant. Almost all of this increase was accounted for by additional detections of the M184V mutation., Conclusions: Future surveillance studies of TDR in the United Kingdom should consider combining standard genotyping and minority-specific assays to provide more accurate estimates, particularly when using specimens collected from chronic HIV infections in which TDR variants may have declined to low levels., (© 2010 British HIV Association.)

Monitoring hepatitis C virus (HCV) infection among injecting drug users (IDUs) in the community is complicated by difficulties in obtaining biological specimens and biases in recruitment and follow-up. This study examined the utility of dried blood spot (DBS) specimens from IDUs recruited using respondent-driven sampling (RDS). Active IDUs underwent a computer-assisted interview and provided a DBS sample, tested for HCV antibody (anti-HCV) and HCV-RNA. HCV incidence was estimated from the proportion of anti-HCV-negative subjects found HCV-RNA-positive and estimates of the duration of this state. Results were adjusted according to RDS derived sample weights. HCV-RNA testing was performed on 288 DBS samples; 173 were anti-HCV-positive (54% weighted), of which 70 (42%, 95%CI 34-50% weighted) were RNA-negative indicating cleared infection. Among the 115 anti-HCV-negatives, 14 were RNA-positive suggesting an incidence of 38-47 per 100pyrs. Incident infections were younger than anti-HCV-negative and prevalent infections: 25 vs. 29 and 34, respectively. Incidence was highest among individuals with poor needle exchange coverage. One hundred and fourteen were genotyped (60 1a, 46 3a): a cluster of 14 had homology of >98.5% including 10 incident infections. Public health surveillance of HCV among IDUs could be enhanced through the collection of DBS samples with appropriate recruitment approaches. DBS allow differentiation between individuals with cleared infections, ongoing infection and those recently infected. They also enable virus characterization at genotype and nucleotide level. This would allow surveillance to inform development of harm reduction interventions, and the international evidence base for these., (© 2010 Blackwell Publishing Ltd.)

Objective(s): To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays., Methods: Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4 °C, 25 °C and 37 °C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay)., Results: Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4 °C or 25 °C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37 °C prior to testing., Conclusions: Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4 °C or 25 °C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays.

Injection site infections in injecting drug users (IDUs) are associated with serious morbidity and healthcare costs. Factors associated with symptoms of these were examined through annual (2006-2008) unlinked-anonymous survey of IDUs in England, Wales and Northern Ireland. Overall 36% (1863/5209) self-reported having a symptom with no trend over time (35% 2006, 37% 2007, 34% 2008). Symptoms were less common in the North East of England; increased with years injecting; and were higher in women, those recently homeless, those recently using a needle exchange, and those injecting both opiates and stimulants. Of those injecting during the previous 4 weeks (n=3733) symptoms were associated with: injecting daily; injecting >or=10 times a day; injecting into hands, groin, or legs; sharing filters; and reusing water to flush syringes. Symptoms of injection site infections are common in IDUs. Better-targeted preventive interventions are needed, and continued surveillance should assist with assessing the impact of new initiatives.

Background: In the UK, needle and syringe programmes (NSP) are delivered via community pharmacies or substance misuse services (SMSNSP). Understanding the profile of drug injectors primarily using different sources of injecting equipment can help service design., Methods: Blood spot samples and behavioural data were collected from drug injectors and tested for antibodies to hepatitis C and hepatitis B. Data were analysed in relation to NSP use by multivariate logistic regression., Results: Of 700 eligible individuals interviewed, 657 provided information on their main source of equipment; 26% reported pharmacy NSP, 56% SMSNSP and 18% secondary distribution. In the adjusted analysis, individuals whose main source was SMSNSP were more likely to report markers of increased risk (homelessness, groin injection, having injected >16 days/month) and had a higher hepatitis B antibody prevalence than individuals primarily using pharmacy NSP. Individuals whose main source was secondary distribution had a different profile (e.g. they were younger, more likely to be recent onset injectors than main source SMSNSP users and less likely to report being in drug treatment)., Conclusion: Differences exist in the populations primarily accessing different NSP and commissioning of services must reflect these differences. Injecting drug users relying on secondary exchange should be targeted to improve health service contact.

Objectives: To identify biological factors associated with HIV transmission in men who have sex with men (MSM)., Design: A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data., Methods: Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling., Results: Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54-0.86], P=0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15-2.25), P=0.005], recent infection [rate ratio 3.88 (95% CI 1.76-8.55), P=0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51-11.29), P=0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07-0.27, P=0.0001)., Conclusion: Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission.

The objective was to investigate herpes simplex virus (HSV) epidemiology amongst HIV-positive and HIV-negative men who have sex with men (MSM) in England and Wales. Unlinked anonymous sera from 3,968 MSM attending 12 sexual health clinics in 2003 were tested for HIV, HSV-2 and HSV-1 antibodies. Fifty-five percent of HIV-positive MSM were HSV-2-seropositive, compared to 17% of HIV-negative MSM (Adj RR: 2.14 [CI: 1.92-2.37]). Amongst HIV-positive individuals, there was no significant difference in HSV-2 seroprevalence by knowledge of HIV status or whether the HIV infection was recently acquired (determined through STARHS). HIV infection was also independently associated with HSV-1 serostatus (Adj RR 1.19 [CI: 1.14-1.24)]). Four of the twelve attendees who received a diagnosis of recurrent anogenital herpes at the clinic visit were HSV-1-seropositive but not HSV-2-seropositive at the time, although no cultures or PCR results were available to type the cause of the ano-genital presenting disease. It is of concern that one in two HIV-positive MSM and one in six HIV-negative MSM may be infected with HSV-2, given increasing evidence of its impact on HIV progression, onward transmission and acquisition. To date results have been disappointing from trials aimed at reducing HIV onward transmission and HIV acquisition using HSV antiviral medication. However, recent research in an African context demonstrates the efficacy of HSV antivirals in delaying HIV progression. The high prevalence of HSV-2 amongst HIV-positive MSM suggests that an increased focus on HSV control in the management of HIV amongst MSM in the United Kingdom may be warranted. Given this and existing research on the high prevalence of genitally acquired HSV-1 amongst MSM in the UK, further research is also warranted into the role of HSV-1 in the HIV epidemic in this context.

Hepatitis C is a global health problem and in the UK seroprevalence studies have mainly concentrated on specific high-risk groups. The aim of this study was to determine changes in the prevalence of antibody to hepatitis C virus in England using residual specimens collected between 1986 and 2000 reflecting the general population. A cross-sectional study design using a convenience collection of serum specimens from adult patients submitted to laboratories in the years 1986, 1991, 1996 and 2000 from a total of 19 laboratories around England were investigated. The main outcome was to determine anti-HCV prevalence and the average incidence occurring between 1986 and 2000 and factors associated with infection. Multivariable analysis of results from all years showed there was a significant difference in prevalence between males and females (P < 0.001), birth cohort (P < 0.001) and by health region (P < 0.001). An average of 0.72% (95% CI 0-1.65%) of those susceptible to HCV born between 1950 and 1970 were estimated to have acquired the infection between 1986 and 2000. Analysis of this convenience serum collection suggests that HCV prevalence is low in the general population, and is associated with period of birth, gender and health region. There was evidence to support a low incidence of HCV infection in those born between 1950 and 1970 over the period 1986-2000 which, at the population level, equated to a substantial burden of infection (approximately 106,000 persons). Continued surveillance and prevention targeted at injecting drug users are essential for the control of hepatitis C in the UK.

A prospective cohort study estimated the incidence of hepatitis C virus (HCV) in drug injectors in South Wales (UK). In total, 286/481 eligible seronegative individuals were followed up after approximately 12 months. Dried blood spot samples were collected and tested for anti-HCV antibody and behavioural data were collected at baseline and follow-up. HCV incidence was 5.9/100 person-years [95% confidence interval (CI) 3.4-9.5]. HCV incidence was predicted by community size [incident rate ratio (IRR) 6.6, 95% CI 2.11-20.51, P = 0.001], homelessness (IRR 2.9, 95% CI 1.02-8.28, P = 0.047) and sharing injecting equipment (IRR 12.7, 95% CI 1.62-99.6, P = 0.015). HCV incidence was reduced in individuals in opiate substitution treatment (IRR 0.34, 95% CI 0.12-0.99, P = 0.047). In order to reduce follow-up bias we used multiple imputation of missing data using switching regression; after imputation estimated HCV incidence was 8.5/100 person-years (95% CI 5.4-12.7). HCV incidence varies with community size, equipment sharing and homelessness are associated with increased HCV incidence and opiate substitution treatment may be protective against HCV.

Surveillance reports and prevalence studies have indicated that injecting drug users (IDUs) contribute more to the hepatitis C epidemic in the United Kingdom than any other risk group. Information on both the prevalence and incidence of hepatitis C in IDUs is therefore essential to understanding the epidemiology of this infection. The prevalence of hepatitis C in specimens from the Unlinked Anonymous Prevalence Monitoring Programme collected in 1995, 1996, 1998, 1999, 2000, and 2001 was determined using residual syphilis serology specimens from IDUs attending 15 genitourinary medicine (GUM) clinics in and outside London. These specimens were tested for antibodies to hepatitis C virus (anti-HCV). Using this cross-sectional design, anti-HCV-negative specimens were tested for HCV RNA to identify incident infections during the 'window' period of infection, and thus to estimate HCV incidence. Results of the multivariable analysis showed that there was marked variation in prevalence by clinic (P<0.0001) and age (P<0.0001). Overall the majority of infections were in males and the overall prevalence in injectors declined over the study period from 36.9% to 28.7%. The annual incidence in these injectors was estimated as being 3.01% (95% CI 1.25-6.73). Over the study period HCV incidence decreased by 1.2% per year. Genotyping of the incident infections identified the most common genotype as type 1 with type 3 being more frequently seen after 1998. Of the prevalent infections, genotype 1 was the most common. The study has confirmed a higher prevalence of anti-HCV in IDUs in the London area compared to those outside London. How representative of the current injecting drug user population are IDUs attending GUM clinics is unclear. Even so, such studies allow prevalence and incidence to be estimated in individuals who have ever injected drugs and inform ongoing public health surveillance.