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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.