Andrew Sutton

Modelling the force of infection for hepatitis B and hepatitis C in injecting drug users in England and Wales

BackgroundInjecting drug use is a key risk factor, for several infections of public health importance, especially hepatitis B (HBV) and hepatitis C (HCV). In England and Wales, where less than 1% of the population are likely to be injecting drug users (IDUs), approximately 38% of laboratory reports of HBV, and 95% of HCV reports are attributed to injecting drug use.MethodsVoluntary unlinked anonymous surveys have been performed on IDUs in contact with specialist agencies throughout England and Wales. Since 1990 more than 20,000 saliva samples from current IDUs have been tested for markers of infection for HBV, HCV testing has been included since 1998. The analysis here considers those IDUs tested for HBV and HCV (n = 5,682) from 1998–2003. This study derives maximum likelihood estimates of the force of infection (the rate at which susceptible IDUs acquire infection) for HBV and HCV in the IDU population and their trends over time and injecting career length. The presence of individual heterogeneity of risk behaviour and background HBV prevalence due to routes of transmission other than injecting are also considered.ResultsFor both HBV and HCV, IDUs are at greatest risk from infection in their first year of injecting (Forces of infection in new initiates 1999–2003: HBV = 0.1076 95% C.I: 0.0840–0.1327 HCV = 0.1608 95% C.I: 0.1314–0.1942) compared to experienced IDUs (Force of infection in experienced IDUs 1999–2003: HBV = 0.0353 95% C.I: 0.0198–0.0596, HCV = 0.0526 95% C.I: 0.0310–0.0863) although independently of this there is evidence of heterogeneity of risk behaviour with a small number of IDUs at increased risk of infection. No trends in the FOI over time were detected. There was only limited evidence of background HBV infection due to factors other than injecting.ConclusionThe models highlight the need to increase interventions that target new initiates to injecting to reduce the transmission of blood-borne viruses. Although from the evidence here, identification of those individuals that engage in heightened at-risk behaviour may also help in planning effective interventions. The data and methods described here may provide a baseline for monitoring the success of public health interventions.

HIV prevalence among injecting drug users in England and Wales 1990 to 2003: evidence for increased transmission in recent years.

Objective:To describe trends in HIV prevalence among injecting drug users in England and Wales between 1990 and 2003. Methods:Analysis of surveillance data from voluntary unlinked anonymous cross-sectional surveys collecting oral fluid samples and behavioural information from injecting drug users recruited from both drug agency (n = 24 304) and community settings (n = 3628). Results:HIV prevalence in England and Wales declined from 5.9% in 1990 to 0.6% in 1996 and then remained stable until 1999, after which it increased to 1.4% in 2003. Few HIV infections were detected among short-term injectors between 1994 and 1999, but in recent years prevalence among this group has increased. Other factors associated with higher odds of HIV infection were being recruited in London and from community settings, and ever having had a voluntary confidential HIV test. Incidence estimated through a force of infection model was 2.8% per annum among those injecting for less than a year in London between 1998 and 2003. Conclusions:These data suggest that incidence and prevalence of HIV may have increased, whereas other indicators suggest an increase in risk behaviour. It is critical that harm reduction measures are reinvigorated, and evolve in response to changes in drug use risk behaviours and policy.

The cost-effectiveness of screening and treatment for hepatitis C in prisons in England and Wales: a cost-utility analysis.

Summary.  Prisoners have a high prevalence of hepatitis C virus (HCV) infection compared with the general population in England and Wales and in many locations throughout the world. This is because of large numbers of injecting drug users that engage in behaviours likely to transmit HCV being present within prison populations. It is, therefore, suggested that prison may be an appropriate location for HCV screening and treatment to be administered. Using cost‐utility analysis, this study considers the costs and benefits of administering a single round of screening on reception into prison to all individuals followed by possible later screening in the community and comparing this to individuals who may only be tested and treated in the community at a later date. The cost/QALY of one round of prison testing and treatment was found to be £54,852, although probabilistic sensitivity analysis showed extensive uncertainty about this estimate. One‐way sensitivity analysis revealed the importance of the parameters describing the progression of chronic HCV and the discount rates. While the results presented here at baseline would suggest that screening and treatment for HCV in prisons is not cost‐effective, these results are subject to much uncertainty. The importance of the rates describing the progression of chronic HCV on the cost‐effectiveness of this intervention has been demonstrated and this suggests that future work should be undertaken to gain further insight into the rates that individuals progress to the later stages of chronic HCV infection.

Estimating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison.

BackgroundIn England and Wales where less than 1% of the population are Injecting drug users (IDUs), 97% of HCV reports are attributed to injecting drug use. As over 60% of the IDU population will have been imprisoned by the age of 30 years, prison may provide a good location in which to offer HCV screening and treatment. The aim of this work is to examine the cost effectiveness of a number of alternative HCV case-finding strategies on prison receptionMethodsA decision analysis model embedded in a model of the flow of IDUs through prison was used to estimate the cost effectiveness of a number of alternative case-finding strategies. The model estimates the average cost of identifying a new case of HCV from the perspective of the health care provider and how these estimates may evolve over time.ResultsThe results suggest that administering verbal screening for a past positive HCV test and for ever having engaged in illicit drug use prior to the administering of ELISA and PCR tests can have a significant impact on the cost effectiveness of HCV case-finding strategies on prison reception; the discounted cost in 2017 being £2,102 per new HCV case detected compared to £3,107 when no verbal screening is employed.ConclusionThe work here demonstrates the importance of targeting those individuals that have ever engaged in illicit drug use for HCV testing in prisons, these individuals can then be targeted for future intervention measures such as treatment or monitored to prevent future transmission.

A comparison between the force of infection estimates for blood-borne viruses in injecting drug user populations across the European Union: a modelling study.

Summary.  A number of studies have been conducted in injecting drug user (IDU) populations in Europe, in which the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was measured together with demographic and epidemiological information such as age and the age at first injection. A measure of the risk of becoming infected is the force of infection (FOI), defined as the per capita rate at which susceptible individuals acquire infection. The objective of this study was to estimate the FOI and its heterogeneity for HBV, HCV and HIV (where available) for IDU populations in a number of countries in Europe. Data were obtained from five countries: Belgium, the United Kingdom, Spain and Italy, and the Czech Republic, which provided two data sets. The model describes the prevalence of infection as a function of the FOI that may vary over time or duration of IDU. In addition to this, if two or more infections were being considered then a parameter describing the potential heterogeneity of the FOI within the IDU population was also estimated. The results here add to the growing evidence that new initiates to injecting are at an increased risk of blood‐borne viral infection compared with more experienced IDUs. In addition, there is evidence of individual heterogeneity of FOI estimates within the overall IDU populations. This suggests that different proportions of individuals in each population are at increased risk of infection compared with the rest of the population. Future interventions should identify and target these individuals. Moreover, changes over time in individual heterogeneity estimates of IDU populations may provide an indicator for measuring intervention impacts.

Increasing incidence of zoonotic visceral leishmaniasis on Crete, Greece.

To determine whether the incidence of canine leishmaniasis has increased on Crete, Greece, we fitted infection models to serodiagnostic records of 8,848 dog samples for 1990–2006. Models predicted that seroprevalence has increased 2.4% (95% confidence interval 1.61%–3.51%) per year and that incidence has increased 2.2- to 3.8-fold over this 17-year period.

Sentinel lymph node biopsy in vulval cancer: systematic review and meta-analysis.

Background:The purpose of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy with technetium 99 (99mTc) and/or blue dye-enhanced lymphoscintigraphy in vulval cancer.Methods:Sensitive searches of databases were performed upto October 2013. Studies with at least 75% of women with FIGO stage IB or II vulval cancer evaluating SLN biopsy with 99mTc, blue dye or both with reference standard of inguinofemoral lymphadenectomy (IFL) or clinical follow-up were included. Meta-analyses were performed using Meta-Disc version 1.4.Results:Of the 2950 references, 29 studies (1779 women) were included; most of them evaluated 99mTc combined with blue dye. Of these, 24 studies reported results for SLN followed by IFL, and 5 reported clinical follow-up only for SLN negatives. Pooling of all studies was inappropriate because of heterogeneity. Mean SLN detection rates were 94.0% for 99mTc, 68.7% for blue dye and 97.7% for both. SLN biopsy had pooled sensitivity of 95% (95% CI 92–98%) with negative predictive value (NPV) of 97.9% in studies using 99mTc/blue dye, ultrastaging and immunohistochemistry with IFL as reference. Pooled sensitivity for SLN with clinical follow-up for SLN-negatives was 91% (85–95%) with NPV 95.6%. Patients undergoing SLN biopsy experienced less morbidity than those undergoing IFL.Conclusions:Sentinel lymph node biopsy using 99mTC, blue dye and ultrastaging with immunohistochemistry is highly accurate when restricted to carefully selected patients, within a rigorous protocol, with close follow-up and where sufficient numbers for learning curve optimisation exist. Patients must make an informed choice between the slightly higher groin recurrence rates of SLN biopsy vs the greater morbidity of IFL.

Twenty years of selective hepatitis B vaccination: is hepatitis B declining among injecting drug users in England and Wales?

Summary.  Injection drug use is a common route of infection for the hepatitis B virus (HBV) in the UK. The aim of this study was to establish the prevalence and force of infection for HBV among injecting drug users (IDUs) recruited from multiple community and drug agency settings in England and Wales between 1990 and 2004. Cross‐sectional studies of IDUs in and out of contact with drug agencies were conducted throughout the 15‐year period. Oral fluid samples were tested for antibodies to the hepatitis B core antigen (anti‐HBc). Logistic regression was used to investigate associations between risk factors and anti‐HBc positivity and force of infection models were explored. In total, 2527 injectors were recruited from community settings, and 29 386 from drug agencies. Anti‐HBc prevalence was 31% (95% CI 30.7–31.8%). It declined in the early 1990s from around 50% in 1992 to 25% in 1999, after which it increased slightly. It was also higher in those who had injected for longer, older IDUs, those recruited in London and North West England, and those reporting having a previous voluntary confidential HIV test. The force of infection models suggested that the incidence of infection increased in 1999–2004 compared with 1993–1998, and was higher in new injectors compared with those injecting for ≥1 year. In conclusion, findings suggest ongoing HBV transmission in recent years despite an overall decline in prevalence in the early and mid‐1990s, and highlight the importance of targeting vaccination programmes at new IDUs who have high incidence rates of infection.

Modelling the hepatitis B vaccination programme in prisons.

A vaccination programme offering hepatitis B (HBV) vaccine at reception into prison has been introduced into selected prisons in England and Wales. Over the coming years it is anticipated this vaccination programme will be extended. A model has been developed to assess the potential impact of the programme on the vaccination coverage of prisoners, ex-prisoners, and injecting drug users (IDUs). Under a range of coverage scenarios, the model predicts the change over time in the vaccination status of new entrants to prison, current prisoners and IDUs in the community. The model predicts that at baseline in 2012 57% of the IDU population will be vaccinated with up to 72% being vaccinated depending on the vaccination scenario implemented. These results are sensitive to the size of the IDU population in England and Wales and the average time served by an IDU during each prison visit. IDUs that do not receive HBV vaccine in the community are at increased risk from HBV infection. The HBV vaccination programme in prisons is an effective way of vaccinating this hard-to-reach population although vaccination coverage on prison reception must be increased to achieve this.

Measuring risk of HIV and HCV among injecting drug users in the Russian Federation.

BACKGROUND The aim of the study was to measure risk of HIV and HCV infection among injecting drug users (IDUs) through force of infection (FOI) models in three cities of the Russian Federation and assess the value of behavioural data and FOI in predicting risk of infection as a method of second-generation surveillance. METHODS FOI models were fitted to prevalence data collected through an anonymous, cross-sectional community-recruited survey of IDUs with oral fluid sample collection for antibodies to HIV and HCV. Risk of infection was estimated from FOI estimates obtained by fitting a model to prevalence data by length of injecting career for each city and then overall. Risk behaviours were examined by injecting career length. RESULTS A total of 1473 IDUs were recruited. Prevalence of HIV was 8.1% (95% CI 6.7-9.6%) and HCV 63.4% (95% CI 60.9-65.9%). A higher FOI in new initiates to injecting (injecting career length <1 year) was found for both HIV and HCV compared with experienced IDUs (injecting career length <5 years). Increased risk of infection was not corroborated by injecting risk behaviours among new initiates into injecting (n = 38). Only 5.7% (n = 2) reported receptive sharing in the last 4 weeks, 57.9% (n = 22) sharing any injecting paraphernalia, 2.6% (n = 1) frontloading and 8.5% (n = 3) ever injecting with used needles/syringes. However, 29% of new initiates reported exchanging sex in the last 4 weeks (29%) compared with 11% long term IDUs. CONCLUSIONS FOI models can play an important role in surveillance of HIV but caution is needed in the interpretation of behavioural data for predicting current or future risk of HIV.