Katherine Mary Elizabeth Turner

The impact of needle and syringe provision and opiate substitution therapy on the incidence of Hepatitis C virus in injecting drug users: pooling of UK evidence.

AIMS To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs). DESIGN Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness. SETTING Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment. PARTICIPANTS A total of 2986 IDUs surveyed during 2001-09. MEASUREMENT Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys. FINDINGS Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST (I2=48%, P=0.09) and NSP (I2=0%, P=0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs)=0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR=0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: -27.3 to -14.4). CONCLUSIONS There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population.

The re-emergence of syphilis in the United Kingdom: the new epidemic phases.

Objective: The objective of this study was to characterize the resurgence of infectious syphilis in the United Kingdom between 1997 and 2003. Study: The authors conducted a retrospective analysis of routine surveillance data from genitourinary medicine clinics and data collected through enhanced surveillance. Results: Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at genitourinary medicine clinics increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM), and 22% in females. These increases have been driven by a series of outbreaks, the largest of which were seen in Manchester (528) and London (1222) up to the end of October 2003. All the outbreaks have been geographically localized and the majority of cases occurred in MSM. A high percentage of concurrent HIV infection was reported, and oral sex was often reported as a route of transmission. Conclusions: Syphilis has re-emerged in response to behavior change, probably driven by changes in the HIV epidemic. The future course of the epidemic is difficult to predict and control remains elusive.

Global Estimates of Prevalent and Incident Herpes Simplex Virus Type 2 Infections in 2012

Background Herpes simplex virus type 2 (HSV-2) infection causes significant disease globally. Adolescent and adult infection may present as painful genital ulcers. Neonatal infection has high morbidity and mortality. Additionally, HSV-2 likely contributes substantially to the spread of HIV infection. The global burden of HSV-2 infection was last estimated for 2003. Here we present new global estimates for 2012 of the burden of prevalent (existing) and incident (new) HSV-2 infection among females and males aged 15–49 years, using updated methodology to adjust for test performance and estimate by World Health Organization (WHO) region. Methods and Findings We conducted a literature review of HSV-2 prevalence studies world-wide since 2000. We then fitted a model with constant HSV-2 incidence by age to pooled HSV-2 prevalence values by age and sex. Prevalence values were adjusted for test sensitivity and specificity. The model estimated prevalence and incidence by sex for each WHO region to obtain global burden estimates. Uncertainty bounds were computed by refitting the model to reflect the variation in the underlying prevalence data. In 2012, we estimate that there were 417 million people aged 15–49 years (range: 274–678 million) living with HSV-2 infection world-wide (11.3% global prevalence), of whom 267 million were women. We also estimate that in 2012, 19.2 million (range: 13.0–28.6 million) individuals aged 15–49 years were newly-infected (0.5% of all individuals globally). The highest burden was in Africa. However, despite lower prevalence, South-East Asia and Western Pacific regions also contributed large numbers to the global totals because of large population sizes. Conclusions The global burden of HSV-2 infection is large, leaving over 400 million people at increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. These estimates highlight the critical need for development of vaccines, microbicides, and other new HSV prevention strategies.

Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012

Background Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated. Methods We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital. Findings We estimated that 3709 million people (range: 3440–3878 million) aged 0–49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67–212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific. Conclusions The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection.

The cost effectiveness of opportunistic chlamydia screening in England.

Background/aim: The National Chlamydia Screening Programme (NCSP) is being implemented in England. This study aims to estimate the cost effectiveness of (a) the NCSP strategy (annual screening offer to men and women aged under 25 years) and (b) alternative screening strategies. Methods: A stochastic, individual based, dynamic sexual network model was combined with a cost effectiveness model to estimate the complications and associated costs of chlamydial infection. The model was constructed and parameterised from the perspective of the National Health Service (NHS) (England), including the direct costs of infection, complications and screening. Unit costs were derived from standard data sources and published studies. The average and incremental cost effectiveness ratio (cost per major outcome averted or quality adjusted life year (QALY) gained) of chlamydia screening strategies targeting women and/or men of different age groups was estimated. Sensitivity analyses were done to explore model uncertainty. Results: All screening strategies modelled are likely to cost the NHS money and improve health. If pelvic inflammatory disease (PID) progression is less than 10% then screening at any level is unlikely to be cost effective. However, if PID progression is 10% or higher the NCSP strategy compared to no screening appears to be cost effective. The incremental cost effectiveness analysis suggests that screening men and women aged under 20 years is the most beneficial strategy that falls below accepted thresholds. There is a high degree of uncertainty in the findings. Conclusions: Offering an annual screening test to men and women aged under 20 years may be the most cost effective strategy (that is, under accepted thresholds) if PID progression is 10% or higher.

Risk of Pelvic Inflammatory Disease Following Chlamydia trachomatis Infection: Analysis of Prospective Studies With a Multistate Model

Our objective in this study was to estimate the probability that a Chlamydia trachomatis (CT) infection will cause an episode of clinical pelvic inflammatory disease (PID) and the reduction in such episodes among women with CT that could be achieved by annual screening. We reappraised evidence from randomized controlled trials of screening and controlled observational studies that followed untreated CT-infected and -uninfected women to measure the development of PID. Data from these studies were synthesized using a continuous-time Markov model which takes into account the competing risk of spontaneous clearance of CT. Using a 2-step piecewise homogenous Markov model that accounts for the distinction between prevalent and incident infections, we investigated the possibility that the rate of PID due to CT is greater during the period immediately following infection. The available data were compatible with both the homogenous and piecewise homogenous models. Given a homogenous model, the probability that a CT episode will cause clinical PID was 0.16 (95% credible interval (CrI): 0.06, 0.25), and annual screening would prevent 61% (95% CrI: 55, 67) of CT-related PID in women who became infected with CT. Assuming a piecewise homogenous model with a higher rate during the first 60 days, corresponding results were 0.16 (95% CrI: 0.07, 0.26) and 55% (95% CrI: 32, 72), respectively.

Developing a realistic sexual network model of chlamydia transmission in Britain

BackgroundA national chlamydia screening programme is currently being rolled out in the UK and other countries. However, much of the epidemiology remains poorly understood. In this paper we present a stochastic, individual based, dynamic sexual network model of chlamydia transmission and its parameterisation. Mathematical models provide a theoretical framework for understanding the key epidemiological features of chlamydia: sexual behaviour, health care seeking and transmission dynamics.ResultsThe model parameters were estimated either directly or by systematic fitting to a variety of appropriate data sources. The fitted model was representative of sexual behaviour, chlamydia epidemiology and health care use in England. We were able to recapture the observed age distribution of chlamydia prevalence.ConclusionEstimating parameters for models of sexual behaviour and transmission of chlamydia is complex. Most of the parameter values are highly correlated, highly variable and there is little empirical evidence to inform estimates. We used a novel approach to estimate the rate of active treatment seeking, by combining data sources, which improved the credibility of the model results. The model structure is flexible and is broadly applicable to other developed world settings and provides a practical tool for public health decision makers.

Transmission of Chlamydia trachomatis through sexual partnerships: a comparison between three individual-based models and empirical data

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in many developed countries. The highest prevalence rates are found among young adults who have frequent partner change rates. Three published individual-based models have incorporated a detailed description of age-specific sexual behaviour in order to quantify the transmission of C. trachomatis in the population and to assess the impact of screening interventions. Owing to varying assumptions about sexual partnership formation and dissolution and the great uncertainty about critical parameters, such models show conflicting results about the impact of preventive interventions. Here, we perform a detailed evaluation of these models by comparing the partnership formation and dissolution dynamics with data from Natsal 2000, a population-based probability sample survey of sexual attitudes and lifestyles in Britain. The data also allow us to describe the dispersion of C. trachomatis infections as a function of sexual behaviour, using the Gini coefficient. We suggest that the Gini coefficient is a useful measure for calibrating infectious disease models that include risk structure and highlight the need to estimate this measure for other STIs.

Investigating ethnic inequalities in the incidence of sexually transmitted infections: mathematical modelling study

Objectives: To investigate ethnic differences in rates of gonorrhoea using empirical sexual behaviour data in a simple mathematical model. To explore the impact of different intervention strategies in this simulated population. Methods: The findings from cross sectional studies of gonorrhoea rates and sexual behaviour in three ethnic groups in south east London were used to determine the parameters for a deterministic, mathematical model of gonorrhoea transmission dynamics, in a population stratified by sex, sexual activity (rate of partner change), and ethnic group (white, black African, and black Caribbean). We compared predicted and observed rates of infection and simulated the effects of targeted and population-wide intervention strategies. Results: In model simulations the reported sexual behaviours and mixing patterns generated major differences in the rates of gonorrhoea experienced by each subpopulation. The fit of the model to observed data was sensitive to assumptions about the degree of mixing by level of sexual activity, the numbers of sexual partnerships reported by men and women, and the degree to which observed data underestimate female infection rates. Interventions to reduce duration of infection were most effective when targeted at black Caribbeans. Conclusions: Average measures of sexual behaviour in large populations are inadequate descriptors for the epidemiology of gonorrhoea. The consistency between the model results and empirical data shows that profound differences in gonorrhoea rates between ethnic groups can be explained by modest differences in a limited number of sexual behaviours and mixing patterns. Targeting effective services to particular ethnic groups can have a disproportionate influence on disease reduction in the whole community.

Costs and cost effectiveness of different strategies for chlamydia screening and partner notification: an economic and mathematical modelling study

Objectives To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. Design An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. Setting England. Population Individuals eligible for the National Chlamydia Screening Programme. Main outcome measures Cost effectiveness of National Chlamydia Screening Programme in 2008–9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions—(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. Results In 2008–9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. Conclusions In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely to cost less than increasing male coverage but also improve the ratio of women to men diagnosed. Further evaluation of the cost effectiveness of partner notification and screening is urgently needed. The spreadsheet tool developed in this study can be easily modified for use in other settings to evaluate chlamydia control programmes.