Has opportunistic screening among young adults in England led to a reduction in Chlamydia trachomatis infection? Identifying and appraising outcome measures for the evaluation of chlamydia control programmes

Genital infection with Chlamydia trachomatis (‘chlamydia’) is the most commonly diagnosed sexually transmitted infection in England. Chlamydia is often asymptomatic and can lead to serious complications, especially in women. Chlamydia screening offers one approach to controlling chlamydia and its consequences. In England, chlamydia screening is offered opportunistically to sexually-active under-25 year-olds through the National Chlamydia Screening Programme, which was introduced in 2003 and nationally implemented by 2008. Evaluating the real-world impact of chlamydia screening against its aims of interrupting transmission and reducing the prevalence of infection presents a considerable challenge, in part due to the absence of a robust outcome measure. The research presented in this thesis sought to address this challenge. Four approaches to outcome measurement were investigated: Analysis of trends in percentage testing positive for chlamydia among 15-24 year-olds accessing chlamydia testing using surveillance data; Pilot of a postal survey of 17-18 year-old women to measure population prevalence; Analysis of chlamydia prevalence among 16-24 year-old participants in the second and third National Surveys of Sexual Attitudes and Lifestyles (Natsal-2: 1999-2000; Natsal-3: 2010-12); Application of a novel antibody assay to stored sera from 16-44 year-old participants in the Health Survey for England (HSE) between 1994 and 2012 to measure prevalence of antibodies in serum as a marker of previous C. trachomatis infection.nIn summary, no definitive evidence was found in these or other published analyses to suggest that chlamydia screening, as delivered in practice, has led to a reduction in the incidence or prevalence of chlamydia infection among young adults in England up to 2012. Possible reasons for the absence of such evidence are discussed in light of findings presented in the thesis. The strengths and limitations of these approaches to outcome measurement are discussed, and recommendations regarding the future evaluation and delivery of chlamydia control programmes are presented

HOSTED—England's Household Transmission Evaluation Dataset: preliminary findings from a novel passive surveillance system of COVID-19

BACKGROUND: Household transmission of SARS-CoV-2 is an important component of the community spread of the pandemic. Little is known about the factors associated with household transmission, at the level of the case, contact or household, or how these have varied over the course of the pandemic. METHODS: The Household Transmission Evaluation Dataset (HOSTED) is a passive surveillance system linking laboratory-confirmed COVID-19 cases to individuals living in the same household in England. We explored the risk of household transmission according to: age of case and contact, sex, region, deprivation, month and household composition between April and September 2020, building a multivariate model. RESULTS: In the period studied, on average, 5.5% of household contacts in England were diagnosed as cases. Household transmission was most common between adult cases and contacts of a similar age. There was some evidence of lower transmission rates to under-16s [adjusted odds ratios (aOR) 0.70, 95% confidence interval (CI) 0.66-0.74). There were clear regional differences, with higher rates of household transmission in the north of England and the Midlands. Less deprived areas had a lower risk of household transmission. After controlling for region, there was no effect of deprivation, but houses of multiple occupancy had lower rates of household transmission [aOR 0.74 (0.66-0.83)]. CONCLUSIONS: Children are less likely to acquire SARS-CoV-2 via household transmission, and consequently there was no difference in the risk of transmission in households with children. Households in which cases could isolate effectively, such as houses of multiple occupancy, had lower rates of household transmission. Policies to support the effective isolation of cases from their household contacts could lower the level of household transmission

Can we use postal surveys with anonymous testing to monitor chlamydia prevalence in young women in England? Pilot study incorporating randomised controlled trial of recruitment methods

OBJECTIVES: Chlamydia prevalence in the general population is a potential outcome measure for the evaluation of chlamydia control programmes. We carried out a pilot study to determine the feasibility of using a postal survey for population-based chlamydia prevalence monitoring. METHODS: Postal invitations were sent to a random sample of 2000 17-year-old to 18-year-old women registered with a general practitioner in two pilot areas in England. Recipients were randomised to receive either a self-sampling kit (n=1000), a self-sampling kit and offer of £5 voucher on return of sample (n=500) or a self-sampling kit on request (n=500). Participants returned a questionnaire and self-taken vulvovaginal swab sample for unlinked anonymous Chlamydia trachomatis testing. Non-responders were sent a reminder letter 3 weeks after initial invitation. We calculated the participation rate (number of samples returned/number of invitations sent) and cost per sample returned (including cost of consumables and postage) in each group. RESULTS: A total of 155/2000 (7.8%) samples were returned with consent for testing. Participation rates varied by invitation group: 7.8% in the group who were provided with a self-sampling kit, 14% in the group who were also offered a voucher and 1.0% in the group who were not sent a kit. The cost per sample received was lowest (£36) in the group who were offered both a kit and a voucher. CONCLUSIONS: The piloted survey methodology achieved low participation rates. This approach is not suitable for population-based monitoring of chlamydia prevalence among young women in England

C. trachomatis pgp3 antibody prevalence in young women in England, 1993-2010

Seroepidemiology of chlamydia can offer study opportunities and insights into cumulative risk of exposure that may contribute to monitoring the frequency of, and control of, genital chlamydia-the most commonly diagnosed STI in England. We undertook retrospective anonymous population-based cross-sectional surveys using an indirect IgG ELISA for chlamydia Pgp3 antibody. Sera from 4,732 women aged 17-24 years were tested. Samples were taken at 3-yearly intervals between 1993 and 2002, a period during which other data suggest chlamydia transmission may have been increasing, and from each year between 2007 and 2010. Seroprevalence increased in 17-24 year olds over time between 1993 and 2002. Between 2007 and 2010, age-standardised seroprevalence among 17-24 year olds decreased from 20% (95% CI: 17-23) to 15% (95%CI 12-17) (p = 0.0001). The biggest drop was among 20 to 21 year olds, where seroprevalence decreased from 21% in 2007 to 9% in 2010 (p = 0.002). These seroprevalence data reflect some known features of the epidemiology of chlamydia infection, and show that exposure to antibody-inducing chlamydia infection has declined in recent years. This decline was concurrent with increasing rates of screening for asymptomatic chlamydia. Serology should be explored further as a tool for evaluation of chlamydia control, including chlamydia screening programmes

Do healthcare professionals and young adults know about the National Chlamydia Screening Programme? Findings from two cross-sectional surveys

The extent to which healthcare professionals (HCPs) and young people (YP) are aware of, and adhere to, National Chlamydia Screening Programme (NCSP) recommendations on testing frequency is unclear. To address this two cross-sectional surveys in 2015-2016: one among genitourinary medicine (GUM) and non-GUM HCPs (n = 109) and the other among YP attending a GUM clinic in England (n = 195). For both, questions were designed to measure awareness of NCSP guidance and whether respondents acted on that knowledge. This included questions about YP's most recent test(s) (if ever) and the time since first and last sex with their most recent partners. Knowledge of NCSP testing guidelines varied among both GUM and non-GUM HCP respondents. However, lack of knowledge of the guidelines did not preclude HCPs from recommending testing in line with NCSP recommendations in practice. While most YP were not aware of NCSP recommendations, around two-thirds had tested for Chlamydia at least once in the last year. However, testing seldom appeared to coincide with partnership change. There is a knowledge gap and a discord between testing recommendations and practice. Interventions are needed to encourage appropriate testing patterns to maximise the individual and public health benefits of testing

Is previous azithromycin treatment associated with azithromycin resistance inNeisseria gonorrhoeae? A cross-sectional study using national surveillance data in England

OBJECTIVES: It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance inNeisseria gonorrhoeae(NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectalChlamydia trachomatis(CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin. METHODS: Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013-2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013-2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012-2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin. RESULTS: Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients. CONCLUSIONS: We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions

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

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

Is chlamydia screening and testing in Britain reaching young adults at risk of infection? Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

In the context of widespread opportunistic chlamydia screening among young adults, we aimed to quantify chlamydia testing and diagnosis among 16-24 year olds in Britain in relation to risk factors for prevalent chlamydia infection