Effects of Second Dose of SARS-CoV-2 Vaccination on Household Transmission, England.

A single SARS-CoV-2 vaccine dose reduces onward transmission from case-patients. We assessed the potential effects of receiving 2 doses on household transmission for case-patients in England and their household contacts. We used stratified Cox regression models to calculate hazard ratios (HRs) for contacts becoming secondary case-patients, comparing contacts of 2-dose vaccinated and unvaccinated index case-patients. We controlled for age, sex, and vaccination status of case-patients and contacts, as well as region, household composition, and relative socioeconomic condition based on household location. During the Alpha-dominant period, HRs were 0.19 (0.13-0.28) for contacts of 2-dose BNT162b2-vaccinated case-patients and 0.54 (0.41-0.69) for contacts of 2-dose Ch4dOx1-vaccinated case-patients; during the Delta-dominant period, HRs were higher, 0.74 (0.72-0.76) for BNT162b2 and 1.06 (1.04-1.08) for Ch4dOx1. Reduction of onward transmission was lower for index case-patients who tested positive ≥2 months after the second dose of either vaccine.

Public health and climate change: How are local authorities preparing for the health impacts of our changing climate?

BACKGROUND: Local authorities have a crucial role in preparing for the impacts of climate change. However, the extent to which health impacts are being prioritized and acted on is not well understood. METHODS: We investigated the role of public health in adapting to climate change through: (i) a content analysis of local authority climate change adaptation strategies in South West England and (ii) semi-structured telephone interviews with local authority public health consultants and sustainability officers and a regional Public Health England representative (n = 11). RESULTS: Adaptation strategies/plans varied in existence and scope. Public health consultants did not have an explicit remit for climate change adaptation, although related action often aligned with public health's emergency planning functions. Key barriers to health-related adaptation were financial constraints, lack of leadership and limited public and professional awareness about health impacts. CONCLUSIONS: Local authorities in South West England have differing approaches to tackling health impacts of climate change, and the prominence of public health arguments for adaptation varies. Improved public health intelligence, concise communications, targeted support, visible local and national leadership and clarity on economic costs and benefits of adaptation would be useful for local authorities in preparing for the health impacts of climate change.

Correction: Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections.

[This corrects the article DOI: 10.1371/journal.pone.0208652.].

Economic evaluation of the cost of different methods of retesting chlamydia positive individuals in England.

OBJECTIVES: The National Chlamydia Screening Programme (NCSP) in England opportunistically screens eligible individuals for chlamydia infection. Retesting is recommended three3 months after treatment following a positive test result, but no guidance is given on how local areas should recall individuals for retesting. Here , we compare cost estimates for different recall methods to inform the optimal delivery of retesting programmes. DESIGN: Economic evaluation. SETTING: England. METHODS: We estimated the cost of chlamydia retesting for each of the six most commonly used recall methods in 2014 based on existing cost estimates of a chlamydia screen. Proportions accepting retesting, opting for retesting by post, returning postal testing kits and retesting positive were informed by 2014 NCSP audit data. Health professionals 'sense-checked' the costs. PRIMARY AND SECONDARY OUTCOMES: Cost and adjusted cost per chlamydia retest; cost and adjusted cost per chlamydia retest positive. RESULTS: We estimated the cost of the chlamydia retest pathway, including treatment/follow-up call, to be between £45 and £70 per completed test. At the lower end, this compared favourably to the cost of a clinic-based screen. Cost per retest positive was £389-£607. After adjusting for incomplete uptake, and non-return of postal kits, the cost rose to £109-£289 per completed test (cost per retest positive: £946-£2,506). The most economical method in terms of adjusted cost per retest was no active recall as gains in retest rates with active recall did not outweigh the higher cost. Nurse-led client contact by phone was particularly uneconomical, as was sending out postal testing kits automatically. CONCLUSIONS: Retesting without active recall is more economical than more intensive methods such as recalling by phone and automatically sending out postal kits. If sending a short message service (SMS) could be automated, this could be the most economical way of delivering retesting. However, patient choice and local accessibility of services should be taken into consideration in planning.

Antibodies Against Chlamydia trachomatis and Ovarian Cancer Risk in Two Independent Populations.

BACKGROUND: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. METHODS: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. RESULTS: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. CONCLUSIONS: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer.

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.

Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections.

BACKGROUND: Seroprevalence surveys of Chlamydia trachomatis (CT) antibodies are promising for estimating age-specific CT cumulative incidence, however accurate estimates require improved understanding of antibody response to CT infection. METHODS: We used GUMCAD, England's national sexually transmitted infection (STI) surveillance system, to select sera taken from female STI clinic attendees on the day of or after a chlamydia diagnosis. Serum specimens were collected from laboratories and tested anonymously on an indirect and a double-antigen ELISA, both of which are based on the CT-specific Pgp3 antigen. We used cross-sectional and longitudinal descriptive analyses to explore the relationship between seropositivity and a) cumulative number of chlamydia diagnoses and b) time since most recent chlamydia diagnosis. RESULTS: 919 samples were obtained from visits when chlamydia was diagnosed and 812 during subsequent follow-up visits. Pgp3 seropositivity using the indirect ELISA increased from 57.1% (95% confidence interval: 53.2-60.7) on the day of a first-recorded chlamydia diagnosis to 89.6% (95%CI: 79.3-95.0) on the day of a third or higher documented diagnosis. With the double-antigen ELISA, the increase was from 61.1% (95%CI: 53.2-60.7) to 97.0% (95%CI: 88.5-99.3). Seropositivity decreased with time since CT diagnosis on only the indirect assay, to 49.3% (95%CI: 40.9-57.7) two or more years after a first diagnosis and 51.9% (95%CI: 33.2-70.0) after a repeat diagnosis. CONCLUSION: Seropositivity increased with cumulative number of infections, and decreased over time after diagnosis on the indirect ELISA, but not on the double-antigen ELISA. This is the first study to demonstrate the combined impact of number of chlamydia diagnoses, time since diagnosis, and specific ELISA on Pgp3 seropositivity. Our findings are being used to inform models estimating age-specific chlamydia incidence over time using serial population-representative serum sample collections, to enable accurate public health monitoring of chlamydia.

Advancing the public health applications of Chlamydia trachomatis serology.

Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications.

Is previous azithromycin treatment associated with azithromycin resistance in Neisseria 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 in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia 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.

Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.

OBJECTIVES: Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI). DESIGN: Systematic review and four meta-analyses conducted using random-effects modelling. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017. ELIGIBILITY CRITERIA: Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics. RESULTS: Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10). CONCLUSIONS: High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women.

Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017.

Between July 2016 and January 2017, 37 confirmed cases of hepatitis A with two unique IA genotype strains primarily among men who have sex with men, were reported across eight areas in England and Northern Ireland. Epidemiological and laboratory investigations indicate that these strains may have been imported several times from Spain, with secondary sexual transmission in the United Kingdom. Local and national public health services are collaborating to control this ongoing outbreak.

Filling in the gaps: estimating numbers of chlamydia tests and diagnoses by age group and sex before and during the implementation of the English National Screening Programme, 2000 to 2012.

To inform mathematical modelling of the impact of chlamydia screening in England since 2000, a complete picture of chlamydia testing is needed. Monitoring and surveillance systems evolved between 2000 and 2012. Since 2012, data on publicly funded chlamydia tests and diagnoses have been collected nationally. However, gaps exist for earlier years. We collated available data on chlamydia testing and diagnosis rates among 15-44-year-olds by sex and age group for 2000-2012. Where data were unavailable, we applied data- and evidence-based assumptions to construct plausible minimum and maximum estimates and set bounds on uncertainty. There was a large range between estimates in years when datasets were less comprehensive (2000-2008); smaller ranges were seen hereafter. In 15-19-year-old women in 2000, the estimated diagnosis rate ranged between 891 and 2,489 diagnoses per 100,000 persons. Testing and diagnosis rates increased between 2000 and 2012 in women and men across all age groups using minimum or maximum estimates, with greatest increases seen among 15-24-year-olds. Our dataset can be used to parameterise and validate mathematical models and serve as a reference dataset to which trends in chlamydia-related complications can be compared. Our analysis highlights the complexities of combining monitoring and surveillance datasets.

Chlamydia trachomatis Pgp3 Antibody Population Seroprevalence before and during an Era of Widespread Opportunistic Chlamydia Screening in England (1994-2012).

BACKGROUND: Opportunistic chlamydia screening of <25 year-olds was nationally-implemented in England in 2008 but its impact on chlamydia transmission is poorly understood. We undertook a population-based seroprevalence study to explore the impact of screening on cumulative incidence of chlamydia, as measured by C.trachomatis-specific antibody. METHODS: Anonymised sera from participants in the nationally-representative Health Surveys for England (HSE) were tested for C.trachomatis antibodies using two novel Pgp3 enzyme-linked immunosorbent assays (ELISAs) as a marker of past infection. Determinants of being seropositive were explored using logistic regression among 16-44 year-old women and men in 2010 and 2012 (years when sexual behaviour questions were included in the survey) (n = 1,402 women; 1,119 men). Seroprevalence trends among 16-24 year-old women (n = 3,361) were investigated over ten time points from 1994-2012. RESULTS: In HSE2010/2012, Pgp3 seroprevalence among 16-44 year-olds was 24.4% (95%CI 22.0-27.1) in women and 13.9% (11.8-16.2) in men. Seroprevalence increased with age (up to 33.5% [27.5-40.2] in 30-34 year-old women, 18.7% [13.4-25.6] in 35-39 year-old men); years since first sex; number of lifetime sexual partners; and younger age at first sex. 76.7% of seropositive 16-24 year-olds had never been diagnosed with chlamydia. Among 16-24 year-old women, a non-significant decline in seroprevalence was observed from 2008-2012 (prevalence ratio per year: 0.94 [0.84-1.05]). CONCLUSION: Our application of Pgp3 ELISAs demonstrates a high lifetime risk of chlamydia infection among women and a large proportion of undiagnosed infections. A decrease in age-specific cumulative incidence following national implementation of opportunistic chlamydia screening has not yet been demonstrated. We propose these assays be used to assess impact of chlamydia control programmes.

Chlamydia sequelae cost estimates used in current economic evaluations: does one-size-fit-all?

BACKGROUND: Current evidence suggests that chlamydia screening programmes can be cost-effective, conditional on assumptions within mathematical models. We explored differences in cost estimates used in published economic evaluations of chlamydia screening from seven countries (four papers each from UK and the Netherlands, two each from Sweden and Australia, and one each from Ireland, Canada and Denmark). METHODS: From these studies, we extracted management cost estimates for seven major chlamydia sequelae. In order to compare the influence of different sequelae considered in each paper and their corresponding management costs on the total cost per case of untreated chlamydia, we applied reported unit sequelae management costs considered in each paper to a set of untreated infection to sequela progression probabilities. All costs were adjusted to 2013/2014 Great British Pound (GBP) values. RESULTS: Sequelae management costs ranged from £171 to £3635 (pelvic inflammatory disease); £953 to £3615 (ectopic pregnancy); £546 to £6752 (tubal factor infertility); £159 to £3341 (chronic pelvic pain); £22 to £1008 (epididymitis); £11 to £1459 (neonatal conjunctivitis) and £433 to £3992 (neonatal pneumonia). Total cost of sequelae per case of untreated chlamydia ranged from £37 to £412. CONCLUSIONS: There was substantial variation in cost per case of chlamydia sequelae used in published chlamydia screening economic evaluations, which likely arose from different assumptions about disease management pathways and the country perspectives taken. In light of this, when interpreting these studies, the reader should be satisfied that the cost estimates used sufficiently reflect the perspective taken and current disease management for their respective context.

Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population.

BACKGROUND: Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS: A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS: Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS: Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.

Changes in chlamydia control activities in Europe between 2007 and 2012: a cross-national survey.

BACKGROUND: In 2012, the levels of chlamydia control activities including primary prevention, effective case management with partner management and surveillance were assessed in 2012 across countries in the European Union and European Economic Area (EU/EEA), on initiative of the European Centre for Disease Control (ECDC) survey, and the findings were compared with those from a similar survey in 2007. METHODS: Experts in the 30 EU/EEA countries were invited to respond to an online questionnaire; 28 countries responded, of which 25 participated in both the 2007 and 2012 surveys. Analyses focused on 13 indicators of chlamydia prevention and control activities; countries were assigned to one of five categories of chlamydia control. RESULTS: In 2012, more countries than in 2007 reported availability of national chlamydia case management guidelines (80% vs. 68%), opportunistic chlamydia testing (68% vs. 44%) and consistent use of nucleic acid amplification tests (64% vs. 36%). The number of countries reporting having a national sexually transmitted infection control strategy or a surveillance system for chlamydia did not change notably. In 2012, most countries (18/25, 72%) had implemented primary prevention activities and case management guidelines addressing partner management, compared with 44% (11/25) of countries in 2007. CONCLUSION: Overall, chlamydia control activities in EU/EEA countries strengthened between 2007 and 2012. Several countries still need to develop essential chlamydia control activities, whereas others may strengthen implementation and monitoring of existing activities.

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).

BACKGROUND: 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. METHODS: Using data from sexually experienced (≥1 lifetime sexual partner) 16-year-old to 24-year-old participants in Britain's third National Survey of Sexual Attitudes and Lifestyles (conducted 2010-2012), we explored socio-demographic and behavioural factors associated with prevalent chlamydia infection (detected in urine; n=1832), self-reported testing and self-reported diagnosis in the last year (both n=3115). RESULTS: Chlamydia prevalence was 3.1% (95% CI 2.2% to 4.3%) in women and 2.3% (1.5% to 3.4%) in men. A total of 12.3% of women and 5.3% men had a previous chlamydia diagnosis. Factors associated with prevalent infection were also associated with testing and diagnosis (eg, increasing numbers of sexual partners), with some exceptions. For example, chlamydia prevalence was higher in women living in more deprived areas, whereas testing was not. In men, prevalence was higher in 20-24 than 16-19 year olds but testing was lower. Thirty per cent of women and 53.7% of men with ≥2 new sexual partners in the last year had not recently tested. CONCLUSIONS: In 2010-2012 in Britain, the proportion of young adults reporting chlamydia testing was generally higher in those reporting factors associated with chlamydia. However, many of those with risk factors had not been recently tested, leaving potential for undiagnosed infections. Greater screening and prevention efforts among individuals in deprived areas and those reporting risk factors for chlamydia may reduce undiagnosed prevalence and transmission.