Objectives To evaluate the impact of a new clinic-based rapid STI testing, diagnosis and treatment service on healthcare delivery and resource needs in a sexual health service. Design Controlled interrupted time series study. Setting Two sexual health services in UK: Unity Sexual Health in Bristol, UK (main site) and Croydon Sexual Health in London (control site). Participants Electronic patient records for all attendances during the period one year before and one year after the intervention. Intervention Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways. Outcome measures Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances, and examinations. Results Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the Unity SHS, and the mean cost per episode decreased by 7.5% (95%CI 5.7%, 9.3%). Conclusions: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing in parallel to postal testing kits had the intended impact, which bolsters the case for more widespread rollout in SHS. Strengths and limitations of this study ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This research was funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust (core NIHR infrastructure funded: NIHR200181). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Ethics Committee of the Health Research Authority (South West) gave approval for this work (reference 18/SW/0090). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Our data sharing agreement with the data controllers prohibits sharing data extracts outside of the University of Bristol research team.

Background Chlamydia trachomatis infection causes reproductive sequelae of pelvic inflammatory disease (PID) and tubal infertility. Previous studies have demonstrated a relationship between levels of chlamydia antibody and these sequelae. We investigated associations of high chlamydial seropositivity with PID and infertility using a Pgp3 antibody (Pgp3Ab) multiplex bead array (Pgp3AbMBA). Methods We performed chlamydia Pgp3AbMBA on sera from women 18–39 years old participating in the 2013–2016 National Health and Nutrition Examination Survey with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI) ≥ 50,000; low-positive was MFI > 551–<50,000; negative was <551. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (CI) were calculated for women with chlamydia, PID and infertility. Results Sera were available from 1,725 (73.7%) of 2,339 women aged 18–39 years; 1,425 were sexually experienced. Overall, 104 women had high-positive Pgp3Ab (5.4% [95% CI 4.0–7.0] of US women); 407 had low-positive Pgp3Ab (25.1% [95% CI 21.5–29.0]), and 914 were negative (69.5% [95% CI 65.5–73.4]). The prevalence of current chlamydia among women with high seropositivity (10.7% [95% CI 5.4–18.6]) was higher than the prevalence of current chlamydia among seronegative women (0.4% [95% CI 0.1–1.3]). Among women with high-positive Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1–3.7) times that among Pgp3Ab-negative women (19.6% [95% CI 10.5–31.7] versus 9.9% [95% CI 7.7–12.4]). For women with low-positive Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6–12.6) compared to 2.3% (95% CI 1.4–3.6) in those with negative Pgp3Ab. Conclusions High chlamydial Pgp3Ab seropositivity was associated with infertility. Small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydia.

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia’s contribution to female infertility.

BACKGROUND:Mycoplasma genitalium (MG) causes a sexually transmitted infection (STI) with a rising rate of antimicrobial resistance. Currently, guidelines do not recommend screening asymptomatic men who have sex with men (MSM). We developed a mathematical model of MG transmission to examine the impact of various screening strategies on the incidence and prevalence of MG among MSM attending a sexual health clinic. METHODS:A compartmental mathematical model of MG transmission among MSM was constructed and calibrated using data from the Melbourne Sexual Health center, where resistance-guided therapy provides high treatment effectiveness (92-95%). The model stratified men by symptom status, sexual risk behaviours and whether or not they had MG with macrolide resistance. We simulated the impact on endemic steady-state MG prevalence and incidence of the following screening scenarios, namely screening: 1) no MSM; 2) only symptomatic MSM (the current recommendation); 3) all symptomatic and high-risk asymptomatic MSM; and 4) all MSM. Our base case analysis assumed a treatment effectiveness of 92-95% using resistance-guided therapy. We also examined the impact of treatment effectiveness (i.e. the proportion of detected MG that were cured) and screening coverage (i.e. testing rate) on MG prevalence. FINDINGS:The model predicts that the overall endemic MG prevalence is 9.1% (95% CI: 7.9-10.0) in the current situation where screening is only offered to symptomatic MSM (base-case). This would increase to 11·4% (95% confidence intervals (CI): 10.2-13.7) if no MSM are offered screening, but would decrease to 7.3% (95% CI: 5.7-8.4) if all symptomatic and high-risk asymptomatic MSM were offered screening and 6.4% (95% CI: 4.7-7·7) if all MSM were offered screening. Increasing coverage of MSM screening strategies shows a similar effect on decreasing endemic MG incidence. When evaluating the simultaneous impact of treatment effectiveness and screening coverage, we found that offering screening to more MSM may reduce the overall prevalence but leads to a higher proportion of macrolide-resistant MG, particularly when using treatment regimens with lower effectiveness. INTERPRETATION:Based on the available treatment options, offering screening for MG to other MSM (beyond the currently recommended group of symptomatic MSM) could slightly reduce the prevalence and incidence of MG. However, further increasing screening coverage must be weighed against the impact of lower treatment effectiveness (i.e. when not using resistance-guided therapy), increasing the selection of macrolide resistance, and other negative consequences related to AMR and management (e.g. unnecessary psychological morbidity from infections that do not need treatment).

Background Online services for STI and HIV self-sampling are increasingly being adopted by sexual health services (SHSs). Exploring the impact on overall cost of introducing a new service can be challenging. We developed a simple costing tool (Healthcare-OP) for use by clinicians and managers to support business case preparation for introducing a new service. Healthcare-OP was used to examine the impact on overall cost for the introduction of an online STI and HIV self-sampling service for asymptomatic clients attending our SHS. Methods Client care-pathways were categorised into 16 types based on clinic workflow and estimated duration of consultation. Each pathway was broken down into discrete ‘processes,’ which were costed based on healthcare professional time and costs of tests/consumables. The probability of clients entering each care-pathway and transitioning between ‘processes’ in Healthcare-OP was estimated using 12 months electronic patient record data. Costs were derived from national pay scales and literature. The model did not include costs which remain the same before and after the introduction of online self-sampling service (e.g. diagnostic costs when the service is provided in-house). When the diagnostic tests are provided externally via a commercial provider, we assumed that only 30% or 50% of the test costs (marginal costs) could be released by microbiology. Results The average weekly staff cost for managing 227 male and 237 female clients was £3104 and £3075, respectively. 50% of 76 male and 78 female asymptomatic clients using the online self-sampling services resulted in: a weekly cost saving of £261 and £49 respectively when provided in-house, and ranged from a weekly cost saving of £103 to an additional £241 for male pathways and an additional £126–£479 for female pathways when provided externally. Conclusions The introduction of online-based self-sampling for asymptomatic patients may reduce the overall cost when provided in-house but not externally.

BACKGROUND:Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS:We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS:Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION:Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

Background The Panther (Hologic Inc) was introduced to our specialist sexual health service at point-of-care, which could provide a rapid gonorrhoea (GC) and chlamydia (CT) nucleic acid amplification test (NAAT) result within 4 hours. GC-culture testing was limited to those testing GC NAAT-positive and/or to those who received treatment before the NAAT result was available. We hypothesised that this would reduce the number of cultures and cost, but not reduce the sensitivity of GC-culture. GC isolates are required for susceptibility testing to optimise antimicrobial therapy and for Anti-microbial Resistance surveillance. Methods We obtained and compared data on NAATs taken 12 months before and 12 months after the introduction of rapid testing in November 2019. We linked GC-cultures taken within 2 weeks of the NAAT. Chi-square was used to compare proportions. Results 23,588 CT/GC NAATs were taken before and 21,588 after the introduction of the new rapid STI service of which 684(2.9%) and 766(3.5%) were GC-positive respectively. GC cultures dropped from 10881 to 6022 after November 2019 with the proportion of cultures to NAATs decreasing from 0.46 to 0.28 (p<0.0001 Chi-square). This proportion decreased over each 4-month period after November 2019: 0.46(3472/7531), 0.29(1999/6950); and 0.08(551/7107) (p<0.0001 Chi-square). There was no significant difference between the proportions of GC NAAT-positive and culture-positive specimens before and after the introduction of the new service: 0.35 (237/684) against 0.35 (265/7660) respectively (p=1.0 Chi-square). The proportion of culture-positive specimens was not significantly different in each 4-month period after Nov-2019: 0.36(91/256); 0.38(102/267) and 0.30(72/243) (p=0.12 Chi-square). 86% of NAAT-positive sites had a culture swab taken in the last 4 months compared to >95% in previous 8 months. Conclusions Implementation of the rapid STI service resulted in fewer GC-culture specimens being taken which reduced the cost of GC-culture but with no loss in GC-culture sensitivity overall.

Background Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has helped reduce new HIV infections. However, bacterial sexually transmitted infections (STIs) have increased among PrEP users. We examined PrEP knowledge, access, and risk perceptions in an age of antimicrobial resistance (AMR). Methods An online anonymous survey was distributed to all cisgender men/transpersons who have sex with men attending a sexual health clinic in Bristol, United Kingdom (October 2018 to November 2019). Interviews with a sample identified at increased risk of HIV were analyzed thematically and integrated with survey data. Results Five hundred and seventy-eight (95%) of 617 cisgender men/transpersons who have sex with men survey respondents were HIV-negative/unknown, of these, 202 (34.9%) had ever used PrEP. Interviewees (n = 24) reported widespread awareness of and enthusiasm for PrEP. Among nonusers, 39% (146/376) were unaware how to access PrEP, and 27% (103/376) could not access PrEP through the national “impact” trial of whom 79% (81/103) were eligible. The PrEP was described as “life-changing,” but expense was the main barrier to use. Sixty-two percent (358/578) of HIV-negative/unknown respondents on PrEP were more likely to have condomless anal intercourse with someone they thought was HIV-negative. Interviewees used PrEP with other risk-reduction strategies. Sexually transmitted infections were seen as “curable” and AMR rarely influenced risk perception or sexual decision making. Conclusions The PrEP awareness was high, but purchase cost limited access. PrEP may increase condomless anal intercourse, but interviewees used PrEP as one of many risk-reduction tools. Reduced fear of HIV transmission and testing was highly valued. Sexually transmitted infection AMR was not seen as an immediate threat and did not influence risk perception or sexual decision making.

Background. Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Plasmid gene protein 3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA). Methods. We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI >= 50 000; low-positive was MFI > 551-<50 000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (CI) were compared for women with chlamydial infection, self-reported PID, and infertility. Results. Of 2339 women aged 18-39 years, 1725 (73.7%) had sera, and 1425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had lowpositive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]). Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab. Conclusions. High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection.

BACKGROUND:Pelvic inflammatory disease (PID) is an outcome measure for the evaluation of chlamydia screening programs. We explore PID diagnoses in specialist sexual health services (SSHSs) in England to inform the evaluation of the National Chlamydia Screening Programme, which was implemented nationally in 2008.METHODS:We conducted descriptive analyses using data on diagnoses of PID-with and without Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC)-by age and year of birth, in SSHSs between 2009 and 2019 from the GUMCAD STI Surveillance System database. Rates were calculated per 100 000 females residing in England.RESULTS:CT screening activity peaked in 2010. The rates of all PID diagnoses decreased between 2009 and 2019 by 39%. CT-associated PID (CT-PID) declined by 58%, and nonspecific PID declined by 37%. GC-PID increased by 34%. CT-PID decreased across all age groups with the highest observed decline, 71%, in 15- to 19-year-olds. A dose-response relationship was observed between CT-PID rates and screening, with rates lowest in those with the greatest exposure to screening.CONCLUSIONS:There was a marked decline in diagnoses of CT-PID, and nonspecific PID, at SSHSs after the introduction of widespread chlamydia screening, whereas GC-PID diagnoses increased. This ecological trend was broadly consistent with what we would have expected to see if widespread screening reduced the incidence of chlamydia-associated PID (and of nonspecific PID), as has been observed in randomized controlled trials of screening.

Abstract Urethritis is defined as detectable urethral inflammation in the presence of symptoms or an observable urethral discharge. It is conventionally classified into gonococcal urethritis (GU, caused by Neisseria gonorrhoeae) and non-gonococcal urethritis (NGU, caused by Chlamydia trachomatis, Mycoplasma genitalium, and other causes, but with no known pathogen detected in over 30% of cases). Diagnosis is by urethral smear and microbiological investigations. Treatment with appropriate antibiotics should be given only to those with proven urethritis, and the diagnosis and its implications should be discussed with the patient. Partner notification is essential, not only to prevent re-infection but also to prevent onward transmission from partner(s) and the development of complications if left untreated.

Chlamydiae are pathogenic bacteria that likely evolved from host-independent, Gram-negative ancestors. Chlamydiae depend on a eukaryotic host cell for their replication which takes place in an inclusion inside the host cell, and for their dispersal, cell lysis, or extrusion subsequently occurs. Although the phylum Chlamydiae (order Chlamydiales) was originally thought to only contain one family, the Chlamydiaceae, a total of nine families are now recognized. The genus Chlamydia remains the most widely studied. The species Chlamydia trachomatis was proposed some decades ago on the basis of 16S rRNA and 23S rRNA sequences, to belong to the genus Chlamydia together with C. muridarum and C. suis. This chapter primarily focuses on the species C. trachomatis, which causes disease of ocular trachoma (serovars A–C), oculo-anogenital tract infection (serovars D–K) and lymphogranuloma venereum (serovars L1–L3). However, infections caused by C. pneumoniae and C. psittaci are also discussed.

This case-control study assesses the association between past Chlamydia trachomatis infection with first-trimester miscarriage by using an enzyme-linked immunosorbent assay to detect antibodies to the protein Pgp3.

Abstract Chlamydiae are pathogenic bacteria that likely evolved from host-independent, Gram-negative ancestors. Chlamydiae depend on a eukaryotic host cell for their replication which takes place in an inclusion inside the host cell, and for their dispersal, cell lysis, or extrusion subsequently occurs. Although the phylum Chlamydiae (order Chlamydiales) was originally thought to only contain one family, the Chlamydiaceae, a total of nine families are now recognized. The genus Chlamydia remains the most widely studied. The species Chlamydia trachomatis was proposed some decades ago on the basis of 16S rRNA and 23S rRNA sequences, to belong to the genus Chlamydia together with C. muridarum and C. suis. This chapter primarily focuses on the species C. trachomatis, which causes disease of ocular trachoma (serovars A–C), oculo-anogenital tract infection (serovars D–K) and lymphogranuloma venereum (serovars L1–L3). However, infections caused by C. pneumoniae and C. psittaci are also discussed.

Chlamydiae are pathogenic bacteria that likely evolved from host-independent, Gram-negative ancestors. Chlamydiae depend on a eukaryotic host cell for their replication which takes place in an inclusion inside the host cell, and for their dispersal, cell lysis, or extrusion subsequently occurs. Although the phylum Chlamydiae (order Chlamydiales) was originally thought to only contain one family, the Chlamydiaceae, a total of nine families are now recognized. The genus Chlamydia remains the most widely studied. The species Chlamydia trachomatis was proposed some decades ago on the basis of 16S rRNA and 23S rRNA sequences, to belong to the genus Chlamydia together with C. muridarum and C. suis. This chapter primarily focuses on the species C. trachomatis, which causes disease of ocular trachoma (serovars A–C), oculo-anogenital tract infection (serovars D–K) and lymphogranuloma venereum (serovars L1–L3). However, infections caused by C. pneumoniae and C. psittaci are also discussed.