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Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT’s ability to promote EMT and to pinpoint the areas that merit further investigation.

BackgroundDue 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.MethodsWe 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.ResultsTests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (pThe 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 (pConclusionRising 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.

ObjectivesTo 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.DesignControlled interrupted time series study.SettingTwo sexual health services in UK: Unity Sexual Health in Bristol, UK (main site) and Croydon Sexual Health in London (control site).ParticipantsElectronic patient records for all attendances during the period one year before and one year after the intervention.InterventionIntroduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways.Outcome measuresTime-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.ResultsTime-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 studyWe used controlled interrupted time series models with confounder adjustment to estimate the effect of the intervention distinct from any background changes and independent of other time varying factors.Model validity was bolstered by using a relatively long time series with good temporal resolution.Data from both the main and control sites was derived from the same electronic patient record system.There was a general consensus between main and sensitivity analyses.Our study was limited by being non-randomised, having only one control site, and the follow up period for females being truncated by the impact of the Covid-19 pandemic.

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– 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.

BackgroundPelvic 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.MethodsWe 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.ResultsCT 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.ConclusionsThere 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.

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 paper, 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.Chlamydia trachomatis (CT) is the most common sexually transmitted bacteria in the world[1]. In CT-infected women who go untreated, approximately 17% develop pelvic inflammatory disease (PID), inflammation of upper genital tract structures, and this may result in chronic sequelae, including ectopic pregnancy and tubal factor infertility (TFI)[2]. In the United Kingdom, it has been estimated that CT causes approximately 35% of PID cases in women under 25 years of age and 20% in aged 16-44 years[2, 3]. Other PID-associated pathogens include Neisseria gonorrhoeae, Mycoplasma genitalium, and bacterial vaginosis-associated bacteria [4]. The majority of symptomatic PID cases have no pathogen identified[2, 4, 5]. Further, many PID cases remain undiagnosed due to atypical or absent symptoms [2-4]. There is good evidence from a longitudinal cohort study of 1884 women with PID that the persistence of fallopian tube pathology (adhesions/scarring) can cause infertility in women – tubal factor infertility (TFI)[5]. Only women with PID who have macroscopic fallopian tube inflammation (salpingitis) are at risk of TFI, which is present in some but not all diagnosed PID[2, 5]. A dose response relationship has been observed with more severe macroscopic salpingitis and more PID episodes leading to a greater risk for adverse reproductive outcomes, especially for CT infection[2, 5, 6]. There is also evidence that upper genital tract CT infection may also impair fertility in the absence of tubal pathology, this is reviewed elsewhere in this supplement by Horner et al

Background A pilot using point-of-care (POC) technology for men with urethritis symptoms found most patients (80%) prefer same day results. We designed a new pathway for managing these patients. Methods Through this pathway, symptomatic men had a nucleic acid amplification test for chlamydia and gonorrhoea (CT/GC NAAT) in clinic, and returned for treatment, usually the same day. Use of Panther (Hologic Inc) at POC provided rapid CT/GC NAAT results within four hours. Microscopy was limited to those testing CT/GC NAAT-negative. GC-culture was sent if GC-positive, when treatment was administered. If CT/GC NAAT-negative and non-gonococcal urethritis (NGU) negative the patient was reassured with information on why they might be experiencing pain (anxiety can increase pelvic floor muscle tone resulting in referred pain and genitourinary symptoms), guided on how to relax their pelvic floor, and advised to re-attend if symptoms persisted. We compared outcomes (Chi-square) over 6 weeks post-implementation in 2020, to 12 weeks in 2014/15. Results Of 265 symptomatic men in the new pathway, 33/265(12.5%) had CT and 30/265 (11.3%) GC, similar to rates (p>0.5) in 2014/15 with 59/431(13.7%) and 45/431(10.4%) respectively. 40/264(15.1%) GC-culture specimens were sent, compared to 385/431 (89.3%)(p With our new pathway, 180/265(67.9%) proceeded to microscopy, with NGU diagnosed in 61 (23%) compared to 385/431(89.3%)(p Conclusions The new rapid service resulted in quicker diagnosis with prompt and specific antimicrobial treatment, reducing the cost and inconvenience of unnecessary microscopy and GC-culture. Patient outcomes and management costs have also improved by reducing reattendance. The new pathway facilitates prompt partner notification, minimising onward STI transmission.

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– 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.

Background Unity Sexual Health in Bristol UK, re-designed its service to improve access and delivery of care. This includes a Panther (Hologic Inc) system at the point of care to provide rapid STI tests, allowing Nucleic acid amplification testing results for STIs including gonorrhoea and chlamydia to be available within four hours. Previously patients waited over a week for results. Methods A qualitative evaluation running alongside the implementation of the new service, to understand experiences, and inform its iterative development. A total of 21 members of staff and 26 patients were interviewed, and 40 hours of observations conducted of the service in operation, were analysed thematically. Results The new service implementation required co-ordinated changes in practice across multiple staff teams. Patients also needed to make changes to how they accessed the service. Multiple small ‘pilots’ of process changes were necessary to find workable options. This responsive model created challenges for delivering comprehensive training/communication in advance to all staff. However, staff worked together to adjust and improve the new service, and morale was buoyed through observing positive impacts on patient care. Patients valued faster results and avoiding unnecessary treatment. They were willing to drop off samples and return for a follow-up appointment the same/next day, enabling infection-specific treatment in accordance with test results thus improving antimicrobial stewardship. Conclusions Implementation of service changes to improve access and delivery of care in the context of stretched resources can pose challenges for staff at all levels. Early evaluation of pilots of process change, provide opportunities for prompt feedback enabling adjustment, is valued. Visibility to staff of positive impacts on patient care is important in maintaining morale. The service was acceptable to patients.

Background Unity Sexual Health, Bristol UK, introduced a Panther (Hologic Inc) system in November 2018 at point-of-care. This rapid Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) nucleic acid amplification test (NAAT) provides results to patients within 4–48 working hours compared with 1–2 weeks previously. Patients are now only treated if CT NAAT-positive, symptomatic and unable to wait for results, or a sexual contact of CT/GC within the preceding 2 weeks. We hypothesised the new service would result in more rapid treatment of CT/GC infections. We evaluate the effect on time to CT treatment. Methods All new CT NAAT-positive cases attending over a 2-month period, 1 year before and 1 year after the introduction of the new service were evaluated (01/01/2018–28/02/2018 and 01/01/2020–28/02/2020). Dates of NAAT testing and treatment were obtained from electronic patient records. The one-sided Mann-Whitney U-test was used to compare time to treatment before and after service introduction. Results 134 CT-positive patients were diagnosed before and 116 were diagnosed after service introduction. Of these, 2 (1.5%) and 8 (6.9%) respectively were treated elsewhere and excluded. Average time to treatment decreased from 6.5 to 4.1 days (p = 0.09). When we excluded patients treated as contacts of CT (before NAAT result was available) the time to treatment decreased from 8.7 to 5.1 days (p Conclusions Introduction of a rapid STI service significantly reduced time from testing to treatment of CT. Availability of microscopy for symptomatic men allows immediate treatment of urethritis, a common presentation of CT in men. This probably explains why men were treated earlier than women. Earlier treatment is expected to reduce both asymptomatic CT transmission, and risk of CT complications, particularly in women.

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 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 The 2019 updated NICE abortion guidance suggested that prophylactic antibiotics should no longer be routinely given for medical abortions and instead recommended individual risk assessment. Untreated Chlamydia trachomatis is an important cause of severe infection post abortion. In 2002, 75 (7.5%) of 998 women having an abortion tested chlamydia-positive using a nucleic acid amplification test (NAAT). Women attending our abortion service have been tested for Chlamydia using a NAAT. We wished to obtain contemporary estimates of Chlamydia prevalence and examine associated risk factors. Methods Data from 13,427 women aged 15–50 years having an abortion between April 2010 and March 2020, was retrospectively analysed (SPSS, IBM). Ethics approval was sought and all data was anonymised. Results Of 13,337 with Chlamydia NAAT results available, 4.2% (565) were Chlamydia-positive. Chlamydia was associated with younger age (p Conclusion Chlamydia prevalence in women undergoing an abortion is lower than that observed in 2002 but is higher than the general population. Although Chlamydiawas associated with 2 or more partners in the previous year in women aged over 19 years, the association is weaker than that observed in the general population and no association was observed with partner change in women aged 15–19 years old

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.

Objective: To examine the association between age at period cessation (by type of period cessation) and trajectories of anthropometry, blood pressure, lipids and HBA1c from midlife to age 70 years. Methods: We used data from the UK Medical Research Council National Survey of Health and Development (NSHD) to examine the association between age at period cessation and trajectories of triglyceride, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and glycated haemoglobin (HBA1c) from 53 to 69 years and measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC) from 36 to 69 years. Results: We found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-c and HDL-c from 53 to 69 years and trajectories of SBP or DBP from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HBA1C, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null. Conclusion: How and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impacts over the long term are small.

ObjectivesAntimicrobial susceptibility data for Chlamydia trachomatis are lacking. Methodologies for susceptibility testing in C. trachomatis are not well-defined, standardized or performed routinely owing to its intracellular growth requirements. We sought to develop an assay for the in vitro susceptibility testing of C. trachomatis isolates from two patient cohorts with different clinical outcomes.MethodsTwenty-four clinical isolates (11 from persistently infected and 13 from successfully treated patients) were overlaid with media containing two-fold serial dilutions of azithromycin or doxycycline. After incubation, aliquots were removed from the stock inoculum (SI) and each antimicrobial concentration for total RNA extraction, complementary DNA generation and real-time PCR. The MIC was defined as the lowest antimicrobial concentration where a 95% reduction in transcription was evident in comparison with the SI for each isolate.ResultsMICs of azithromycin were comparable for isolates from the two patient groups (82% ≤ 0.25 mg/L for persistently infected and 100% ≤ 0.25 mg/L for successfully treated patients). Doxycycline MICs were at least two-fold lower for isolates from the successfully treated patients (53.9% ≤ 0.064 mg/L) than for the persistently infected patients (100% ≥ 0.125 mg/L) (P = 0.006, Fisher’s exact test). Overall, 96% of isolates gave reproducible MICs when re-tested.ConclusionsA reproducible assay was developed for antimicrobial susceptibility testing of C. trachomatis. MICs of azithromycin were generally comparable for the two different patient groups. MICs of doxycycline were significantly higher in the persistently infected patients. However, interpretation of elevated MICs in C. trachomatis is extremely challenging in the absence of breakpoints, or wild-type and treatment failure MIC distribution data.

BackgroundHighly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings.MethodsSamples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests.ResultsT. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24/530, symptomatic) and 1.7% (27/1584, asymptomatic); in primary care 2.7% (94/3499, symptomatic) and 1.2% (41/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost £260 per positive case diagnosed compared with £716 using current microbiological tests.ConclusionsAptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.

BackgroundThere is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens.MethodsThe online databases PubMed and Medline were searched using terms “Mycoplasma genitalium”, “macrolide” or “azithromycin” and “resistance” up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates.ResultsEight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027).ConclusionAzithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.

Mycoplasmagenitalium is one of the major causes of nongonococcal urethritis (NGU) worldwide but an uncommon sexually transmitted infection (STI) in the general population. The risk of sexual transmission is probably lower than for Chlamydia trachomatis. Infection in men is usually asymptomatic and it is likely that most men resolve infection without developing disease. The incubation period for NGU caused by Mycoplasma genitalium is probably longer than for NGU caused by C. trachomatis. The clinical characteristics of symptomatic NGU have not been shown to identify the pathogen specific etiology. Effective treatment of men and their sexual partner(s) is complicated as macrolide antimicrobial resistance is now common in many countries, conceivably due to the widespread use of azithromycin 1 g to treat STIs and the limited availability of diagnostic tests for M. genitalium. Improved outcomes in men with NGU and better antimicrobial stewardship are likely to arise from the introduction of diagnostic M. genitalium nucleic acid amplification testing including antimicrobial resistance testing in men with symptoms of NGU as well as in their current sexual partner(s). The cost effectiveness of these approaches needs further evaluation. The evidence that M. genitalium causes epididymo-orchitis, proctitis, and reactive arthritis and facilitates human immunodeficiency virus transmission in men is weak, although biologically plausible. In the absence of randomized controlled trials demonstrating cost effectiveness, screening of asymptomatic men cannot be recommended.

Serological assays can be used to investigate the population burden of infection and potentially sequelae from Chlamydia. We investigated the PGP3 ELISA as a sero-epidemiological tool for infection or sub-fertility in Australian and Samoan women. The PGP3 ELISA absorbance levels were compared between groups of women with infertility, fertile, and current chlamydial infections. In the Australian groups, women with chlamydial tubal factor infertility had significantly higher absorbance levels in the PGP3 ELISA compared to fertile women (P, The PGP3 ELISA has potential for sero-epidemiological studies of current and/or past chlamydial infection of women in a variety of settings, including high prevalence.

Rates of bacterial sexually transmitted infections (STIs) continue to rise, demanding treatments to be highly effective. However, curing infections faces significant challenges due to antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium and especially treating STIs at extragenital sites, particularly rectal chlamydia and oropharyngeal gonorrhoea. As no new antimicrobials are entering the market, clinicians must optimize the currently available treatments, but robust data are lacking on how the properties or pharmacokinetics of antimicrobials can be used to inform STI treatment regimens to improve treatment outcomes. This paper provides a detailed overview of the published pharmacokinetics of antimicrobials used to treat STIs and how factors related to the drug (tissue distribution, protein binding and t½), human (pH, inflammation, site of infection, drug side effects and sexual practices) and organism (organism load and antimicrobial resistance) can affect treatment outcomes. As azithromycin is commonly used to treat chlamydia, gonorrhoea and M. genitalium infections, and its pharmacokinetics are well studied, it is the main focus of this review. Suggestions are also provided on possible dosing regimens when using extended and/or higher doses of azithromycin, which appropriately balance efficacy and side effects. The paper also emphasizes the limitations of currently published pharmacokinetic studies including oropharyngeal gonococcal infections, where very limited data exist around ceftriaxone pharmacokinetics and its use in combination with azithromycin. In future, the different anatomical sites of infections may require alternative therapeutic approaches.

Background and objectivesThe evidence base supporting the National Chlamydia Screening Programme, initiated in 2003, has been questioned repeatedly, with little consensus on modelling assumptions, parameter values or evidence sources to be used in cost-effectiveness analyses. The purpose of this project was to assemble all available evidence on the prevalence and incidence ofChlamydia trachomatis(CT) in the UK and its sequelae, pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI) to review the evidence base in its entirety, assess its consistency and, if possible, arrive at a coherent set of estimates consistent with all the evidence.MethodsEvidence was identified using ‘high-yield’ strategies. Bayesian Multi-Parameter Evidence Synthesis models were constructed for separate subparts of the clinical and population epidemiology of CT. Where possible, different types of data sources were statistically combined to derive coherent estimates. Where evidence was inconsistent, evidence sources were re-interpreted and new estimates derived on a post-hoc basis.ResultsAn internally coherent set of estimates was generated, consistent with a multifaceted evidence base, fertility surveys and routine UK statistics on PID and EP. Among the key findings were that the risk of PID (symptomatic or asymptomatic) following an untreated CT infection is 17.1% [95% credible interval (CrI) 6% to 29%] and the risk of salpingitis is 7.3% (95% CrI 2.2% to 14.0%). In women aged 16–24 years, screened at annual intervals, at best, 61% (95% CrI 55% to 67%) of CT-related PID and 22% (95% CrI 7% to 43%) of all PID could be directly prevented. For women aged 16–44 years, the proportions of PID, EP and TFI that are attributable to CT are estimated to be 20% (95% CrI 6% to 38%), 4.9% (95% CrI 1.2% to 12%) and 29% (95% CrI 9% to 56%), respectively. The prevalence of TFI in the UK in women at the end of their reproductive lives is 1.1%: this is consistent with all PID carrying a relatively high risk of reproductive damage, whether diagnosed or not. Every 1000 CT infections in women aged 16–44 years, on average, gives rise to approximately 171 episodes of PID and 73 of salpingitis, 2.0 EPs and 5.1 women with TFI at age 44 years.Conclusions and research recommendationsThe study establishes a set of interpretations of the major studies and study designs, under which a coherent set of estimates can be generated. CT is a significant cause of PID and TFI. CT screening is of benefit to the individual, but detection and treatment of incident infection may be more beneficial. Women with lower abdominal pain need better advice on when to seek early medical attention to avoid risk of reproductive damage. The study provides new insights into the reproductive risks of PID and the role of CT. Further research is required on the proportions of PID, EP and TFI attributable to CT to confirm predictions made in this report, and to improve the precision of key estimates. The cost-effectiveness of screening should be re-evaluated using the findings of this report.FundingThe Medical Research Council grant G0801947.

BackgroundSeroprevalence 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.MethodsWe 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.Results919 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.ConclusionSeropositivity 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.

© 2018 Elsevier Ltd 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.

Chronic pelvic pain is a common condition in men that is defined as 3 months of pain or discomfort in the pelvic region associated with urinary symptoms and/or sexual dysfunction. It is a diagnosis of exclusion and the aetiology is poorly understood. Hypotheses include increased pelvic floor tone as well as infective and inflammatory causes. Given the wide variation in symptoms and potential causes, it is important to spend time collating an individual patient's symptom profile so that the management plan can be tailored appropriately. A national multidisciplinary consensus guideline recommends a multidisciplinary team approach with pharmacotherapeutic, physical and psychosocial components integrated into a holistic treatment programme individualized to the patient. Management is likely to include a combination of interventions such as antibiotics, α-adrenergic antagonists and simple analgesics, alongside pelvic floor relaxation and psychological support. Detailed discussion with patients about the feedback loops involved in pelvic muscle tension and pelvic pain has also been found to be therapeutically beneficial.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

Where did it all go wrong? Azithromycin, a second generation macrolide antimicrobial, has been demonstrated to be highly efficacious both in vitro (low minimum inhibitory concentration (MIC)) and in vivo against the common bacterial STIs Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) and has good treponemicidal activity in animal studies.1 ,2 w1 w2 What's more its long half-life particularly intracellularly enabled it to be administered as single-dose directly observed therapy, the preferred dosing schedule for STIs where poor compliance, and thus potential reduced efficacy, was considered a major concern with multidose regimens.3 Indeed its efficacy against chlamydia was considered to be so good, a test of cure was not considered necessary. I argue that the evidence indicates that azithromycin 1 g is no longer at least 95% effective in achieving microbiological cure for bacterial STIs as recommended by WHO for first-line treatment and therefore should not be used for treatment.4 In addition, as monotherapy, it is likely to be doing harm by inducing macrolide antimicrobial resistance. First, it is necessary to consider the mode of action and pharmacokinetics of azithromycin given as a 1 g stat regimen (figure 1) and its mechanism of action; second, the mechanism of macrolide antimicrobial development and third, reappraise the evidence of efficacy in vivo against the common bacterial STIs, NG, syphilis, CT, MG and non-gonococcal urethritis (NGU). Figure 1 Anticipated serum and tissue concentrations after administration of azithromycin 1 g (adapted from Foulds and Johnson)1 and hypothetical change in serum concentration 5–10 days postadministration. Courtesy of Mr Peter Greenhouse FRCOG. CT, Chlamydia trachomatis ; MG, Mycoplasma genitalium ; MIC, minimum inhibitory concentration. Azithromycin is a bacteriostatic antibiotic and duration of exposure to levels >MIC 90 are likely to be important in determining microbiological cure, particularly if the micro-organism is slow growing.5 …

Miscarriage affects ~20% of pregnancies and maternal infections account for ~15% of early miscarriages. Chlamydia trachomatis (Ct) has been associated with miscarriage but the underlying mechanisms are unknown. Successful implantation requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy requires angiogenesis, establishment of the correct cellular milieu and trophoblast invasion, all of which involve the action of chemokines. Our objective was to determine whether Ct infection impacts upon ESC decidualisation and chemokine secretion. Human primary ESC were decidualised in-vitro, infected with Ct serovar E, and changes in expression of genes of interest were measured using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that Ct can infect and proliferate in ESC. Expression of the decidualisation marker prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct infection altered the chemokine profile of decidualised ESC as shown by proteomic array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were analysed further and expression was reduced in infected decidualised cells at mRNA and protein levels. Our data indicate that Ct infection of ESC impairs decidualisation and alters chemokine release. These findings at least partially explain how Ct infection could result in adverse pregnancy outcomes.

Making a prompt and accurate diagnosis of genital tract infections is the key to instituting appropriate treatment and the linchpin of sexually transmitted infection control. We present a brief history, not covering syphilis, of diagnostic events for each of six bacteria and one protozoan from the time of discovery up to the molecular revolution. The latter is touched upon but its impact will form the substance of a further presentation. Here, hindsight is helpful in understanding the way in which progress was made over 135 years, often when microbiology, not even seen as a distinct discipline, had a difficult time in providing what was required in terms of dependable diagnostic techniques. Gram-staining, growth on artificial media, growth in cultured cells, enzyme immunoassays, metabolic and immunofluorescence tests have all had their place and some still do despite the avalanche of the molecular era. Serology to determine the existence of organism-specific antibodies has been important in managing syphilis, but has only sometimes been helpful in supporting a diagnosis for other infections and has rarely been the primary deciding factor.

OBJECTIVES: To estimate the costs and benefits of clinical pathways incorporating a point of care (POC) nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea in genitourinary medicine (GUM) clinics compared with standard off-site laboratory testing. METHOD: We simulated 1.2 million GUM clinic attendees in England. A simulation in Microsoft Excel was developed to compare existing standard pathways of management for chlamydia and gonorrhoea with a POC NAAT. We conducted scenario analyses to evaluate the robustness of the model findings. The primary outcome was the incremental cost-effectiveness ratio. Secondary outcomes included the number of inappropriate treatments, complications and transmissions averted. RESULTS: The baseline cost of using the point of POC NAAT was £103.9 million compared with £115.6 million for standard care. The POC NAAT was also associated with a small increase of 46 quality adjusted life years, making the new test both more effective and cheaper. Over 95 000 inappropriate treatments might be avoided by using a POC NAAT. Patients receive diagnosis and treatment on the same day as testing, which may also prevent 189 cases of pelvic inflammatory disease and 17 561 onward transmissions annually. DISCUSSION: Replacing standard laboratory tests for chlamydia and gonorrhoea with a POC test could be cost saving and patients would benefit from more accurate diagnosis and less unnecessary treatment. Overtreatment currently accounts for about a tenth of the reported treatments for chlamydia and gonorrhoea and POC NAATs would effectively eliminate the need for presumptive treatment.

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.

SUMMARYInformation on the incidence of Chlamydia trachomatis (CT) is essential for models of the effectiveness and cost-effectiveness of screening programmes. We developed two independent estimates of CT incidence in women in England: one based on an incidence study, with estimates ‘recalibrated’ to the general population using data on setting-specific relative risks, and allowing for clearance and re-infection during follow-up; the second based on UK prevalence data, and information on the duration of CT infection. The consistency of independent sources of data on incidence, prevalence and duration, validates estimates of these parameters. Pooled estimates of the annual incidence rate in women aged 16–24 and 16–44 years for 2001–2005 using all these data were 0·05 [95% credible interval (CrI) 0·035–0·071] and 0·021 (95% CrI 0·015–0·028), respectively. Although, the estimates apply to England, similar methods could be used in other countries. The methods could be extended to dynamic models to synthesize, and assess the consistency of data on contact and transmission rates.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

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Objectives This study aims to describe the patterns of testing and retesting for chlamydia in Cornwall during the first 5 years of the National Chlamydia Screening Programme. We evaluate the factors associated with retesting and estimate the incidence of chlamydia diagnosis and repeat diagnosis. Methods Study design: Secondary database analysis. Selection criteria: men and women tested for chlamydia between March 2003 and January 2009 in Cornwall, aged ≥12 years and ≤25 years at the first test. The factors associated with retesting in those with at least one known test result and at least 14 days follow-up time were analysed using Cox regression and the incidence of diagnosis and repeat diagnosis were calculated. Results The final dataset consisted of 71 066 records from 49 941 individuals; of whom 59.0% were female and 75.4% were only tested once. There were 48 375 individuals with at least one known test result (negative or positive) and at least 14 days follow-up, included in the Cox regression analysis. Factors associated with testing more than once were (adjusted HR, 95% CI): being female (2.24; 2.14 to 2.34) and initially testing positive (1.43; 1.35 to 1.51). The positivity at first episode declined from 13.2% (1077 cases) in 2003/2004 to 5.8% (843 cases) in 2008/2009. The incidence of diagnosis at the second test was 5.9 per 100 person years in those testing negative at the first test compared with 18.1 per 100 person years in those initially positive. Discussion Most individuals in this analysis were tested only once, but the testing volume and proportion of repeat tests were highest at the end of the study period. As the testing rate stabilises to 30% coverage, maintaining retesting rates in those previously tested and especially in those previously diagnosed with chlamydia will be necessary for the sustainability of the screening programme. Conclusions A key feature of the next 5 years of the screening programme will be to maintain screening and rescreening.

Individuals with lymphogranuloma venereum (LGV), caused by Chlamydia trachomatis serovar L2, are commonly co-infected with human immunodeficiency virus type 1 (HIV-1), for reasons that remain unknown. One hypothesis is that a biological synergy exists between the two pathogens. We tested this by characterising for the first time in vitro C. trachomatis L2 replication in the presence of HIV-1. The human epithelial cell-line, MAGI P4R5 was infected with C. trachomatis L2 and HIV-1 (MN strain). Co-infected cultures contained fewer and larger chlamydial inclusions, but the inclusions did not contain morphologically aberrant organisms. C. trachomatis remained infectious in the presence of HIV-1 and showed neither an alteration in genome accumulation, nor in the acumulation of ompA, euo or unprocessed 16S rRNA transcripts. However, omcB was slightly elevated. Taken together, these data indicate that HIV-1 co-infection did not significantly alter C. trachomatis replication and the association between HIV-1 and LGV is likely due to other factors that require further investigation. The fewer, larger inclusions observed in co-infected cultures probably result from the fusion of multiple inclusions in HIV-1 induced syncytia and indicate that C. trachomatis-host-cell interactions continue to function, despite considerable host-cell re-modelling.

Background Opportunistic chlamydia screening of

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michael's Hospital in Bristol, United Kingdom, during the period 1985-1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis Further studies using modern assays in contemporary, representative populations should be undertaken.

ly systematic review and meta-analysis of azithromycin 1 g treatment studies of Mycoplasma genitalium ,b y Lau et al

SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.