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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., (Published by Oxford University Press 2018.)

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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: SCW, AN and GM are employed by Public Health England. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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

Understanding of the burden of Chlamydia trachomatis infection and its clinical sequelae is hampered by the absence of accurate, well-characterized tests using serological methods to determine past exposure to infection. An "in-house" immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) based on the C. trachomatis-specific antigen Pgp3 was produced and evaluated against three commercial ELISAs derived from the major outer membrane protein: the Medac pELISA plus, the Savyon SeroCT-IgG ELISA, and the Ani Labsystems IgG enzyme immunoassay. Sensitivities and specificities were determined using sera from both male and female patients (n = 356) for whom C. trachomatis had been detected in the lower genital tract at least 1 month prior to the testing of the sample and from 722 Chlamydia-negative children aged 2 to 13 years. The Pgp3 ELISA was significantly more sensitive (57.9% [95% confidence interval {95% CI}, 52.7 to 62.9%]) than the Ani Labsystems (49.2% [95% CI, 44.0 to 54.3%]; P = 0.003), SeroCT (47.2% [95% CI, 42.1 to 52.4%]; P < 0.0005), and Medac (44.4% [95% CI, 39.3 to 49.6%]; P < 0.0005) ELISAs. The Pgp3, Ani Labsystems, and SeroCT assays, but not the Medac assay, had significantly higher sensitivity for female specimens than for male specimens (73.8 versus 44.2%, 59.8 versus 40.5%, 55.5 versus 40%, and 45.7 versus 43.7%, respectively). For female patients, the Pgp3 assay was 14.0% (95% CI, 5.5 to 22.5%) more sensitive than the next most sensitive ELISA, the Ani Labsystems assay (P = 0.001). There was no significant difference in specificity between the Pgp3 (97.6% [95% CI, 96.2 to 98.6%]), Ani Labsystems (99% [95% CI, 97.7 to 99.6%]), SeroCT (97.2% [95% CI, 95.7 to 98.2%]), and Medac (96% [95% CI, 94.3 to 97.2%]) ELISAs. None of the ELISAs showed evidence of cross-reactivity with antibodies to Chlamydia pneumoniae.

Background: Although understanding chlamydia incidence assists prevention and control, analyses based on diagnosed infections may distort the findings. Therefore, we determined incidence and examined risks in a birth cohort based on self-reports and serology.Methods: Self-reported chlamydia and behavior data were collected from a cohort born in New Zealand in 1972/3 on several occasions to age 38 years. Sera drawn at ages 26, 32, and 38 years were tested for antibodies to Chlamydia trachomatis Pgp3 antigen using a recently developed assay, more sensitive in women (82.9%) than men (54.4%). Chlamydia incidence by age period (first coitus to age 26, 26-32, and 32-38 years) was calculated combining self-reports and serostatus and risk factors investigated by Poisson regression.Results: By age 38 years, 32.7% of women and 20.9% of men had seroconverted or self-reported a diagnosis. The highest incidence rate was to age 26, 32.7 and 18.4 years per 1000 person-years for women and men, respectively. Incidence rates increased substantially with increasing number of sexual partners. After adjusting age period incidence rates for partner numbers, a relationship with age was not detected until 32 to 38 years, and then only for women.Conclusions: Chlamydia was common in this cohort by age 38, despite the moderate incidence rates by age period. The strongest risk factor for incident infection was the number of sexual partners. Age, up to 32 years, was not an independent factor after accounting for partner numbers, and then only for women. Behavior is more important than age when considering prevention strategies. [ABSTRACT FROM AUTHOR]