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      Evaluation of a PGP3 ELISA for surveillance of the burden of Chlamydia infection in women from Australia and Samoa

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          ABSTRACT

          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 ( < 0.0001), but not when compared to women with current chlamydial infection ( = 0.44). In the Samoan study, where the prevalence of chlamydial infections is much higher there were significant differences in the PGP3 ELISA absorbance levels between chlamydial sub-fertile women and fertile women ( = 0.003). There was no difference between chlamydial sub-fertile women and women with a current infection ( = 0.829). The results support that the PGP3 assay is effective for sero-epidemiological analysis of burden of infection, but not for evaluation of chlamydial pathological sequelae such as infertility.

          Abstract

          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.

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          Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women.

          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.
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            Chlamydia trachomatis Pgp3 Antibody Persists and Correlates with Self-Reported Infection and Behavioural Risks in a Blinded Cohort Study

            Chlamydia trachomatis (Ct) serological studies in populations could help monitor changes in lifetime cumulative risk of infection. We developed a double-antigen sandwich ELISA based on the Ct-specific Pgp3 antigen, then tested blind stored sera from over 800 participants in a New Zealand birth cohort from Dunedin at ages 26, 32 and 38. The double-antigen sandwich ELISA was more sensitive than our previously characterised indirect Pgp3 ELISA. Pgp3 antibody was detected more often in women compared to men and correlated with increasing numbers of sexual partners, self-reported Ct, and younger age at sexual debut in both women and men. At age 26, 24.1% (99/411) of women were Pgp3 seropositive, as were 79.5% (35/44) of those reporting Ct infection; Pgp3 antibody persisted to age 38 in 96.5% (83/86). In men at age 26, the figures were 10.7% (47/442) and 25.0% (6/24), respectively, with high (83.9%) antibody persistence to age 38. At age 38, among those Pgp3 seropositive, 63.3% of women and 83.1% of men had not reported Ct infection. Thus, Ct-specific Pgp3 antibody was detected in most women reporting Ct infection and correlated with risk of infection in those who did not, with most infections remaining undetected. As this antibody persisted for at least twelve years in 96% of these women, serology could be used to evaluate Ct prevention programmes among women.
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              Chlamydia trachomatis Pgp3 Antibody Population Seroprevalence before and during an Era of Widespread Opportunistic Chlamydia Screening in England (1994-2012)

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

                Journal
                Pathog Dis
                Pathog Dis
                femspd
                Pathogens and Disease
                Oxford University Press
                2049-632X
                14 June 2019
                April 2019
                14 June 2019
                : 77
                : 3
                : ftz031
                Affiliations
                [1 ]School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia
                [2 ]Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia
                [3 ]Centre for International Health, University of Otago, Dunedin, 9016, New Zealand
                [4 ]School of Languages and Cultures, Victoria University of Wellington, Wellington, 2820, New Zealand
                [5 ]Samoa Cancer Society, Moto'otua Street, Apia, Samoa
                [6 ]Centre for Samoa Studies, National University of Samoa, Le Papaigalagala Campus, To'omatagi, Samoa
                [7 ]Samoa Family Health Association, Apia, Samoa
                [8 ]National Department of Health, Apia, Samoa
                [9 ]Samoan National Council of Churches, Apia, Samoa
                [10 ]Preventive and Social Medicine, Dunedin School of Medicine, The University of Otago, Dunedin, 9016, New Zealand
                [11 ]Planning, Funding and Health Outcomes, Waitemata and Auckland District Health Boards, Auckland, New Zealand
                [12 ]MIMR-PH Institute of Medical Research, Monash, Australia
                [13 ]UC Health Clinical School, The Wesley Hospital, Auchenflower, Queensland, 4066, Australia
                [14 ]Population Health Sciences, University of Bristol, Bristol, United Kingdom
                Author notes
                Corresponding author: PO BOX 123, Faculty of Science, University of Technology Sydney, Broadway, NSW, 2007, Australia. E-mail: Wilhelmina.Huston@ 123456uts.edu.au
                Article
                ftz031
                10.1093/femspd/ftz031
                6607412
                31201421
                f7d16bb6-dc90-4da1-af2a-da9ab3783b2b
                © FEMS 2019.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 03 September 2018
                : 10 June 2019
                Page count
                Pages: 5
                Funding
                Funded by: University of Technology Sydney 10.13039/501100001775
                Categories
                Research Article

                chlamydia,elisa,sero-epidemiology,serology,sub-fertility,tubal factor infertility

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