Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care

Abstract

BackgroundIn women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated. It is unknown whether anorectal CT may play a role in post-treatment transmission. This study, called FemCure, in women who receive routine treatment (either azithromycin or doxycycline) aims to understand the post-treatment transmission of anorectal CT infections, i.e., from their male sexual partner(s) and from and to the genital region of the same woman. The secondary objective is to evaluate other reasons for CT detection by nucleic acid amplification techniques (NAAT) such as treatment failure, in order to inform guidelines to optimize CT control.MethodsA multicentre prospective cohort study (FemCure) is set up in which genital and/or anorectal CT positive women (n = 400) will be recruited at three large Dutch STI clinics located in South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and 12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT type (by multilocus sequence typing). Sexual exposure is assessed by online self-administered questionnaires and by testing samples for Y chromosomal DNA. Using logistic regression models, the impact of two key factors (i.e., sexual exposure and alternate anatomic site of infection) on detection of anorectal and genital CT will be assessed.DiscussionThe FemCure study will provide insight in the role of anorectal chlamydia infection in maintaining the CT burden in the context of treatment, and it will provide practical recommendations to reduce avoidable transmission. Implications will improve care strategies that take account of anorectal CT.Trial registrationClinicalTrials.gov Identifier: NCT02694497.

Viability-PCR Shows That NAAT Detects a High Proportion of DNA from Non-Viable Chlamydia trachomatis

“…Furthermore, the clinical sample size in this study was with 50 women, relatively small. In a currently ongoing study, FemCure [30], we will focus on the assessment of CT viability by V-PCR in clinical samples of a larger cohort of CT positive women. Finally, heat-inactivation of CT cultures has shown to be an effective method to obtain non-viable CT samples used for the method validation in this study.…”

Participation, retention, and associated factors of women in a prospective multicenter study on Chlamydia trachomatis infections (FemCure)

“…The first doxycycline and azithromycin doses were directly observed. In this context, we set up a cohort study with 3 months of follow-up (Fig 1) [15].…”

“…Here, we report on the FemCure study, the first prospective research that systematically addresses rectal Chlamydia trachomatis (CT) in women [15]. FemCure included 560 women from three Dutch STI clinics and followed them for 3 months with systematic rectal and vaginal CT assessment.…”

“…The main treatments are doxycycline and azithromycin [19,20], although, the efficacy of azithromycin in the treatment of CT is debatable [21]. FemCure was set up to improve our understanding of posttreatment rectal and vaginal CT detection in women, by assessing risks due to sexual exposure (horizontal transmission) or exposure from adjacent body sites (self-infection), and by assessing the role of possibly suboptimal treatment effectiveness [15].…”

Pathogenic Interplay Between Chlamydia trachomatis and Neisseria gonorrhoeae that Influences Management and Control Efforts—More Questions than Answers?

“…A 2018 study of human gastrointestinal biopsy tissue found CT in the appendix of one female specimen, but this was compatible with sexually transmitted ascending infection [26], and there is no empirical evidence of autoinfection. A prospective cohort study in the Netherlands (FemCure), which will collect specimens for routine NAATs, PCR for detection of CT viability, culture, and genotyping, should help shed light on the potential role of rectal CT in women [27].…”