The Epidemiology and Management of Rectal Chlamydia

© 2021 Andrew LauThesis Summary Introduction Chlamydia trachomatis (“chlamydia”) is the most commonly reported sexually transmitted infection (STI) in the world. Untreated, chlamydia is associated with serious reproductive sequelae in women including infertility. Rectal chlamydia is an important public health problem in Australia with rates rising dramatically among men who have sex with men (MSM), increasing evidence to suggest it is also an issue for women, and ongoing concern about rectal chlamydia treatment failure. This PhD program of research aims to investigate the epidemiology of rectal chlamydia with particular focus on treatment. It includes the first double-blind randomised control trial to identify the most efficacious treatment (azithromycin vs doxycycline), a cross-sectional study to further our understanding about the management of rectal chlamydia infection in men who have sex with men, and a systematic review and meta-analysis of the factors associated with rectal chlamydia positivity in women. Chapter outline The objectives of this thesis were: 1) To determine whether azithromycin or doxycycline is the most efficacious treatment for rectal chlamydia infection; 2) To examine the factors associated with the resumption of sexual activity following treatment for rectal chlamydia among MSM; and 3) To investigate the factors associated with rectal chlamydia in women with concurrent infection at other sites, and to compare these with those observed for rectal gonorrohoea. This thesis is comprised of three major components: 1) the protocol, statistical analysis plan, and results of a double-blind randomised controlled trial (RCT) comparing the efficacy of 1g azithromycin with 7-day 100mg doxycycline (twice a day) for the treatment of rectal chlamydia; 2) a cross-sectional study examining factors associated with resuming sexual activity following treatment for rectal chlamydia among MSM; and, 3) a systematic review and meta-analysis on the factors associated with rectal chlamydia positivity in women. Chapter 1 is a comprehensive literature review on what we know about the chlamydia and in particular, rectal chlamydia. The review discusses the factors for rectal chlamydia, its management, and the treatment concerns to provide context and rationale for this thesis. The literature review demonstrates that rectal Chlamydia trachomatis infection remains an important public health concern with increasing prevalence in both men and women and ongoing uncertainty in the efficacy differences for the treatments used. Several gaps remain in the epidemiology and control of rectal chlamydia including: 1) uncertainty about the most efficacious treatment for rectal chlamydia - azithromycin 1g single dose versus 7-day of doxycycline 100mg (twice a day); 2) the risk of onward transmission or reinfection following treatment among men who have sex with men, and the risk of selection pressure and resistance with continued use of azithromycin; 3) the factors associated with rectal chlamydia among women, in particular with concomitant infection at other sites. Chapters 2 to 4 presents the protocol, statistical analysis plan, and results of the RCT to compare the efficacy of 1g azithromycin to 100mg doxycycline twice daily for seven days for the treatment of rectal chlamydia – the first such trial in the world. The trial observed a microbiologic cure of 281/290 (96.9%; 95CI% 94.9, 98.9) for doxycycline and 227/297 (76.4%; 95%CI 73.8, 79.1) for azithromycin, with an adjusted risk difference of 19.9% (95%CI 14.6, 25.3; p