The epidemiology of Chlamydia trachomatis and Mycoplasma genitalium in young Australian women. Jennifer Walker Submitted in total fulfilment of the requirements of the degree of Doctor of Philosophy. January 2011 School of Population Health The University of Melbourne. ABSTRACT Chlamydia trachomatis is the most common notifiable sexually transmissible infection in young Australian women and has considerable public health consequences, yet the true burden of disease caused by chlamydia remains unknown. There are also no population data for Mycoplasma genitalium, another emerging sexually transmissible infection in young women. This thesis aims to address two issues relevant to C. trachomatis and M. genitalium . The first aim was to determine the effectiveness of an intervention in general practice to increase chlamydia testing rates, and the second aim was determine the community burden of both C. trachomatis and M. genitalium in young women in Australia. Chapter 4 describes the C-Alert study which was a randomised controlled trial to determine the effectiveness of a computer alert in general practice on C. trachomatis testing rates in young women. The computer alert increased testing by 27% [AOR:1.27 (95%CI: 1.11-1.45)], and this small but significant increase suggests alerts might be beneficial along with other interventions to increase C. trachomatis testing in general practice. Chapters 5, 6, 7, 8, 9 and 10 describe the CIRIS study which was a cohort study involving 1116 young Australian women. C. trachomatis prevalence at baseline was 4.9% (95%CI: 2.9-7.0) and incidence rate for the 12–month study period was 4.4 per 100 women-years (95%CI: 3.3-5.9). Prevalent C. trachomatis was associated with having had C. trachomatis previously [AOR:2.0 (95%CI: 1.1-3.9)], increased numbers of sexual partners [AOR:6.4 (95%CI: 3.6-11.3)] and unprotected sex [AOR:3.1 (95%CI: 1.0-9.5)]. Antibiotic use and older age were protective against having a prevalent infection ([AOR:0.4 (95%CI: 0.2-1.0)] and [AOR:0.9 (95%CI: 0.8-1.0)] respectively) and an incident infection ([AHR:0.1 (95%CI: 0.0-0.6)] and [AHR:0.4 (95%CI: 0.2-0.8)] respectively). Incident C. trachomatis was also associated with more partners [AHR:4.0 (95%CI: 1.9-8.6)]. iii More than 20% of women with C. trachomatis had a re-infection during the study [20.3% (95% CI: 11.6, 31.7)] with an infection rate of 20.0 (95% CI: 11.9, 33.8) per 100 women years. In Chapter 8, M. genitalium prevalence was found to be 2.4% (95%CI: 1.5-3.3) and incidence rate was 1.1 per 100 women-years (95%CI: 0.4-1.6). Prevalent M. genitalium was associated with Indigenous status [AOR:4.5 (95%CI: 1.4-14.9)], increased numbers of partners [AOR:2.2 (95% CI:1.0-4.6)] and unprotected sex [AOR:16.6 (95%CI: 2.0-138.0)]. Incident M. genitalium was associated with recruitment from sexual-health clinics [HR:4.5 (95%CI: 1.0-14.7)], having more partners [HR:5.2 (95%CI: 1.0-26.5)] and having had a C. trachomatis infection [HR:4.2 (95%CI: 1.1-16.5)]. In Chapter 9, a psychosocial analysis found that testing was acceptable to women and women who tested positive were less affected by having a positive result than negative women anticipated they would be. Chapter 10 describes the rate of induced abortion [rate: 2.1 per 100 women-years (95%CI: 1.4-3.2)], which was an incidental finding. These results demonstrate there is a significant proportion of C. trachomatis and M. genitalium in young women in Australia that is not captured by current testing methods. These results provide the first population based incidence and re-infection data for young women in Australia. This will be crucial in the design and measuring the effectiveness of a chlamydia screening program and further inform discussion about M. genitalium control. iv DECLARATION This is to certify that: i. the thesis comprises only my original work towards the Doctor of Philosophy except where indicated in the Preface, ii. due acknowledgement has been made in the text to all other material used, iii. the thesis is less than 100,000 words in length, exclusive of tables, maps, bibliographies and appendices. Jennifer G Walker 21 st January 2011 v vi PREFACE Contribution of author, Jennifer Walker This thesis comprises of two studies which were designed, implemented and managed by Jennifer Walker. In particular, Jennifer was responsible for the following as part of her candidature: • The design each study, the development of questionnaires and ethics applications. • The recruitment of all the clinics in the C-Alert study and management the recruitment of all the clinics in the CIRIS study. • The management of the recruitment and follow up of all the women in the CIRIS study. • The management of the team of research assistants who recruited and followed up the participants during the study. • The management of the mail outs for the CIRIS study and the other associated clerical duties. • The management of all the women who tested positive as a result of the CIRIS study, including organising consultations, treatment and follow up. • Data entry and management of the data for both studies including the bulk of the analysis of the results. • The collation of the material required for the C-Alert general practitioners’ education pack and CIRIS participants’ recruitment packs. vii Contribution of others The C-Alert study was led by Professor Christopher Fairley and supervised by a team of investigators including: Associate Professor Jane Hocking, Professor Jane Gunn, Dr Marie Pirotta, Associate Professor Lyle Gurrin, and Associate Professor Rob Carter. This study was funded by an NHMRC grant. The CIRIS study was led by Associate Professor Jane Hocking and supervised by a team of investigators and including: Professor Kit Fairley, Associate Professor Sepehr Tabrizi, Dr Catriona Bradshaw, Associate Professor Marcus Chen, Professor Basil Donovan, Professor John Kaldor, Dr Kathleen McNamee, Dr Marian Currie, Mr Hudson Birden, Professor Francis Bowden, Professor Jane Gunn, Dr Marie Pirotta, Associate Professor Lyle Gurrin, Professor Veerakathy Harindra, and Professor Suzanne Garland. The study was funded by the Department of Health and Ageing as part of the Chlamydia Targeted Grants Funding. Dr Catriona Bradshaw, Professor Kit Fairley and Associate Professor Marcus Chen provided clinical treatment and management of the women who tested positive during the study. Other clinical staff at the Melbourne Sexual Health Centre offered their clinical services and advice as well when required. Associate Professor Sepehr Tabrizi and the staff at the Department of Molecular Microbiology at the Royal Women’s Hospital in Melbourne conducted all the testing for the CIRIS study including molecular analyses. Associate Professor Jane Hocking, Rachelle Gerber, Dr Stella Heley, Dr Tim Read and Claire Foreman produced, wrote, directed and performed in the C-Alert DVD for the general practitioner education kit. Dr Sandra Walker collected and collated the data for the C-Alert trial and assisted with the analysis. Sandra also had a major role in the development of the psychosocial questions for the final CIRIS questionnaire. Sandra Walker and Eve Urban were involved in the day to day running of the CIRIS study ensuring the study was conducted smoothly, ethically and efficiently. Sandra and Eve also were involved in recruiting clinics, managing some staff and data entry. viii A team of research assistants recruited participants for the CIRIS study including: Debbie Edwards, Ros McLennan, Marilyn Hines, Jo Horn, Maree White, Bernie Monaghan, Eliza Marks, Rose Goodenough, Kaz Krajlic, Gabrielle Le Brocq, Jennifer Coyle, Karla Kalen, Leigh Hodgkinson, Jo Ruppin, Di Baker, Christine Hou, Christina Brieglab, Helen Tang, Tara Young, Christine Selman, Stefannie Lummas, Donna Cleall, Rachel Ujma, Hongxia Shao, Stephenie Neblett, Eris Smyth, Annie Green, Leonie Baker, Stephanie Lenko, Paula Nathan, and Kavitha Somasundaram. The bulk of questionnaire data entry was done by Mika Tsukiyama. ix x ACKNOWLEDGEMENTS Firstly I would like to thank my principal supervisor Associate Professor Jane Hocking who has been an exceptional supervisor during the period of my candidature. Jane’s knowledge of chlamydia, and her ability to steer large and complex research projects has been implicit in the success of both projects in my PhD. Also, Jane has encouraged me to challenge myself during the PhD, and helped me keep my sense of humour along the way. I was also privileged to have Professor Christopher (Kit) Fairley as a supervisor. Kit’s clinical experience and global understanding of STI research has been invaluable. Kit has been kind, supportive and practical with his supervision and was particularly helpful with the management of the large group of staff employed to work on the CIRIS project and managing the large cohort of young women in the study. I would like to also thank my other supervisors, Dr Catriona Bradshaw and Associate Professor Lyle Gurrin. Catriona has always been available for advice for which I was particularly grateful when managing CIRIS participants’ clinical outcomes, she was also intrinsic to the Mycoplasma genitalium component of this thesis. Lyle was invaluable to my understanding of how to manage to statistical analysis for both my projects. Jane and Lyle taught me the importance of being able to do my own analysis and were there to help me through challenging obstacles. I would also like to thank Associate Professor Sepehr Tabrizi, Dr Jimmy Twin, Nicole Taylor and the laboratory staff at the Molecular Microbiology Laboratory at the Royal Women’s Hospital who conducted all the chlamydia and Mycoplasma genitalium testing and molecular analyses for this thesis.