Melbourne School of Population and Global Health

Pelvic inflammatory disease (PID) is a serious reproductive health issue for women that occurs when infection ascends from the lower to the upper genital tract. Possible sequalae include infertility, ectopic pregnancy and chronic pelvic pain. The sexually transmitted infections (STIs) Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) are commonly implicated, however the microbial aetiology is often unknown. PID diagnosis is imprecise due to its many possible clinical features and absence of an objective reliable non-invasive diagnostic test. As PID epidemiology varies between countries and population groups due to different STI prevalence and healthcare systems, country specific estimates are critical. This thesis aims to improve understanding of the epidemiology of PID diagnosed in Australia, particularly with reference to chlamydia infection as this is the most frequently diagnosed STI in Australia. Chapters 1 and 2 discuss the evidence and describe what is known about the aetiology and epidemiology and PID, providing the rationale for this PhD program of research. Chapter 3 involved an analysis of data for 15,690 women aged 16-49 attending a sexual health clinic, to examine the microbial characteristics of PID. At a population level, chlamydia was the more commonly identified microbial organism, with 8.2% (95% Confidence Interval (CI) 7.7, 8.6) of women chlamydia positive, 2.8% (95%CI 2.5, 3.0) diagnosed with PID, and, the adjusted population attributable fraction (aPAF) of PID associated with chlamydia was 14.1% (95%CI 9.9, 18.0). Among a subset (n=8,839) of women, 0.3% (95%CI 0.2, 0.5) were gonorrhoea positive only, 0.2% (95%CI 0.2, 0.4) were gonorrhoea and chlamydia positive, 4.7% (95%CI 4.3, 5.2) were diagnosed with PID, and the aPAF for gonorrhoea was 1%. There was a higher odds of PID for women with gonorrhoea or chlamydia (4.4-fold vs 3-fold, respectively) compared with no infection. A sub-analysis for asymptomatic women showed that 28% of PID was associated with chlamydia but only 0.6% of asymptomatic women were diagnosed with PID. Chapter 4 involved a separate comprehensive analysis of the same dataset as in Chapter 3, to investigate the characteristics of clinically diagnosed PID where no infection was identified (pathogen-negative PID). Among 330 women with PID who were tested for chlamydia, gonorrhoea, Mycoplasma genitalium and bacterial vaginosis, 62% had no infection diagnosed. Multivariable logistic regression showed that women with pathogen-negative PID were more likely to be aged >30 years (Adjusted Odds Ratio (AOR) 1.7, 95%CI 1.0, 3.0) and less likely to have evidence of vaginal inflammation (AOR 0.5, 95%CI 0.3, 0.9) or report recent unprotected sex (AOR 0.6, 95%CI 0.4, 1.0) than women with pathogen-positive PID. Chapter 5 investigated PID diagnosis characteristics and time trends at a large sexual health clinic, before and after clinical audit feedback. The study found that between 2002 and 2016, the yearly PID diagnosis rate increased from 0.8% (37/4836) to 2.9% (209/7088) and an increasing proportion of women reported any symptoms (35.7% to 56.6%) or were diagnosed with an STI or bacterial vaginosis (9.4% to 21.4%). Univariable generalised linear models showed PID rates increased after audit feedback in 2007 by 8% yearly (incidence rate ratio (IRR) 1.08, 95%CI 1.06, 1.11), but were unchanged (aIRR 1.01, 95%CI 0.98, 1.03) when patient characteristics were included in multivariable analysis. Since audit feedback, the clinic has reoriented services to increase capacity for high risk patients that appear to have had a greater impact on PID diagnosis rates than audit feedback. Chapter 6 estimated yearly (2009-2014) population rates of PID diagnosis using hospital admissions and emergency department data from three Australian states (Victoria, New South Wales, Queensland). Zero inflated Poisson regression models were used to examine variation in rates by year, age-group and residential area. In 2014 the overall PID rate per 100,000 women aged 15-44 years, was 63.3 (95%CI 60.8, 65.9) for admissions and 97.0 (95%CI 93.9, 100.2) for emergency department presentations. Comparing 2014 with 2009, the overall PID rate in admissions did not change, but when examined by type of PID, admission rates increased for chlamydial and/or gonorrhoeal PID (aIRR 1.73, 95%CI 1.31, 2.28) and unspecified PID (aIRR 1.09, 95%CI 1.00, 1.19) but declined for chronic PID (aIRR 0.83, 95%CI 0.73, 0.95). PID rates in emergency departments were higher (aIRR 1.34, 95%CI 1.24, 1.45) in 2014 than 2009 and substantially higher for women aged 15-24 (aIRR 2.78, 95%CI 2.62, 2.94) than 35-44 years. In conclusion, this thesis provided the first Australian estimates of the population level risk of PID associated with chlamydia and gonorrhoea. This new information based on the PAF suggests that eliminating chlamydia in a high prevalence population might only reduce PID by 14% and around 1% if gonorrhoea were eliminated. For low chlamydia prevalence populations, the PAF findings suggest that only a small number of PID cases might be avoided by widespread chlamydia screening. This thesis provided updated evidence for the frequency of PID pathogens in Australia, and, the many cases without an identified pathogen highlighted the need for non-invasive bio-markers for upper genital tract inflammation. In the absence of bio-markers the decision to commence PID treatment should continue to be based on clinical features and sexual risk. This thesis found that PID remains a substantial cause of attendances at sexual health clinics and hospitalisations for reproductive related health issues for women in Australia. Analyses of sexual health clinic data demonstrated the importance of adjustment for patient characteristics in interpreting time trends, and, investigation of hospital data showed how ecological analyses of data from health settings where women with PID are managed can be used to measure PID trends. Evidence was provided for an increase in PID diagnosed in Australian emergency departments that could reflect increasing PID incidence, shifting healthcare usage from primary care, or, inadequacies in PID diagnosis and management in primary care. Primary care data and systems to monitor PID incidence are needed to better understand PID epidemiology, healthcare usage, and the impact of chlamydia and STI control policies.

Chlamydia trachomatis is one of the most common bacterial sexually transmitted infections worldwide, with particularly high prevalence in young people under 25 years. Left untreated it can lead to serious reproductive morbidity in women including pelvic inflammatory disease, ectopic pregnancy and infertility. Given that up to 90% of infections in men and women are asymptomatic, increased testing is required to effectively detect and control infection and limit its associated morbidity. The aim of this thesis was to examine a number of specific strategies aimed at increasing screening and improving the control of chlamydia in Australia. The strategies centered on interventions in primary care to increase chlamydia screening and improve the partner notification practices of general practitioners and individuals recently diagnosed with chlamydia. This thesis reports on six separate studies undertaken to address this aim.

Melbourne School of Population and Global Health - Theses

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