Abstract
Bacterial sexually transmitted infections including Chlamydia trachomatis and Neisseria gonorrhoeae remain an important public health concern. We aimed to assess the population-based incidence of C. trachomatis and N. gonorrhoeae in an age-standardized cohort over time. A retrospective study of a large Canadian health region was undertaken between 2010 and 2015 using linked census and digital laboratory data. C. trachomatis and N. gonorrhoeae tests were linked to patient data. Sex and age-standardized incidence rates (IR) and ratios (IRR) were calculated for cases and testing rates. The annual mean population was 1,150,556 individuals (50.1% female). A total of 15,109 cases of chlamydia and 981 cases of gonorrhoea occurred. The overall IR for chlamydia ranged from 18.81 to 25.63 cases per 10,000 person-years. The IRR was 1.27 (95% CI 1.20–1.34, p < 0.001) for the comparison of 2015 and 2010 rates. For gonorrhoea, overall rates ranged from 0.92 to 1.86 cases per 10,000 person-years. The IRR for gonorrhoea was 2.02 (95% CI 1.56–2.59, p < 0.001) for 2015 and 2010 rates. In our large population-based study spanning six years, we observed increasing rates of C. trachomatis and N. gonorrhoeae with low testing rates.
Introduction
Chlamydia trachomatis and Neisseria gonorrhoeae are common bacterial sexually transmitted infections (STIs) that are associated with significant morbidity and health care costs.1,2 Both chlamydial and gonococcal infections can lead to pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, and infertility in females.3–7 Both infections can also increase risk of acquiring human immunodeficiency virus infections through altered susceptibility and transmission.8,9 Additionally, chlamydial infections with certain strains may contribute to increased risk of cervical cancer. 10 Both chlamydial and gonococcal infections are readily diagnosed and can largely be cured with a single antibiotic dose. Thus, early detection and treatment of chlamydial and gonococcal infections is critical to reduce the burden and achieve population-level disease control.
Despite increased public health awareness and interventions, Canadian rates of C. trachomatis and N. gonorrhoeae have increased since the 1990s. 11 Similar epidemiologic trends have been observed in the United States, England, and Australia. Factors thought to be attributed to the increase include enhanced laboratory tests, changes in sexual behaviours, and increasing antimicrobial resistance to N. gonorrhoeae. Specifically, C. trachomatis is the most commonly reported STI, and national rates increased by 57.6% from 189.6 to 298.7 cases per 100,000 persons from 2003 through 2012. 11 Similarly, N. gonorrhoeae rates increased by 38.9% from 26.0 to 36.2 cases per 100,000 persons in the same period. 11
Diagnosis of chlamydial and gonococcal infection early in the course remains challenging as the majority of men and women remain asymptomatic with chlamydial infection, and many women may be asymptomatic with gonorrhoea.7,12 There is also a significant disparity in STI testing between men and women, with men being referred to as a ‘missing reservoir’, leading to underdiagnosis.13,14 Notably, infection transmission may occur in an asymptomatic state, and individuals remain at risk for infection-associated complications. Current Canadian screening guidelines recommend testing sexually active individuals aged younger than 25 years as well as other at-risk populations, including pregnant women. 15 Although a number of medical organizations have recommended screening of adolescents and young adults for asymptomatic chlamydial infection,16–18 it is unclear if routine screening reduces subsequent anogenital incident infections.19,20
Screening guidelines for STIs, including chlamydia and gonorrhoea, are commonly based on prevalence estimates from reported cases. As cases are largely underreported, using clinic-based estimates to guide screening is a suboptimal approach, and population-based estimates may provide a superior measure of the epidemiology and trends of screening and case prevalence. Aside from national surveillance data inclusive of 2012, 1 and previous regional studies of chlamydia and gonorrhoea,21,22 no recent population-based prevalence studies have examined age-standardized testing and positivity rates in our health region. Thus, we aimed to assess the population-level incidence and geographical variation of C. trachomatis and N. gonorrhoeae over a six-year period in a large Canadian health region.
Material and methods
Patient selection
A retrospective cohort study of a large Canadian health region population who underwent testing for C. trachomatis and N. gonorrhoeae between 2010 through 2015 was undertaken. Population estimates were obtained from the Calgary Economic Development commission, and census data were obtained for 2011 from Statistics Canada. Age-group standardized estimates were interpolated from the overall population estimates for 2010, and 2012 through 2015; census data were utilized for 2011.
Data source
We examined the digital records of all testing for C. trachomatis and N. gonorrhoeae that was performed by Microbiology, Calgary Laboratory Services (CLS) in Calgary, Alberta. Each test was linked to demographic information including sex, and age using the provincial health care number. As both C. trachomatis and N. gonorrhoeae are largely readily treated with antimicrobials, but can often be asymptomatic, our dataset includes incident and prevalent cases. CLS is a large regional diagnostic laboratory that provides comprehensive testing services to an urban population in the province of Alberta of ∼1.5 million individuals. Clinical microbiology testing is performed in this single centralized facility on all hospitalized, ambulatory, and long-term care patients. Both C. trachomatis and N. gonorrhoeae testing is done using a commercial nucleic acid amplification method – APTIMA Combo 2® Assay on a TIGRIS DTS system (Hologics, San Diego, CA). APTIMA has established sensitivity and specificity of >95% for a variety of specimens.23,24 Obtained samples are transported promptly to CLS following collection. Detailed instructions regarding specimen collection requirements are available in the CLS Guide to Services found at https://www.calgarylabservices.com/lab-services-guide/specimen-collection/. 25
Ethics
This study was approved by the Conjoint Health Research Ethics Board, Alberta Health Services and University of Calgary (REB13-1126).
Statistical analysis
The incidence and age-standardized rates of C. trachomatis and N. gonorrhoeae were calculated for the period of 2010–2015 using previously established methods. 26 We calculated annual incidence rates (IRs) by gender and age groups using laboratory and population estimates or census data. Age-specific IRs in southern Alberta were calculated for five-year groups from 0 to 75+ years in each year. Study outcomes were established prior to data collection. Testing proportion was derived from CLS test numbers compared with the population, and positivity proportions were calculated based on test numbers annually. Incidence rate ratios (IRRs) were calculated to determine differences in testing and positivity rates over the study period. Figures of sex and age-standardized rates were constructed using 2011 as a representative of the total data. All hypotheses were two sided with α significance of 0.05. Clinical data were analysed using STATA 13.1 software (College Station, Texas).
Results
During the study period, the mean annual total population was 1,150,556 persons (SD 62,208) and was comprised of 50.1% females. There were a total of 15,109 cases of C. trachomatis and 981 cases of N. gonorrhoeae between 2010 and 2015. The overall annual IR for C. trachomatis ranged from 18.81 to 25.63 cases per 10,000 person-years over the study period. Although there was a downward trend in males and females from 2010 through 2012, the rates increased annually from 2013 through 2015 (Figure 1). There was an increased incidence over the study period with an IRR of 1.27 (95% CI 1.20–1.34) for C. trachomatis for 2015 as compared with 2010 rates (25.63 versus 20.21 cases/10,000 person-years, p < 0.001). For N. gonorrhoeae, overall rates ranged from 0.92 to 1.86 cases per 10,000 person-years with a similarly increasing trend (with the exception of female rate in 2013) over the study period (Figure 2). The IRR for 2015 compared with 2010 gonococcal rates was 2.02 (95% CI 1.56–2.59; 1.86 versus 0.92 cases/10,000 person-years, p < 0.001).
Annual incidence rates of C. trachomatis by sex from 2010 through 2015 in Calgary, Alberta, Canada. Annual incidence rates of N. gonorrhoeae by sex from 2010 through 2015, in Calgary, Alberta, Canada.

When C. trachomatis rates were assessed by gender, rates were significantly greater in females than males particularly in the >15 to <40 age groups (p < 0.001). As a representative, sex and age-specific rates of C. trachomatis for 2011 and N. gonorrhoeae are depicted in Figures 3 and 4, respectively. Conversely, with N. gonorrhoeae, although a trend was noted to increased positivity in males in the 20–29 age groups, it did not reach statistical significance (Figure 4). Testing for C. trachomatis and N. gonorrhoeae generally increased over the study period, and annual mean test run was 74,239.2 (SD 12,546.3) for females and 8620.0 (SD 1707.6) for males. The IRR for total annual tests of 2015 compared with 2010 was 1.28 (95% CI 1.27–1.29, p < 0.001) reflecting an overall increase in population-based testing. Further, for both C. trachomatis and N. gonorrhoeae, testing rates were up to ten times higher in females than males particularly for the 15–44-year-old age groups (p < 0.001). However, annual testing remained relatively low for these pathogens with rates of 6.2–8.4% overall, 1.25–1.95% for females, and 11.2–14.6% for males (Figure 5).
Sex and age-specific five-year incidence rates of C. trachomatis for 2011 in Calgary, Alberta, Canada. Sex and age-specific five-year incidence rates of N. gonorrhoeae for 2011 in Calgary, Alberta, Canada. Overall testing rates and C. trachomatis positivity rates from 2010 to 2015 in Calgary, Alberta, Canada.


Discussion
In our comprehensive six-year population-based study of C. trachomatis and N. gonorrhoeae epidemiology in a large Canadian health care region, we observed an increasing rate of both pathogens over the study period. Although there was a significant sex disparity in C. trachomatis similar to published national rates, rates of N. gonorrhoeae between females and males were similar across age groups. Further, a similar rate increase occurred between females and males for both C. trachomatis and N. gonorrhoeae between 2010 and 2015. Testing rates were significantly higher for females than males but rates remained relatively low over the study period. Both testing rates and positive cases were greatest as expected in the 15–40 years age groups. Age-specific rates had a clear spike between ages 15 and 34 years for both C. trachomatis and N. gonorrhoeae in both males and females. Mapping of testing rates showed a significant heterogeneity in the health region reflecting gaps in STI testing.
Rates of N. gonorrhoeae were much lower than C. trachomatis as expected and were similar to national trends. 1 As gonorrhoea is more frequently associated with symptoms than chlamydia, and especially so in men, individuals are more likely to seek medical care and be diagnosed. Gonorrhoea may also have a shorter duration of illness relative to chlamydial infection, leading to a decreased relative prevalence. However, other populations have previously observed a significantly higher population incidence and prevalence of N. gonorrhoeae upwards of 5.3% in adults 18–35 years of age. 27 In addition to demographic differences, geographic distribution and clustering is thought to play a role in gonorrhoea rates. Further, the increasing rates we observed in our study albeit lower than chlamydial rates, in the context of rising antimicrobial resistance are of concern.
Prior Canadian studies have been largely limited to the Manitoba health region which demonstrated improvements in STI rates following implementation of a control programme, and more recently identified significant geographic variability in chlamydia and gonorrhoea rates. Alberta previously had rates exceeding the national average for both chlamydia and gonorrhoea based on the 2012 national STI report. As population-based studies provide a more accurate reflection of STI incidence and prevalence,12,28 our study aimed to assess the more recent epidemiologic trends. Although we noted lower than 2012 national rates of C. trachomatis and N. gonorrhoeae, updated national surveillance data are required for comparative analysis.
Limitations of our study examining STI rates included the sample and test utilized for diagnosis and is common to studies assessing STI incidence or prevalence. The included tests for anogenital disease could be from urine, cervical, or rectal samples, and as the test characteristics vary based on sampling site, it is possible that a small number of cases may have been missed. As we included all tests for chlamydia and gonorrhoea, it is possible some of the tests were not related to anogenital causes. However, as the highest rates were seen in the ∼15–40 age group, this was unlikely to have impacted our study results. As testing rates increased during the population period, it is possible that some of the positivity increases may have been attributed to testing rates. However, as national rates have also risen, it may also reflect changes in sexual behaviour patterns, and community resistance profiles, or may be uncovering the true incidence through improved detection. Nucleic acid amplification test (NAAT) testing for chlamydia and gonorrhoea was available for the entire study duration thus eliminating the impact of a changing study platform on infection prevalence. Although treatment algorithms changed, screening recommendations for chlamydia and gonorrhoea did not change significantly over the study period. It is possible that patients had multiple positive tests for the same infection, but as public health follows all positive cases in the health region, it more likely reflected new cases. Our study calculated IRs but the cases were likely a mix of incident and prevalent cases due to the often asymptomatic nature of these infections. However, IR calculation is a standard measure of STI rates in the literature. If individuals had travelled or moved from the health region and had testing elsewhere, that was not captured in the study. However, our large population surveillance spanning six years provided a representative reflection of STI rates in this health care region.
The high chlamydial rates, and gonorrhoeal rates to an extent, reflect the inadequacies of current STI screening strategies. Despite having highly sensitive NAAT testing, and readily available antimicrobials for cure, there is significant under-testing and diagnosis of these infections. As males undergo far less testing than females, they likely represent a large community reservoir of infection and have been frequently historically excluded from testing guidelines. Even when guidelines exist, much of screening may be subjective, and not all those who meet criteria are tested. Further, there may be differences between public and private sectors and financial concerns associated with testing rates. The low testing rates highlight the need for widespread multi-pronged approach to STI testing and management.
Much has been studied regarding the transmission dynamics of STI pathogens including C. trachomatis and N. gonorrhoeae. Using population-level modelling, it has been established that control of these infections requires targeting of core groups with higher infection rates to prevent spread of STIs in the population.
Conclusion
C. trachomatis and N. gonorrhoeae are STIs that remain a significant public health concern. Our population-based study over six years demonstrated rising chlamydia and gonorrhoea rates in males and females. Although testing rates increased over the study period, they nonetheless remained very low. Moving forward, control of these infectious pathogens will require a multi-faceted approach including targeting of core groups with high risk of infection to achieve control of STI transmission in the population.28–30
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
