Bakken, Inger Johanne PhD*; Nordbø, Svein Arne MD, PhD†; Skjeldestad, Finn Egil MD, PhD*
YOUNG, SEXUALLY ACTIVE PEOPLE are at high risk for genital infections caused by Chlamydia trachomatis.1 In women, untreated infection can cause ectopic pregnancy2 and tubal factor infertility.3
Chlamydial infections are easy to diagnose and curable with a single dose of oral antibiotics. Early diagnosis is important to avoid transmission of the infection to sexual partners and to prevent long-term morbidity.
Large-scale chlamydia screening programs are established in the United States4,5 and in the United Kingdom.6 In Norway, however, no national or local screening programs have been established. The health authorities recommend that men and women younger than 25 years with a new sexual partner should be tested for C. trachomatis.
Although prevalence of chlamydial infection has been assessed in a large number of studies,4–12 C. trachomatis testing patterns and screening coverage are not often reported.13–17 In one report, screening coverage was indirectly estimated by combining surveillance reports (i.e., data on positive tests) and prevalence data from family planning clinics.13 In the other studies, chlamydia screening coverage was assessed in selected general practices14,15 or managed care organizations.16,17
In Sør-Trøndelag county, Norway, a single medical microbiology laboratory is responsible for analysis of all C. trachomatis tests from every facility. We used routinely collected laboratory data for analysis of C. trachomatis testing patterns, prevalence, and incidence among men and women aged 15 to 24 years over the period November 1990 to December 2003.
Materials and Methods
The study was carried out in Sør-Trøndelag county, central Norway. Of Sør-Trøndelag’s 270,000 inhabitants, approximately 150,000 are living in the major city, Trondheim.
The medical microbiology laboratory at the Trondheim University Hospital serves as a regional facility for C. trachomatis diagnostics in central Norway. The laboratory receives all tests from Sør-Trøndelag and a substantial volume of tests from the 2 neighboring counties.
From November 1990, all laboratory reports have been stored electronically. The database comprises the patient’s unique 11-digit personal identifier, demographic data (sex, year of birth, and residency), and test data (date, detection method, sample type, and test result). Registration of personal identification and residency is regulated through the national health insurance system and is necessary for reimbursement purposes. From this database, data on C. trachomatis tests were extracted for the period November 15, 1990 to December 31, 2003.
Population figures by sex, age, and year were provided by Statistics Norway (www.ssb.no).
A total of 111,511 individuals were tested for C. trachomatis over the study period.
Data from 35,935 persons residing outside Sør-Trøndelag county, 3183 children younger than 15, and 42,088 individuals 25 years and older at first registered test were excluded. In addition, data from 1706 young women registered with study allocation numbers indicating that they were enrolled in research projects comprising frequent C. trachomatis testing were excluded.
The final study population comprised 28,599 persons, 15 to 24 years old at first test and residing in Sør-Trøndelag county.
Data on specimens collected within 60 days from a previous test were excluded from analysis.
Throughout the study period, several methods have been used for detection of C. trachomatis. The enzyme immunoassay method (IDEIA Chlamydia Test; Celltech Diagnostics/Novo BioLabs/DAKO) was replaced by nucleic acid hybridization for detection of ribosomal RNA in the target organism (PACE 2; Gen-probe, San Diego, CA) in 1992. In 1999, polymerase chain reaction (PCR; Amplicor; Roche Molecular Systems) became the routine detection method for C. trachomatis. All specimens with a positive test result were retested with the same test. If the positive result was reproduced after retesting, the test result was reported as positive. Discrepant results (negative test result after retesting) gave rise to a second retesting (same test), which led to a final conclusive result (negative if 2 of 3 tests were negative, positive if 2 of 3 tests were positive).
The data were analyzed using SPSS for Windows, version 11.0 (SPSS, Chicago, IL) for the periods 1990–1993, 1994–1996, 1997–1999, 2000–2002, and 2003, with person as the unit of analysis. Age-specific testing rates (per 1000) (first test) are the number of first tests in each age group divided by the population size. Cumulative incidences of first test before the age of 25 were calculated for the cohorts for which follow up was complete (birth years 1976–1979). Cumulative incidence of infection for the women in these cohorts was calculated by taking all relevant tests into account. As a result of low testing coverage, this outcome was not calculated for men.
We used chi-squared tests for linear trend. Cox regression modeling was used to estimate hazard ratios for repeat testing and incident infection by outcome of first test. We checked proportional hazards assumptions by using log–log plots. Data from 1990–1993 were excluded from these analyses, because this period had a large contribution from people who had been tested before the establishment of the database. Persons first registered in 2003 were not included as a result of lack of follow-up time. The possible confounding effects of age group, sex, and time period (1994–1996, 1997–1999, and 2000–2002) were assessed. We also tested for interaction between outcome of first test and age, sex, and time period, but multiplicative terms were not significant.
In analyses of repeat testing, the 15,236 persons registered with their first test 1994–2002 were observed until December 31 the year after the inclusion period (e.g., persons first registered in the period 1994–1996 were observed until December 31, 1997).
Kaplan-Meier analyses were used for estimation of 12-month incidence of chlamydial infection among the 7197 individuals who had multiple tests by these criteria. Within the observation windows defined here, these persons were observed from their first test until their first positive or last negative test.
For all analyses, a P value of <0.05 was considered significant.
The study was approved by the Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate. Authorization for the use of sensitive health data was obtained from the Norwegian Ministry of Health and Social Affairs.
A total of 28,599 persons, 4717 men (16.5%) and 23,882 women (83.5%), were tested for C. trachomatis over the study period.
In both age groups and throughout the whole study period, C. trachomatis testing rates (first test) were significantly lower for men than for women (Table 1). Male testing rates (both age groups) and female testing rates (20–24 years) increased significantly over the study period (P <0.001). Urine-based tests were first registered in 2001, and in 2003, 36% (202 of 554) of first tests for men were based on urine. Only 38 female first-time testers were registered with urine-based tests.
Four percent of men and 44% of women born 1976–1979 had been C. trachomatis tested at least once by the age of 20. By the age of 25, 21% of men and 84% of women in these cohorts had been tested (Table 2).
Analyses of repeat testing showed that 58% of persons with a positive first test and 46% of persons with a negative first test had a repeat test within the defined observation periods, corresponding to a hazard ratio of 1.9 (95% confidence interval [CI], 1.8–2.1). Women more often had a repeat test than men (data not shown).
Throughout the period, prevalence of C. trachomatis at first test was higher for men than for women (Table 3). Among women, prevalence increased by more than 50% from 1997–1999 to 2000–2002 but changed little thereafter. Among men aged 15 to 19 years, prevalence was at its peak in 1994–1996 and has been decreasing since then. Prevalence was much higher among men with swab tests than among men with urine tests (data not shown).
By the age of 20 and 25, 6% and 15%, respectively, of women born 1976–1979 had been diagnosed with C. trachomatis infection at least once (Table 4).
The 7197 persons included in the analyses of incident chlamydial infection were observed for a total of 138,790 months, with a median observation time of 18 months. Nineteen percent of initially positive persons and 11% of initially negative persons had a C. trachomatis infection within the defined observation periods, corresponding to a hazard ratio of 1.8 (95% CI, 1.5–2.1) (Table 5). Male sex and young age at first test were also associated with a higher relative risk for subsequent C. trachomatis infection.
Twelve-month incidence estimates were 3.8% (95% CI, 3.2–4.3%) for women with a negative first test and 8.6% (95% CI, 6.3–10.8%) for women with a positive first test. For men with a negative and positive first test, 12-month incidence estimates were 10.8% (95% CI, 8.0–13.6%) and 15.7% (95% CI, 10.3–21.1%), respectively.
Population-based data on C. trachomatis testing patterns are scarce. The current study includes data from the single laboratory covering all C. trachomatis diagnostics in a defined geographic area (county) over a 13-year period. Within the 1976–1979 cohorts of women, 85% were registered at least once with a test for C. trachomatis before 25 years of age. Male testing rates and testing rates for the youngest females increased significantly over the study period.
Our data show higher testing rates (first test) and more repeat testing among women than among men, which confirms previous studies from Norway (1991),18 Denmark (1999–2000),15 and England (1999).14
In our study, the more frequent testing among women than among men was also reflected in the general testing rates (all tests taken into account, data not shown). Among women, general testing rates were relatively stable over the study period (one test for every 6 women 15–19 years and one test for every 3 women 20–24 years annually). Among men, the general testing rates increased over the study period but were only slightly higher than the rates of first-time testing.
Compared with general testing rates among young women in England,14 rates of first-time testing in the current study were high.
Forty-four percent of the women in our study population had been tested before the age of 20. Assuming that 80%19 of the women had debuted sexually at this age, 55% of sexually active women had been tested. According to estimates based on surveillance data, 60% of sexually active females aged 15–19 years in the United States were screened for chlamydia in 2000.13 Screening coverage estimates for women in managed care organizations during 1999–2001 from the Centers for Disease Control and Prevention (CDC) using data on both positive and negative tests were, however, considerably lower.16 Neither of these studies13,16 reported the estimated proportion of sexually active women on which the analyses were based.
The prevalence of chlamydial infection among first-time testers was high throughout the study period. Among women in both age groups, the C. trachomatis prevalence increased strongly from 1997–1999 to 2000–2002. More targeted screening of high-risk women has probably not contributed significantly to this increase, because testing rates for women were high throughout the study period. In 1999, the testing platform in our laboratory changed from a nucleic acid probe assay to a PCR test. Among women tested that year, the proportion that had positive tests was only slightly higher when the new testing platform was applied (5.8%) compared with when the nucleic acid probe assay was used (5.0%). Thus, although it is important to take changes in test platforms into account when interpreting data on chlamydia trends,20 the switch of laboratory tests can only to a small degree explain the large increase in prevalence among women observed from 1997–1999 to 2000–2002.
C. trachomatis prevalence was higher among men than among women, probably as a result of more indication-based testing (symptoms/positive partner) among men. Low testing rates and a high proportion of indication-based testing suggest that the prevalence of chlamydial infection is lower in the general male population than what we found for male first-time testers in the current study. In a large cross-sectional study among men in clinical and nonclinical settings in 4 U.S. cities,21 the prevalence among men with symptoms was similar to the prevalence among men reported here (20%). We observed considerably lower prevalence among men with urine specimens compared with men with urethral swab specimens. Urine-based PCR tests have been shown to have high sensitivity and specificity,22 and we speculate that the discrepancy in prevalence can be explained by a higher frequency of urethral symptoms among men with swab specimens.
The prevalences in our study were almost identical to those reported from the national C. trachomatis screening program in England6 and from other studies.9,11 However, lower prevalences than reported in the current study were found in random population samples of young men and women in the United Kingdom23 and in the United States10 and among female high school students in Belgium.12
The main limitation of the study is lack of clinical information at the time of specimen collection. The low testing rates and high prevalence among men may indicate that many men were tested as a result of symptoms or in relation to contact tracing. To a smaller degree, this will also be the case for women.
Estimation of incidence based on retrospective cohort data comprising persons with multiple tests has been criticized, because such cohorts typically include persons who are at high risk.24 With high general testing rates, however, estimated incidence will approach true incidence. In our study population, 85% of the women had had at least one C. trachomatis test before the age of 25, and more than half of tested women were registered with 2 or more tests. Men, on the other hand, had low testing rates and repeat testing was uncommon. Our estimates for 12-month incidence were 11% or 16% for men and 4% or 9% for women, depending on whether the first test was negative or positive, respectively. By assuming that subjects who did not return for additional testing were negative throughout the whole observation period, minimum figures for 12-month incidence among first-time testers were estimated to be 2% for initially negative persons and 5% for those who were initially positive with negligible sex differences (data not shown).
The high prevalences at first test and the high proportion of women in the population with at least one diagnosed C. trachomatis infection before the age of 25 indicate that chlamydial infections may have major implications for reproductive health in Norway. In economic analysis on societal costs and benefits, routine C. trachomatis testing is found to be cost-effective at prevalences of 3% to 10% for women25 and 5% for men.26 Holding these results together with the high prevalences and 12-month incidence estimates found in the current study indicates that annual testing of all young sexually active people is recommended. However, economic modeling outcomes are extremely sensitive to assumptions on complication rates, and in general, high complication rates have been applied.27
In conclusion, this study confirms previous studies showing high prevalences of C. trachomatis infection among young people. Our data show that testing rates among men (15–24 years) and female teenagers are too low, and screening strategies for C. trachomatis should target these groups specifically. Furthermore, subjects testing positively should be encouraged to return more frequently for repeated testing. Implementation of organized contact tracing programs within the public health system is necessary to reduce spreading of chlamydial infection and to reduce the burden of disease associated with such infections.
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