An estimated 2.8 million new chlamydia cases occur each year in the United States.1,2 The great majority of Chlamydia trachomatis infections are asymptomatic, and one of the most concerning aspects of chlamydia is its possible serious sequelae. In women, these include pelvic inflammatory disease (PID), ectopic pregnancy, infertility, and chronic pelvic pain. In men, symptomatic chlamydia may lead to urethritis. Chlamydia may also be associated with an increased risk of HIV acquisition for both women and men.3,4
The Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force and other agencies and professional organizations have guidelines recommending annual chlamydia screening of young, sexually active women aged <25 years and at-risk older women.5 As a result of these recommendations, chlamydia screening of women has substantially increased. The proportion of eligible women enrolled in commercial and Medicaid health care plans in the United States who were screened for chlamydia annually increased from 25.3% in 2000 to 41.6% in 2007.6 Trends in chlamydia incidence are more difficult to ascertain and assess. Chlamydia is a nationally notifiable infection for which case report rates have steadily increased over the past 20 years.2 Although a true increase in infection burden is possible, these trends are more likely to reflect the impact of expanded screening coverage, use of increasingly sensitive diagnostic tests, and improved reporting.7,8 The impacts of chlamydia on reproductive sequelae, if any, have been difficult to assess as a result of changes in treatment, practice patterns, and the difficulty of tracking chlamydia-associated PID and ectopic pregnancy.9 However, the available data on PID and ectopic pregnancy do not show increases, and PID data generally show recent and long-term declines.2,10,11
Routine chlamydia screening is not currently recommended for men, and the evidence base for male chlamydial screening is still evolving.3,12 Opportunistic testing of men likely increased in many health care venues with the availability of urine-based testing in the early 2000s.13 The national chlamydia case rates for men, reported by the Centers for Disease Control and Prevention, have increased 43% from 2003 to 2007.2 Studies of nongonococcal urethritis find chlamydia in 30% to 40% of cases,14 studies of gonococcal urethritis find chlamydia in 4% to 35% of cases.14,15 In the absence of widespread chlamydia screening among men, trends in urethritis may more closely reflect trends in chlamydia incidence. Concurrent trends in chlamydia testing coverage, chlamydia prevalence, and male urethritis within a defined population are largely unexamined.
The purpose of the present study was to evaluate long-term trends in chlamydia testing and infection diagnosis rates and concurrent trends in PID and ectopic pregnancy in women and urethritis in men in a defined population of health plan enrollees aged 15 to 44 years.
This study was conducted at Group Health Cooperative (GH), a mixed model managed care system serving Washington State and Western Idaho and included the years January 1, 1997 to December 31, 2007. The demographic composition of the GH population is generally representative of the surrounding community. The racial distribution in the 15 to 44 year age range is 78% to 82% white (community is 76% white). At the midpoint of this interval (2002), enrollment in the GH integrated group practice (where enrollees receive the majority of their care through GH) was 161,000 women and men aged 15 to 44 years. Enrollment declined by about 25% between 1997 and 2007, overall, with similar declines in the five-year age subgroups. Approximately 8% to 10% of enrollees received Medicaid or subsidized health care during this interval.
GH has long monitored health status and utilization among its enrollees through extensive computerized data systems, including data on hospitalizations, ambulatory care, laboratory testing and results, pharmacy prescription fills, claims for outside services, and membership and enrollment. For each enrollee and in each year enrolled at GH during the study period, we identified the following from these computerized databases: chlamydia tests and their results; and, on the basis of the ICD-9 codes listed in Table 1, we identified diagnoses of PID, ectopic pregnancy, and male urethritis. For the denominator data (person-years [py]), we identified the total number of enrollees by age and gender and their length of enrollment for each year. We also identified a subgroup of sexually active women aged 15 to 24 years using automated indices of sexual activity (pregnancy testing, visits for contraception, prescriptions for oral contraceptives, testing for sexually transmitted diseases, Pap testing), to derive a denominator similar to the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set (HEDIS) denominator used in many health plans to evaluate chlamydia testing performance in women.16
We calculated annual rates by gender and 5-year age categories. For rates of chlamydia testing, chlamydia diagnosis, PID, ectopic pregnancy, and urethritis, the denominator was enrollees' age- and gender-specific length of enrollment for the relevant year. All rates were calculated per 100,000 py, with the exception of chlamydia testing, which occurred more frequently and was calculated per 1000 py. We evaluated linear trends over the study period using Poisson regression, with calendar year fitted as a continuous variable in the model.
For women receiving PID and ectopic pregnancy diagnoses, we also evaluated where treatment was provided, calculating the proportion of cases treated in inpatient, ER, urgent care, and outpatient settings. If diagnoses for the same case occurred in more than one setting, we assigned only one setting, in the order listed above.
Overall chlamydia testing coverage for women aged 15 to 44 years increased during the study interval from 220 tests/1000 py in 1997 to 270/1000 in 2007 (Fig. 1). The chlamydia testing rate was the highest, and the proportionate increase in testing the largest (32%), in women aged 20 to 24 years. Testing rates were markedly higher in those women between the ages of 15 and 24 years who were classified as sexually active, per the automated sexual activity (HEDIS denominator) variables (694 tests/1,000 py in 1997 to 747/1,000 in 2007); however, these testing rates did not change markedly over the study interval. Of women tested, the overall proportion testing positive ranged from a low of 1.7% (2002) to a high of 3.2% (2006), but did not increase steadily over time (P value for linear trend = 0.06). The 15 to 19 year-old age group had the highest proportions testing positive, with the highest proportion, 7.8%, occurring in 2006 (P value for increasing linear trend = 0.0002). In each succeeding 5-year age group, the proportions testing positive were lower, and by age 40 to 44 were approximately 1%, with a decreasing trend (P value for trend = 0.02).
From 1997 to 2007, we identified 4756 chlamydial infections in 3991 women aged 15 to 44 years. As with testing coverage, rates of chlamydial infection also increased significantly from 449 infections/100,000 py in 1997 to 805/100,000 py in 2007 (P value for linear trend over time = 0.01) (Table 2; Fig. 1). When evaluating age groups, increasing linear trends in chlamydia diagnosis rates over the 11-year study period were statistically significant for the 15 to 19, 20 to 24, and 25 to 29 years age groups. Rates were the highest in women aged 15 to 24 years, particularly for the HEDIS-based sexually active subgroup (2505/100,000 in 1997 and 3482/100,000 in 2007). The highest infection rates for the entire interval occurred in the last 3 years (2005–2007) and were largely the result of increases in infections among women aged 15 to 29 years. This was also the interval during which use of amplified tests increased markedly at GH. In 2004, nucleic acid amplification tests (NAAT) comprised approximately 20% of tests in women, increased to approximately 76% in 2005, and to >98% in 2007.
We identified a total of 5096 cases of PID from 1997 to 2007 (Table 3, Pelvic inflammatory disease; Fig. 2). In contrast with the increases in chlamydia rates, PID rates decreased significantly throughout the study interval (Fig. 2). Overall, rates of PID declined by 43%, from 823 diagnoses/100,000 py in 1997 to 473/100,000 in 2007 (P value, linear trend <0.01), and declined significantly in every 5-year age group except 35- to 39-year-old women (Table 3, Pelvic inflammatory disease). The highest rate occurred in the 20 to 24 year age group 1727/100,000 py in 2006 (Table 3, Pelvic inflammatory disease). In examining the treatment settings, 6% to 12% of PID cases received inpatient treatment in a given year, and the great majority of diagnoses (60%–68%) occurred solely in outpatient settings. Our review of medical records for 393 randomly selected women who received PID diagnosis codes between 2003 and 2007 found that 74 were not true cases, a positive predictive value (PPV) of 78.8% after excluding 44 charts with no information.
In contrast to PID, we did not observe a decline in ectopic pregnancy rates over the study period (Table 3, Ectopic pregnancy; Fig. 2). A total of 986 ectopic pregnancy diagnoses were identified. Rates of ectopic pregnancy were highest among women aged 25 to 29 years. Although there were no statistically significant linear trends over the study period, rates of ectopic pregnancy appeared to increase slightly in recent years after a low in 2003.
Although much lower overall than for women, the chlamydia testing rate among men increased much more steeply, rising from about 12 tests/1000 person years in 1997 to 42/1000 in 2007 (Fig. 3). The largest increases in testing occurred during the last 3 years (2005–2007).
Chlamydia diagnosis rates for men rose steadily and significantly throughout the study interval, overall and for all age groups (Table 4, Chlamydia). Rates of testing coverage and diagnosis were highest in the years 2005–2007. Overall infection rates increased from 91 diagnoses/100,000 py in 1997 to 218/100,000 in 2007 and were highest in the 20- to 24-year age group. As with women, this was the interval during which use of NAAT increased markedly.
While few urethritis cases were identified per study year (range, 18–49), rates of urethritis also increased significantly for the overall group (P value, linear trend <0.0001) and for a number of the age-specific subgroups. On average, rates were highest in the 25- to 29-year age group (Fig. 3).
This evaluation of 11-year trends in chlamydia testing, chlamydia diagnoses, and the associated outcomes of PID and ectopic pregnancy in women and urethritis in men, all within a single, defined, privately-insured population, yielded several findings of note.
Incorporating comparisons between age groups, gender, and evaluation of these indices in a subset of women classified as sexually active per automated indices, we observed significant and substantial increases in long-term chlamydia diagnosis rates for both women and men, with some of the largest rate increases occurring in the last 3 years (2005–2007). Upward trends in rates of chlamydia diagnosis are likely due in part to increased testing, along with more appropriate targeting of testing; the biggest increases in testing throughout the analysis timeframe occurred in the subgroup of women identified as being sexually active. Increases also are likely to be because of the transition to more sensitive test technology, which can artificially increase observed prevalence.17,18 In 2000, the primary chlamydia testing technology in the United States was DNA probe testing (approximately 62% of chlamydia tests at surveyed US public health labs).19 The current preferred test technology for diagnosing chlamydia is NAAT, which offer significant improvements in sensitivity when compared with previous tests.20 Between 2000 and 2007, the proportion of NAAT performed at surveyed public health laboratories increased from 25% to 82%.21,22 At GH, the main transition to NAAT occurred during 2005–2007. This likely drove the increased testing during these years, particularly for men. It is also likely to be a major contributor to the observed increases in chlamydia rates in women during these same years.
National case report rates for chlamydia steadily increased from 1997 to 2007, similar to the increased overall rates we observed at GH. However, most investigations of trend data have the limitations noted earlier (expanded chlamydia testing, increased use of more sensitive tests, etc.).7 The observation of increasing chlamydia testing rates and transitions in testing technology concurrent with increasing chlamydia diagnosis rates noted in this population highlight the importance of considering the role of changing clinical options and practices and the advantage of improved automated systems in tracking these changes over time.
Other studies of chlamydia prevalence among universally tested populations of women have found trends to be stable or decreasing.18,23 A recent analysis of nationally representative data from the National Health and Nutrition Examination Survey reported an overall decline in chlamydia prevalence from 1999 to 2006 among men and women aged 14 to 39 years.23 Likewise, Satterwhite et al reported decreasing prevalence among high-risk participants entering the National Job Training Program, a program targeting socioeconomically disadvantaged young women and men aged 16 to 24 years.18 However, a recent analysis of chlamydia positivity trends among women aged 15 to 24 years who attended family planning clinics in US Public Health Service Region X (Washington, Idaho, Alaska, Oregon) from 1997 to 2004 reported increasing trends, after controlling for demographics, self-reported sexual risk behaviors, and test technology.24 The authors concluded that a true increase in chlamydia positivity occurred over that study time frame, which did not include data from 2005 to 2007, as this report does. However, Region X results are consistent with our findings and suggest that, while some proportion of the detected increase in chlamydia rates may be due to other factors, true increases in disease burden cannot be ruled out.
Although markedly lower than for women, both chlamydia testing and chlamydia diagnosis rates increased sharply for men, particularly in the most recent 3 years. These increases may well reflect some of the same factors associated with the trends among women, with the added importance of the availability of urine-based testing. Nationally, infection rates for men also showed substantial increases, particularly during the last 3 years. Long-term trends in male urethritis rates in the GH population tracked closely with chlamydia diagnosis trends. This suggests that chlamydia infection rates in this population may actually be increasing, assuming that the proportion of chlamydia resulting in symptoms is stable over time. However, the low number of urethritis cases detected argues for cautious interpretation of these data.
As noted, a number of factors complicate the interpretation of the observed trends for chlamydia diagnosis. This lends added importance to trends in reproductive sequelae of chlamydia, particularly because they represent the major societal and individual burdens of these infections. Untreated chlamydia leads to PID in an estimated 10% to 15% of cases.25 In contrast with increases in chlamydia trends, PID rates in women from 1997 to 2007 appear to have declined steadily. Declines were seen in all clinical settings, including ambulatory care, which is consistent with reports from other data sources.10,11 Our medical record review of PID cases identified using the standard ICD-9-CM codes found that about 21% were not true cases (PPV, 78.8%). However, while the rates may incorporate error, the proportion of error is likely to be fairly uniform over time and, thus, may not greatly compromise the accuracy of the trends, which are the focus of this report. While only ecological comparisons can be made between trends in chlamydia rates and PID trends, declines in PID over time suggest that chlamydia prevention efforts may be having some impact, despite possible increases in infection burden.15 The steepest declines occurred in women between 15 and 24, the group who also experienced the largest increases in chlamydia testing. While declining PID trends could reflect declines in other organisms involved in PID causation, at least 1 pathogen of interest, gonorrhea, has been infrequent in this health plan population for many years.
Ectopic pregnancy rates over this time frame remained fairly flat. When compared with PID, ectopic pregnancy is a more distant adverse outcome of chlamydia. National data on ectopic pregnancy have been considered unreliable for many years because of changes in practice and treatment8; the last report using national ectopic pregnancy rates based on the National Hospital Discharge Survey was in 1989. However, recent evaluations of trends in US populations, including an examination of a national administrative claims database, also have reported fairly flat rates (not declines) over time26,27 as has a recent evaluation of trends in this health plan.28 Monitoring these trends is important, but determining the association between chlamydia diagnosis trends and ectopic pregnancy trends is difficult, due largely to the presumed length of time between acquisition of chlamydia and a subsequent related ectopic pregnancy and to the proportion of chlamydia infections that go undetected.
These administrative data are limited in not allowing for the evaluation of more detailed risk factor information such as would be obtained from questionnaires, and the findings may not be generalizable beyond the Pacific Northwest region. However, our findings are generally consistent with available national data sources. These data also are limited in that we could only evaluate chlamydia positivity and not prevalence, because we did not test all members of the population. Finally, as noted, these are ecological comparisons of trends in related health outcomes and are not individual-level data. However, with some added effort, individual-level data from defined populations such as Group Health's can be ascertained and examined.
Strengths of these data include their comprehensiveness and longevity, which provided the opportunity to calculate rates and track concurrent trends in chlamydia testing, diagnoses and related sequelae over a lengthy interval within a defined health plan population. For women, we evaluated these rates in several ways—overall, by 5-year age groups, and among young women classified as sexually active using administrative indices. They also provide information on privately insured populations, which are often not well-represented in national data. In addition, administrative data such as these are a potentially valuable resource for further epidemiologic and health services research and surveillance.8,9,29,30 For example, Group Health is a member of the Health Maintenance Organization Research Network (HMORN), a nationwide consortium that can share programming and standard data elements across 15 sites that cover approximately 13 million enrollees.29
In this study population, the observed increase in chlamydia diagnoses in women was not mirrored by upturns in the reproductive outcomes of PID and ectopic pregnancy, overall or in 5-year age groups. In contrast, men were found to have consistently upward trends in testing, chlamydia infection diagnoses, and urethritis rates. Data such as those used in this report are now widely available in many health care systems and have the potential to contribute to more widespread assessment of the public health burden of these conditions and to ongoing surveillance and research.
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