CHLAMYDIA TRACHOMATIS (CT) INFECTIONS ACCOUNT for the largest proportion of sexually transmitted infections reported to the Centers for Disease Control and Prevention (CDC), with an estimated 2.8 million new cases per year in the United States.1 American Indians/Alaskan Natives (AI/AN) represent a racial minority population within the United States with a unique social, cultural, and biologic background. AI/AN bear a disproportionate burden of illness for many diseases, including sexually transmitted infections.1–4
A high prevalence of chlamydial infection has been reported in AI/AN communities, ranging from 24% to 30% among prenatal patients in the Southwest5,6 to 23% of all women screened in a remote Alaskan village.7 In 2004, women aged 15 to 44 years screened for chlamydia in 2 Indian Health Service (IHS) regions had chlamydia positivities of 10.7% versus 6.3% for women screened in family planning clinics nationwide.8 In a recent report, the overall chlamydia rate in 2004 among AI/AN residing in IHS provision areas was 2.3 times higher than the corresponding US rates, with 3 IHS areas having chlamydia rates 4.9 to 6 times higher than the US rate.3 However, there are few analyses of chlamydia infections over time in AI/AN populations.
We sought to more clearly define the clinical epidemiology and trends in test positivity of chlamydial infections in AI/AN women by examining data representing 15- to 24-year-old AI/AN women attending family planning clinics in the Region X Infertility Prevention Project (IPP) network during the years 1997–2004. This represents a cohort of women for whom universal screening for chlamydia was recommended throughout the study period.9,10
Materials and Methods
Sources of Data
Data on chlamydia tests were obtained from the Region X IPP, an ongoing program since 1988 that provides for the screening and treatment of chlamydial infections throughout Alaska, Idaho, Oregon, and Washington states. All women aged 15 to 24 years who presented to family planning clinics enrolled in the IPP and who self-identified as AI/AN, whether as a sole racial category or in combination with another racial or ethnic category, were included in this analysis. Since inception of the IPP in 1988, screening has been recommended for all women aged 24 years and younger for chlamydial infection at least annually as recommended by the CDC and the US Preventive Services Task Force.10,11
All Region X family planning clinics used a common medical record form and laboratory slip to record a standard set of information. Information collected included age, race, ethnicity, specimen collection date, reason for visit, specified clinical exam findings (ectopy, friable cervix, pelvic inflammatory disease, cervicitis), self-reported sexual risk behaviors (having had a new sex partner in the past 60 days, multiple sex partners in the past 60 days, a symptomatic sex partner in the past 60 days, a sex partner who was diagnosed with chlamydia, and condom use during last sex), having had chlamydia in the past year, laboratory test type, and chlamydia test result. CT diagnostic tests with unsatisfactory or indeterminate results were excluded from the analysis.
CT testing for the family planning clinics was performed by 4 state public health laboratories (Alaska, Idaho, Oregon, and Washington), a county health district laboratory (Spokane), and the University of Washington Chlamydia Laboratory. From 1997 through 2004, these laboratories adopted nucleic acid amplification tests (NAATs) in favor of less sensitive assays. During the study period, non-NAATs included (in order of decreasing usage) enzyme immunoassay (MicroTrak II, Syva and Behring Diagnostic Products, Cupertino, CA); nucleic acid hybridization test (Pace 2, Gen-Probe, San Diego, CA); nucleic acid hybridization assays (Hybrid Capture 2, Digene, Gaithersburg, MD) and cell culture. The majority of NAATs used in Region X were ligase chain reaction tests (LCx, Abbott, Abbott Park, IL) and target capture transcription-mediated amplification assays (Aptima Combo 2, Gen-Probe, San Diego, CA).12
Chlamydia positivity was calculated by dividing the number of positive tests by the total number of tests performed. Categorical variables were analyzed with the method of chi-squared, with time trends in demographic variables examined for both heterogeneity and trend. Potential predictors of chlamydia positivity were identified by univariate analysis of odds ratios. Stepwise forward logistic regression modeling was used to identify factors independently associated with chlamydia positivity, including demographic characteristics, clinical findings, self-reported sexual risk behaviors, type of laboratory test (NAAT vs. non-NAAT), and year of test. In comparing observed chlamydia positivity in AI/AN versus non-AI/AN women in Region X, direct standardization was used to correct for age differences between the 2 populations. All values are reported at the 95% confidence interval.
As conversion to a more sensitive laboratory test can result in an increase in observed chlamydia positivity even with no increase in true disease prevalence,13,14 we adjusted for change in test type used over time. We used the sensitivity and specificity of each laboratory test method to calculate an adjusted positivity [test-specific adjusted positivity = (test-specific observed positivity + test specificity − 1)/(test sensitivity + test specificity − 1)].15 Overall adjusted positivity was calculated as a weighted sum of the adjusted positivity for each test type. This method has previously been used in reporting of chlamydia positivity data by the CDC as detailed by Fine and Dicker et al.8,12,13 The sensitivity and specificity estimates used for the adjustment were culture (sensitivity 0.747, specificity 1.000); enzyme immunoassay tests with negative gray zone confirmation (sensitivity 0.810, specificity 0.996); other non-NAATs including Gen-Probe Pace 2 and Digene Hybrid Capture 2 assay (sensitivity 0.619, specificity 0.997); and NAATs (sensitivity 0.855, specificity 0.997).16,17 We compared the differences in trends for observed and adjusted chlamydia positivity.
From 1997 to 2004, a total of 581,106 CT tests were performed, with 7449 tests performed in AI/AN women. Of the 7449 chlamydia tests performed among women who self-reported as AI/AN, 75 (1.0%) had unsatisfactory, indeterminate, or missing results and were excluded from further analysis. Of the remaining 7374 chlamydia tests, 67% were done in Washington state, 18% in Oregon, 10% in Alaska, and 5% in Idaho. By racial/ethnic categories, 90% of women tested reported being AI/AN alone, 8% reported AI/AN race with Hispanic ethnicity, and 2% reported more than 2 racial/ethnic categories. Nearly all chlamydia tests performed on both AI/AN and non-AI/AN women were based on cervical specimens (91.4% and 94.5%, respectively) with urine specimens being the next most common specimen site (8.4% and 5.4%, respectively). The use of NAAT-based test methods increased rapidly beginning in 1997. During the study period, the use of NAAT-based tests rose from 13% to 60% in the region at large and from 13% to 78% among AI/AN women. From 1997 to 2004, other test methods used among AI/AN women changed as follows: enzyme immunoassay (46%–0%), culture (27%–0.8%), and non-NAAT nucleic acid hybridization (14%–22%).
Among AI/AN women, those aged 15 to 17 accounted for 30.4% of tests, aged 18 to 19 for 25.8%, and aged 20 to 24 for 43.8% of tests (Table 1). Most women (70.2%) presented for a “routine visit” (initial or annual gynecologic exam, primary care visit, reproductive health exam). Thirteen percent of women had a “pregnancy related” visit, defined as request of a pregnancy test, prenatal care, pregnancy management, or pre/postabortion services, and 16.1% reported the reason for visit as having symptoms (abnormal vaginal or urethral discharge, dysuria, abdominal or pelvic pain, or abnormal vaginal bleeding). Overall, 33.3% of women reported 1 or more behavioral risk factors in the 60 days before testing, including 28.9% with a new partner, 14.5% with more than 1 sex partner, and 3.1% with a symptomatic sex partner. Condom use at last sexual encounter was low at 27.3%. Few women (8.8%) had clinical findings on examination. Seven percent of women reported having a chlamydial infection in the 12 months before the most recent test.
Through the study period, the age structure and risk profile of the AI/AN women aged 15 to 24 being tested at IPP family planning clinics demonstrated considerable variation (Fig. 1). The proportion of women aged 15 to 17 rose from 33.5% in 1997 to a peak of 35.6% in 2000 and then fell to 26.1% in 2004 (P <0.0001). There was a similar rise in reported sexual risk behaviors over this period, with women reporting one or more risk factors of new sexual partner, multiple partners, or symptomatic partner rising from 26.8% in 1997 to a peak of 35.4% in 2000 and then falling to 25.7% in 2004 (P <0.0001). Reported condom use did not vary over time. Toward the end of the study period, more women reported being diagnosed with chlamydia in the past 12 months, rising from 3.9% in 1997 to 8.3% in 2004 (P = 0.002).
Compared with women aged 15 to 24 tested at family planning in Region X from 1997 to 2004 who reported non-AI/AN race, there were differences in age and risk profiles. AI/AN women were younger: proportion aged 15 to 17 years, 30.4% versus 22.8% (P <0.0001); aged 18 to 19, 25.8% versus 26.5% (P = 0.21); and age 20 to 24, 43.8% versus 50.7% (P <0.0001). AI/AN women were more likely to report having genitourinary symptoms at the time of visit (16.1% vs. 13.2%, P <0.001) and were more likely to present for a pregnancy related visit (13.1% vs. 8.1%, P <0.001) than non-AI/AN women. Sexual behavioral risks in the 60 days before testing were more commonly reported among AI/AN women: new sex partner, 28.9% versus 22.9% (P <0.0001); multiple sex partners, 14.5% versus 9.7% (P <0.0001); symptomatic sex partner, 3.1% versus 2.4% (P = 0.0004); and 1 or more behavioral risks, 33.3% versus 25.6% (P <0.0001). Reported condom use at last sex was low in both groups, 27.3% for AI/AN women versus 25.8% (P = 0.007). Notably, AI/AN women were more likely to have been diagnosed with chlamydia in the past 12 months, 7.2% versus 3.9% (P <0.0001).
Observed, unadjusted chlamydia positivity for AI/AN women was 8.6% versus 5.2% in the non-AI/AN population. After direct standardization was used to correct for age differences between the AI/AN population and the Region X non-AI/AN population, observed positivity changed minimally (8.6%–8.4%).
Trends in chlamydia positivity over time, adjusted for test type, are displayed in Figure 2. Adjusted positivity in AI/AN women rose from 7.8% in 1997 to a peak of 12.1% in 1999, concluding at 11.0% in 2004. These changes in positivity were temporally associated with a rise in reported risk behaviors and a decline in the age of the population being tested. Adjusted chlamydia positivity in non-AI/AN women rose steadily from 4.6% in 1997 to 7.1% in 2004. Comparing test type adjusted positivity by calendar year, AI/AN women had chlamydia positivity ranging from 1.5 to 2.2 times the non-AI/AN population levels (absolute difference 2.8%–6.6%). At all time points, chlamydia positivity in AI/AN women was higher than that reported in both the non-AI/AN and Region X populations.8,12
Table 2 displays risk factors independently associated with chlamydia positivity among AI/AN women as determined by multivariable logistic regression. Despite the observation that use of NAAT was associated with increased positivity, as expected, several other risks were independently associated with positivity. These included younger age (<20 years), report of one or more behavioral risk factors, presence of one or more clinical findings, report of diagnosis of chlamydia in the past 12 months or of a partner with chlamydia, and presentation for pregnancy related visit. After accounting for each of these factors, there was no independent association of year of visit with chlamydia positivity. Additionally, there was no independent association of positivity with condom use, symptoms at the time of visit, or having a partner with gonorrhea.
In comparison to the non-AI/AN population of women being tested for chlamydia infection at Region X IPP family planning clinics, AI/AN women were younger and reported higher levels of behavioral risk factors. AI/AN women had levels of chlamydia positivity ranging from 7.8% to 12.1% during the study period, which was 1.5 to 2.2 times higher than positivity in the non-AI/AN population. These differences persisted even after adjusting for age differentials between the 2 populations.
Factors associated with chlamydia positivity in AI/AN women, including age, test type used, behavioral risks, clinical findings, exposure to chlamydia, and a prior positive test, were similar in type and magnitude to other analyses of Region X data.12 Of note, a visit related to pregnancy (seeking pregnancy services or pregnancy testing) was associated with chlamydia positivity in this population. A recent survey in South Carolina, part of the Region IV IPP network, found that women aged 15 to 25 years presenting to family planning clinics for pregnancy testing alone had a chlamydia positivity of 15%.18 These findings emphasize that chlamydia testing should be performed in the population of 15- to 24-year-old AI/AN women seeking pregnancy testing or pregnancy services.
Our analysis is subject to several limitations. First, these data do not necessarily reflect chlamydia positivity for all AI/AN women. AI/AN communities are diverse geographically, socially, and culturally. Importantly, our data do not account for areas within tribal reservation lands, which may have unique issues related to sexual networks and access to screening. A recent report from the CDC highlighted differential chlamydia positivity between aggregate United States data and data arising from counties predominantly served by the IHS. Chlamydia rates in these IHS areas were 2.3 times the national average, with 11 of 12 IHS service areas having rates higher than the US average.3
Second, the IPP program collects data on a limited number of risk factors. AI/AN persons may have as yet unidentified protective factors or risk factors for chlamydial infection. Identifying these factors would be valuable for future prevention and screening programs. Assessment of the influence of substance use, sexual networks, and availability of partner treatment services in this population should be considered.
Third, we do not have data on the extent of coverage of chlamydia screening for AI/AN women, although previous reports have estimated screening coverage at 50% to 60% in Region X in general.19,20 The combined influences of area of residence, urban versus rural versus geographically isolated, and clinic participation in the IPP on screening coverage for AI/AN women is unknown.
Multiple previous studies have disclosed high levels of racial misclassification among AI/AN in public health surveillance systems, including cancer registries, death certificate recording, and reporting of HIV/AIDS and STDs.21–30 Studies of mandatory, state level sexually transmitted disease reporting in both Washington and Oregon in 1995–2000 disclosed that 36% and 55%, respectively, of reported STD cases among AI/AN were misclassified. After adjusting for racial misclassification, case ascertainment among AI/AN rose by 29% in Washington and by 76% in Oregon.25,28 The data collection protocol used in our study is designed such that clients self-report their racial and ethnic background, hopefully minimizing racial misclassification at the provider level. We did not have the ability to link individual or composite visit data to existing registries of AI/AN populations to aid in verifying the accuracy of the racial reporting in this study.
Additionally, the population being screened over time may be changing. Of note, our analysis demonstrated an increase in women who reported a history of chlamydial infection in the past 12 months. This observation may reflect a true rise in background positivity, a higher-risk group being screened, changes in clinic practice encouraging rescreening, or an increase in the number of women presenting for rescreening following a prior chlamydia diagnosis as now recommended by the CDC.10
Finally, our data are not linked to individual identifiers; thus, we cannot distinguish between women being screened repeatedly within a defined time period. Chlamydia positivity is an estimate of prevalence, but does not represent true prevalence in the population. Positivity may include women who are tested 2 or more times during a single time period. Previous comparisons of positivity versus prevalence in family planning clinics within the IPP, including Region X, have shown only small differences between positivity and prevalence. In that analysis positivity was similar to or slightly higher than prevalence with an absolute difference of less than 0.5%. Within Region X from 1988 to 1996, on average, 93.8% of women had only 1 chlamydia test per year.31 Similar data are not available for the time period of this study for direct comparison.
In summary, AI/AN women continue to suffer from a higher burden of disease caused by CT, as amply demonstrated in our analysis. The explanation for this differential remains unclear. Further investigation of risk factors for CT, related outcomes including pelvic inflammatory disease and tubal infertility, access to screening and treatment, sexual networks, more effective approaches to partner management, and more widespread surveillance would be beneficial to future health improvement and disease control measures in this vulnerable population.
1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2004. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.
2. Division of Program Statistics, Office of Program Support, Office of Public Health, Indian Health Service, U.S. Department of Health and Human Services. Trends in Indian Health 2000–2001. U.S. Department of Health and Human Services, 2004.
3. Wong D, Swint E, Paisano EL, et al. Indian Health Surveillance Report—Sexually Transmitted Diseases 2004. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and Indian Health Service, 2006.
4. Kaufman CE, Shelby L, Mosure D, et al. Within the hidden epidemic: Sexually transmitted diseases and HIV/AIDS among American Indians and Alaska natives. Sex Transm Dis 2007; 34:767–777.
5. Cullen TA, Helgerson SD, LaRuffa T, et al. Chlamydia trachomatis
infection on Native American women in a southwestern tribe. J Fam Pract 1990; 31:552–554.
6. Harrison HR, Boyce WT, Haffner WH, et al. The prevalence of genital Chlamydia trachomatis
infections during pregnancy in an American Indian population. Sex Transm Dis 1983; 10:184–186.
7. Toomey KE, Rafferty MP, Stamm WE. Unrecognized high prevalence of Chlamydia trachomatis
cervical infection in an isolated Alaskan Eskimo population. JAMA 1987; 258:53–56.
8. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2004 Supplement, Chlamydia Prevalence Monitoring Project Report. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.
9. U.S. Preventive Services Task Force. Screening for chlamydial infection: Recommendations and rationale. Am J Prev Med 2001;20(3 suppl):90–94.
10. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Morb Mortal Wkly Rep 2006; 55(RR-11):1–100.
11. U.S. Preventive Services Task Force. Screening for chlamydial infection: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2007; 147:128–134.
12. Fine D, Dicker L, Mosure D, et al., Region X Infertility Prevention Project. Increasing chlamydia positivity in women screened in family planning clinics: Do we know why? Sex Transm Dis 2008; 35:47–52.
13. Dicker LW, Mosure DJ, Levine WC, et al. Impact of switching laboratory tests on reported trends in Chlamydia trachomatis
infections. Am J Epidemiol 2000; 151:430–435.
14. Burckhardt F, Warner P, Young H. What is the impact of change in diagnostic test method on surveillance data trends in Chlamydia trachomatis
infection? Sex Transm Infect 2006; 82:24–30.
15. Rogan W, Gladen B. Estimating prevalence from the results of a screening test. Am J Epidemiol 1978; 107:71–76.
16. Newhall WJ, DeLisle S, Fine D, et al. Head-to-head evaluation of five chlamydia tests relative to a quality-assured culture standard. J Clin Microbiol 1999; 37:681–685.
17. Black CM, Marrazzo J, Johnson RE, et al. Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis
infection in women performed with an improved reference standard. J Clin Microbiol 2002; 40:3757–3763.
18. Geisler W, James AB. Chlamydial and gonococcal infections in women seeking pregnancy testing at family planning clinics. Paper presented at: 17th Biennial meeting of the International Society for Sexually Transmitted Disease Research; 2007; Seattle, Washington.
19. Gunter D, Fine D, Dicker L, et al. Methods for estimating chlamydia screening coverage among women attending family planning clinics. Paper presented at: 16th Biennial meeting of the International Society for Sexually Transmitted Disease Research; 2005; Amsterdam, The Netherlands.
20. Levine WC, Dicker LW, Devine O, et al. Indirect estimation of chlamydia screening coverage using public health surveillance data. Am J Epidemiol 2004; 160:91–96.
21. Bertolli J, Lee LM, Sullivan PS. Racial misidentification of American Indians/Alaska Natives in the HIV/AIDS reporting systems of five states and one urban health jurisdiction, U.S., 1984–2002. Public Health Rep 2007;122:382–392.
22. Epstein M, Moreno R, Bacchetti P. The underreporting of deaths of American Indian children in California, 1979 through 1993. Am J Public Health 1997; 87:1363–1366.
23. Frost F, Taylor V, Fries E. Racial misclassification of Native Americans in a surveillance, epidemiology, and end results cancer registry. J Natl Cancer Inst 1992; 84:957–962.
24. Frost F, Tollestrup K, Ross A, et al. Correctness of racial coding of American Indians and Alaska Natives on the Washington State death certificate. Am J Prev Med 1994; 10:290–294.
25. Jackson S, Sweigman K, Robertson LD. Racial misclassification for sexually transmitted diseases among American Indians and Alaska Natives in Oregon State, 1995–2000. IHS Prim Care Provid 2003; 28:268–271.
26. Kelly J, Chu S, Diaz T, et al. Race/ethnicity misclassification of persons reported with AIDS. The AIDS Mortality Project Group and The Supplement to HIV/AIDS Surveillance Project Group. Ethn Health 1996; 1:87–94.
27. Lieb LE, Conway GA, Hedderman M, et al. Racial misclassification of American Indians with AIDS in Los Angeles County. J Acquir Immune Defic Syndr 1992; 5:1137–1141.
28. Puuka E, Jackson S, Stehr-Green P. Sexually Transmitted Diseases Among American Indians and Alaska Natives in Washington State, 1995–2000. Portland, OR: The Northwest Tribal Epidemiology Center, Northwest Portland Area Indian Health Board.
29. Stehr-Green P, Bettles J, Robertson LD. Effect of racial/ethnic misclassification of American Indians and Alaskan Natives on Washington State death certificates, 1989–1997. Am J Public Health 2002; 92:443–444.
30. Thoroughman DA, Frederickson D, Cameron HD, et al. Racial misclassification of American Indians in Oklahoma State surveillance data for sexually transmitted diseases. Am J Epidemiol 2002; 155:1137–1141.
31. Dicker LW, Mosure DJ, Levine WC. Chlamydia positivity versus prevalence: What's the difference? Sex Transm Dis 1998; 25:251–253.