Nonpregnant women: Thirty-three studies comparing two or more screening tests in the same study population were included in the systematic review (68-101). These included 22 studies reporting culture results, 10 antigen detection tests, 14 LCR, 18 PCR, and 4 transcription-mediated amplification of RNA.
Culture specimens had 100% specificity (because most studies defined culture as the gold standard) and widely varying sensitivity, ranging from 42% to 100%. Antigen detection tests obtained by endocervical swab (EIA, DFA) had improved sensitivity, with most results between 70% and 80% but with some decline in specificity (96% to 100%). New DNA amplification tests, PCR and LCR, had higher sensitivity and specificity than the antigen detection tests. PCR swab and urine specimens had similar sensitivities of 82% to 100% and specificities of 98% to 100%. LCR swab specimens had sensitivities of 81% to 98% and specificities of 96% to 100%; LCR urine tests had sensitivities of 70% to 96% and specificities of 99% to 100%. Only four studies of transcription-mediated amplification of RNA tests were identified from our search, and these performed comparably to the DNA amplification tests.
Endocervical swab specimens and first-void urine specimens had similar performance using DNA amplification tests. Urine tests allow noninvasive testing for women without the need for a pelvic examination, thereby expanding opportunities for screening (102). No studies addressed the adverse effects of using these newer technologies.
Pregnant women: Two studies compared urine LCR with endocervical culture in pregnant women and found LCR to be more sensitive and easier to use than culture (68,103). Another study compared culture to DFA, EIA, and PCR (all obtained by endocervical swabs) and concluded that the nonculture techniques provided improved sensitivity compared to culture even in a population with a prevalence rate as low as 4.3% (104). Another study reported 100% specificity and 97.2% sensitivity by using PCR on swab-obtained introital specimens compared to PCR endocervical specimens (105).
Men: We reviewed 32 studies on test performance in men (69, 74-79, 83-85, 91-94, 99, 100, 106-121). These included 15 studies reporting culture results, 18 antigen detection tests, 10 LCR, 14 PCR, and 3 transcription-mediated amplification of RNA. These studies compared two or more of these tests in the same study population.
Culture specimens had 100% specificity and widely varying sensitivity, ranging from 37% to 97%. Antigen detection tests (EIA, DFA) that used swab specimens had improved sensitivity compared to culture, averaging 80% but with some decline in specificity (96% to 100%). The new DNA amplification tests, PCR and LCR, had higher sensitivity and specificity than the antigen detection tests in ranges similar to the studies described above for women. Results of swab specimens compared to first-void urine specimens using DNA tests were similar. The 3 studies of transcription-mediated amplification of RNA reported results similar to the DNA amplification tests.
Most of these studies of men were conducted in STD clinics, and many were located outside the United States. The study population usually included both symptomatic and asymptomatic men, and few studies reported results separately. Very little demographic information was provided about the study population. The lack of test performance studies in community-based, lower-prevalence populations limits their generalizability.
Although studies indicate that urine techniques are capable of improved sensitivity compared to culture, the importance of detecting and treating culture-negative infections is not yet known. Asymptomatic, culture-negative infections may represent those with lower organism counts. The clinical importance and rate of transmission of these low-level infections have not yet been studied.
Recurrent chlamydial infections in women have been associated with increased risks for PID and long-term complications. A published retrospective cohort study evaluated the risks of hospitalization for ectopic pregnancy or PID for 11,000 Wisconsin women with documented single and recurrent chlamydial infections (24). Rates of hospitalization for ectopic pregnancy increased with the number of infections (13 of 10,000 for one infection, 49 of 10,000 for two infection, 140 of 10,000 for three or more infections). Similarly, rates of hospitalization for PID also increased with the number of infections (11 of 10,000 for one infection, 54 of 10,000 for two infection, 110 of 10,000 for three or more infections). Adjusted multivariable analyses indicated that women who had two and three or more chlamydial infections had elevated risks of ectopic pregnancy compared to those with one infection (two infections: OR=2.1; 95% CI=1.3 to 3.4; three or more infections: OR=4.5; 95% CI=1.8 to 5.3), and elevated risks for PID (two infections: OR=4.0; 95% CI=1.6 to 9.9; three or more infections: OR=6.4; 95% CI=2.2 to 18.4). Recurrent or persistent chlamydial infections were more likely to occur among women who were young, black, residents of Milwaukee County (large urban population), received care in STD clinics, or had documented gonorrhea infection.
Although the clinical importance of recurrent chlamydial infections in women is known, information about the effectiveness of screening for recurrence is limited. This type of information would be helpful in determining screening intervals for groups at risk of recurrences. We found three cohort studies that evaluated recurrence rates in high-risk teenage populations. These studies did not differentiate between recurrences because of reinfection and treatment failures. A prospective study of 3202 high-risk, sexually active women aged 12 to 19 years found that the median time to the first positive chlamydia test result was 7.2 months and only 6.3 months to a repeat positive test among those with repeat visits (34). A study of chlamydial infection among residents of Manitoba found that 13.4% of those initially infected had a subsequent recurrent infection (122). In this study, recurrence was more common in women than in men, in those aged 15 to 24 years, in registered Native American Indians, and in those with concomitant gonorrhea. Another study of sexually active urban adolescents in Birmingham, Alabama, detected an initial chlamydial infection rate of 23.2%. Of those initially infected, 20.8% presented with a positive test on follow-up (123).
A research abstract from the CDC evaluated persistent and recurrent chlamydial infections in women presenting to STD, family planning, and adolescent clinics (124). Six percent of participants had chlamydial infections detected at 1-month follow-up visits and 7.5% at 4 months. Factors related to persistence and recurrence were young age (14 to 21 years) and incomplete therapy.
We identified no studies of the adverse effects of screening for chlamydial infection. The inconvenience of testing, stigma of being diagnosed with an STD, and potential sexual partner discord were areas that we considered. The adverse effects of antibiotic treatment were reported in the treatment studies as mild-to-moderate gastrointestinal symptoms (nausea, diarrhea, abdominal pain) (41). Adverse effects of antibiotics were not specifically addressed in the context of screening.
Several economic evaluations of chlamydia screening have been published (125-132), although they infrequently used the societal perspective and have methodologic limitations. Findings suggest that screening programs for detecting and treating chlamydia in nonpregnant women provide cost savings in populations with moderate-to-high prevalence of chlamydial infection (125,126). Selective screening is more cost-effective than universal screening under most assumptions, although universal screening may be cost-effective in populations in which the prevalence of chlamydia is high or sensitivity of selective screening criteria is low. (125-128) Also, DNA amplification assays may improve the cost-effectiveness of chlamydial screening if estimates of its accuracy are correct (129,130).
Table 1 (Text Version) summarizes the evidence obtained for this systematic review by indicating the type of study design and quality of evidence for each key question, using criteria developed by the U.S. Preventive Services Task Force. The most compelling argument for screening in women is based on evidence for improvement of health outcomes. A randomized, controlled trial of selective screening and treatment indicated a significant reduction in rates of PID among screened women compared to non-screened women (46). We found no new information on screening pregnant women, although previous studies indicated improved birth outcomes when pregnant women were screened and treated. The evidence for screening in men is limited, although the rationale for screening is reasonable because chlamydia is sexually transmitted.
The most difficult aspect of screening, however, is determining exactly who to screen and how frequently to do so. The most consistent evidence available supports age-based screening in women. These strategies appear to be effective even in settings with low-to-moderate prevalence rates (3% to 6%). Universal screening has been shown to be valuable in settings with higher prevalence rates (above 6%). Use of other selected risk factors may be helpful, but they vary between studies and may not translate to all clinical settings. Little information is available on how frequently to screen.
Chlamydia can be easily diagnosed by a number of new tests with relatively high sensitivity and specificity that outperform the traditional gold standard of culture. The DNA and RNA amplification tests that use urine specimens perform well in studies for both men and women and provide a quick, noninvasive method of screening.
Recurrent infections are associated with worse health outcomes, such as PID and ectopic pregnancies in women. Treating partners is important to prevent reinfection. Contract tracing and partner management, currently largely in the domain of public health programs not clinical practices, were not reviewed in this report. As the responsibility for these duties shifts to HMOs, clinicians may become more involved in these interventions (133).
To demonstrate chlamydial screening outcomes based on assumptions from recent studies, we created a balance sheet for 10,000 women aged 18 to 34 years (Table 2, Text Version). Three populations are represented, including a low-risk HMO population using a risk factor questionnaire and modeled after assumptions from a randomized, controlled trial of screening previously described (46), a theoretical high-risk population, and a theoretical low-risk population not using a risk factor questionnaire. In the first scenario, a questionnaire is mailed to 10,000 women in a low-risk population with a prevalence rate of 3%. Of 5701 women who respond to the questionnaire, 713 are identified as high-risk and offered chlamydial testing. Of these women, 457 (64%) are tested, and 32 are diagnosed with chlamydial infection and treated. By using this strategy, nine cases of PID are prevented. The number needed to screen (NNS) with a questionnaire to prevent one case of PID is 1130. Eighty-one women would need to be invited for screening and 57 tested to prevent one case of PID.
If, instead of using a questionnaire, all women in this population were offered screening, 53 cases of PID might be prevented, but the number needed to invite for screening would be 188 (120 tested). In a high-risk population with a prevalence of 9.4%, offering a chlamydial test to all women would prevent 167 cases of PID, and the number needed to invite for screening would be 60 (39 tested). For this strategy, the NNS depends heavily on the prevalence of the disease. Figure 2 (4 KB) shows the relationship between the NNS and prevalence of chlamydia based on the balance sheet assumptions. The NNS rises sharply at prevalence rates less than 3%.
There are important gaps in the evidence that limit support for routine screening of men, women, and pregnant women for chlamydial infection. Studies are needed that test screening criteria, diagnostic protocols, and testing intervals in community-based settings to determine the effectiveness of various screening strategies and their adverse effects. Research could include comparisons of universal, age-based, and risk factor-based criteria among populations with various prevalence rates. Studies of the effectiveness of screening in preventing infections and long-term complications, as well as in reducing rates of transmission and recurrence in both sexes, would improve screening programs. Research on the effectiveness of screening and treating asymptomatic men in preventing transmission to women is of potentially enormous benefit. Additional research is needed on the role of partner notification and presumptive treatment of partners to reduce transmission and reinfection. High-quality cost analyses of current clinical options such as screening criteria, treatment regimens, types of diagnostic tests, partner notification, and screening intervals could provide important information for health system program planning. Additional studies of the effectiveness of chlamydia tests, using urine specimens in community-based settings, are also needed to determine the clinical applications of this new technology.
This study was conducted by the Oregon Health Sciences University Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (Contract No. 290-97-0018), Rockville, MD.
This article is based on a more comprehensive Systematic Evidence Review. That document was reviewed by content experts, including Edward W. Hook III, M.D., University of Alabama at Birmingham, Jeanne Marrazzo, M.D., M.P.H., University of Washington, and Felicia H. Stewart, M.D., University of California, San Francisco; professional organizations, including American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists; and the American College of Preventive Medicine; and public health organizations, including the Canadian Task Force on Preventive Health Care, the Indian Health Service, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Veteran's Administration. Review by these individuals and groups does not necessarily imply endorsement of this article or of the accompanying recommendations of the U.S. Preventive Services Task Force.
Task Force members Carolyn Westhoff, M.D., M.Sc., and Jeffrey F. Peipert, M.D., M.P.H., Task Force chair Alfred O. Berg, M.D., M.P.H., AHRQ senior health policy analyst, David Atkins, M.D., M.P.H., as well as Somnath Saha, M.D., M.P.H. and Delia Scholes, Ph.D., also contributed to this project.
1. Cates W Jr. Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. American Social Health Association Panel. Sex Transm Dis 1999;26 (suppl 4):S2-7.
2. Groseclose SL, Zaidi AA, DeLisle SJ, Levine WC, St. Louis ME. Estimated incidence and prevalence of genital Chlamydia trachomatis infections in the United States, 1996. Sex Transm Dis 1999, 26:339-344.
3. Rolfs RT, Galaid EI, Zaidi AA. Pelvic inflammatory disease: trends in hospitalizations and office visits, 1979 through 1988. Am J Obstet Gynecol 1992, 166:983-990.
4. Cohen I, Veille JC, Calkins BM. Improved pregnancy outcome following successful treatment of chlamydial infection. JAMA 1990, 263:3160-3163.
5. Ryan GM Jr, Abdella TN, McNeeley SG, Baselski VS, Drummond DE. Chlamydia trachomatis infection in pregnancy and effect of treatment on outcome. Am J Obstet Gynecol 1990, 162:34-39.
6. Harrison HR, Alexander ER, Weinstein L, Lewis M, Nash M, Sim DA. Cervical Chlamydia trachomatis and mycoplasmal infections in pregnancy. Epidemiology and outcomes. JAMA 1983, 250:1721-1727.
7. Martin DH, Koutsky L, Eschenbach DA, et al. Prematurity and perinatal mortality in pregnancies complicated by maternal Chlamydia trachomatis infections. JAMA 1982, 247:1585-1588.
8. Schachter J, Grossman M, Sweet R.L, Holt J, Jordan C, Bishop E. Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA 1986, 255:3374-3377.
9. Centers for Disease Control and Prevention. Recommendations for prevention and management of Chlamydial trachomatis infections. MMWR Morbid Mortal Wkly Rep 1993;42:1-39.
10. Rich E, Hook EW III, Alarcon GS, Moreland LW. Reactive arthritis in patients attending an urban sexually transmitted diseases clinic. Arthritis Rheum 1996, 39:1172-1177.
11. Kousa M, Saikku P, Richmond S, Lassus A. Frequent association of chlamydial infection with Reiter's syndrome. Sex Transm Dis 1978, 2:57-61.
12. McMillan A, Pakianathan M, Mao JH, Macintyre CCA. Urethral stricture and urethritis in men in Scotland. Genitourin Med 1994, 70:403-405.
13. Bollmann R, Engel S, Sagert D, Gobel UB. Investigations on the detection of Chlamydia trachomatis infections in infertile male outpatients. Andrologia 1998, 30:23-27.
14. Laga M, Manoka A, Kivuvu M. et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993, 7:95-102.
15. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999, 75:3-17.
16. Institute of Medicine. Committee on Prevention and Control of Sexually Transmitted Diseases. In: Eng TR, Butler WR, eds. The hidden epidemic: confronting sexually transmitted diseases. Washington, DC: National Academy Press; 1997.
17. Phillips RS, Hanff PA, Holmes MD, Wertheimer A, Aronson MD. Chlamydia trachomatis cervical infection in women seeking routine gynecologic care: criteria for selective testing. Am J Med 1989, 86:515-520.
18. Schachter J, Stoner E, Moncada J. Screening for chlamydial infections in women attending family planning clinics. West J Med 1983, 138:375-379.
19. Stamm WE, Holmes KK. Chlamydia trachomatis infections of the adult. In: Holmes KK, Mardh PA, Sparling PF, et al, eds. Sexually transmitted diseases. New York, NY: McGraw-Hill; 1990:181-93.
20. Zimmerman HL, Potterat JJ, Dukes RL, et al. Epidemiologic differences between chlamydia and gonorrhea. Am J Public Health 1990, 80:1338-1342.
21. McCormack WM, Alpert S, McComb DE, Nichols RL, Semine DZ, Zinner SH. Fifteen-month follow-up study of women infected with Chlamydia trachomatis. N Engl J Med 1979, 300:123-125.
22. Stamm WE. Chlamydia trachomatis infections: progress and problems. J Infect Dis 1999;179 (suppl 2):S380-3.
23. Quinn TC, Gaydos C, Shepherd M, et al. Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships. JAMA 1996, 276:1737-1742.
24. Hillis SD, Owens LM, Marchbanks PA, Amsterdam LF, Mac Kenzie WR. Recurrent chlamydial infections increase the risks of hospitalization for ectopic pregnancy and pelvic inflammatory disease. Am J Obstet Gynecol 1997, 176:103-107.
25. Oakeshott P, Kerry S, Hay S, Hay P. Opportunistic screening for chlamydial infection at time of cervical smear testing in general practice: prevalence study. BMJ 1998, 316:351-352.
26. Park BJ, Stergachis A, Scholes D, Heidrich FE, Holmes KK, Stamm WE. Contraceptive methods and the risk of Chlamydia trachomatis infection in young women. Am J Epidemiol 1995, 142:771-778.
27. Bontis J, Vavilis D, Panidis D, Theodoridis T, Konstantinidis T, Sidiropoulou A. Detection of Chlamydia trachomatis in asymptomatic women: relationship to history, contraception, and cervicitis. Adv Contracept 1994, 10:309-315.
28. Gershman KA, Barrow JC. A tale of two sexually transmitted diseases. Prevalences and predictors of chlamydia and gonorrhea in women attending Colorado family planning clinics. Sex Transm Dis 1996, 23:481-488.
29. Sessa R, Latino MA, Magliano EM, et al. Epidemiology of urogenital infections caused by Chlamydia trachomatis and outline of characteristic features of patients at risk. J Med Microbiol 1994, 41:168-172.
30. Oh MK, Smith KR, O'Cain M, Kilmer D, Johnson J, Hook EW III. Urine-based screening of adolescents in detention to guide treatment for gonococcal and chlamydial infections. Translating research into intervention. Arch Pediatr Adolesc Med 1998, 152:52-56.
31. Gaydos CA, Howell MR, Pare B, et al. Chlamydia trachomatis infections in female military recruits. N Engl J Med 1998, 339:739-744.
32. Mosure DJ, Berman S, Kleinbaum D, Halloran ME. Predictors of Chlamydia trachomatis infection among female adolescents: a longitudinal analysis. Am J Epidemiol 1996, 144:997-1003.
33. Cook RL, St. George K, Lassak M, Tran N, Anhalt JP, Rinaldo CR. Screening for Chlamydia trachomatis infection in college women with a polymerase chain reaction assay. Clin Infect Dis 1999;28:1002-7.
34. Burstein G.R, Gaydos C.A, Diener-West M, Howell M.R, Zenilman J.M, Quinn TC. Incident Chlamydia trachomatis infections among inner-city adolescent females. JAMA 1998, 280:521-526.
35. Neu NM, Grumet S, Saiman L, McMahon DJ, Westhoff C. Genital chlamydial disease in an urban, primarily Hispanic, family planning clinic. Sex Transm Dis 1998, 25:317-321.
36. Finelli L, Nakashima AK, Hillis S, Crayne E, Spitalny KC. Selective screening versus presumptive treatment criteria for identification of women with chlamydial infection in public clinics: New Jersey. Am J Obstet Gynecol 1996, 174:1527-1533.
37. Gunn RA, Hillis SD, Shirey P, Waterman SH, Greenspan JR. Chlamydia trachomatis infection among Hispanic women in the California-Mexico border area, 1993: establishing screening criteria in a primary care setting. Sex Transm Dis 1995, 22:329-334.
38. van Duynhoven YT, van de Laar MJ, Fennema JS, van Doornum GJ, van den Hoek JA. Development and evaluation of screening strategies for Chlamydia trachomatis infections in an STD clinic. Genitourin Med 1995, 71:375-381.
39. Mosure DJ, Berman S, Fine D, DeLisle S, Cates W Jr, Boring JR III. Genital Chlamydia infections in sexually active female adolescents: do we really need to screen everyone? J Adolesc Health 1997, 20:6-13.
40. Green TA, Black CM, Johnson RE. Evaluation of bias in diagnostic-test sensitivity and specificity estimates computed by discrepant analysis. J Clin Microbiol 1998, 36:375-381.
41. Stamm WE, Hicks CB, Martin DH, et al. Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study. JAMA 1995, 274:545-549.
42. Centers for Disease Control. Guidelines for treatment of sexually transmitted diseases. MMWR Morb Mortal Wkly Rep 1998;47:49-60.
43. Steingrimsson O, Olafsson JH, Sigvaldadottir E, Palsdottir R. Clinical evaluation of an automated enzyme-linked fluorescent assay for the detection of chlamydial antigen in specimens from high risk patients. Diagn Microbiol Infect Dis 1994, 18:101-104.
44. Thorpe EM, Stamm WE, Hook EW, Gall SA, Jones RB, Henry K. Chlamydial cervicitis and urethritis: single-dose treatment compared with doxycycline for seven days in community based practices. Genitourin Med 1996, 72:93-97.
45. Brocklehurst P, Rooney G. Interventions for treating genital chlamydia trachomatis infection in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 4, 2000. Oxford: Update Software.
46. Scholes D, Stergachis A, Heidrich FE, Andrilla H, Holmes KK, Stamm WE. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 1996, 334:1362-1366.
47. Stergachis A, Scholes D, Heidrich FE, Sherer DM, Holmes KK, Stamm WE. Selective screening for Chlamydia trachomatis infection in a primary care population of women. Am J Epidemiol 1993, 138:143-153.
48. Kamwendo F, Forslin L, Bodin L, Danielsson D. Decreasing incidences of gonorrhea- and chlamydia-associated acute pelvic inflammatory disease. A 25-year study from an urban area of central Sweden. Sex Transm Dis 1996, 23:384-391.
49. Egger M, Low N, Smith GD, Lindblom B, Herrmann B. Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis. BMJ 1998, 316:1776-1780.