Other Supporting Document for Chlamydia and Gonorrhea: Screening
Release Date: September 23, 2014
By Bernadette Zakher, MBBS; Amy G. Cantor, MD, MHS; Miranda Pappas, MA; Monica Daegas, BA; and Heidi D. Nelson, MD, MPH
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published online first at www.annals.org on September 23, 2014. Select for copyright and source information.
Background: Previous research has supported screening for gonorrhea and chlamydia in asymptomatic, sexually active women (including pregnant women) who are younger than 25 years or at increased risk but not in other patient populations.
Purpose: To update the 2005 and 2007 systematic reviews for the U.S. Preventive Services Task Force on screening for gonorrhea and chlamydia in men and women, including pregnant women and adolescents.
Data Sources: MEDLINE (1 January 2004 to 13 June 2014), Cochrane databases (May 2014), and reference lists.
Study Selection: English-language trials and observational studies about screening effectiveness, test accuracy, and screening harms.
Data Extraction: Extracted study data were confirmed by a second investigator, and study quality and applicability were dual-rated using prespecified criteria.
Data Synthesis: Screening a subset of asymptomatic young women for chlamydia in a good-quality trial did not significantly reduce the incidence of pelvic inflammatory disease over the following year (relative risk, 0.39 [95% CI, 0.14 to 1.08]); however, one previous trial reported a reduction. An observational study evaluating a risk prediction tool to identify persons with chlamydia in high-risk populations had low predictive ability and applicability. In 10 new studies of asymptomatic patients, nucleic acid amplification tests demonstrated sensitivity of 86% or greater and specificity of 97% or greater for diagnosing gonorrhea and chlamydia, regardless of specimen type or test.
Limitations: There were few relevant studies of screening benefits and harms. Only screening tests and methods cleared by the U.S. Food and Drug Administration for current clinical practice were included to determine diagnostic accuracy.
Conclusion: Chlamydia screening in young women may reduce the incidence of pelvic inflammatory disease. Nucleic acid amplification tests are accurate for diagnosing gonorrhea and chlamydia in asymptomatic persons.
Primary Funding Source: Agency for Healthcare Research and Quality.
In 2005, on the basis of epidemiologic studies of screening and studies of the diagnostic accuracy of screening tests1–3, the U.S. Preventive Services Task Force (USPSTF) recommended screening for gonorrhea in all sexually active or pregnant women at increased risk for infection4. It recommended against routine screening in low-risk men and nonpregnant women and found insufficient evidence to recommend for or against routine screening in high-risk men and low-risk pregnant women.
In 2007, on the basis of studies of the effectiveness of screening, harms, and diagnostic accuracy of screening tests1–3, the USPSTF recommended screening for chlamydia in all sexually active or pregnant women younger than 25 years and in older, high-risk women5. It recommended against routine screening in low-risk women, regardless of pregnancy status, and found insufficient evidence to recommend for or against screening in men.
Gonorrhea and chlamydia are the 2 most commonly reported sexually transmitted infections (STIs) in the United States6. In 2012, 334,826 cases of gonorrhea and 1,422,976 cases of chlamydia were reported to the Centers for Disease Control and Prevention (6). However, the true incidence of gonorrhea and chlamydia is difficult to estimate because most infections are undetected.
In women, gonorrhea and chlamydia infections are most often asymptomatic but can cause cervicitis and complications of pelvic inflammatory disease (PID), ectopic pregnancy, infertility, and chronic pelvic pain6, 7. In men, these infections can cause urethritis and epididymitis6, 8. Most men with gonococcal urethritis are symptomatic, prompting timely treatment that prevents serious complications9. However, gonococcal infections at extragenital sites, including the pharynx and rectum, and genital chlamydia infections are typically asymptomatic. Gonorrhea and chlamydia can also facilitate HIV transmission in both men and women6, 10, 11. Infection with either gonorrhea or chlamydia in pregnant women can lead to adverse neonatal outcomes, including preterm birth and transmission of infection to the newborn. Chlamydia infection also causes neonatal ophthalmia and pneumonia in infants.
Age is a strong predictor of risk for both gonorrhea and chlamydia, and infection rates are greatest among persons aged 15 to 24 years6. Although rates are greater for women than men (108.7 cases of gonorrhea per 100,000 women vs. 105.8 per 100,000 men; 643.3 cases of chlamydia per 100,000 women vs. 262.6 cases per 100,000 men), rates have increased more rapidly among men in recent years6. Other risk factors include having new or multiple sex partners or a partner with an STI, inconsistent condom use, and history of previous or coexisting STIs1, 2. These risk factors are often used to define persons at increased risk in screening recommendations. Rates differ among population subgroups, and blacks and Hispanics generally have greater rates of infections compared with whites6, 12. Men who have sex with men who were tested in STD Surveillance Network clinics in 2012 had median prevalence rates of 16.4% for gonorrhea and 12.0% for chlamydia6.
This systematic review is an update of previous reviews for the USPSTF1–3. It focuses on new studies of the effectiveness and adverse effects of gonorrhea and chlamydia screening in asymptomatic men and women, including pregnant women and adolescents, as well as the diagnostic accuracy of screening tests.
Methods are further described in a technical report13. We followed a standard protocol consistent with the Agency for Healthcare Research and Quality (AHRQ) methods for systematic reviews14. On the basis of evidence gaps identified from previous reviews1–3, the USPSTF and AHRQ determined the key questions for this update15. The investigators created analytic frameworks incorporating the key questions and outlining the patient populations, interventions, outcomes, and potential adverse effects (Supplements 1 and 2, available at www.annals.org). A work plan was externally reviewed and modified but was not registered.
The target populations included asymptomatic, sexually active men and women, including pregnant women and adolescents. The key questions focused on the effectiveness of screening compared with not screening in preventing adverse health outcomes; effectiveness of different strategies of screening; diagnostic accuracy of screening tests; and potential harms of screening. Screening strategies included selective screening of high-risk groups; sampling from various anatomical sites; cotesting for concurrent STIs, including HIV; and using different screening intervals, among others. Outcomes included reduction of complications of infection and transmission or acquisition of disease, including gonorrhea, chlamydia, and HIV. For pregnant women, outcomes also included reduction in maternal complications and adverse pregnancy and infant outcomes. Harms of screening included labeling, anxiety, false-positive and false-negative test results, and other consequences of testing. The efficacy and harms of antibiotic treatments were well-established and not further evaluated.
Data Sources and Searches
We searched Ovid MEDLINE (1 January 2004 to 13 June 2014), the Cochrane Central Register of Controlled Trials (May 2014), the Cochrane Database of Systematic Reviews (May 2014), the Health Technology Assessment Database (May 2014), the Database of Abstracts of Reviews of Effects (May 2014), and ClinicalTrials.gov (May 2014) and reviewed reference lists for additional citations13. Search terms are provided in Supplement 3 (available at www.annals.org).
Abstracts were selected for full-text review if they included asymptomatic, sexually active men and women, including pregnant women and adolescents; were relevant to a key question; and met additional prespecified inclusion criteria for each key question13. Although this update was intended to evaluate studies published since previous USPSTF reviews, the scope, key questions, and inclusion criteria differ across reviews, resulting in the inclusion of older studies that have not been previously reviewed. We included only English-language articles and excluded studies that were only published as abstracts or did not report original data. The selection of studies is summarized in a literature flow diagram (Supplement 4, available at www.annals.org). Two reviewers independently evaluated each study to determine inclusion eligibility.
Only randomized, controlled trials (RCTs) and controlled observational studies were included to evaluate the effectiveness of screening, whereas uncontrolled observational studies were additionally included to determine adverse effects. Studies of screening strategies were included if they adequately described the study population and comparison groups, features of the screening program, and outcome measures. Inclusion criteria were less restrictive for effectiveness studies than diagnostic accuracy studies because the main comparison concerned outcomes related to the overall approach of screening compared with nonscreening rather than the characteristics of the individual tests.
Studies of the accuracy of diagnostic tests were included if they evaluated screening tests in asymptomatic participants using technologies and methods that have been cleared by the U.S. Food and Drug Administration (FDA) and are available for clinical practice in the United States. These inclusion criteria reflect the scope of the USPSTF recommendations about technologies and medications. On the basis of these criteria, rectal, pharyngeal, and self-collected vaginal specimens obtained in nonclinical settings and point-of-care or in-house tests were excluded. Tests that were previously cleared and subsequently removed from the U.S. market (such as the ligase chain reaction test) were also excluded16. Included studies used credible reference standards, adequately described the study population, defined positive test results, and reported performance characteristics of tests (such as sensitivity and specificity) or provided data to calculate them.
Data Abstraction and Quality Rating
A single investigator abstracted details about study design, patient population, comparison groups, setting, screening method, analysis, follow-up, and results. A second investigator reviewed data abstraction for accuracy. By using prespecified criteria for RCTs, cohort, and diagnostic accuracy studies developed by the USPSTF14, 2 investigators independently rated the quality of studies (good, fair, or poor) and resolved discrepancies by consensus.
Data Synthesis and Analysis
Two independent reviewers assessed the internal validity (quality) of the body of evidence for the new studies for each key question using methods developed by the USPSTF, on the basis of the number, quality, and size of studies; consistency of results among studies; and directness of evidence14, 15. Statistical meta-analysis was not done because of methodological limitations of the studies and heterogeneity in study designs, interventions, populations, and other factors. Studies included in previous reviews were reviewed for consistency with current results; however, lack of studies and differences in scope, key questions, and inclusion criteria limited aggregate synthesis with the updated evidence.
Role of the Funding Source
This research was funded by AHRQ under a contract to support the work of the USPSTF. The investigators worked with USPSTF members and AHRQ staff to develop and refine the scope, analytic frameworks, and key questions; resolve issues during the project; and finalize the report. The Agency for Healthcare Research and Quality had no role in study selection, quality assessment, synthesis, or development of conclusions. The Agency for Healthcare Research and Quality provided project oversight; reviewed the draft report; and distributed the draft for peer review, including to representatives of professional societies and federal agencies. The Agency for Healthcare Research and Quality performed a final review of the manuscript to ensure that the analysis met methodological standards. The investigators are solely responsible for the content and the decision to submit the manuscript for publication.
Effectiveness of Screening Asymptomatic Men and Nonpregnant Women, Including Adolescents
No studies of gonorrhea screening met inclusion criteria for the previous USPSTF reviews or this update. The 20011 and 20073 USPSTF reviews on chlamydia screening identified 2 trials of screening women at increased risk for chlamydia17, 18 (Table 1 and Supplement 5, available at www.annals.org). Incidence of pelvic inflammatory disease was significantly reduced among women screened in a good-quality RCT of 2607 women aged 18 to 34 years who were recruited from a health maintenance organization in the United States (relative risk [RR], 0.44 [95% CI, 0.20 to 0.90])17, 18. Reductions were of borderline statistical significance in a poor-quality RCT of Danish students (RR, 0.50 [CI, 0.23 to 1.08])17, 18.
One new RCT of chlamydia screening in women (but none in men) met inclusion criteria for this update. The Prevention of Pelvic Infection trial was a good-quality RCT of 2529 sexually active young women recruited from universities in the United Kingdom (mean age, 21 years [range, 16 to 27 years])19 (Table 1 and Supplement 5). Participants provided chlamydia tests using self-collected vaginal swabs. Specimens from participants randomly assigned to the screening group were immediately tested for chlamydia, whereas specimens from control participants were tested 1 year later. After 1 year, 94% of participants completed questionnaires about symptoms of PID and sexual behavior during the previous year. Medical records of women suspected of having PID on the basis of their questionnaire responses were reviewed by 3 blinded genitourinary physicians for diagnostic confirmation.
Pelvic inflammatory disease occurred in 1.3% of screened versus 1.9% of control participants during follow-up (RR, 0.65 [CI, 0.34 to 1.22])19. Among a subgroup of participants who reported no symptoms during the 6 months before the study (that is, pelvic pain, dyspareunia, abnormal vaginal bleeding, or discharge), 0.6% (5 of 787) of screened participants versus 1.6% (14 of 861) of control participants developed PID during follow-up (RR, 0.39 [CI, 0.14 to 1.08]) (Sarah Kerry, personal communication). In this trial, 79% (30 of 38) of PID cases occurred in women who tested negative at baseline. In addition, 22% of participants were tested for chlamydia outside of the study protocol during follow-up.
Effectiveness of Screening Strategies
Previous reviews did not directly address the effectiveness of different screening strategies but summarized risk factors associated with gonorrhea and chlamydia infections1, 2. An observational study comparing 9 sets of selective screening criteria for chlamydia infection among women attending family planning and STI clinics in the United States (20) indicated that age alone had similar or better sensitivity and specificity as more extensive criteria. In this study, nearly 80% of cases were identified while testing 50% of the population when using an age cutoff of 22 years or younger.
Only one new study of screening strategies met inclusion criteria. An observational study conducted in the Netherlands evaluated a risk prediction tool to identify persons infected with chlamydia in high-risk populations21. Screening criteria were developed on the basis of questionnaire responses from sexually active participants who were subsequently tested for chlamydia and included items on age, education, ethnicity, lifetime sex partners, and condom use. When applied to high-risk populations, this risk tool was not an accurate predictor of infection (area under the receiver-operating characteristic curve, 0.66 to 0.68). The applicability of this study to U.S. populations is also limited.
Diagnostic Accuracy of Screening Tests for Gonorrhea and Chlamydia
The previous reviews reported high sensitivity and specificity in studies of the diagnostic accuracy of gonorrhea and chlamydia tests1, 2. However, several studies included symptomatic persons and non–nucleic acid amplification tests (NAATs), including tests that are not currently available, diminishing their clinical applicability.
Ten new fair-quality studies reporting test characteristics of FDA-cleared NAATs met inclusion criteria (Table 2 and Supplements 6 and 7, available at www.annals.org): 6 for gonorrhea 22–27 and 8 for chlamydia22–24, 27–31. Methodological limitations include unclear descriptions of sampling methods, whether interpretations of the screening test were independent of the reference standard22–25, 28–30, and whether the analysis included participants with uninterpretable results22, 24, 25, 28, 30. Three studies described additional methodological difficulties related to the reference standard29 and technical approach25, 28. Most studies reported more than 5% prevalence of infection among participants, although rates were lower in 3 studies24, 26, 27. Although sensitivity varied, specificity was high (≥97%) across all studies for gonorrhea and chlamydia in men and women, regardless of specimen or test.
For women, 4 studies testing endocervical specimens using transcription-mediated amplification (TMA); polymerase chain reaction (PCR), including a new rapid test27; or strand displacement amplification (SDA) reported sensitivities ranging from 90.0% to 100.0%24–27 (Figure 1). Sensitivity using self-collected vaginal specimens obtained in a clinician's office was 98.0% by TMA26 and 100% by PCR27. Results of female urine specimens using TMA, PCR, or SDA ranged from 78.6% to 100%24, 25, 27. However, the study reporting the lowest sensitivities for urine used urine volumes larger than recommended by the manufacturer of the screening test25. When recommended urine volumes were used in a second study, the sensitivity of the same TMA test improved from 78.6% to 95.7%24.
For men, testing male urethral specimens with SDA and TMA and testing male urine using TMA, SDA, or PCR resulted in similarly high sensitivities across tests in 4 studies (urethra, 100%; urine, 90.0% to 100%)22, 23, 25, 27 (Figure 1).
Among 5 studies of endocervical specimens, sensitivity of TMA was 89.0% to 97.1%, SDA was 86.4% to 96.2%, and PCR was 86.4% to 95.8%24, 27, 28, 30, 31 (Figure 2). Clinician-collected vaginal swabs tested with TMA and PCR provided sensitivities of 89.9% and 98.8%28, and self-collected vaginal swabs from clinical settings provided sensitivities of 97.0% with TMA31 and 90.7% (28) and 98.0% 27 with PCR. Female urine samples tested with TMA, PCR, and SDA provided sensitivities of 72.0% to 98.2%24, 27, 28, 30. Lower sensitivities for urine samples using TMA (72.0%) and PCR (84.0%) were reported in a study that experienced technical and specimen processing errors28.
A single study of PCR reported sensitivities that were markedly lower than other studies29, and results were not included in Figure 2. This study used a more conservative approach to analysis that required complete sets of results from 9 testing strategies. Also, the reference standard included positive NAAT results from 2 separate specimens. When a specimen-specific reference standard was used, sensitivities were similar to other studies (data were not provided).
Sensitivities for male urethral and urine specimens were consistently high, regardless of test, across 4 studies reporting sensitivities from 86.1% to 100% for TMA, SDA, or PCR22, 23, 27, 30 (Figure 2).
Harms of Screening Asymptomatic Men and Nonpregnant Women, Including Adolescents
The previous reviews indicated low false-positive and false-negative results for screening tests1–3 that were confirmed by the 10 new diagnostic accuracy studies described above. In the new studies without major methodological limitations, false-positive result rates for gonorrhea and chlamydia were 3% or lower, and false-negative result rates ranged from 0% to 9% for gonorrhea and 0% to 14% for chlamydia across all NAATs and specimen types22–31.
A previous review(3 included results of qualitative interviews about the experience of chlamydia testing from women having opportunistic screening32. Although many women believed that screening was beneficial and important, common responses to a positive test result included feeling dirty, ashamed of passing on the infection, and suspicious about the origins of the infection.
Benefits and Harms of Screening Asymptomatic Pregnant Women
No studies were available to address several key questions, including the effectiveness of screening for gonorrhea in all population groups and for chlamydia in men, pregnant women, and adolescents specifically; the effectiveness of screening strategies; and harms of screening unrelated to the diagnostic accuracy of tests.
Only one new trial evaluated the effectiveness of screening for chlamydia in nonpregnant women19 (key question 1). In the Prevention of Pelvic Infection trial, screening a subset of asymptomatic young women for chlamydia did not significantly reduce PID over the following year compared with no screening (RR, 0.39 [CI, 0.14 to 1.08]). Although it met the criteria for good quality, the trial was limited by inadequate recruitment, testing for chlamydia outside of the study protocol during follow-up in nearly one quarter of participants, and difficulties in ascertaining PID cases. These limitations imply that the study may have been underpowered and the intervention effects attenuated. In addition, most cases of PID occurred in women who tested negative at baseline, suggesting that frequent targeted screening of women at greater risk for infection, including those with new sexual partners or recent history of chlamydia, may be more important than a 1-time routine screen.
Two earlier trials also evaluated the incidence of PID after chlamydia screening for women at increased risk17, 18. Although a good-quality trial in the United States reported a statistically significant reduction in PID incidence in the screened versus usual care group after 1 year of follow-up (RR, 0.44 [CI, 0.20 to 0.90])17, 18, reduction in PID incidence was not statistically significant in a poor-quality trial in Denmark comparing 1-time home-based screening with usual care17, 18. Although all 3 trials reported point estimates suggesting reduced PID, only the U.S. trial showed a statistically significant reduction. This trial met criteria for good quality, is the largest trial, and is the most applicable to clinical practice in the United States.
Additional relevant studies of screening did not meet inclusion criteria because they did not provide results for asymptomatic participants or reported infection rates rather than health outcomes. These studies found no significant improvements in clinical outcomes among those screened for chlamydia, including a large Danish trial of more than 30,000 young men and women33, a retrospective population-based cohort study of more than 40,000 Swedish women34, and a register-based screening trial of more than 300,000 men and women in the Netherlands35. A time trend analysis of a U.S. managed care population between 1997 and 2007 indicated increased cases of chlamydia for both men and women but decreased PID36. It is not clear how screening influenced these outcomes.
The only new study addressing the effectiveness of different screening strategies (key question 2) was an observational study evaluating a risk prediction tool to identify persons with chlamydia in high-risk populations21. However, it was not an accurate predictor and its relevance to current practice in the United States is uncertain. An older observational study comparing 9 sets of selective screening criteria for chlamydia infection among women20 supported age-based screening in current guidelines but has not been updated by newer research. Future studies to address this key question would compare the effectiveness of screening versus not screening in populations with different levels of risk; include specimens from different anatomical sites; include cotesting for concurrent STIs, including HIV; and evaluate different screening intervals.
Ten studies of the diagnostic accuracy of screening tests met inclusion criteria22–26, 28–31, 37 (key question 3). The current review differs from previous reviews1, 2 by including only results from asymptomatic participants, a focus that is more clinically relevant to screening populations. Various types of NAATs are highly accurate in diagnosing gonorrhea and chlamydia in asymptomatic persons, regardless of specimen, site, or test22–25, 28, 30, 37. Sensitivity was 85% or greater and specificity was 97% or greater in studies without major methodological limitations, resulting in generally low false-negative and false-positive results. The high accuracy of NAATs reported by these studies is consistent with previous reviews1, 2 and is the basis for the Centers for Disease Control and Prevention's recommendation to use NAATs for gonorrhea and chlamydia testing38.
Several studies of harms did not meet inclusion criteria for the update because they focused on the effects of receiving a positive test result, included symptomatic participants, and lacked comparison groups39–42 (key question 4). In these studies, persons testing positive for chlamydia had greater anxiety39, 40, 42 and more partner break-ups39, 40 than those testing negative, who were generally relieved40, 42.
No studies meeting inclusion criteria addressed screening in pregnant women despite the need for additional research in this population. For example, testing during the first trimester may not be sufficient, based on findings from an observational study suggesting that chlamydia test results during the first trimester may not predict chlamydia status during the third trimester43. Although studies of repeated testing have been conducted in high-risk populations44, more research is warranted to further evaluate the value of repeated testing during pregnancy to reduce potential complications, such as preterm delivery and premature rupture of membranes45.
Limitations of this review include using only English-language articles, which could result in language bias, although we did not identify non–English-language studies that otherwise met inclusion criteria in our searches. We only included studies with asymptomatic participants and settings and tests applicable to current practice in the United States to improve clinical relevance for the USPSTF, excluding much research in the field. Studies were lacking for most key questions, and the number, quality, and applicability of studies varied widely. Also, the available screening trials evaluated only PID as the main outcome, and other outcomes are also important.
Nucleic acid amplification tests have been cleared by the FDA for use with male and female urine, endocervical, and male urethral specimens, and some NAATs are cleared for clinician- and self-collected vaginal specimens in clinical settings. Studies have also reported similar test characteristics for nurse- and patient-collected rectal swabs in men who have sex with men26, 28, 29, 31, 46. Additional studies of NAATs using self-collected specimens could provide more evidence for FDA clearance of this technique and increase testing access and acceptability. This could potentially expand screening strategies to home-based, mail-in, or Internet-based screening and encourage the uptake of screening among persons at increased risk.
Limiting our review to FDA-cleared tests excluded studies of rectal and pharyngeal specimens that also demonstrate high accuracy in studies of NAATs26, 28, 29, 31, 46] and are currently recommended by the Centers for Disease Control and Prevention (38). Expanding the range of specimen types for screening has the potential to increase identification of infected persons, especially asymptomatic men who have sex with men, for whom nearly 90% of all gonorrhea infections are in nongenital sites[[47. Among this population, NAATs have greater sensitivity at extragenital sites compared with culture, potentially because of lower bacterial loads at the pharynx and rectum48, 49. In a study of men who have sex with men, 85% of rectal infections were asymptomatic and only detectable with routine screening50. Urethral testing alone missed 84% of chlamydia and gonorrhea infections compared with 9.8% missed by rectal and pharyngeal testing in another study47.
In summary, screening for chlamydia may reduce the incidence of PID in young women. Risk prediction tools may be useful in identifying persons with infections but require validation in the populations of intended use. Nucleic acid amplification tests are accurate for diagnosing gonorrhea and chlamydia in asymptomatic persons, regardless of specimen, site, or test. Further research is needed to determine the effectiveness of screening in multiple populations and on various clinical outcomes, including but not limited to PID; effective screening strategies; and harms of screening.
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Copyright and Source Information
Source: This article was published online first at www.annals.org on September 23, 2014.
Disclaimer: The findings and conclusions in this article are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this article should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Andrew Hamilton, MLS, MS, Oregon Health & Science University, who conducted literature searches for this systematic review. They also thank AHRQ Medical Officer Karen Lee, MD, MPH, and the U.S. Preventive Services Task Force Leads Linda Baumann, PhD, RN; Kirsten Bibbins-Domingo, PhD, MD, MAS; Francisco Garcia, MD, MPH; and Michael LeFevre, MD, MSPH.
Grant Support: By AHRQ (contract HSSA 290-2007-10057-I).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1022.
Corresponding Author: Heidi D. Nelson, MD, MPH, Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Mailcode BICC, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239-3098; e-mail, firstname.lastname@example.org.
Table 1. Summary of Evidence
|Main Findings From Previous USPSTF Reviews||Studies in Update||Quality of Evidence||Limitations||Consistency||Applicability||Summary of Findings|
|Effectiveness of screening asymptomatic men and nonpregnant women, including adolescents|
|Chlamydia screening reduced PID incidence in a good-quality RCT (RR, 0.44 [95% CI, 0.20–0.90]) but not in a poor-quality RCT (RR, 0.50 [CI, 0.23–1.08]).||1 good-quality RCT of chlamydia screening in women||Fair||Trial potentially underpowered; no studies of gonorrhea screening; no studies of chlamydia screening in other populations||Point estimates consistent with previous trials, although significance varies||Study conducted in the United Kingdom using self-collected samples||Screening a subset of asymptomatic young women for chlamydia did not significantly reduce PID incidence over the following year (RR, 0.39 [95% CI, 0.14–1.08]); 1 previous trial reported a reduction.|
|Effectiveness of different screening strategies|
|9 sets of selective screening criteria for chlamydia infection indicated that age alone had sensitivity and specificity that were similar to or better than more extensive criteria.||1 observational study of chlamydia screening in women||Poor; studies are lacking||No studies of effectiveness or comparing cotesting or different screening intervals||NA||Study conducted in the Netherlands with limited applicability to the United States||A risk prediction tool to identify persons with chlamydia in high-risk populations was not an accurate predictor; a previous study indicated that an age cutoff of ≤22 y would identify 80% of cases while testing 50% of women.|
|Diagnostic accuracy of screening tests for detecting gonorrhea and chlamydia|
|25 studies for gonorrhea and 33 for chlamydia indicated high accuracy, although studies included symptomatic participants and tests that are no longer used.||10 diagnostic accuracy studies of NAATs*||Good||Unclear sampling methods and interpretation of tests and inclusion of patients with uninterpretable results; some studies had technical shortcomings||Consistent||Studies included high-prevalence populations (>5%)||Gonorrhea: Sensitivity of 91%–100% and specificity of ≥97%†
Chlamydia: Sensitivity of 86%–100% and specificity of ≥97%†
Previous findings are similar but may not be clinically applicable.
|Harms of screening asymptomatic men and nonpregnant women, including adolescents|
|25 studies of tests for gonorrhea and 33 for chlamydia reported diagnostic accuracy. One qualitative interview study indicated anxiety with a positive test result.||10 diagnostic accuracy studies of NAATs*||Good for false-positive and false-negative result rates; lack other outcomes||No studies on other harms of screening met inclusion criteria||Consistent||Studies included high-prevalence populations (>5%)||Gonorrhea: False-positive results, ≤3%; false-negative results, 0% to 9%†
Chlamydia: False-positive results, ≤3%; false-negative results, 0% to 14%†
Previous findings are similar but may not be clinically applicable
|Effectiveness of screening asymptomatic pregnant women|
|No studies; previous reviews cited descriptive studies predating the searches||No studies||NA||NA||NA||NA||NA|
|Harms of screening asymptomatic pregnant women|
|No studies met inclusion criteria.||No studies met inclusion criteria.||NA||NA||NA||NA||NA|
NA = not applicable; NAAT = nucleic acid amplification test; PID = pelvic inflammatory disease; RCT = randomized, controlled trial; RR = relative risk; STI = sexually transmitted infection; USPSTF = U.S. Preventive Services Task Force.
* Specimens include endocervical, clinician-collected vaginal, self-collected vaginal, male urethral, and urine.
† For studies without major methodological limitations.
Table 2. Diagnostic Accuracy Studies (2004-2013) of Nucleic Acid Amplification Tests for Gonorrhea and Chlamydia Screening
|Screening Test||Sensitivity/Specificity by Specimen Type, %|
|Endocervical||Clinician-Collected Vaginal||Self-Collected Vaginal||Male Urethral||Urine|
|Gen-Probe APTIMA Combo 2 Assay|
|Van Der Pol et al, 201224||100/100||-||-||-||Female: 95.7/100|
|Van Der Pol et al, 201225||96.4/99.5||-||-||100/99.2||Female: 78.6/100
|Stewart et al, 2012 26||90.0/100||-||98.0/100||-||-|
|Taylor et al, 201223||-||-||-||100/100||Male: 100/100|
|Gen-Probe APTIMA GC Assay|
|Chernesky et al, 2005 (22)||100/97.1||Male: 90.9/99.5|
|BD ProbeTec ET System|
|Van Der Pol et al, 201225||92.9/99.3||-||-||100/100||Female: 82.1/99.5
|BD ProbeTec CT/GC Qx Amplified DNA Assay|
|Van Der Pol et al, 201224||91.3/99.8||-||-||Female: 100/99.9|
|Van Der Pol et al, 201225||96.3/99.5||-||-||100/99.2||Female: 100/99.5
|Taylor et al, 201223||-||-||100/100||Male: 100/99.8|
|Roche Cobas 4800 CT/NG Test|
|Van Der Pol et al, 201224||95.7/100||-||-||-||Female: 100/100|
|Taylor et al, 201223||-||-||-||-||Male: 100/100|
|Cepheid GeneXpert CT/NG Assay|
|Gaydos et al, 201327||100/100||-||100/99.9||-||Female: 91.7/99.9
|Roche Cobas Amplicor CT/NG Test|
|Schachter et al, 2003 28||90.7/99.4||93.3/98.8||90.7/99.0||-||Female: 84.0/99.0|
|Shrier et al, 2004 (29)||51.9/100||55.6/100||51.9/99.0||-||Female: 44.4/100|
|Gen-Probe APTIMA Combo 2 Assay|
|Schoeman et al, 2012 (31)||89.0/100||-||97.0/99.9||-||-|
|Taylor et al, 201223||-||-||94.1/98.9||Male: 98.0/99.0|
|Taylor et al, 2012 (30)||92.9/99.0||-||-||90.9/98.8||Female: 98.2/99.5
|Van Der Pol et al, 201224||97.1/99.5||-||-||-||Female: 92.5/99.8|
|Gen-Probe APTIMA CT Assay|
|Schachter et al, 2003 28||89.1/99.3||89.9/99.4||93.3/99.6||-||Female: 72.0/99.5|
|Chernesky et al, 2005 22||-||98.9/97.5||Male: 98.9/98.0|
|BD ProbeTec ET System|
|Taylor et al, 201130||86.4/100||-||-||86.1/98.9||Female: 89.8/99.7
|BD ProbeTec CT/GC Qx Amplified DNA Assay|
|Taylor et al, 201223||-||-||-||86.5/99.8||Male: 96.2/99.5|
|Taylor et al, 201230||93.0/98.0||-||-||88.6/98.9||Female: 94.7/99.5
|Van Der Pol et al, 201224||96.2/99.7||-||-||-||Female: 96.2/99.7|
|Roche Cobas 4800 CT/NG Test|
|Taylor et al, 201223||-||-||-||-||Male: 98.1/99.5|
|Van Der Pol et al, 201224||89.5/100||-||-||-||Female: 89.1/99.8|
|Cepheid GeneXpert CT/NG Assay|
|Gaydos et al, 201327||95.8/99.4||-||98.0/99.4||-||Female: 96.1/99.8
BD = Beckton, Dickinson and Company; CT = Chlamydia trachomatis; DNA = deoxyribonucleic acid; FDA = U.S. Food and Drug Administration; GC = gonorrhea/chlamydia; NG = Neisseria gonorrhoeae.
Figure 1. Diagnostic accuracy of nucleic acid amplification tests for gonorrhea screening in men and women.
* The study reporting lower sensitivities for urine specimens in women (78.6% and 82.1%) used urine volumes that were larger than recommended (25), differing from the other studies.
† Two studies produced identical data points for tests of the endocervix.
‡ Three data points for urethral and 3 data points for urine specimens.
§ Two data points for urethral specimens.
Figure 1 displays two scatterplots that demonstrate the sensitivity and specificity of nucleic acid amplification tests for gonorrhea screening in men and women respectively. Data for Figure 1 are presented in Table 1. The scatterplot for women depicts a tightly clustered group of data for endocervix, self-collected vaginal, and urine samples with sensitivities ranging from 90 to 100 percent, and specificities ranging from 78.6 to 95.7 percent. Two outliers with lower sensitivities of 78.6 percent and 82.1 percent come from a study using larger than recommended urine volumes, differing from other studies. The scatterplot for men depicts data for urethra and urine samples with sensitivity ranging from 90 to 100 and specificities of 97 to 100. Both scatterplots are further described in the evidence section for Key Question 3.
Figure 2. Diagnostic accuracy of nucleic acid amplification tests for chlamydia screening in men and women.
* The study reporting lower sensitivities for urine specimens in women (72.0% and 84.0%) experienced technical and specimen-processing errors (27), differing from the other studies.
Figure 2 displays 2 scatter plots. One details the accuracy of nucleic acid amplification tests for chlamydia screening in women and the other details the accuracy of screening in men. For women, 4 studies testing endocervical specimens using TMA; PCR, including a new rapid test; or SDA reported sensitivities ranging from 90.0% to 100.0%. Sensitivity using self-collected vaginal specimens obtained in a clinician's office was 98.0% by TMA and 100.0% by PCR. Results of female urine specimens using TMA, PCR, or SDA ranged from 78.6% to 100.0%. However, the study reporting the lowest sensitivities used urine volumes larger than recommended by the manufacturer of the screening test. For men, testing male urethral specimens with SDA and TMA and testing male urine using TMA, SDA, or PCR resulted in similarly high sensitivities across tests in 4 studies.
Internet Citation: Evidence Summary: Chlamydia and Gonorrhea: Screening. U.S. Preventive Services Task Force. September 2016.