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Nelson HD, Zakher B, Cantor A, et al. Screening for Gonorrhea and Chlamydia: Systematic Review to Update the U.S. Preventive Services Task Force Recommendations [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Sep. (Evidence Syntheses, No. 115.)

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Screening for Gonorrhea and Chlamydia: Systematic Review to Update the U.S. Preventive Services Task Force Recommendations [Internet].

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3RESULTS

Men and Nonpregnant Women, Including Adolescents

Key Question 1. How Effective Is Screening for Gonorrhea and Chlamydia in Reducing Complications of Infection and Transmission or Acquisition of Disease in Asymptomatic, Sexually Active Men and Nonpregnant Women, Including Adolescents?

Summary

No studies of screening for gonorrhea met inclusion criteria for the prior USPSTF reviews or this update. One study of the effectiveness of screening for chlamydia met inclusion criteria. The Prevention of Pelvic Infection (POPI) trial reported a nonstatistically significant reduction in incident PID among asymptomatic, sexually active young women screened for chlamydia compared with unscreened women (relative risk [RR], 0.39 [95% CI, 0.14 to 1.08])26 (S Kerry, written communication, May 2013).

The 20013 and 20075 USPSTF reviews on screening for chlamydia identified two trials of screening in women at increased risk for chlamydia (Table 2 and Appendix C1).27,28 PID was statistically significantly reduced among women screened in a good-quality RCT of young women recruited from a health maintenance organization in the United States (RR, 0.44 [95% CI, 0.20 to 0.90]).27,28 Reductions were of borderline statistical significance in a poor-quality RCT of Danish students (RR, 0.50 [95% CI, 0.23 to 1.08]).27,28

Table 2. Randomized, Controlled Trials of Screening for Chlamydia to Reduce Adverse Health Outcomes.

Table 2

Randomized, Controlled Trials of Screening for Chlamydia to Reduce Adverse Health Outcomes.

Evidence

Gonorrhea. No effectiveness studies of screening for gonorrhea met inclusion criteria for this update or for prior USPSTF reviews.

Chlamydia. One new RCT of screening for chlamydia in women, but none in men, met inclusion criteria for this update. The POPI trial was a good-quality RCT of 2,529 sexually active young women (mean age, 21 years [range, 16 to 27 years]) recruited from universities and colleges in the United Kingdom (Appendixes C1 and C2).26 Participants were randomized to screening or deferred groups (considered unscreened), completed questionnaires, and provided self-collected vaginal swabs. Swabs from the screening group were immediately tested for chlamydia, while those from the deferred group were stored and tested 1 year later. Infected women were contacted and referred to their local clinic for treatment and partner notification. After 1 year, participants completed questionnaires about symptoms of PID and sexual behavior during the previous year (94% followup overall). Medical records of women suspected of having PID based on their questionnaire responses were obtained and reviewed by three blinded genitourinary physicians for diagnostic confirmation.

The published results of the trial provided RR estimates for developing PID during followup for symptomatic (35%) and asymptomatic (65%) participants combined (RR, 0.65 [95% CI, 0.34 to 1.22]).26 Since asymptomatic women are the focus of this Key Question, the trial investigators provided additional estimates for this subgroup upon request. Among a subgroup of participants who reported no symptoms during the 6 months before the study (i.e., pelvic pain, dyspareunia, abnormal vaginal bleeding or discharge), 0.6 percent (5/787) of the screened group versus 1.6 percent (14/861) of the control group developed PID during followup (RR, 0.39 [95% CI, 0.14 to 1.08]) (S Kerry, written communication, May 2013).

In this trial, 79 percent (30/38) of PID cases overall occurred in women who tested negative at baseline. In addition, 22 percent of participants were tested for chlamydia independently during followup (23% and 22% of the screened and deferred groups, respectively). More women in the deferred group who tested positive for chlamydia had independent testing versus those who tested negative.

The 20013 and 20075 USPSTF reviews on screening for chlamydia identified two trials of the effectiveness of screening for prevention of PID in nonpregnant women (Table 2). A good-quality RCT of 2,607 women at increased risk for chlamydia in a health maintenance organization in Washington state reported a statistically significant reduction in PID in the screened versus usual care group after 1 year of followup (RR, 0.44 [95% CI, 0.20 to 0.90]).27 In this trial, women randomized to screening were tested in study clinics. A poor-quality RCT of 1,761 female high school students in Denmark found that one-time, home-based screening compared with usual care (opportunistic physician-based screening) was associated with lower incidence of chlamydia (RR, 0.45 [95% CI, 0.24 to 0.84]) and PID (RR, 0.50 [95% CI, 0.23 to 1.08]) after 1 year of followup.28 Since few participants were actually screened in the usual care group, they were considered to be similar to an unscreened comparison group.

Key Question 2. How Effective Are Different Screening Strategies in Identifying Persons With Gonorrhea and Chlamydia?

Summary

No studies compared the effectiveness of different screening strategies for gonorrhea or chlamydia in asymptomatic persons or the effectiveness of sampling from various anatomical sites, cotesting for concurrent STIs, or using different screening intervals. Several studies of screening in high-risk groups have been published, but they did not meet inclusion criteria because they enrolled both symptomatic and asymptomatic persons, lacked comparison groups, or did not report relevant outcomes. An observational study in the Netherlands evaluated a risk prediction tool to identify persons with chlamydia in high-risk populations.29 However, the tool was not an accurate predictor, and its applicability to practice in the United States is unclear. Prior reviews did not directly address the effectiveness of different screening strategies, but rather summarized risk factors associated with gonococcal and chlamydial infections.3,4 An observational study comparing nine sets of selective screening criteria for chlamydial infection among women attending family planning and STI clinics in the United States30 indicated that age alone had similar or better sensitivity and specificity as more extensive criteria. In this study, nearly 80 percent of cases were identified when testing 50 percent of the population and using an age cutoff of 22 years or younger.

Evidence

An observational study conducted in the Netherlands evaluated a risk prediction tool to identify persons with chlamydia in high-risk populations (Appendixes C3 and C4).29 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 two high-risk populations, this risk tool was not an accurate predictor of infection (area under the receiver operating curve, 0.66 and 0.68, respectively). The applicability of this study to U.S. populations is also limited.

Key Question 3. How Accurate Are Screening Tests for Detecting Gonorrhea and Chlamydia?

Summary

Ten new fair-quality diagnostic accuracy studies reporting test characteristics of FDA-cleared NAATs met inclusion criteria, including six for gonorrhea and eight for chlamydia. Most studies evaluated the performance characteristics of NAATs compared with culture or expanded reference standards in asymptomatic persons in high prevalence (>5%) settings. Studies reporting the lowest values had important methodological limitations.

For gonorrhea, test sensitivity ranged from 90 to 100 percent in studies without major limitations, and specificity was greater than 97 percent across all specimens and tests. For chlamydia, test sensitivity ranged from 86 to 100 percent in studies without major limitations, and specificity was greater than 97 percent across all specimens and tests. In women, NAATs showed little variation across endocervical, clinician- and self-collected vaginal, and urine specimens. In men, urine specimens had slightly higher sensitivity than urethral specimens.

The prior reviews reported similar findings, but included several studies of non-NAAT tests, including some that are not currently available, as well as studies of symptomatic persons.3,4

Evidence

This review focused on the performance characteristics of screening tests in asymptomatic persons compared with either culture or expanded reference standards (i.e., positive result on two nonculture tests, positive result on two different specimens, or positive result on the original test and a confirmatory test). These studies included only FDA-cleared tests and specimen types (Table 3).

Table 3. Included Studies of Nucleic Acid Amplification Tests for Screening for Gonorrhea and Chlamydia At Various Anatomical Sites.

Table 3

Included Studies of Nucleic Acid Amplification Tests for Screening for Gonorrhea and Chlamydia At Various Anatomical Sites.

Ten new fair-quality studies reporting test characteristics of FDA-cleared NAATs met inclusion criteria, including six for gonorrhea (Appendix C5)31-36 and eight for chlamydia (Appendix C6).31-33,36-40 Methodological limitations include unclear descriptions of sampling methods, whether screening tests were interpreted independent of the reference standard,31-34,37-39 and whether analyses included patients with uninterpretable results (Appendix C7).31,33,34,37,39 Three studies described additional methodological difficulties related to the reference standard38 and technical approach.34,37 Most studies reported an infection prevalence of greater than 5 percent among participants, although rates were lower in three studies.33,35,36

Gonorrhea. Test characteristics of NAATs for gonorrhea are provided in Table 4 for women and Table 5 for men. All but three studies33,35,36 reported an infection prevalence of greater than 5 percent among participants. Specificity was high (≥97%) across all studies for men and women regardless of specimen or test.

Table 4. Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea in Women.

Table 4

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea in Women.

Table 5. Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea in Men.

Table 5

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea in Men.

For women, four studies testing endocervical specimens with transcription mediated amplification (TMA); polymerase chain reaction (PCR), including a new rapid test;36 or strand displacement amplification (SDA) reported sensitivities ranging from 90 to 100 percent (Table 6 and Figure 3).33-36 Sensitivity was 98 percent for TMA35 and 100 percent for PCR36 using self-collected vaginal specimens obtained in a clinician's office. Results for TMA, PCR, or SDA ranged from 78.6 to 100.0 percent using female urine.33,34,36 However, the study reporting the lowest sensitivity used urine volumes larger than recommended by the manufacturer of the screening test.34 When recommended urine volumes were used in a second study, the sensitivity of the same TMA test improved from 78.6 to 95.7 percent.33

Table 6. Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea and Chlamydia at Various Anatomical Sites.

Table 6

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea and Chlamydia at Various Anatomical Sites.

Figure 3 displays 2 scatter plots. One details the accuracy of nucleic acid amplification tests (NAATs) for gonorrhea screening in women and the other details the accuracy of NAATs for gonorrhea screening in men. Data for Figure 3 are presented in Table 6. Both scatter plots are described on page 12 of the report as follows: “For women, four studies testing endocervical specimens using transcription mediated amplification tests (TMA); polymerase chain reaction (PCR), including a new rapid test; or strand displacement amplification (SDA) reported sensitivities ranging from 90.0 to 100.0 percent (Table 6 and Figure 3). Sensitivity using self-collected vaginal specimens obtained in a clinician's office was 98.0 percent by TMA and 100.0 percent by PCR. Results of female urine specimens using TMA, PCR, or SDA ranged from 78.6 to 100.0 percent. However, the study reporting the lowest sensitivities used urine volumes larger than recommended by the manufacturer of the screening test. When recommended urine volumes were used in a second study, the sensitivity of the same TMA test improved from 78.6 to 95.7 percent. 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 four studies (urethra: 100%; urine: 90.0 to 100.0%), (Table 6 and Figure 3).”

Figure 3

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Gonorrhea in Men and Women. * The study reporting lower sensitivities for urine specimens in women (78.6% and 82.1%) used larger than recommended urine volumes, differing from the (more...)

For men, testing male urethral specimens with SDA and TMA and testing male urine with TMA, SDA, or PCR resulted in similarly high sensitivities across tests in four studies (urethra, 100%; urine, 90% to 100%) (Table 6 and Figure 3).31,32,34,36

The 2005 evidence review on screening for gonorrhea reported sensitivity of 90 percent or greater and specificity of 97 percent or greater when cervical specimens were tested with NAATs or nucleic acid hybridization tests.4 Testing female urine samples with PCR, TMA, or SDA had lower sensitivity (64.8% to 100.0%) than testing cervical specimens, although specificity was high across all specimens and tests. Male urine samples tested with PCR had lower sensitivity than testing urethral specimens, although this difference was not seen with SDA, and specificity was similar between specimen types for both tests. Many of these studies were conducted in high-prevalence populations and included both symptomatic and asymptomatic persons; few reported results by symptom status.

Chlamydia. Test characteristics of NAATs for chlamydia are provided in Table 7 for women and Table 8 for men. All but one study36 reported greater than 5 percent prevalence of infection among participants. Specificity was high (≥96%) across all studies for men and women regardless of specimen or test.

Table 7. Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Women.

Table 7

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Women.

Table 8. Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Men.

Table 8

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Men.

Five studies of endocervical specimens reported sensitivity of TMA ranging from 89.0 to 97.1 percent, sensitivity of SDA ranging from 86.4 to 96.2 percent, and sensitivity of PCR ranging from 86.4 to 95.8 percent (Table 6 and Figure 4).33,36,37,39,40 Testing clinician-collected vaginal swabs with TMA or PCR resulted in sensitivities of 89.9 and 98.8 percent,37 respectively, and testing self-collected vaginal swabs obtained in clinical settings resulted in sensitivities of 97.0 percent with TMA40 and 90.737 and 98.0 percent36 with PCR. Testing female urine samples with TMA, PCR, and SDA resulted in sensitivities ranging from 72.0 to 98.2 percent.33,36,37,39 Lower sensitivities for testing urine samples with TMA (72%) and PCR (84%) were reported in one study that experienced technical and specimen processing errors.37

Figure 4 displays a scatter plot detailing the accuracy of nucleic acid amplification tests (NAATs) for chlamydia screening in women. Data for Figure 4 are presented in Table 6. The scatter plot is described on page 13 of the report as follows: “Among five studies of endocervical specimens, sensitivity of TMA was 89.0 to 97.1 percent, SDA 86.4 to 96.2 percent, and PCR 86.4 to 95.8 percent (Table 6 and Figure 4). Testing clinician-collected vaginal swabs with TMA and PCR provided sensitivities of 89.9 and 98.8 percent, and self-collected vaginal swabs from clinical settings provided sensitivities of 97.0 percent with TMA and 90.7 and 98.0 percent with PCR. Female urine samples tested by TMA, PCR, and SDA provided sensitivities of 72.0 to 98.2 percent. Lower sensitivities for urine samples using TMA (72.0%) and PCR (84.0%) were reported in a study that experienced technical and specimen processing errors. A single study using PCR reported sensitivities that were markedly lower than other studies(endocervical, 51.9%; urine, 44.4%; clinician-collected vaginal, 55.6%; self-collected vaginal, 51.9%). This study used a more conservative approach to analysis that only included women with complete sets of results from nine different testing strategies. Also, the reference standard included positive NAATs from two separate specimens. When a specimen-specific reference standard was used, as is common in the other studies, sensitivities were comparable to other studies (data not provided). Since these data represent outliers resulting from a different method, they are not included in Figure 4.”

Figure 4

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Women. * The study reporting lower sensitivities for urine specimens in women (72.0% and 84.0%) experienced technical and specimen processing errors, differing from (more...)

One study using PCR reported sensitivities that were markedly lower than those in other studies (endocervical, 51.9%; urine, 44.4%; clinician-collected vaginal, 55.6%; self-collected vaginal, 51.9%).38 This study used a more conservative approach to analysis that only included women with complete sets of results from nine different testing strategies. In addition, the reference standard included positive NAAT results from two separate specimens. When a specimen-specific reference standard was used, as was common in the other studies, sensitivities were comparable with those in other studies (data not provided). Since these data represent outliers resulting from a different method, they are not included in Figure 4.

Sensitivities of testing male urethral and urine specimens with TMA, SDA, or PCR were consistently high across four studies, regardless of test, and ranged from 86.1 to 100.0 percent (Figure 5).31,32,36,39

Figure 5 displays a scatter plot detailing the accuracy of nucleic acid amplification tests for chlamydia screening in men. Data for Figure 5 are presented in Table 6. The scatter plot is described on page 13 of the report as follows: “Sensitivities for male urethral and urine specimens were consistently high regardless of test across four studies reporting sensitivities ranging from 86.1 to 100.0 percent for TMA, SDA, or PCR (Figure 5).”

Figure 5

Diagnostic Accuracy of Nucleic Acid Amplification Tests for Screening for Chlamydia in Men.

The 2001 evidence review on screening for chlamydia found that testing endocervical swabs with enzyme immunoassay yielded lower sensitivity (70% to 80%) than PCR (82% to 100%), although specificity was similarly high (≥96%).3 Testing urine with PCR performed comparably with testing endocervical swabs, and TMA was comparable with PCR. Testing male swab specimens with enzyme immunoassay had an average sensitivity of 80 percent and specificity of 96 to 100 percent, and testing with PCR resulted in higher sensitivity and specificity compared with enzyme immunoassay, similar to results for female specimens. Testing either male swab specimens or urine with PCR or TMA gave comparable performance results. Studies were conducted in high-prevalence populations and combined asymptomatic and symptomatic persons.

Key Question 4. What Are the Harms of Screening for Gonorrhea and Chlamydia?

Summary

New diagnostic accuracy studies without major methodological limitations indicated that false-positive rates for gonorrhea and chlamydia were 3 percent or less, and false-negative rates ranged from 0 to 9 percent for gonorrhea and 0 to 14 percent for chlamydia across all NAATs and specimen types. These results are consistent with prior reviews.3-5 Several studies of psychosocial harms related to testing, such as anxiety, have been published, but did not meet inclusion criteria because they included symptomatic persons and focused on reactions to positive test results rather than screening itself.

A prior review5 included results of qualitative interviews about the experience of chlamydia testing from women undergoing opportunistic screening.41 Although many women felt that screening was beneficial and important, common responses to a positive test result included feeling dirty, ashamed at passing on the infection, and suspicious about the origins of the infection.

Evidence

Gonorrhea. Study results of screening tests for gonorrhea are provided in Table 4 for women and Table 5 for men. False-positive results were uniformly low across studies regardless of test or specimen, ranging from 0 to 2.9 percent. False-negative results had a wider range from 0 to 21.4 percent, although the highest rates can be attributed to studies with important methodological limitations (described previously).

No studies that addressed other harms, such as labeling or anxiety from screening, met inclusion criteria. The 2005 evidence review on screening for gonorrhea indicated similar findings for false-positive and false-negative results and did not address other harms of screening.4

Chlamydia. Study results of screening tests for chlamydia are provided in Table 7 for women and Table 8 for men. False-positive results were low across all studies regardless of specimen or test, ranging from 0 to 3.6 percent. Most studies of NAATs reported false-negative findings ranging from 0 to 28 percent, although the highest rates can be attributed to studies with important methodological limitations (described previously).37,38 No studies that addressed other harms, such as labeling or anxiety from screening, met inclusion criteria.

The performance characteristics of chlamydia tests were evaluated in the 2001 review and were similar to this update, although the 2001 review included more studies of non-NAATs. The 20013 and 2007 reviews5 identified no studies of harms of screening for chlamydia, but the more recent review contextually described three qualitative studies of the impact of receiving a positive chlamydia test result.

Pregnant Women

Key Question 1. How Effective Is Screening for Gonorrhea and Chlamydia in Reducing Complications of Infection and Transmission or Acquisition of Disease in Asymptomatic Pregnant Women?

No studies met inclusion criteria for this review as well as for the 2005 review on gonorrhea4 and the 2007 review on chlamydia.5 The 2001 review on chlamydia described a time-series and a case-control study predating the review conducted in the 1980s, but identified no new relevant studies.3

Key Question 2. What Are the Harms of Screening for Gonorrhea and Chlamydia in Asymptomatic Pregnant Women?

No studies met inclusion criteria, although the rates of false-positive and false-negative results for nonpregnant women are applicable to pregnant women. The prior reviews did not identify any relevant studies.

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