RESULTS

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

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.

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.

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

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 for women and 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 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 ( and ).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.

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%) ( and ).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 for women and 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 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 ( and ).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

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 .

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 ( ).31,32,36,39

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.