Meatal Swabs Contain Less Cellular Material and Are Associated with a Decrease in Gram Stain Smear Quality Compared to Urethral Swabs in Men

摘要

Chlamydia trachomatis and Neisseria gonorrhoeae infections continue to rise, with 1.4 million and 350,000 cases reported, respectively, in the United States in 2015 (1); nongonococcal urethritis (NGU) remains the most common form of urethritis in men (2). For screening at-risk individuals, the Centers for Disease Control and Prevention (CDC) recommends highly sensitive nucleic acid amplification testing (NAAT) of urine or a urethral swab of urethral secretions (3). Meatal swabs have been suggested as a less invasive alternative to urethral swabs for specimen collection for NAAT and are amenable to self-obtained patient collection because they elicit less discomfort (4). Although not yet FDA approved or CDC recommended for NAAT in men, meatal swabs are recommended for NAAT in prepubertal boys with discharge, given concerns about urethral trauma from swabs (3, 5). In men, self-obtained meatal swabs appear to be equivalent to clinician-collected urethral swabs for diagnosing C. trachomatis/N. gonorrhoeae infection by NAAT, although there have been mixed reports of the sensitivity of this sample type (6, 7). Currently, no rapid (30-min) point-of-care NAAT is available to diagnose N. gonorrhoeae infection or NGU, and Gram stain smear (GSS) testing of urethral secretions remains the test of choice in settings where rapid diagnosis is needed and microscopy can be performed. The 2015 Sexually Transmitted Diseases Treatment Guidelines specify that GSS testing of male urethral secretions is appropriate for diagnosing N. gonorrhoeae infection or NGU, although no preferred swab type is indicated for specimen collection (5). Meatal swabs are recommended as an alternative for collecting urethral secretions in specific populations, though they have yet to be approved for NAAT in men. In contrast to NAAT, which amplifies nucleic acids from lysed cells, GSS testing requires collection of intact cells. As meatal swabs may sample a smaller surface area and a higher proportion of cornified squamous epithelium from the meatus than urethral swabs, it is possible that the number of intact cells collected using a meatal swab may be insufficient to reliably diagnose N. gonorrhoeae infection or NGU by GSS testing. To address this concern, we enrolled both symptomatic and asymptomatic men and systematically assigned them to undergo either meatal or urethral swabbing, and we measured the swabs' cellular content using the Cepheid Xpert CT/NG sample adequacy control crossing threshold (SACCT) (8) and determined the failure rate of GSS testing for each swab type. The SACCT is an internal control of the Xpert CT/NG assay and denotes the cycle number at which human hydroxymethylbilane synthase, a single-copy housekeeping gene, is first detected by real-time PCR amplification. Included in each assay to ensure specimen sample adequacy (9), the SACCT is inversely proportional to the amount of cellular material present in the specimen. The primary outcome of our study was to determine, compared with urethral swabs, if meatal swabs were associated with a lower cellular content and a higher GSS failure rate. A secondary objective was to determine how meatal swabs were influenced by the presence or absence of discharge.