Literature review > Issue_5 > Review on Chernesky et al. 

Culture and nonamplified direct specimen tests such as immunofluorescence, enzyme immunoassay (EIA), and nucleic acid hybridization (NAH) are typically performed on endocervical or male urethral swab specimens for diagnosis of Chlamydia trachomatis infection. Some laboratories have developed in-house protocols for testing noninvasive urine specimens with these assays, but they lack sensitivity when compared to swab specimens. It was not until the development of nucleic acid amplification tests (NAATs) that urine specimens could be used for diagnosis of chlamydial infections and have a sensitivity comparable to that of swab specimens. Most studies evaluating the use of urine specimens in these tests have used first-catch or first-void urine, defined as the first 20 to 30 mL of the initial urine stream, collected at least 1 hour after the most recent urination. First-void urine would be expected to contain the largest number of elementary bodies and yield the greatest sensitivity but few studies have actually evaluated the use of sequentially collected first-void, second-void, and third-void urine specimens in nonculture-based tests for C. trachomatis.

Chernesky et al. compared NAAT, NAH, EIA, and leukocyte esterase dipstick tests on first, second, and third volumes of urine for diagnosis of chlamydial infections in men. A total of 237 men attending a sexually transmitted disease clinic collected three containers of urine, each containing 20 to 30 mL, representing first-void, second-void, and third-void specimens. After urination, a urethral swab specimen was also collected for culture. Each urine specimen was tested by NAAT (LCx Chlamydia trachomatis, Abbott), NAH (PACE 2 Chlamydia trachomatis, Gen-Probe), EIA (Chlamydiazyme, Abbott), and leukocyte esterase dipstick (Chemstrip 2LN, Boehringer Mannheim). Not surprisingly, the first-void urine positivity rates were higher than those of the second-void and third-void urine specimens for all four of the nonculture-based tests. The number of positives by LCx dropped from 26 with the first-void urine, to 20 with the second-void urine, and to 19 with the third-void urine - a 26.9% reduction. Compared to LCx, the other three assays started with fewer positives with the first-void urine (14 by Chlamydiazyme, 7 by PACE 2, and 11 by Chemstrip 2LN) and the number of positives declined more rapidly with the second-void and third-void urines. Only 6 of the urethral swab specimens were positive by culture.

Recent studies have confirmed that the greater sensitivity of NAATs compared to culture and other nonculture-based tests permits the use of urine and other noninvasive specimens for diagnosis of C. trachomatis infection. Gaydos et al. [1] evaluated the performance of NAAT (APTIMA Combo 2, Gen-Probe) using endocervical swab specimens and first-catch urine specimens collected from women seen at several clinical sites in the United States. Specimens were also tested for C. trachomatis by two other NAATs to determine patient infection status. The Combo 2 assay showed a sensitivity of 94.2% and a specificity of 97.6% for C. trachomatis with swab specimens and a comparable sensitivity of 94.7% and a specificity of 98.9% with first-catch urine specimens.

In another study by Gaydos et al. [2], three NAATs (LCx; BD ProbeTec ET Chlamydia trachomatis, Beckton Dickinson; and APTIMA Combo 2) were compared for detection of C. trachomatis in first-catch urine specimens collected from high-risk adolescent males and females. All three assays demonstrated high performance, with a sensitivity of at least 96% and a specificity greater than 99%. Thus, NAATs have greatly improved the noninvasive detection of C. trachomatis in urine specimens.

In the study by Chernesky et al., the number of PACE 2- and culture-positives was surprisingly low compared to LCx. LCx was positive for C. trachomatis for 26 first-void urine specimens compared to only 7 PACE 2 positives and 6 culture positives. These unexpectedly large differences in the number of positives by LCx compared to PACE 2 and culture may have been due to suboptimal performance of PACE 2 with urine specimens, which are not recommended by the manufacturer, and suboptimal culture results due to collection of the urethral swab specimens after urination. Black et al. [3] reported that NAATs performed on endocervical swabs or first-catch urines significantly improved detection of C. trachomatis when compared to PACE 2 or culture performed on endocervical swabs, but the difference in performance of these tests was not nearly as great as that reported by Chernesky et al.

Finally, the drop in the number of positives with sequentially collected urine specimens reported by Chernesky et al. emphasizes the importance of proper collection of a first-void urine for diagnosis of C. trachomatis infection. Second-void or third-void urines should not be used.

References:

1. Gaydos CA, Quinn TC, Willis D, Weissfeld A, Hook EW, Martin DH, Ferrero DV, Schachter J. Performance of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in female urine and endocervical swab specimens. J Clin Microbiol 2003; 41:304-309.

2. Gaydos CA, Theodore M, Dalesio N, Wood BJ, Quinn TC. Comparison of three nucleic acid amplification tests for detection of Chlamydia trachomatis in urine specimens. J Clin Microbiol 2004; 42:3041-3045.

3. Black CM, Marrazzo J, Johnson RE, Hook EW, Jones RB, Green TA, Schachter J, Stamm WE, Bolan G, St. Louis ME, Martin DH. Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis infection in women performed with an improved reference standard. J Clin Microbiol 2002; 40:3757-3763.

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