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Literature review > Issue_12 > Review |
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Because the majority of chlamydial infections are asymptomatic, screening is vital in detecting infection. Chlamydia trachomatis diagnostic assays continue to evolve and currently, nucleic acid amplification tests (NAATs) have been shown to be the most sensitive assays. The basis for the higher sensitivity of NAATs over non-amplified assays is that the amplification in NAATs facilitates the detection of a much lower load of chlamydial organisms (measured as inclusion-forming unit [IFU] counts with cell culture). Prior studies have demonstrated that C. trachomatis IFU counts are impacted by patient characteristics. Eckert et al. previously reported IFU counts were highest in young Caucasian women infected with B-class C. trachomatis serovars [1]. Geisler et al. previously demonstrated that in women, C. trachomatis IFU counts were highest in those with a diagnosis of mucopurulent cervicitis (MPC) or evidence of endocervical inflammation (cervical mucopus, easily-induced endocervical bleeding, or >30 polymorphonuclear cells per oil field on Gram stain) [2]. Prior studies evaluating NAAT performance in women have not directly studied the impact of clinical characteristics (e.g., blood or endocervical mucosal inflammation) on NAAT sensitivity and specificity, and this was the primary objective of the study by Marrazzo et al. It would be important to demonstrate that NAAT retains higher sensitivity over non-NAAT assays across a diverse spectrum of clinical presentations if one is to justify the use of the more costly NAAT over non-NAAT tests for screening. Marrazzo et al. assessed the performance of two NAATs, ligase chain reaction (LCR) and first generation uniplex polymerase chain reaction (PCR), on urine and endocervical swab specimens relative to an unamplified DNA probe assay (PACE2) at the cervix, and studied the impact of patient characteristics on test performance. In order to estimate test performance for each test at each site (endocervical and urine), a two-specimen reference standard was utilized by which a participant was classified as chlamydia-infected if at least two reference tests from any anatomical site were positive. While the choice of reference standard when defining the characteristics of a more sensitive test continues to be problematic, the use of the two-specimen reference standard should minimize the overestimation of sensitivity and the underestimation of specificity inherent in analyses that define the performance of more sensitive tests. Although NAATs were selectively impacted by some patient characteristics, they detected more chlamydial infections than PACE2, especially in older women (>20 years) and those without MPC. The study by Marrazzo et al. did not evaluate newer NAATs, such as the second generation PCR, strand displacement amplification assay, or transcription mediated amplification assay, which are more commonly used for chlamydia screening and likely have a greater sensitivity than LCR or the first generation uniplex PCR in most clinical settings. The authors conclude that their findings support expanded use of NAAT for screening in diverse clinical populations of women. However, the study sites were primarily STD clinics and all sites had high chlamydia prevalences. NAAT performance on vaginal swab specimens was also not evaluated, though it is unlikely NAAT performance would have been influenced much differently by patient characteristics than with cervical swabs. Therefore, the findings more accurately support NAAT screening on urine or endocervical swab specimens in high chlamydia prevalence settings with diverse clinical presentations. Other limitations may have influenced study findings. Earlier data analyses from the patient cohort revealed significant differences in NAAT performance across centers, and analyses in this study did not control for potential confounding by research center, which may be important if the performance differences were due to a given patient characteristic. They did use statistical methods to incorporate between-center differences, perhaps limiting the confounding. Also, data was not collected on easily-induced endocervical bleeding, which could influence their results in two ways: 1) some subjects with this manifestation would have been misclassified as not having MPC, perhaps lessening the difference in test performance between those with and without MPC, and 2) blood present on the endocervical swab could have impacted test performance. Finally, the estimated test sensitivities were not adjusted for race/ethnicity, which can influence the chlamydial organism burden. Despite these limitations, this study by Marrazzo et al. provides further evidence that NAATs are excellent screening tests in women, especially because of their ability to detect asymptomatic infection in women without clinical manifestations of disease. References: 1. Eckert LO, Suchland RJ, Hawes SE, Stamm WE. Quantitative Chlamydia trachomatis cultures: correlation of chlamydial inclusion-forming units with serovar, age, sex, and race. J Infect Dis 2000;182:540-4. 2. Geisler WM, Suchland RJ, Whittington WLH, Stamm WE. Quantitative culture of Chlamydia trachomatis: correlation of inclusion-forming units produced in culture with clinical manifestations of urogenital disease. J Infect Dis 2001;184:1350-4. |
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