Literature review > Issue 7 > Review on Harindra et al. 

The objective of this report by Harindra et al., was to compare the sensitivity of the Abbott ligase chain reaction (LCx) test, a nucleic acid amplification test (NAAT) for Chlamydia trachomatis, with an enzyme immunoassay (EIA) previously used as the routine diagnostic method, in a large, population-based, prospective study. It has been known for some years, however, that NAAT, including the Roche Amplicor PCR, Abbott LCx, Digene Hybrid Capture II, BD ProbeTec SDA, and GenProbe TMA, if correctly used, all achieve higher sensitivities than either standard culture methods or antigen detection tests [1,2]. Sampling is another advantage of NAAT. Compared with EIA requiring invasive urethral or cervical swab specimens, NAAT can effectively be used with relatively noninvasive specimens such as urines and for case finding in asymptomatic patients [2,3].

This report successfully documents the higher sensitivity of the LCx for detection of chlamydial infection. More than 1,100 positive specimens were obtained from just over 17,000 patients. Among all positive specimens by either assay, 27% of women and 40% of men were reported as LCx positive but EIA negative. Despite their advantages in sensitivity and use of noninvasive specimens, however, NAAT and the LCx are not entirely problem-free. For example, an appreciable number of equivocal LCx results found in this study were not addressed, but a similar study suggested that equivocal results were potential problems in reproducibility [4]. In this study 2% of the overall positive specimens were EIA positive, confirmed by DFA, but were LCX negative. Inhibitors in some specimens tested by the LCx may have therefore been present [5]. The order of sampling may also have been an issue in this comparative study. Swabs were taken for EIA testing before the urines for NAAT at the GUM clinics and 2 weeks after the urine samples were collected at other clinical sites in the study. In addition, a direct fluorescence assay (DFA) was used to confirm EIA positives, but the LCx-positive results remained unconfirmed since the LCx results were repeated with the LCx test only.

Before selecting a NAAT method for routine diagnosis, factors such as the type of assay, its cost, the complexity of running the assay, availability of well-trained technical staff, and need for constant quality assessment all must be carefully considered. Unfortunately, as previously indicated on this STD Diagnostics Initiative web site, the performance of the LCx and the potential applicability of these findings to improve diagnosis of chlamydial infection is currently somewhat of a moot point. Abbott Laboratories discontinued production and distribution of their pioneering LCx test in 2003.

References:

1. Naher H, Drzonek H, Wolf J, von Knebel Doeberitz M, Petzoldt D. Detection of C trachomatis in urogenital specimens by polymerase chain reaction. Genitourin Med. 1991; 67(3): 211-4.

2. Lee HH, Chernesky MA, Schachter J, Burczak JD, Andrews WW, Muldoon S, Leckie G, Stamm WE. Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet. 1995 Jan 28; 345 (8944): 213-6

3. Johnson RE, Green TA, Schachter J, Jones RB, Hook EW 3rd, Black CM, Martin DH, St Louis ME, Stamm WE. Evaluation of nucleic acid amplification tests as reference tests for Chlamydia trachomatis infections in asymptomatic men. J Clin Microbiol. 2000; 38(12): 4382-6.

4. Castriciano S, Luinstra K, Jang D, Patel J, Mahony J, Kapala J, Chernesky M. Accuracy of results obtained by performing a second ligase chain reaction assay and PCR analysis on urine samples with positive or near-cutoff results in the LCx test for Chlamydia trachomatis. J Clin Microbiol. 2002; 40(7): 2632-4.

5. Berg ES, Anestad G, Moi H, Storvold G, Skaug K. False-negative results of a ligase chain reaction assay to detect Chlamydia trachomatis due to inhibitors in urine. Eur J Clin Microbiol Infect Dis. 1997; 16(10): 727-31..

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