Ligase chain reaction assay of urine was sensitive for detecting chlamydial infection of the genital tract in women
ACP J Club. 1995 July-Aug;123:16. doi:10.7326/ACPJC-1995-123-1-016
Lee HH, Chernesky MA, Schachter J, et al. Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine. Lancet. 1995 Jan 28;345:213-6.
To determine the accuracy of ligase chain reaction (LCR) testing of first-void urine samples for the diagnosis of chlamydial infection of the genital tract in women.
Blinded comparison of an LCR-based assay in first-void urine with culture of endocervical swabs, supplemented by blinded direct antibody assay and LCR with probes based on a portion of the Chlamydia trachomatis major outer protein gene.
Obstetric and gynecology clinic in Birmingham, Alabama; sexually transmitted disease (STD) clinics in Seattle, Washington, and San Francisco, California; and an abortion clinic and student health clinic in Hamilton, Ontario.
1937 women attending the clinics where STD symptoms were recorded. Women who had received antibiotics in the previous 2 weeks were excluded.
Description of test and diagnostic standard
The first 15 to 20 mL of first-void urine was collected at any time of the day. An LCR-based assay test was done to detect C. trachomatis plasmid DNA. Endocervical swab specimens were tested by culture according to standard protocols. Discordant results from matched samples were resolved by blinded supplementary testing. For all samples that were culture negative and LCR positive, the Microtrak (Syva) direct fluorescence antibody assay was done on the sediment of the original culture. If that result was negative, the urine samples were tested by LCR with probes based on a portion of the C. trachomatis major outer membrane protein gene. For all samples that were culture positive and LCR negative, the sediment from the culture isolate and the processed urine were tested by LCR with the major outer membrane protein probe set.
Main outcome measures
Likelihood ratios, sensitivity, and specificity.
104 women were positive for C. trachomatis by endocervical culture, whereas first-void urine samples from 150 women were positive by LCR. The test characteristics for the LCR assay and culture are shown in the Table.
A positive ligase chain reaction assay of first-void urine was virtually diagnostic of chlamydial infection of the genital tract in women, whereas a negative test markedly decreased the probability of infection.
Source of funding: Not stated.
For article reprint: Not available.
Table. Test characteristics for ligase chain reaction (LCR) and culture of endocervical swabs for detecting C Trachomatis*
|Tests||Sensitivity (95% CI)||Specificity (CI)||+LR||-LR|
|LCR||94% (89 to 97)||99.9% (99 to 100)||1666||0.06|
|Culture||65% (58 to 72)||100%||Infinity||0.35|
*LRs defined in Glossary; LRs and CI calculated from data in article.
Genital chlamydial infections are the most common bacterial STDs in the world, causing more adverse reproductive outcomes than their more heralded counterpart, gonorrhea (1). Because most chlamydial infections in both men and women are asymptomatic, efforts to control this STD have been based on widespread screening. Currently available chlamydial detection techniques, however, are limited by their relative insensitivity and their requirement for endocervical or urethral specimens. Fortunately, we are now in the era of molecular amplification techniques. In the next 5 years, these tools will increasingly expand our diagnostic repertoire for all STDs, including chlamydia (2).
Why are these advances so important? Quite simply, they answer the 2 main limitations of the available chlamydial detection techniques. First, the test sensitivity is markedly enhanced; the tests have the ability to detect 1 gene copy per specimen. Thus, the underlying reservoir of asymptomatic, currently undetectable genital chlamydial infections can be identified and treated. Second, this increased sensitivity allows more "user-friendly" specimen collection. Urine samples can provide enough DNA to detect chlamydia in both men and women. Thus, it is possible to screen for STDs in high-risk populations, such as adolescents, during routine school physical examinations or in other settings where pelvic examinations are not feasible.
Those interested in STD control will rejoice at having a new molecular tool for wider screening. Several potential problems still remain: 1) The commercial availability of these amplification techniques in North America is uncertain; 2) the performance of the tests in "real-world" clinical laboratories outside of research centers needs to be assessed; 3) the budget-cutting mood of federal and state governments in the United States threatens all STD control programs in that country; and 4) the cost of these amplification techniques compared with other methods for detecting chlamydia awaits the market forces. Perhaps a positive benefit-to-cost ratio of STD control measures will increase the willingness of the increasingly cost-conscious managed care organizations to underwrite STD screening.
Willard Cates Jr, MD, MPH
Family Health InternationalDurham, North Carolina, USA