The HCII CT/GC test proved to be sensitive for detection of cervical infection with C. trachomatis or N. gonorrhoeae. It offered the advantage of being able to detect the presence of both organisms in a single test. As the test is configured, the initial positive signal is the trigger for a second test to identify the specific organism responsible for the initial positive one. Thus, one can test for the presence of chlamydia and gonorrhea using a test that takes 4 h to perform, and if a positive result is obtained, one can identify whether the infectious agent is chlamydia or gonococcus in another 4-h test. The general format of this test is a strength. That the initial result is for the presence of either of two pathogens provides benefits. In the majority of settings, the great proportion of tests performed will be negative for both pathogens. Thus, there is the potential for efficiency and economy of reagents and personnel. This could permit a more rapid turnaround of results and lower costs, as the number of tests required to confirm positive results would be fewer than the number that would be required if separate tests were performed. For example, if the prevalence of these two sexually transmitted diseases is 10 to 20%, the total number of tests performed would be 55 to 60% of the number required if two single tests were performed.
The HCII CT-ID and GC-ID tests were reasonably specific, at approximately 98% for either organism. It is likely that this specificity is an underestimation. Subsequent PCR testing of some of the apparent false-positive results showed that most actually contained chlamydial or gonococcal genes. The true specificity is probably >99%. It is clear that the HCII CT/GC test must be further evaluated in direct comparisons with NAATs that are more sensitive than culture.
In this evaluation it was impossible to determine whether the HCII CT/GC test is more sensitive than gonococcal culture, since that was the only other test performed on all specimens and additional testing was not performed on all of the specimens with apparent false-positive results. If most of them actually were positive for gonococcal DNA, then the test would be marginally more sensitive than gonococcal culture. This would be similar to the results obtained by ligase chain reaction (6
In the current evaluation, where culture or DFA was used as the “gold standard” for chlamydial infection, the HCII CT/GC test was approximately 10% more sensitive than culture. The sensitivity of culture for chlamydiae on single specimens from women is at best in the 85 to 90% range. These studies were performed in expert laboratories with what is likely to be a higher culture sensitivity than would be seen in a routine clinical lab. Thus, this nonculture format would undoubtedly perform better in most settings where culture is performed. Certainly a nonculture test will be used more widely than will culture.
Because most of the specimens with apparent false-positive results could be shown to have chlamydial or gonococcal DNA, the specificity is likely to be higher than the 97.7% obtained in this study. Thus, it is likely that this is a test that could easily be used for screening low-prevalence populations. What is important for specificity calculations is the recognition that culture is clearly an inadequate gold standard for such evaluations. The addition of DFA for C. trachomatis improves the situation, but it still is not adequate for a final determination. The PCR results for a subset of those specimens that were positive by the HCII CT/GC screen but negative by culture leads to the inference that the specificity of the HCII CT/GC test is actually better than what we have calculated based on the use of just culture and DFA. Of course this is an extremely important issue when screening low- to moderate-prevalence populations. Our results suggest that the test will provide adequate specificity.
It is impossible to determine the true sensitivity of the HCII CT/GC test for C. trachomatis in this evaluation beyond saying that it is more sensitive than culture. Further evaluation of this signal amplification test is needed, especially by direct comparison to the target NAATs that have also been found to be far more sensitive than culture. The HCII CT/GC test, based on hybridization and signal amplification, is based on a different principle than the three commercially available NAATs, which are based on amplifying target or probe.
The HCII CT/GC test format is quite reproducible, as its performance varied little from site to site. There was also very little difference in test results between patients who were symptomatic versus asymptomatic.
Although not performed with the same patients, the sensitivity of the HCII CT/GC test with specimens collected with a swab compared to that with specimens collected with a cervical brush appears somewhat lower. The results for diagnosis of gonococcal infections were not statistically different with the two specimen types. However, with chlamydial infection, the performance with the endocervical brush was statistically superior in terms of sensitivity. Brushes typically collect more epithelial cells than do swabs, and the squamocolumnar epithelial cells within the transitional zone represent the site that C. trachomatis
infects. Culture results are acutely dependent on sampling adequate epithelial cells, as are DFA results. It would have been more desirable from a screening viewpoint if the swab- and brush-collected specimens yielded equivalent performances because brushings are contraindicated during pregnancy and pregnant women are one of the priority groups for screening for chlamydial and gonococcal infections. It should be stressed that even though swabs appear to be somewhat less sensitive for specimen collection with this test, the sensitivity of the HCII CT/GC test with the swab-collected specimens was still higher than the sensitivity of culture and predictably would be higher than either antigen detection or RNA hybridization without amplification (3
) assays. Further studies are needed to better define the effect of collection device on test performance.
In summary, the HCII CT/GC test is relatively easy to perform and provides a nonculture method of diagnosing chlamydial and gonococcal infections that is of similar sensitivity to gonococcal culture and more sensitive than chlamydial culture. The ability to detect chlamydial and gonococcal infection with a single test is an attractive option. Urethral swabs and urine specimens from men, and vaginal swabs and urine from women, need to be evaluated for performance before the ultimate usefulness of the HCII CT/GC test in screening or diagnosis can be determined. Further evaluation in direct comparison with target NAATs is clearly called for. If the economics are attractive the HCII CT/GC test could offer a reasonable alternative to other methods of diagnosing chlamydial and gonococcal infections.