From the Guidelines
Interpreting syphilis serology requires a combination of nontreponemal and treponemal tests to ensure accurate diagnosis and monitoring of treatment response. When evaluating results, it is essential to understand the differences between these two types of tests. Nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR), measure antibody response to cardiolipin and become positive 1-4 weeks after infection 1. A positive nontreponemal test should be confirmed with a treponemal test, such as the fluorescent treponemal antibody absorbed (FTA-ABS) or microhemagglutination assay for antibody to T. pallidum (MHA-TP), which detects antibodies specific to T. pallidum and remains positive for life in most patients 1.
Some key points to consider when interpreting syphilis serology include:
- Nontreponemal test antibody titers usually correlate with disease activity, and results should be reported quantitatively 1
- A fourfold change in titer, equivalent to a change of two dilutions, is usually considered necessary to demonstrate a clinically significant difference between two nontreponemal test results 1
- Treponemal test antibody titers correlate poorly with disease activity and should not be used to assess treatment response 1
- Most patients who have reactive treponemal tests will have reactive tests for the remainder of their lives, regardless of treatment or disease activity 1
The use of only one type of test is insufficient for diagnosis, and both nontreponemal and treponemal tests should be used in combination to ensure accurate diagnosis and monitoring of treatment response. It is also important to note that nontreponemal tests can revert to negative after successful treatment, while treponemal tests typically remain positive for life regardless of treatment success 1. In patients with HIV, more frequent monitoring and potentially longer treatment courses may be necessary due to higher rates of neurological involvement.
From the Research
Interpreting Syphilis Serology
- Syphilis serology can be complex and time-consuming to diagnose and stage appropriately 2
- The diagnosis of syphilis typically involves the use of both nontreponemal and treponemal antibody tests for screening and confirmation of active Treponema pallidum infection 3, 4, 2
- Nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test, detect antibodies against lipoidal material released from damaged host cells and possibly from the treponeme itself 4
- Treponemal tests, such as the fluorescent treponemal antibody absorption (FTA-ABS) test and the syphilis recombinant ELISA, detect antibodies against Treponema pallidum antigens 4
Test Performance
- The sensitivities of the VDRL, ELISA, and FTA-ABS tests were 97.9%, 100%, and 96.3%, respectively 4
- The VDRL and ELISA tests showed a specificity of 100%, and the FTA-ABS test showed a specificity of 99.5% 4
- The accuracy of the VDRL test was 98.9%, the ELISA was 100%, and the FTA-ABS test was 97.9% 4
- A point-of-care immunochromatographic test for the simultaneous detection of both nontreponemal and treponemal antibodies in the sera of patients with syphilis showed reactive concordance of 98.4% with the RPR test and 96.5% with the TP-PA assay 3
Clinical Implications
- The use of treponemal tests can provide advantage of better detection during early, late, and latent stages of syphilis with equal or higher sensitivity and specificity in comparison to non-treponemal tests 5
- A retrospective comparison between non-treponemal and treponemal tests for screening of blood donors for syphilis showed discordance of 62% and 32% for reactive results by RPR and TPHA respectively when compared with Chemiluminescence 5
- The clinical relevance of penicillin resistance-related gene mutations of Treponema pallidum to treatment failure in patients with early syphilis is unresolved and requires further study 6