From the Guidelines
Testing for syphilis requires a two-test approach, typically involving an initial screening with a non-treponemal test, such as the rapid plasma reagin (RPR) test, followed by a more specific treponemal test, such as the Treponema pallidum particle agglutination (TP-PA) test, to confirm the diagnosis. According to the 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology 1, this two-test approach is the most commonly used method for diagnosing syphilis in the United States. The initial screening test, such as RPR, is often used due to its low cost, but it can produce false-positive results, making it essential to confirm positive results with a more specific treponemal test.
Some laboratories have reversed the testing sequence, starting with a specific treponemal test, such as an enzyme immunoassay (EIA) or chemiluminescence immunoassay, and then retesting reactive results with a non-treponemal test, such as RPR, to confirm the diagnosis 1. This approach can help identify individuals who have been previously infected and treated, as well as those with a low likelihood of infection. However, if the follow-up confirmation test (RPR) is negative, a different treponemal-specific test, such as the fluorescent treponemal antibody-absorbed (FTA-ABS) test, may be necessary to guide management decisions 1.
Key points to consider when testing for syphilis include:
- The use of a two-test approach to confirm the diagnosis
- The importance of confirming positive results from non-treponemal tests with a more specific treponemal test
- The potential for false-positive results with non-treponemal tests
- The need for a different treponemal-specific test if the follow-up confirmation test is negative
- The importance of early detection and treatment to prevent serious health problems.
From the Research
Testing Methods for Syphilis
The diagnosis of syphilis is mainly dependent on serological tests 2. The most widely used screening tests for syphilis are:
- VDRL (Venereal Disease Research Laboratory) test
- Rapid plasma reagin (RPR) test For confirmation, the following tests are used:
- Fluorescent treponemal antibody (FTA) test
- Treponema pallidum hemagglutination (TPHA) test
Serological Tests
Treponemal serological tests, such as T. pallidum IgG chemiluminescence immunoassay (CLIA) and the T. pallidum particle agglutination (TPPA), are commonly used to investigate possible syphilis cases 3. The nontreponemal rapid plasma reagin (RPR) flocculation test is used to assess disease activity.
Performance of Treponemal Tests
Treponemal immunoassays have been compared to traditional treponemal tests in patients with and without syphilis 4. The results show that:
- FTA-ABS was less sensitive for primary syphilis (78.2%) than the immunoassays or TPPA (94.5%-96.4%)
- All immunoassays were 100% sensitive for secondary syphilis
- TPPA had 100% specificity
- Treponemal immunoassays demonstrated excellent sensitivity for secondary, early latent, and seropositive primary syphilis
Diagnosis of Neurosyphilis
For the diagnosis of neurosyphilis, the cerebrospinal fluid (CSF) parameters available are insufficient 2. The albumin quotient for estimation of the blood-brain barrier function is recommended, as well as the IgG index, which is a measure of intrathecal immunoglobulin production. Treponemal antibodies in CSF have high sensitivity for neurosyphilis, although the specificity is low.