From the Guidelines
A non-reactive non-treponemal test with a reactive Treponema pallidum particle agglutination (TPPA) test indicates a past or previously treated syphilis infection.
Key Points
- Syphilis diagnosis typically involves a combination of non-treponemal and treponemal tests, such as the RPR and TPPA tests, respectively 1.
- A non-reactive non-treponemal test, such as the RPR, can indicate that the patient has been successfully treated for syphilis or that the infection is in a late stage 1.
- A reactive treponemal test, such as the TPPA, usually indicates a current or past infection with Treponema pallidum, the bacterium that causes syphilis 1.
- Some patients may remain serofast, with persistent low-level antibodies, even after successful treatment 1.
- The TPPA test is a specific test for syphilis and is often used to confirm the diagnosis after a non-treponemal test has been performed 1.
Testing Algorithm
- The traditional testing algorithm involves an initial non-treponemal test, followed by a treponemal test if the first test is reactive 1.
- Some laboratories have reversed this algorithm, starting with a treponemal test and then confirming with a non-treponemal test if the first test is reactive 1.
- The choice of testing algorithm may depend on the clinical context and the patient's medical history 1.
From the Research
Interpretation of Test Results
- A non-reactive non-treponemal test with a reactive Treponema pallidum particle agglutination (TPPA) test may indicate a few possible scenarios:
- Latent or late syphilis: The patient may have been infected with syphilis in the past, but the non-treponemal test is no longer reactive due to successful treatment or the natural course of the disease 2.
- Fully treated patients: The patient may have been treated for syphilis in the past, and the non-treponemal test is no longer reactive, but the treponemal test remains reactive 2.
- Early infection: The patient may be in the early stages of syphilis infection, and the non-treponemal test has not yet become reactive, but the treponemal test is already positive 3.
Diagnostic Algorithms
- The traditional algorithm for syphilis diagnosis starts with a non-treponemal test, and a reactive result is confirmed with a treponemal test 4.
- The reverse sequence algorithm uses a treponemal test for screening, and a reactive result is confirmed by a quantitative non-treponemal test 4.
- If the non-treponemal test is negative, a second different treponemal test, preferably the TPPA, is used to confirm the diagnosis 4.
Test Characteristics
- The TPPA test has a high sensitivity and specificity for detecting syphilis antibodies 5, 3.
- Non-treponemal tests, such as the Venereal Disease Research Laboratory (VDRL) test, have a lower sensitivity and specificity compared to treponemal tests 3, 6.
- The combination of non-treponemal and treponemal tests may not provide additional diagnostic gain, but rather represents additional laboratory work time 6.