The Serological Test for Syphilis, known by the acronym STS, is a common laboratory procedure used to screen for and help diagnose infection caused by the bacterium Treponema pallidum. Syphilis is a sexually transmitted disease that can lead to severe long-term health problems if left untreated. The STS is an important public health tool, widely employed in screening programs for pregnant individuals and blood donors to prevent transmission. These tests detect the body’s immune response to the infection rather than the bacteria itself.
The Mechanism of Serological Testing
The STS falls into the category of non-treponemal tests, meaning they do not directly look for antibodies specific to the Treponema pallidum spirochete. Instead, they detect a non-specific antibody called reagin, which the body produces when tissues are damaged by the syphilis infection. These reagin antibodies are directed against lipid material released from damaged host cells, which is chemically similar to components of the bacterial cell wall.
The test works by mixing the patient’s blood serum with an antigen composed of cardiolipin, cholesterol, and lecithin. If reagin antibodies are present, they bind to this lipid antigen, causing a visible clumping, or flocculation, of the particles. A positive result signals the presence of these non-specific antibodies, indicating an active syphilis infection.
Key Non-Treponemal Tests (RPR and VDRL)
The two most common non-treponemal STS tests are the Venereal Disease Research Laboratory (VDRL) test and the Rapid Plasma Reagin (RPR) test. Both assays utilize the flocculation principle, where antigen particles visibly aggregate when they encounter reagin antibodies. The RPR test uses an antigen card with charcoal particles attached to the lipids, making the resulting clumping easier to see. This visual simplicity allows the RPR test to be performed quickly, making it highly effective for large-scale public health screening.
The VDRL test, while similar, requires a microscope to see the fine flocculation of the antigen particles. The VDRL test is unique because it can be reliably performed on cerebrospinal fluid (CSF), making it the standard method for diagnosing neurosyphilis. A practical difference is that the RPR test uses unheated serum, whereas the VDRL test traditionally requires the serum to be heated before testing. Both tests are used as initial screening tools due to their high sensitivity in detecting active infection.
Interpreting Test Results
The results of an STS test are reported as either “reactive” (positive) or “non-reactive” (negative). A reactive result indicates that the reagin antibodies were detected, suggesting an active or recently treated syphilis infection. If the result is reactive, the sample is then serially diluted to determine the antibody concentration, which is known as a titer.
The titer is expressed as a ratio (e.g., 1:4, 1:8, or 1:16), representing the highest dilution at which the sample still causes a visible reaction. This quantitative result is used to monitor the effectiveness of syphilis treatment. Successful treatment is indicated by a sustained fourfold or greater decrease in the titer (e.g., a drop from 1:16 to 1:4). If the titer increases fourfold after treatment, it signals a treatment failure or a new infection.
A biological false positive (BFP) occurs when the test is reactive even though the patient does not have syphilis. This happens because other conditions cause the body to produce antibodies that cross-react with the cardiolipin antigen. Common causes of these false positives include:
- Autoimmune disorders like systemic lupus erythematosus.
- Recent vaccinations.
- Pregnancy.
- HIV.
- Malaria.
- Hepatitis C.
- Intravenous drug use.
The Importance of Follow-Up Confirmation
Because non-treponemal STS tests are susceptible to biological false positives, a reactive result is never sufficient for a definitive syphilis diagnosis. Any reactive STS test must be followed immediately by a second, different type of serological test for confirmation. These follow-up procedures, called treponemal tests, are designed to detect antibodies specific to the Treponema pallidum organism.
Examples of treponemal tests include the Treponema pallidum Particle Agglutination (TP-PA) assay or the Fluorescent Treponemal Antibody Absorption (FTA-ABS) test. If both the initial STS test and the treponemal confirmation test are reactive, the diagnosis of syphilis is considered confirmed. Unlike the non-treponemal antibodies, the specific antibodies detected by treponemal tests usually remain in the bloodstream for the rest of a person’s life, even after the syphilis infection has been successfully treated.