The Rapid Plasma Reagin (RPR) test is a widely used screening tool for syphilis, an infection caused by the bacterium Treponema pallidum. The test detects specific antibodies produced by the body in response to the infection, rather than the bacterium itself. An RPR test “with reflex titer” means the laboratory automatically performs a follow-up measurement if the initial screening result is positive. This standardized protocol provides immediate information about the potential concentration of the infection to guide diagnosis.
The RPR Screening Test
The RPR test is classified as a non-treponemal test because it measures non-specific antibodies called “reagin.” These antibodies are generated by the immune system against substances, primarily cardiolipin, released from host cells damaged by the syphilis bacteria. The test kit contains a mixture of cardiolipin, lecithin, and cholesterol particles that react with these non-specific antibodies in the patient’s blood serum.
When these antibodies are present, they cause the particles in the test solution to visibly clump together, a process called flocculation. A result is reported as “reactive” if clumping occurs, suggesting the possible presence of syphilis infection. A “non-reactive” result indicates no detectable antibodies and typically suggests the patient does not have active syphilis.
The non-specific nature of the RPR test makes it a fast and cost-effective screening method. Since the test measures antibodies to cardiolipin, other conditions can sometimes trigger a positive result due to cross-reactivity. Therefore, a reactive screening result is never used alone to confirm a diagnosis.
Understanding the Quantitative Titer
When the initial RPR screening test is reactive, the laboratory automatically performs the quantitative titer, or “reflex titer.” This measurement determines the concentration of the non-specific antibodies in the blood. The titer is reported as a ratio (e.g., 1:2, 1:8, or 1:32), indicating the highest dilution of the patient’s blood that still yields a reactive result.
The process involves serial dilution, where the patient’s serum is repeatedly mixed with equal parts of a saline solution. For example, a 1:8 titer means one part of the patient’s serum was reactive even when diluted with seven parts of saline. A higher titer, such as 1:64, signifies a greater amount of antibodies, generally correlating with a more active or recent infection.
The quantitative titer has two primary applications: staging the infection and monitoring treatment effectiveness. A high titer may suggest a secondary stage of syphilis, where the bacterial load is highest. Successful treatment is defined by a significant, sustained drop in the RPR titer, typically a fourfold decrease (e.g., from 1:32 to 1:8) over 6 to 12 months.
Interpreting Results and Confirmation
A reactive RPR requires further interpretation because of the test’s non-specific nature. The RPR test can produce a “false positive” result, meaning the test is reactive even though the patient does not have syphilis. False positives can occur due to various other medical conditions, including autoimmune diseases like lupus, pregnancy, or acute infections like pneumonia, malaria, or mononucleosis.
To differentiate a true syphilis infection from a false positive, the reactive RPR must be followed by a treponemal confirmation test. These confirmatory tests, such as the fluorescent treponemal antibody-absorption (FTA-ABS) or the T. pallidum particle agglutination (TP-PA) test, look for antibodies specifically directed against the Treponema pallidum bacterium. If the RPR is reactive but the treponemal test is non-reactive, the RPR result is considered a biological false positive, and no syphilis treatment is necessary.
Post-Treatment Monitoring
The RPR titer is also used for post-treatment monitoring to assess if the infection has been successfully cleared. If the titer does not fall by at least a fourfold dilution within the expected timeframe, it may suggest treatment failure, reinfection, or persistent infection. Some patients may become “serofast,” maintaining a low but persistent RPR titer (e.g., 1:2 or 1:4) for life despite successful treatment, which requires careful clinical judgment.