Interpretive

Key

(+) = Positive

Equiv = Equivocal

(-) = Negative

N/A = Not applicable

Syphilis screening is performed using the reverse algorithm, which first tests sera for Treponema pallidum antibodies using an automated chemiluminescence immunoassay.  A positive treponemal antibody test suggests infection with Treponema pallidum at some point in the past, but does not distinguish between treated and untreated infections. This is because treponemal tests may remain reactive for life, even following adequate therapy. Therefore, the results of a nontreponemal assay, such as rapid plasma reagin (RPR), are needed to provide information on a patient's disease state and history of therapy.

In some patients, the results of the treponemal screening test (syphilis antibody) and RPR may be discordant (e.g., syphilis antibody positive and RPR negative). To discriminate between a falsely reactive screening result and past syphilis, the CDC recommends performing a second treponemal-specific antibody test using a method that is different from the initial screen test (eg, Treponema pallidum particle agglutination: TP-PA). In addition to CDC recommendations, the manufacturer of the RPR test recommends confirmation of positive RPR tests for the following reasons:

1. The RPR test is not reliable for patients < 6 months of age.
2. In pregnancy, false positives may occur with immunoassay tests. Samples positive for Syphilis Antibody and RPR on females < 45 yrs of age are sent for confirmation.
3. RPR assay interference resulting in false positive results may occur due to cross-reacting antibodies from a variety of clinical conditions, including Systemic Lupus Erythematosus, malaria, autoimmune disease, viral pneumonia, intravenous drug use, and in people who have been recently immunized for SARS-CoV-2 or smallpox.  

At Bronson, a sample from any positive RPR test is sent to the Michigan Dept of Health and Human Services for the TP-PA confirmatory testing. (order code MHTP). There is no charge for this additional testing.

• In the setting of a positive syphilis antibody screening result and a negative RPR, a positive TP-PA result is consistent with either 1) past, successfully treated syphilis, 2) early syphilis with undetectable RPR titers, or 3) late/latent syphilis in patients who do not have a history of treatment for syphilis. Further historical evaluation is necessary to distinguish between these scenarios.
• In the setting of a positive syphilis antibody screening result and a negative RPR, a negative TP-PA result is most consistent with a falsely reactive syphilis antibody screen.  If syphilis remains clinically suspected, a second specimen should be submitted for testing.
• In the setting of a positive syphilis antibody screening result and a positive RPR, a negative TP-PA result is most consistent with a falsely reactive syphilis antibody and/or  RPR test due to non-specific antibodies affecting the immunoassay method (Roche). If syphilis remains clinically suspected, a second specimen should be submitted for testing.