Clinical Information

Syphilis is a disease caused by infection with the spirochete Treponema pallidum subspecies pallidum. The infection is systemic, and the disease is characterized by periods of latency. These features, together with the fact that T pallidum cannot be isolated in culture, mean that serologic techniques play a major role in the diagnosis and follow-up of treatment for syphilis.

Syphilis is categorized by an early primary infection in which patients may have nonspecific symptoms and, potentially, genital lesions. Patients tested by serology during the primary phase may be negative for antibodies, especially if testing is performed during the first 1 to 2 weeks after symptom onset. As the disease progresses into the secondary phase, antibodies to T pallidum reach peak titers and may persist indefinitely regardless of the disease state or prior therapy. Therefore, detection of antibodies to nontreponemal antigens, such as cardiolipin (a lipoidal antigen released by host cells damaged by T pallidum) may help to differentiate between active and past syphilis infection. Non-treponemal antibodies are detected by the rapid plasma reagin (RPR) assay, which is typically positive during current infection and negative following treatment or during late/latent forms of syphilis.

Historically, the serologic testing algorithm for syphilis included an initial nontreponemal screening test, such as the RPR or VDRL tests. Because these tests measure the host's antibody response to nontreponemal antigens, they may lack specificity. Therefore, a positive result by RPR or VDRL requires confirmation by a treponemal-specific test, such as the T pallidum particle agglutination (TP-PA) assay. Although technically simple to perform, the TP-PA assay is labor intensive and requires subjective interpretation by testing personnel.

Due to the increased specificity of treponemal assays and the objective result interpretation of automated treponemal immunoassays, many large clinical laboratories have switched to screening for syphilis using a reverse algorithm. Per this algorithm, serum samples are first tested by an automated treponemal immunoassay, and positive samples are reflexed to the RPR assay to provide an indication of the patient's disease state and history of treatment. For specimens testing positive by the screening treponemal assay and negative by RPR, a second treponemal test (eg, TP-PA) is performed. The results of TP-PA assist in determining whether the results of a screening treponemal test are truly or falsely positive.