Clinical Information

Syphilis is a disease caused by infection with the spirochete Treponema pallidum. The infection is systemic and the disease is characterized by periods of latency. These features, together with the fact that Treponema 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 non-specific symptoms, and potentially, genital lesion(s). 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 Treponema 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 Treponema pallidum) may help to differentiate between active and past syphilis infection. Nontreponemal 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.   

For prenatal syphilis screening, the syphilis IgG test (SYPGN / Syphilis Antibody, IgG, Serum) is recommended. Testing for IgM-class antibodies to Treponema pallidum should not be performed during routine pregnancy screening unless clinically indicated.

Historically, the serologic testing algorithm for syphilis included an initial nontreponemal screening test, such as the RPR or the venereal disease research laboratory (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 fluorescent treponemal antibody-absorbed (FTA-ABS) or the Treponema pallidum particle agglutination (TP-PA). Although the FTA-ABS and TP-PA are technically simple to perform, they are labor intensive and require subjective interpretation by testing personnel.

Due to the low prevalence of syphilis in the United States, the increased specificity of treponemal assays, and the objective interpretation of automated treponemal EIA and multiplex flow immunoassays (MFI), 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 assay (eg, EIA or MFI). Specimens testing positive by these assays are then reflexed to the RPR assay to provide an indication of the patient's disease state and history of treatment. Recently, the Centers for Disease Control and Prevention recommended that specimens testing positive by a screening treponemal assay and negative by RPR be tested by a second treponemal test (eg, TP-PA). The results of TP-PA assist in determining whether the results of a screening treponemal test are truly or falsely positive.