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.

Historically, the serologic testing algorithm for syphilis included an initial nontreponemal screening test, such as the rapid plasma reagin (RPR) or the venereal disease research laboratory (VDRL) tests. Because these tests measure the host's antibody response to nontreponemal antigens, they 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 microhemagglutination assay (MHA-TP). Although the FTA-ABS and MHA-TP are technically simple to perform, they are labor intensive and require subjective interpretation by testing personnel.

Recently, EIA and multiplex flow immunoassays (MFI) were introduced to assess serologic response to Treponema pallidum. The Bio-Rad BioPlex Syphilis IgG assay is an example of MFI technology, which utilizes specific, treponemal antigens coated on microspheres for the detection of IgG-class antibodies to Treponema pallidum. The BioPlex Syphilis IgG assay is highly sensitive and specific (see Supportive Data), and allows for an objective interpretation of results. Due to several factors including the low prevalence of syphilis in the United States, the increased specificity of treponemal assays, and the objective interpretation of MFI and EIA technology, initial serologic testing by a treponemal-specific assay (eg, EIA or MFI) is now commonly performed in clinical laboratories. Specimens testing positive by the treponemal-specific assay are then tested by RPR to provide supplementary serologic data, as well as to provide an indication of the patient's disease state and history of treatment.

During early primary syphilis, the first antibodies to appear are of the IgM-class, with IgG-class antibodies reaching significant titers later in the primary phase. As the disease progresses into the secondary phase, IgG-class antibodies to Treponema pallidum reach peak titers, and may persist indefinitely regardless of the disease state or prior therapy.   

For prenatal syphilis screening, the IgG test is recommended. IgM testing should not be performed during routine pregnancy screening unless clinically indicated.

Treponema pallidum IgG antibodies persist indefinitely, regardless of the course of the disease. If treatment of an original Treponema pallidum infection was not monitored, a diagnosis of reinfection may actually represent either a resurgence of an inadequately treated earlier infection or persistent IgG antibodies from a resolved infection.