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Why is a second test used to confirm a positive syphilis screening result?

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Scanning electron micrograph of Treponema pallidum, the spirochete bacterium that is the causative agent of syphilis. — syphilis Scanning electron micrograph of *Treponema pallidum*, the spirochete bacterium that is the causative agent of syphilis.

A second test is required to confirm a positive syphilis screening result because initial screening tests, such as the rapid plasma reagin (RPR) and the Venereal Disease Research Laboratory (VDRL) test, are not fully specific to syphilis.1

These nontreponemal tests detect reagin, an antibody-like substance that can produce "false positive" results due to reactions with various other conditions, including malaria, mononucleosis, or even influenza. Because of this lack of specificity, positive screening results are routinely followed by more complex and specific treponemal tests—such as the TPHA or FTA-ABS—which are designed to detect antibodies that specifically target Treponema pallidum, the spirochete responsible for the disease. In some cases, clinicians may also use dark-field microscopy to directly identify the organism in tissue samples to confirm the diagnosis.12