Nontreponemal tests for syphilis

Nontreponemal tests refer to a class of syphilis diagnostics that detect infection by indirect markers of infection. Nontreponemal Tests detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete. In contrast treponemal tests look for antibodies that are a direct result of the infection thus, anti-treponeme IgG, IgM and to a lesser degree IgA

Nontreponemal tests

Syphilitic infection leads to the production of nonspecific antibodies that react to cardiolipin. This reaction is the foundation of “nontreponemal” assays such as the VDRL (Venereal Disease Research Laboratory) test and Rapid Plasma Reagin (RPR) test. Both these test are flocculation type tests that use an antigen-antibody interaction. The complexes remain suspended in solution and therefore visible due to the lipid based antigens.

All nontreponemal tests measure immunoglobulins G (IgG) and M (IgM) anti-lipid antibodies formed by the host in response both to lipoidal material released from damaged host cells early in infection and to lipid from the cell surfaces of the treponeme itself.

These nontreponemal tests are widely used for qualitative syphilis screening. However, their usefulness is limited by decreased sensitivity in early primary syphilis and during late syphilis, when a large number of untreated patients will be negative by these methods.

With nontreponemal tests, false-positive reactions can occur for a large number of reasons, the most common of which is other infections, both viral and bacterial. Additionally these tests may show false-negative when the patient’s antibody titer is very high due to a hook effect (also called a prozone effect). Because of the issues with false positives, confirmation with a second treponemal test that is specific for T. pallidum antibodies is recommended.

The tests are relatively simple to perform and interpret, and can allow rapid return of results and are very cheap. However, they still require some laboratory equipment (especially the VDRL) and trained personnel to perform and interpret test reactions.