Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum subspecies pallidum. The route of transmission is almost always through sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero.

Two types of antibody responses occur when the body comes into contact with Treponema pallidum:

(1) Non-specific (anti-cardiolipin): While non-specific antibodies occur in the majority of those infected, many other conditions can give rise to false positive results, yielding an overall specificity for this analyte of about 50% in the general population. One of the major reasons for the continued use of non-specific tests (RPR, VDRL, and Wasserman etc.) is based on the observation that with antibiotic treatment, a significant decrease in titer usually takes place. This is therefore seen as an indicator of the effectiveness of the treatment. These assays are characterized as inexpensive and with high sensitivity, but low specificity.

(2) Specific (anti-treponemal): Treponemal specific tests are based on the use of treponemal antigens in the assay. Prior to the HIV era, treponemal tests were largely used to confirm positive results obtained by non-specific screen tests. Although older treponemal tests (such as MHA-TP and FTA-Abs) are generally considered reliable for past and current infection (regardless of treatment), their specificity is limited due to the presence of non-specific antigens in preparations of in vivo cultivated T. pallidum. Unless applied during early primary syphilis, treatment does not significantly affect the treponemal antibody status; hence no assumptions about efficacy of treatment or staging of disease can be made. The assay methods described above, all require visual interpretation and are limited to subjective interpretation by the operator. The assays are highly specific, but may lack some sensitivity.

The use of the more specific Enzyme ImmunoAssay (EIA) has received wide spread acceptance due to the colorimetric results in a 96 well microplate format that can be automated and read objectively using a spectrophotometer. The use of recombinant treponemal antigens in Total Antibody ELISA has enhanced both sensitivity and specificity further.

Algorithm approaches to testing for Syphilis differ globally but essentially fall into two categories:


· Screening: Non-treponemal test, e.g. RPR or VDRL assay.

· Supplemental test: Treponemal test, e.g. TP-PA or ELISA

· Confirmation: Treponemal test, e.g. FTA-Abs or Western Blot


· Screening: Treponemal test, e.g. TP-PA, or ELISA

· Supplemental test: Non-treponemal test, e.g. RPR or VDRL assay.

· Confirmation: Treponemal test, e.g. FTA-Abs or Western Blot.