Syphilis testing can be a challenging exercise. Even the ‘Positive’ CDC testing algorithms terminate with ‘Presumptive diagnosis of Syphilis’ which sounds frustratingly ambiguous.

Syphilis tests are available in two categories: treponemal tests (antibody tests to the organism itself, Treponema pallidum) and non-treponemal tests (such as RPR, which detects non-treponemal reagin antibodies; commonly seen with syphilis, but present in many other disease and non-disease states).  

A presumptively positive diagnosis of syphilis requires TWO positive tests, ideally from each category (treponemal and non-treponemal tests). Most clinicians are familiar with the ‘Traditional Algorithm,’ which is as follows:

  • RPR as the primary screen (the non-treponemal test), which if positive is followed by…
  • A treponemal, confirmatory test such as FTA-ABS, TP-PA or Syphilis Antibody testing. If both the non-treponemal and treponemal tests are positive, a presumptive diagnosis of syphilis can be made. If the confirmatory/treponemal test is negative, the initial RPR is deemed to be a false positive (which is not uncommon).
    • The list of potential causes of a false positive RPR is long, and includes pregnancy, aging (>10% of people over 80 will develop a positive RPR) and even immunizations (including flu shots). See the table below for a more complete list.

However, aside from the more commonly known FTA-ABS there are additional, new tests to consider as well as the ‘Reverse Algorithm.’

The ‘Reverse Algorithm’ begins with a Treponemal test instead of RPR. At PathAdvantage, we use the Syphilis Total (IgG and IgM) Antibody test, which is shown to be just as sensitive as RPR, while being much more specific. If positive, this is then confirmed by RPR (Non-treponemal) testing. A graphic of this reverse algorithm is below (sourced by AACC). 

The caveat to this algorithm is that if the Syphilis Total Antibody test is positive and RPR is negative, this may mean a (rare) false positive Syphilis Total Antibody test, or a resolved (RPR negative) case of Syphilis. To help resolve this dilemma, a ‘tie-breaker’ second treponemal test is recommended—usually using TP-PA (Treponema Pallidum Particle Agglutination).  

If this third test (TP-PA) is positive, this supports true exposure to Syphilis (resolved.) If negative, this favors an uncommon (<1%) false positive Syphilis Total Antibody test.  

At PathAdvantage, as we deal with a tremendously high pregnant population, we prefer the Reverse algorithm over the Traditional algorithm, as using the Syphilis Total (IgG and IgM) Antibody test first, yields much fewer false positive test results.