Change in Syphilis Testing Algorithm

Effective Monday, February 25, 2013, the University of Iowa Hospitals and Clinics core clinical chemistry laboratory will begin running an automated syphilis IgG immunoassay test and institute a new algorithm for syphilis testing.  The syphilis IgG screen is an entirely new method relative to the RPR (rapid plasma reagin).  The RPR detects non-treponemal antibodies (cardiolipin, cholesterol, and lecithin), whereas the new test detects IgG antibodies to T. pallidum proteins (15 kDa, 17 kDa, 47 kDa).

The new approach to syphilis is termed ‘reverse algorithm’ in that RPR is not done as first test (traditional algorithm) but as the confirmation (i.e., reverse of the traditional algorithm).  A negative syphilis IgG means that past and present syphilis infection is unlikely.  A positive syphilis IgG can indicate a past or present infection.  Specimens showing positive syphilis IgG will be reflexed automatically to RPR.  If there is discrepancy between syphilis IgG and RPR, TPPA (T. pallidum particle agglutination) is additionally performed.

Details on the new set of syphilis tests are as follows:

Test name Epic # Specimen
Syphilis IgG With Reflex Confirmation (Reverse Algorithm) LAB7824 Red top
Syphilis Treatment Follow-up (RPR with Titer) LAB7843 Red top

The interpretation is as follows using CDC guidelines:

Syphilis IgG RPR TPPA Interpretation
Negative (Not performed) (Not performed) Syphilis infection unlikely
Positive Positive (Not performed) Syphilis – recent infection likely
Positive Negative Positive Syphilis – past or present infection
Positive Negative Negative Infection unlikely – false positive syphilis IgG

There are several advantages of the reverse algorithm:
• Rapid turnaround time – within 2 hours of receipt in laboratory 24 hours a day, 7 days a week [current turnaround time is usually 2-4 days for RPR due to batching of tests]
• Avoids the false positives seen with RPR in autoimmune disease (e.g., lupus), infectious mononucleosis, viral pneumonia, and non-syphilis treponemal diseases (e.g., yaws)
• Detects early primary and latent infection that may be missed with traditional RPR screening

Some key points to remember with the new algorithm:
• Syphilis IgG can persist for many years.  A positive result does not necessarily indicate active disease.  In patients with positive syphilis IgG, the RPR provides information on active versus past infection.
• For assessing treatment efficacy in patients who have been treated for syphilis, “Syphilis Treatment Follow-up (RPR with Titer)” (LAB7843) should be ordered.  Successful treatment is generally indicated by a 4-fold reduction in RPR titer (e.g., 1:32 to 1:8).
• The syphilis IgG can have rare false positives.  These will be indicated by negative RPR and TPPA confirmation.  Given the generally low prevalence of syphilis in Iowa, false positives will be a significant fraction of positive screening test results regardless of testing method used (this has been seen with RPR and VDRL testing at UIHC over the last 10 years).
• Iowa Department of Public Health will investigate positive syphilis IgG results only after confirmatory testing results are available.  The full set of results guides investigation and follow-up.

To aid in the transition to the new syphilis algorithm, a pathologist will provide follow-up to all positive syphilis IgG results.

Questions should be directed to Matthew Krasowski, MD, PhD, medical director of the Clinical Chemistry Laboratory (384-9380,