Interpretation of syphilis serological results is one of the more common reasons for referrals to infectious disease physicians in Singapore. Back in the restructured hospitals, syphilis serology was usually performed as part of a panel for patients with altered mental status, or occasionally for those with cerebrovascular accidents or peripheral neuropathy (because neurosyphilis may present with such features). In the private hospitals, I was astonished to be called by colleagues who rarely – if ever – have to manage such patients (i.e. cardiologists, surgeons, etc). But I quickly found out that this is because syphilis serological testing is part of many health screening packages, probably because it can be done very cheaply and easily, and appears to “value-add” to the package. Here are the health screening packages from SATA CommHealth and Parkway Shenton as examples.

One of the most comprehensive descriptions of syphilis laboratory testing, including causes of false positive tests and sensitivity/specificity of each test, was written by Dr. Sam Ratnam and published in the Canadian Journal of Infectious Diseases & Medical Microbiology in 2005 (article available free). I provide a simplified table below:

Combinations of syphilis serological testing results and their interpretations.

Treponemal antibody tests, as the name suggests, attempt to detect antibodies produced by the body against the bacterium Treponema pallidum (Note however that there are actually 4 subspecies of T. pallidum: T. pallidum subspecies pallidum causes the disease we know as syphilis and is globally present; T. pallidum subsp. carateum causes the disease called “pinta” mainly in South America; T. pallidum subsp. endemicum causes the disease “bejel” in the eastern Mediterranean and West African region; and T. pallidum subsp. pertenue causes “yaws” in the tropics – and all four is routinely diagnosed using the same serological tests described here). There are many different tests available commercially, but these all share similar characteristics:

• Highly specific for syphilis (therefore can be used for confirmation of diagnosis or for screening purposes).
• The antibodies tend to be detectable slightly earlier than those for the non-treponemal antibody tests (therefore in primary syphilis, these may be the only antibodies present depending on the time of testing).
• Tend to be present “for life” (hence the positive result cannot be correlated with stage of disease or its activity or the success of therapy), even after treatment.

The non-treponemal antibody tests detect the presence of antibodies against tissue substances released by cells damaged by syphilis. There are mainly two tests available in Singapore, the venerable venereal disease laboratory research (VDRL) and the newer rapid plasma reagin (RPR) test. For practical purposes (unless one works in the laboratory!), they are the same and interpreted similarly. Because they are non-specific, these antibodies can be detected in other conditions such as autoimmune diseases, other infections, and even in cancer or pregnancy. They can, however, be used for monitoring the progress of treatment of syphilis (by tracking the titres of either VDRL or RPR). Very rarely, there are reports of cases of neurosyphilis with negative serum VDRL (or RPR), hence a certain degree of clinical judgment is required when reviewing the results of the tests and correlating them back to the patient. In the vast majority of cases, say – evaluating stroke patients or those with altered mental status – a negative non-treponemal antibody test (VDRL or RPR) coupled with a positive treponemal antibody test (TPPA, TPHA, FTA-ABS, EIA, etc.) means that the patient in question has latent syphilis but not neurosyphilis. In the well patient with a similar result on health screening, it means latent syphilis and a careful history should be taken to determine whether the patient had previously been diagnosed with syphilis, and/or has received treatment for it.