Syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum. Syphilis has diverse clinical manifestations and shares many clinical features with other treponemal and nontreponemal diseases (because of this, syphilis has been called “The Great Pretender”). The etiological agent, Treponema pallidum, cannot be cultured, and there is no single optimal alternative test.
Commonly used laboratory diagnostic testing available for syphilis are:
Direct Diagnosis
Direct laboratory methods for diagnosing syphilis include the detection of Treponema pallidum by microscopic examination of fluid or smears from lesions, histological examination of tissues, or nucleic acid amplification methods such as polymerase chain reaction (PCR). Tests used for the direct detection of Treponema pallidum are;
Dark-field microscopy
Dark-field microscopy is used to demonstrate the presence of motile Treponema pallidum in lesions or aspirates in early-stage (primary or secondary) syphilis before healing lesions.
Direct fluorescent antibody test for Treponema pallidum
Nucleic acid amplification (PCR based) methods
Indirect diagnosis/serological methods
It is based on serological tests for the detection of antibodies. Serological testing is the mainstay in the laboratory diagnosis and follow-up of syphilis. Serological tests fall into two categories: nontreponemal tests for screening, and treponemal tests for confirmation.
Nontreponemal tests
They measure both immunoglobulin (IgG and IgM) antiphospholipid antibodies formed by the host in response to lipoidal material released by damaged host cells early in infection and lipid from the cell surfaces of the treponeme itself. Commonly used nontreponemal tests are
Rapid plasma reagin (RPR) test
Toluidine red unheated serum test (TRUST)
Venereal Disease Research Laboratory (VDRL) test
Treponemal Tests
All treponemal tests use Treponema pallidum or its components as the antigen.
Treponemal tests are used as confirmatory tests to verify reactivity in non-treponemal tests. Once positive, treponemal tests remain positive throughout life with or without treatment, so these tests can not be used to know the response to treatment.
Commonly used treponemal tests are:
Fluorescent treponemal antibody absorption test (FTA-ABS) test
Treponema pallidum particle agglutination (TP-PA) test
Treponema pallidum Hemagglutination Assay (TPHA)
Flow-chart for laboratory diagnosis of syphilis
If lesion exudate or tissue is available, a direct examination is performed, followed by a nontreponemal serology test. A treponemal test then confirms a reactive nontreponemal test.
A confirmed serological test result indicates the presence of treponemal antibodies. Still, it does not indicate the stage of disease and, depending on the test, may not differentiate between past and current infections.
