Question
Laboratory diagnosis of syphilis
Answer
Laboratory diagnosis of syphilis (caused by Treponema pallidum)
1. Direct demonstration (in early primary syphilis, from chancre exudate):
- Dark-field microscopy — direct visualization of motile spirochetes; the T. pallidum organism cannot be cultured on artificial media, making this and molecular methods the only means of direct detection.
- PCR — increasingly used for direct detection from lesion exudate, particularly where dark-field microscopy is unavailable.
2. Non-treponemal (screening) tests: detect non-specific antibody (reagin) against a cardiolipin-lecithin-cholesterol antigen.
- VDRL (Venereal Disease Research Laboratory) test.
- RPR (Rapid Plasma Reagin) test. Both are inexpensive, useful for screening and for monitoring treatment response (titres decline with successful treatment, unlike treponemal tests), but can give false positives (autoimmune disease, pregnancy, other infections), requiring confirmation.
3. Treponemal (confirmatory) tests: detect specific antibody against T. pallidum antigens.
- TPHA (Treponema pallidum Haemagglutination Assay).
- FTA-ABS (Fluorescent Treponemal Antibody-Absorption test) — historically the gold-standard confirmatory test.
- TPPA (Treponema pallidum Particle Agglutination assay). More specific than non-treponemal tests, but generally remain positive for life even after successful treatment, so not useful for monitoring treatment response.
4. CSF examination: for suspected neurosyphilis — CSF VDRL (highly specific though insensitive) along with CSF cell count/protein.
Testing algorithm: a reactive non-treponemal screening test (VDRL/RPR) is confirmed with a treponemal test (TPHA/FTA-ABS/TPPA); some laboratories use a “reverse algorithm,” starting with an automated treponemal test (EIA/CLIA) followed by a non-treponemal test for titre-based monitoring.
Note on congenital syphilis: diagnosed by comparing infant and maternal non-treponemal titres (a fourfold or greater rise in the infant relative to the mother suggests active congenital infection, since maternal IgG can passively cross the placenta) and by clinical/radiographic findings.