Clinical meaning
Treponema pallidum evades immune surveillance through antigenic variation of its outer membrane proteins and minimal surface antigen expression. The humoral immune response produces both non-treponemal antibodies (anti-cardiolipin, detected by RPR/VDRL) and treponemal-specific antibodies (detected by FTA-ABS, TP-PA). Non-treponemal titers correlate with disease activity and decline with treatment, while treponemal antibodies persist lifelong. The traditional screening algorithm uses non-treponemal tests first (RPR/VDRL), confirmed by treponemal tests. The reverse algorithm, increasingly adopted, screens with treponemal immunoassay (EIA/CIA) first. Discordant results (positive treponemal, negative non-treponemal) require TP-PA confirmation and may represent very early infection, late latent syphilis, or previously treated disease. The clinician must interpret complex serologic patterns, manage stage-appropriate treatment, evaluate for neurosyphilis, and manage syphilis in special populations including HIV co-infection and pregnancy.
Diagnosis & workup
Diagnostics & workup: - Apply traditional or reverse screening algorithm based on institutional protocol - Traditional: RPR/VDRL screen → confirmatory FTA-ABS or TP-PA - Reverse: treponemal EIA/CIA screen → reflex quantitative RPR → TP-PA if discordant - Interpret quantitative RPR titers: baseline and serial monitoring at 6, 12, 24 months - Order lumbar puncture with CSF analysis for neurosyphilis when indicated: neurological symptoms, treatment failure, HIV with late latent syphilis, RPR ≥1:32 with HIV - CSF findings in neurosyphilis: elevated WBC (>5 cells/μL), elevated protein, positive CSF-VDRL (highly specific but low sensitivity) - Order ophthalmologic examination for ocular syphilis: uveitis, optic neuritis