Paper I
Question
Pathogenesis and lab diagnosis of syphilis.
Answer
Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subspecies pallidum, a thin, tightly coiled spirochete.
Pathogenesis The organism enters through breaches in skin or mucosa during sexual contact (or transplacentally in congenital syphilis), multiplies locally, and disseminates via lymphatics and blood early in infection. Disease progresses through stages:
- Primary syphilis — a painless indurated ulcer (chancre) at the site of inoculation, appearing ~3 weeks after exposure, with regional non-tender lymphadenopathy; heals spontaneously.
- Secondary syphilis — occurs weeks to months later due to haematogenous spread; generalized skin rash (including palms/soles), mucous patches, condylomata lata, generalized lymphadenopathy — reflects an immune-complex mediated vasculitis.
- Latent syphilis — asymptomatic seropositive stage.
- Tertiary syphilis — years later; gummas (granulomatous lesions), cardiovascular syphilis (aortitis, aneurysm), and neurosyphilis (tabes dorsalis, general paresis) — driven by a delayed-type hypersensitivity/obliterative endarteritis response to the few remaining organisms.
- Congenital syphilis — transplacental transmission causing stillbirth, or early/late congenital syphilis (Hutchinson’s triad in the late form).
Laboratory diagnosis
- Direct demonstration (from chancre/mucous patch exudate): dark-field microscopy for motile spirochetes; direct fluorescent antibody test (DFA-TP).
- Non-treponemal (screening) serology: VDRL and RPR — detect antibody (reagin) against cardiolipin antigen; cheap, used for screening and monitoring treatment response (titres fall with treatment), but can give biological false positives (malaria, leprosy, SLE, pregnancy).
- Treponemal (confirmatory) serology: TPHA (T. pallidum haemagglutination assay), FTA-ABS (fluorescent treponemal antibody-absorption), and treponemal ELISA — specific, remain positive for life even after treatment, so not useful for monitoring cure.
- CSF examination — for neurosyphilis, CSF-VDRL.
- PCR — on lesion exudate, increasingly used, especially when dark-field is unavailable.