Syphilis
BASHH Syphilis 2024: Updated Guideline. Last updated Sep 2024.
NICE CKS Syphilis. Last updated Mar 2025.
Guidelines
Investigation and Diagnosis
Screening Tests
Screening test of choice: EIA/CLIA (treponemal tests)
If screening test is +ve →
- Confirm with a different treponemal test and a second specimen
- Perform quantitative non-treponemal test (RPR test)
Serology Interpretation
There are 2 main serology test types:
| Test type | Examples | Antibody detected | Use and interpretation |
|---|---|---|---|
| Treponemal | EIA, CLIA, TPHA, TPLA | IgM/IgG antibodies specific to T. pallidum antigens | Confirms active infection.
BUT once +ve, remains +ve lifelong even after successful treatment. Therefore, cannot distinguish between active and past infections |
| Non-treponemal | VDRL, RPR | Antibodies against cardiolipin-lecithin-cholesterol complexes released from damaged host cells | Non-treponemal tests are quantitative tests (reported as titre) used for:
Non-treponemal tests usually takes ~6 weeks after infection to be +ve. |
To differentiate between treponemal and non-treponemal tests:
- Treponemal tests all end with the letter “A” (EIA, CLIA, TPHA, TPLA)
- Non-treponemal tests all contain the letter “R” and do NOT contain the letter “A” (VDRL, RPR)
Interpretation of paired serology tests:
| Treponemal test | Non-treponemal test | Interpretation |
|---|---|---|
| +ve | +ve | Active, untreated syphilis |
| +ve | -ve | Successfully treated syphilis or very early primary syphilis |
| -ve | +ve | False +ve
Causes (false +ve non-treponemal test) → PAIN
|
| -ve | -ve | No syphilis or very early primary syphilis |
Syphilis serology has a window period of up to 90 days (3 months), therefore a -ve test within 3 months of infection cannot exclude syphilis.
Key points regarding syphilis serology interpretation:
- Treponemal tests remain +ve for life after infection, even after treatment. Should only be used to aid diagnosis, not monitor treatment
- Non-treponemal tests reflect disease activity and often return to -ve after successful treatment.
Laboratory Diagnosis
Direct detection
Direct detection of T.pallidum is indicated when a patient presents with a mucocutaneous lesion consistent with syphilis (e.g., chancre/condyloma)
The following can be used:
- Dark ground microscopy (on possible chancres) – direct visualisation of T. pallidum spirochetes
- High specificity, but moderate sensitivity (negative result does NOT exclude syphilis) [Ref]
- Should NOT be used for oral lesions (i.e., oral chancre) as it cannot differentiate T.Pallidum from nonpathogenic oral spirochaetes
- PCR testing (suitable for oral and other lesions)
CSF Analysis
Where there is clinical evidence of neurological involvement, CSF analysis is required (in addition to serology) for a diagnosis of neurosyphilis
CSF examination must include the following:
- Total protein (typically ↑)
- White cell count (typically ↑)
- A Non-treponemal test (reactive)
Management
Pharmacological Management
Early Syphilis
Early syphilis includes:
- Primary syphilis
- Secondary syphilis
- Early latent syphilis
1st line: benzathine penicillin G 2.4 MU IM single dose
2nd line:
- Procaine penicillin G 600,000 units IM once daily for 10 days
- Doxycycline 100 mg orally twice daily for 14 days
- Ceftriaxone 500 mg–1 g IM/IV once daily for 10 days
Late Syphilis
Late syphilis includes:
- Late latent disease
- Tertiary syphilis
1st line: benzathine penicillin G 2.4 MU IM 3 doses (once weekly)
Prednisolone 40-60mg starting for 3 days, starting 24 hr before antibiotics is recommended to prevent Jarisch-Herxheimer reaction
Neurosyphilis
1st line: procaine penicillin G 1.8-2.4 MU IM OD + probenecid 500mg QDS for 14 days
Benzathine penicillin G is avoided due to poor CSF penetration
Follow Up
RPR test (non-treponemal test) is recommended to monitor treatment effect:
- Measure at baseline
- Measure at 3, 6, 12 months post treatment
- If titres remain reactive / do not decline successfully (see below) monitoring is continued every 6 months until non-reactive or stable low titre (“serofast”)
Interpretation:
- ≥ 4‑fold fall in titre (e.g. RPR 1:32 → 1:8) suggests successful treatment
- Sustained ≥ 4‑fold rise suggests reinfection or treatment failure
Treponemal tests remain +ve for life, do NOT use them to assess treatment response.
Partner Notification and Management
Look back intervals (for sexual contacts):
- Primary syphilis: contacts in the past 3 months
- Secondary / early latent: extend to 2 years
- Tertiary syphilis: all partners should be clinically assessed and undergo serological testing (& treated based on results); no-specific look-back interval mentioned
Epidemiological (prophylactic) treatment indicated in:
- Asymptomatic contacts of early syphilis (and repeat screening at 12 weeks post-exposure)
- Asymptomatic contacts during the window period
If indicated, epidemiological/prophylactic treatment is the same as early syphilis infection:
- 1st line: benzathine penicillin G 2.4 MU IM single dose
- Alternative: doxycycline 100 mg PO BD for 14 days
References
Original Guideline