Background Information
Aetiology
Syphilis is caused by the spirochete bacterium Treponema pallidum
The most common route of transmission is sexual transmission during direct contact. Less commonly, congenital syphilis results from vertical transmission during pregnancy (NB syphilis is routinely screened in antenatal care).
Clinical Features
Classic 4-stages of syphilis:
| Stage | Timing | Clinical features |
|---|---|---|
| Primary syphilis | Onset: 9-90 days after exposure (mean: 21 days)
Resolves spontaneously over 3-8 weeks |
Chancre
Painless lymphadenopathy |
| Secondary syphilis | Onset: 3-10 weeks after initial chancre appearance
Resolves over 3-12 weeks if untreated, but may recur |
Skin lesions (in ~90% cases)
Mucous patches
Systemic features (fever, headache, malaise, generalised lymphadenopathy, hepatitis, splenomegaly, glomerulonephritis, myalgia) Early neurosyphilis (in 1-2% cases)
|
| Latent syphilis | Early latent: <2 years from initial infection
Late latent: >2 years from initial infection |
Clinically asymptomatic but presence of serological evidence of infection |
| Tertiary syphilis | 20-40 years after initial infection | Gummatous syphilis
Cardiovascular syphilis
Neurosyphilis
|
Chancre is different from chancroid:
| Feature | Chancre | Chancroid |
|---|---|---|
| Cause | Syphilis | Haemophilus ducreyi |
| Number of ulcers | Single | Multiple |
| Pain | Painless | Painful |
| Ulcer appearance | Clear base and well-defined margin | Ragged, irregular, purulent base |
| Lymph nodes | Painless lymphadenopathy | Painful lymphadenopathy (buboes) |
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)
Due to high rates of co-infection, it is important to test patients diagnosed with syphilis for HIV as well.
Serology Tests
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, it 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)
Serology Interpretation
| 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 of false +ve can be remembered with the mnemonic 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 non-pathogenic 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 (<2 years from initial infection)
1st line: benzathine penicillin G IM single dose
2nd line:
- Procaine penicillin G IM once daily for 10 days
- Doxycycline orally twice daily for 14 days
- Ceftriaxone IM/IV once daily for 10 days
Late Syphilis
Late syphilis includes:
- Late latent disease (>2 years from initial infection)
- Tertiary syphilis
1st line: benzathine penicillin G IM 3 doses (once weekly)
Prednisolone starting 24 hr before antibiotics is recommended to prevent Jarisch-Herxheimer reaction
Neurosyphilis
1st line: procaine penicillin G 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 IM single dose
- Alternative: doxycycline 100 mg PO BD for 14 days
References