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Syphilis

BASHH Syphilis 2024: Updated Guideline. Last updated Sep 2024. NICE CKS Syphilis. Last updated Mar 2025.

Guidelines

Screening test of choice: EIA/CLIA (treponemal test)


If screening test is +ve →
  • Connfirm with a different treponemal test and second specimen
  • Perform quantitative PRP test (non-treponemal test)
 

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:
  • Screening and disease activity
  • Monitor treatment response

Non-treponemal tests usually takes ~6 weeks after infection to be +ve.
   

To differentiate between treponemal and non-treponemal tests:

  • Treponemal tests all ends with the letter "A" (EIA, CLIA, TPHA, TPLA)
  • Non-treponemal tests all contains 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 active syphilis
+ve -ve Successfully treated syphilis 

(or very early primary syphilis)
-ve +ve False +ve

(Common causes include antiphospholipid syndrome, viral infections, pregnancy, IVDU)
-ve -ve Syphilis unlikely

(If high clinical suspicion and exposure <2 weeks → re-test after 2 weeks)
 

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 diseae activity and often return to -ve after successful treatment.

The following is recommended to demonstrate T. pallidum:

  • Dark ground microscopy (on possible chancres) - direct visualisation of T. pallidum spirochetes
  • PCR testing (suitable for oral and other lesions)

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

For late latent disease / cardiovascualr syphilis / gummatous 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

For neurosyphilis (including early neurological involvement):
  • 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

RPR test (non-treponemal test) is recommended to monitoring treatment effect
  • Measure at baseline
  • Measure at 3, 6, 12 months post treatment, if still reactive then every 6 months until non-reactive of 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 remains +ve for life, do NOT use them to assess treatment response.

Look back intervals:
  • Primary syphilis: contacts in the past 3 months
  • Secondary / early latent: extend to 2 years

Epidemiological treatment indicated in:
  • Asymptomatic contacts of early syphilis (anmd repeat screening at 12 weeks post-exposure)
  • Asymptomatic contacts during window period

References

Author: Adams Lau
Reviewer:
Last edited: 04/05/25