neobookRx

Syphilis Serology and Treatment

Sexually Transmitted Infections

Medicine Treatment

Referral


ICD-10 Code: A53.9

Syphilis serology

  • The Rapid Plasmin Reagin (RPR) measures disease activity, but is not specific for syphilis
  • False RPR-positive reactions may occur, notably in patients with connective tissue disorders (false positive reactions are usually low titre <1:8)
  • For this reason, positive RPR results should be confirmed due to syphilis by further testing of the serum with a specific treponemal test, e.g.:
    • Treponema pallidum haemagglutination (TPHA) assay
    • Treponema pallidum particle agglutination (TPPA) assay
    • Fluorescent Treponemal Antibody (FTA) assay
    • Treponema pallidum ELISA
    • Rapid treponemal antibody test (TPAb)

Screening can also be done the other way around starting with a specific treponemal test followed by a RPR in patients who have a positive specific treponemal test. This is sometimes referred to as the “reverse algorithm”.

  • Once positive, specific treponemal tests generally remain positive for life and therefore the presence of specific treponemal antibodies cannot differentiate between current and past infections
  • A person with previously successfully treated syphilis will retain lifelong positive specific  treponemal test results

The RPR can be used:

  • To determine if the patient’s syphilis disease is active or not,
  • To measure a successful response to therapy (at least a fourfold reduction in titre, e.g. 1:256 improving to 1:64), or
  • To determine a new re-infection

Some patients, even with successful treatment for syphilis, may retain life-long positive RPR results at low titres (≤1:8), which do not change by more than one dilution difference (up or down) over time (so-called serofast patients).


Note:
- Up to 30% of primary syphilis cases, i.e. those with genital ulcers may have a negative RPR
- The RPR is always positive in the secondary syphilis stage and remains high during the first two (infectious) years of syphilis


LoE:II275

For syphilis treatment in pregnancy, See: Syphilis in pregnancy

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MEDICINE TREATMENT

Early syphilis treatment

Check if treated at initial visit

  • Benzathine benzylpenicillin, IM, 2.4 MU immediately as a single dose
    • Dissolve benzathine benzylpenicillin, IM, 2.4 MU in 6 mL lidocaine 1% without epinephrine (adrenaline)

In penicillin-allergic patients if benzathine benzylpenicillin is unavailable: 
ICD-10 Code: Z88.0

  • Doxycycline, oral, 100 mg twice daily for 14 days

LoE:III276

If pregnant and benzathine benzylpenicillin is unavailable:

  • Amoxicillin, oral, 1 g, 8 hourly for 14 days (Doctor initiated)

AND

  • Probenecid. oral 250 mg, 8 hourly for 14 days (Doctor initiated)

If penicillin-allergic and pregnant: Refer for penicillin desensitisation

LoE:III277

Late/ late latent syphilis treatment

Check if treatment was commenced at initial visit.

  • Benzathine benzylpenicillin, IM, 2.4 MU once weekly for 3 weeks
    • Dissolve benzathine benzylpenicillin, IM, 2.4 MU in 6 mL lidocaine 1% without epinephrine (adrenaline)

In penicillin-allergic patients or if benzathine benzylpenicillin is unavailable 
ICD-10 Code: Z88.0

  • Doxycycline, oral, 100 mg, 12 hourly for 30 days

LoE:III278

If pregnant and benzathine benzylpenicillin is unavailable:

  • Amoxicillin, oral, 1 g 8 hourly for 28 days (Doctor initiated)

 AND 

  • Probenecid, oral 250 mg, 8 hourly for 28 days (Doctor initiated)

If penicillin-allergic and pregnant: Refer for penicillin desensitisation

LoE:III279

REFERRAL

  • Tertiary syphilis: neurosyphilis, cardiovascular syphilis; gummatous syphilis
  • Clinical congenital syphilis

Standard Treatment Guidelines and Essential Medicines List for South Africa, Primary Healthcare Level, 2024 Edition

Drugs mentioned

ICD-10 codes

NeoHealth® ID 19092 · updated 8/12/2025