Syphilis is caused by the spirochaete Treponema pallidum. Syphilis is categorized into early infection (less than 2 years duration), which includes primary, secondary and early latent disease, and late infection (more than 2 years duration), which includes late latent and late clinical disease. There is currently an epidemic of syphilis among men who have sex with men (MSM) in Australia. A high proportion of such men are HIV positive or taking pre-exposure prophylaxis against HIV. There is also an increasing incidence of gonorrhoea in heterosexual populations, including sex workers.


Detection of spirochaetes in primary chancres or moist lesions of secondary syphilis.

  • The lesion is cleaned with saline, squeezed gently, and a drop of expressed exudate placed onto a glass slide. If darkfield microscopy is immediately available, motile treponemes can be seen directly in the wet preparation. False positive darkfield microscopy findings are uncommon, but do occur, presumably due to other commensal spirochaetes. False negative results are common, particularly from older crusted lesions, or where there has been prior systemic or topical antibiotic treatment.
  • Polymerase chain reaction (PCR) for detection of T pallidum DNA from lesion swabs is much more sensitive than darkfield microscopy, and is highly specific.

Specific treponemal antibody tests include Enzyme (or Chemi-luminescence immunoassay (EIA or CLIA) and Treponema pallidum particle agglutination (or haemagglutination) assays (TPPA/TPHA).These are virtually always positive at the time of presentation of primary chancres but the RPR is negative in around 30% of cases. RPR will almost always be reactive 6 weeks after recent infection and is always reactive in secondary syphilis. The presence of anti-T pallidum IgM is a strong, but not infallible, indicator of early infection.

Non-reactive serology after 3 months excludes the possibility of syphilis. The RPR is used to assess the activity of disease. In early syphilis where the RPR titre is raised, the RPR titre falls following adequate treatment.
Even without treatment, the RPR titre gradually declines over years.

Specific treponemal tests (EIA/CLIA Total Antibody, TPPA/TPHA, FTA-Abs) generally remain positive for life in most cases, regardless of treatment, though cases of primary syphilis treated early can lose all serological markers.


A high proportion of cases of early and infectious syphilis are asymptomatic. All men who have sex with men should be offered serology for syphilis at least once a year. This should be more frequent in those at higher risk: 3-6 monthly. HIV infected men who have sex with men should have serology for syphilis included in the routine bloods taken for monitoring HIV, generally every 3 to 6 months. Screening and early detection of syphilis will reduce the duration of infectiousness of syphilis and therefore transmission.


The choice of treatment in cases of syphilis depends on clinically staging the infection into early and late syphilis as defined above.

Benzathine penicillin is the preferred treatment. Procaine penicillin is effective but requires daily injections. Non-penicillin regimens have not been thoroughly evaluated and should be used only when penicillin is contraindicated. Any alternative to penicillins should be discussed with a specialist and used with caution.

Penicillin-allergic pregnant women with syphilis pose additional management problems, and should be managed in consultation with an experienced specialist.

The possibility of neurosyphilis should be considered in all cases of syphilis. Cases with abnormal neurological or ophthalmological symptoms or signs should be referred for consideration of lumbar puncture, CSF examination and possible admission for daily IV penicillin. Treatment of neurosyphilis may require prior treatment with steroids to prevent worsening of symptoms. See the separate Guideline on neurosyphilis.

Early syphilis
  • Benzathine penicillin G 1.8g IM single dose OR 
  • Procaine penicillin G 1.0g IM daily for 10 days OR 
  • Doxycycline 100mg twice daily for 14 days (if allergic to penicillin and not pregnant)
Late latent syphilis
  • Benzathine penicillin G 1.8 g IM, 3 doses given one week apart OR 
  • Procaine penicillin G 1.0g IM daily for 15 days OR 
  • Doxycycline 100mg twice daily for 28 days (if allergic to penicillin and not pregnant)
Cardiovascular syphilis and neurosyphilis
  • Treatment for these should be discussed with a specialist

Patients being treated for early syphilis should be warned of the possibility of the Jarisch- Herxheimer reaction which often occurs several hours after the first injection of penicillin. Patients should be reassured that this is transient and the symptoms can be relieved with paracetamol or aspirin. This reaction is not a sign of an allergy to penicillin.


The RPR should be repeated on the day of treatment to establish the baseline titre. MSM who have been treated for early syphilis are at risk of re-infection and should be strongly encouraged to attend 3 monthly for syphilis testing as part of comprehensive STI screening. This should include HIV testing if they are HIV negative.
Following treatment, the RPR titre, if raised, should fall fourfold (2 dilutions) within 6 months.

If the RPR titre falls satisfactorily following treatment only to increase again, this signifies re-infection. Where the RPR titre fails to fall, reinfection or treatment failure and CSF examination to exclude asymptomatic neurosyphilis should be considered.

Patients who have not received the standard treatment for syphils (i.e. benzathine penicillin or procaine pencillin) should have follow up syphilis serology at 3 month and 6 months to ensure a satisfactory decrease in RPR titre.

Syphilis and HIV infection

Patients with syphilis should be tested for HIV. The possibility of neurosyphilis should always be considered in the differential diagnosis of neurological disease in HIV infection. Case reports have suggested that treatment failures may be more common when syphilis occurs in HIV positive patients. However, the recommended treatment regimens in HIV positive persons are the same as for HIV uninfected persons.


Partner notification should be discussed with patients diagnosed with syphilis with a low threshold for referral to PNOs. Consider referring patients to the Let Them Know website ( which is designed to support patients to undertake partner notification and which facilitates sending of SMS and email messages to partners. Partners should be contacted, tested and offered treatment with a single dose of benzathine penicillin without waiting for the results of serology which can be negative in early infection. Doxycycline can be used if contacts are penicillin allergic. Individuals should abstain from sex with their partners until 7 days after both have received treatment.

The content of these treatment guidelines is for information purposes only. The treatment guidelines are generic in character and should be applied to individuals only as deemed appropriate by the treating practitioner on a case by case basis. Alfred Health, through MSHC, does not accept liability to any person for the information or advice (or the use of such information or advice) which is provided through these treatment guidelines. The information contained within these treatment guidelines is provided on the basis that all persons accessing the treatment guidelines undertake responsibility for assessing the relevance and accuracy of the content and its suitability for a particular patient. Responsible use of these guidelines requires that the prescriber is familiar with contraindications and precautions relevant to the various pharmaceutical agents recommended herein. 

Last Updated August 2018