Syphilis is caused by the spirochaete Treponema pallidum. Syphilis is staged as 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 (also referred to as tertiary syphilis). There is currently an epidemic of syphilis among men who have sex with men (MSM) in Australia. A high proportion of such men are also HIV positive.

  • Demonstration of spirochaetes by dark field microscopy in primary chancres or mucous membrane lesions of secondary syphilis. The lesion is cleaned with saline, squeezed gently, and a drop of expressed exudate placed onto a glass slide. If dark-field 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 spirochaetes.
  • PCR from the lesion may be positive when dark ground is negative.  A positive PCR result from a lesion may precede development of any or all of the serological markers
  • Enzyme immunoassay for anti-T. pallidum antibodies is 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 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.
  • A non-reactive test 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 Total Antibody, 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.
  • Occasionally RPR and EIA tests (and rarely TPPA/TPHA) may have false positive results in healthy people without syphilis infection.  Interpretation of results such as these should be discussed with an Sexual Health Physician, Infectious Disease Physician or Pathologist if indicated.

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 or procaine penicillin are the preferred treatments. Benzathine penicillin requires fewer injections and is used most commonly in practice. Any alternatives to these should be discussed with a specialist and used with caution.

Non-penicillin regimens have not been thoroughly evaluated and should be used only when penicillin is contraindicated. 

Penicillin-allergic pregnant women with syphilis pose additional management problems, and should be managed in consultation with an experienced specialist. See MSHC treatment guideline on syphilis in pregnancy.The possibility of neurosyphilis should be considered in all cases of syphilis.  Cases with abnormal neurological or ophthalmological symptoms or signs should not be treated until neurosyphilis has been excluded or confirmed by lumbar puncture and CSF examination.  Treatment of cranial neurosyphilis may require prior treatment with steroids to prevent worsening of symptoms.

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.


The RPR titre should be repeated on the day of treatment. Men who have sex with men 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, if raised, the RPR titre generally 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. 

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. 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 October 2014