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 an ongoing epidemic of syphilis among men who have sex with men (MSM) in Australia and since 2015 increasing cases among heterosexual males and females in Victoria. A high proportion of MSM with syphilis are HIV positive or taking pre-exposure prophylaxis (PrEP) against HIV.

Syphilis can lead to serious complications including neurosyphilis and ocular syphilis. Infection in pregnant women can lead to congenital syphilis.


Direct detection of Treponema pallidum in primary chancres or moist lesions of secondary syphilis.

Polymerase chain reaction (PCR) for detection of T. pallidum DNA from lesion swabs is sensitive and highly specific.

Where available dark field microscopy for treponemes can identify motile spirochaetes; however, this is less sensitive than PCR. For dark field microscopy, the lesion is cleaned with saline, squeezed gently, and a drop of expressed exudate placed onto a glass slide. False positive darkfield microscopy findings are uncommon, but can occur, due to the presence of other commensal spirochaetes. False negative results are common, particularly from older crusted lesions, or where there has been prior systemic or topical antibiotic treatment.


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 usually always positive at the time of presentation of primary chancres but the RPR is negative in around 30% of cases. The 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 an indicator of early infection but may be positive in the absence of recent 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 MSM 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 positive MSM should have serology for syphilis included in the routine bloods taken for monitoring HIV. MSM on PrEP should have syphilis serology as part of their 3 month monitoring. Heterosexual males and females who are sexually active and in regions where syphilis is circulating among heterosexuals should be screened for syphilis. Pregnant women should be screened for syphilis and rescreened later in pregnancy if at risk for infection later in pregnancy. 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. Benzyl penicillin Is not the correct treatment for syphilis. Procaine penicillin is effective but requires daily injections and is generally not used. 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 intavenous 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 1.5g 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 1.5g IM daily for 15 days OR
Doxycycline 100mg twice daily for 28 days (if allergic to penicillin and not pregnant)

Cardiovascular syphilis, ocular syphilis and neurosyphilis

If suspected these should be referred to the appropriate specialist for diagnosis and management.

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 RPR titre as this may be higher upon repeating. 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 (benzathine penicillin) 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 treated 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 November 2018