Lucan · Conditions

Syphilis

Australian guidance: Australian STI Management Guidelines — Syphilis + ASHM

1. Definition and epidemiology

Syphilis is a systemic bacterial infection caused by the spirochaete Treponema pallidum subspecies pallidum, transmitted primarily via direct contact with infectious lesions during sexual activity or vertically from mother to foetus. Australian notifications have doubled over the last decade and in 2025 the Australian Government declared syphilis a Communicable Disease Incident of National Significance, reflecting ongoing epidemic spread beyond traditional high-risk populations. Approximately 50% of people with syphilis are asymptomatic and are identified only through serological screening, making opportunistic testing in primary care critical.

2. Pathophysiology

Treponema pallidum is an obligate intracellular spirochaete that cannot be cultured on standard media. After inoculation at a mucosal or skin surface, the organism penetrates tissue and disseminates via lymphatics and the bloodstream within hours, well before the primary chancre becomes clinically apparent. The host mounts a predominantly cell-mediated immune response characterised by CD4+ T-cell and macrophage infiltration, producing the classic obliterative endarteritis with perivascular plasma cell cuffing seen histologically at all stages. This vascular inflammation underpins the ischaemic tissue destruction responsible for chancre formation in primary disease, the diffuse organ seeding in secondary disease, and the gummatous necrosis and aortic root inflammation of tertiary disease. The organism is capable of immune evasion by downregulating surface lipoprotein expression, allowing persistence despite an intact antibody response. In congenital infection, transplacental passage after 16 weeks gestation can cause severe foetal inflammation, hydrops, and death. Neurosyphilis can arise at any stage via direct meningeal invasion (Robbins Ch 8).

3. Clinical presentation and diagnostic criteria

Staging guides both diagnosis and management. Primary syphilis presents as a painless, indurated genital, anal, or oral ulcer (chancre) with inguinal lymphadenopathy; the ulcer heals spontaneously within 3 to 6 weeks. Secondary syphilis develops weeks later and produces fever, malaise, generalised lymphadenopathy, a diffuse maculopapular rash that classically involves the palms and soles, alopecia, and oral or genital condylomata lata. Early latent syphilis is defined by positive serology without symptoms acquired within the past 2 years, supported by a negative test or a 4-fold rise in rapid plasma reagin (RPR) within 2 years. Late latent syphilis is positive serology without symptoms and no negative test within the preceding 2 years. Neurosyphilis can complicate any stage and may present with visual changes, tinnitus, deafness, cranial nerve palsies, severe headache, or meningitis. Tertiary syphilis manifests as destructive skin gummata, cardiovascular involvement including aortitis, or neurological disease.

4. Investigations and AU-specific cutoffs

Initial testing uses a syphilis antibody (treponemal) test performed by chemiluminescent microparticle immunoassay (CMIA) or enzyme immunoassay (EIA). A positive CMIA/EIA is confirmed by reflex Treponema pallidum particle agglutination assay (TPPA) or Treponema pallidum haemagglutination assay (TPHA). RPR is then performed as a quantitative marker of disease activity and treatment response; a 4-fold decline in RPR titre (e.g. 1:32 to 1:8) indicates adequate treatment response. If active lesions are present, Syphilis NAAT or PCR swab of the lesion is performed in addition to serology. All patients should be co-tested for HIV unless known HIV positive. Serology interpretation algorithm: antibody negative with high exposure risk warrants repeat serology; antibody positive with RPR negative and known past treated syphilis requires no further treatment; antibody positive with RPR positive and no documented prior treatment indicates active or possible early or late syphilis requiring treatment.

5. Management

Treatment is stratified by stage. For primary and secondary syphilis, or early latent syphilis presenting with symptoms or signs, the recommended regimen is benzathine benzylpenicillin 2.4 million units (1.8 g) intramuscular as a single dose, given as two injections of 1.2 MU (0.9 g) each. For all other cases including late latent and non-infectious syphilis, benzathine benzylpenicillin 2.4 MU is given weekly for 3 doses. Pregnant patients, children, patients with neurological symptoms or signs, and those with penicillin allergy or unavailability of benzathine benzylpenicillin require urgent specialist referral. Partners of infectious syphilis cases require contact tracing and presumptive treatment. Patients should be advised to avoid sexual contact for 7 days after treatment is administered. State and territory health departments must be notified per local procedures. A specialist should be consulted when serology interpretation is complex, when the patient is diagnosed during pregnancy, when the patient is a child, when neurological signs are present, when HIV co-infection exists, or when a 4-fold RPR decline is not achieved by 12 months.

6. Pharmacology and AU PBS notes

Benzathine benzylpenicillin (Bicillin LA) is the first-line agent for all stages of syphilis. It is supplied as 1.2 MU pre-filled syringes in Australia; each dose of 2.4 MU requires two syringes injected at separate sites in the same visit. It is not available on the PBS as a community pharmacy item and must be obtained through hospital or sexual health clinic channels. For penicillin-allergic patients where allergy cannot be confirmed or desensitisation is not feasible, doxycycline 100 mg orally twice daily for 14 days (primary or secondary) or 28 days (late latent) is the standard alternative, though expert guidance is required. Doxycycline is PBS listed (unrestricted). Azithromycin is no longer recommended due to documented macrolide resistance in Australian Treponema pallidum strains. Neurosyphilis requires aqueous crystalline benzylpenicillin 18 to 24 million units per day intravenously for 10 to 14 days, administered in a hospital setting.

7. Complications and monitoring

Untreated syphilis progresses to tertiary disease in approximately one third of cases, with complications including gummatous destruction of skin, bone and viscera; cardiovascular syphilis causing aortitis, aortic regurgitation, and coronary ostial stenosis; and neurosyphilis causing tabes dorsalis, general paresis, and Argyll Robertson pupils. Congenital syphilis carries severe morbidity and mortality including foetal hydrops, stillbirth, interstitial keratitis, sensorineural deafness, saddle nose deformity, and Hutchinson teeth. The Jarisch-Herxheimer reaction is an acute febrile response occurring within hours of first penicillin treatment, caused by spirochaetal lysis; it is managed supportively and is not a contraindication to continued treatment. Serological follow-up after treatment uses RPR at 3, 6, and 12 months. Adequate response is defined as a 4-fold decline in RPR titre by 6 to 12 months. If RPR rises 4-fold after an adequate decline, re-infection should be suspected and treatment repeated. Contact tracing windows are 3 months plus duration of symptoms for primary syphilis, 6 months plus duration of symptoms for secondary syphilis, 12 months for early latent, and long-term partners only for late latent.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.