Syphilis

Syphilis is a systemic sexually transmissible infection (STI) caused by the spirochaete Treponema pallidum subspecies pallidum. It progresses through distinct clinical stages — primary, secondary, latent, and tertiary — each with characteristic manifestations. Without treatment, syphilis can cause severe neurological, cardiovascular, and other organ complications. Vertical transmission causes congenital syphilis with devastating fetal and neonatal consequences.

Australia has experienced a sustained increase in syphilis notifications since 2011. The Kirby Institute's 2023 Annual Surveillance Report documents over 10,000 syphilis notifications annually, with infectious syphilis (primary, secondary, early latent) accounting for the majority. Two overlapping epidemics are occurring simultaneously: an outbreak predominantly affecting heterosexual Aboriginal and Torres Strait Islander people in remote and regional areas of Queensland, Northern Territory, Western Australia, and South Australia; and a longer-standing epidemic in MSM in metropolitan areas. Congenital syphilis cases — preventable with antenatal screening — continue to be reported, reflecting gaps in testing and treatment during pregnancy.

Syphilis is a notifiable condition in all Australian jurisdictions. Health practitioners are legally required to notify cases to their state or territory health authority within specified timeframes.

Treponema pallidum is a motile, obligate intracellular spirochaete that cannot be cultured on artificial media. Transmission occurs via direct contact with infectious lesions (chancres, mucous patches, condylomata lata) during sexual activity, or vertically from mother to fetus via the placenta (after 16–18 weeks gestation) or at delivery. Blood-borne transmission via transfusion or needle sharing is rare but documented.

After inoculation, treponemes disseminate rapidly via lymphatics and bloodstream. The primary lesion (chancre) results from a local host immune response. Secondary syphilis reflects systemic dissemination. Spirochaetes can enter immune-privileged sites (CNS, eye, cochlea) early in infection, forming the basis for neurosyphilis and ocular syphilis even in early disease. During latency, organisms persist in tissues without causing clinical symptoms. Tertiary syphilis (gummatous, cardiovascular, neurosyphilis) results from chronic granulomatous inflammation and endarteritis.

Clinical Staging

Primary Syphilis

• Chancre: Single (occasionally multiple), painless, indurated ulcer with clean base and raised edges at inoculation site (genital, anal, oral, extragenital). Highly infectious direct contact.
• Regional lymphadenopathy: Firm, non-tender, bilateral inguinal lymphadenopathy.
• Healing: Resolves spontaneously within 3–6 weeks without treatment, leaving a thin scar.

Secondary Syphilis

• Rash: Generalised, non-pruritic maculopapular rash classically involving palms and soles. May be subtle. Papular, pustular, or other morphologies possible.
• Condylomata lata: Flat, moist, highly infectious warty lesions in anogenital and intertriginous areas.
• Mucous patches: Painless, grey-white erosions on oral and genital mucosae.
• Constitutional symptoms: Fever, malaise, headache, myalgia, arthralgia, generalised lymphadenopathy.
• Alopecia: Patchy "moth-eaten" alopecia of scalp and eyebrows.
• Hepatitis, nephritis, uveitis: Less common but documented organ involvement.

Neurosyphilis / Ocular Syphilis

• Early neurosyphilis (meningitis): Headache, meningism, cranial nerve palsies (VII, VIII most common), altered consciousness.
• Ocular syphilis: Any visual complaint in a patient with syphilis — visual loss, floaters, photophobia, eye pain. Prompt ophthalmology referral required.
• Late neurosyphilis: Tabes dorsalis (lightning pains, ataxia, Argyll Robertson pupils), general paresis (dementia, psychiatric symptoms), meningovascular syphilis (stroke).

Serological Testing

Syphilis diagnosis relies on a combination of treponemal and non-treponemal serological tests. No single test is sufficient. Australian laboratories use one of two testing algorithms:

• Essential
  Treponemal EIA / CLIA (screening)

  Treponemal enzyme immunoassay or chemiluminescence immunoassay — highly sensitive automated screening test used by most Australian labs. Remains positive for life after infection (even after treatment). A reactive result requires confirmatory testing with RPR and TPPA/MHA-TP.
• Essential
  RPR (Rapid Plasma Reagin)

  Non-treponemal test. Titre correlates with disease activity — rises with active infection, falls with treatment. A 4-fold titre decline (e.g. 1:16 → 1:4) indicates adequate treatment response. Request titres, not just reactive/non-reactive. False positives occur with pregnancy, autoimmune disease, IV drug use, other infections.
• Essential
  TPPA or MHA-TP (confirmatory treponemal)

  Treponema pallidum particle agglutination or microhaemagglutination assay. Confirmatory treponemal test. Remains positive for life. Used in conjunction with RPR to confirm reactive screening EIA and to differentiate active from previously treated infection.
• Essential
  HIV serology

  All patients with syphilis should be offered HIV testing. HIV co-infection alters syphilis serology interpretation and increases risk of neurosyphilis.
• Available
  Dark-field microscopy / T. pallidum PCR

  Dark-field microscopy of exudate from chancre or condylomata lata can confirm diagnosis before serology becomes reactive (seronegative window). T. pallidum PCR on ulcer swab is available at reference labs and is more sensitive and specific. Useful in early primary syphilis.
• Specialist
  Lumbar puncture (CSF analysis)

  Indicated if neurological or ocular symptoms present, RPR titre ≥1:32, treatment failure, or HIV with CD4 <350 cells/μL and RPR ≥1:32. CSF: VDRL (specific but insensitive — if positive, confirms neurosyphilis), FTA-ABS (sensitive but non-specific), cell count (>5 WBC/μL), protein. CSF VDRL reactive = neurosyphilis. Consult infectious disease if uncertain.
• Available
  Point-of-care syphilis testing

  Rapid treponemal tests (e.g. DPP Syphilis Screen & Confirm) available for use in remote settings and antenatal care. Approved for use in Australia. Reactive POCT requires confirmatory serology and RPR titres from reference lab. Facilitates same-visit treatment in remote communities.

Interpreting Serology

Primary, Secondary, and Early Latent Syphilis (<2 years)

Late Latent Syphilis or Unknown Duration

Neurosyphilis and Ocular Syphilis

Congenital Syphilis

Penicillin Allergy Management

• Non-pregnant adults: Doxycycline 100 mg BD for 14 days (early syphilis) or 28 days (late latent). Equivalent efficacy to benzathine penicillin for early syphilis in non-pregnant, HIV-negative patients.
• Pregnant women: Penicillin is the ONLY validated treatment to prevent congenital syphilis. Penicillin-allergic pregnant women MUST undergo penicillin desensitisation. Refer urgently to an allergist or hospital with desensitisation protocols. Doxycycline, tetracycline, and azithromycin are NOT acceptable alternatives in pregnancy.
• Allergy assessment: Most patients labelled penicillin-allergic are not truly allergic. Formal allergy assessment and skin testing should be pursued where time permits.
• Ceftriaxone: Limited evidence for syphilis treatment; not routinely recommended. May be considered in selected cases under specialist guidance (e.g. 1 g IM/IV daily for 10 days for early syphilis).

HIV Co-infection

• Treatment regimens: Same as HIV-negative patients for most stages. Some experts recommend 3 doses of benzathine penicillin for early syphilis in HIV-positive patients (especially if RPR ≥1:32), though evidence is limited.
• Neurosyphilis risk: Higher risk of neurosyphilis in HIV-positive patients, particularly with low CD4 count. Lower threshold for CSF examination.
• Serology interpretation: HIV may cause unusual serological responses (false-negative or very high titres). Clinical judgement required.
• Follow-up: More frequent serological monitoring — RPR at 3, 6, 9, 12, and 24 months.

Neurosyphilis and ocular syphilis require the full IV penicillin course to achieve treponemicidal CSF concentrations. Oral/IM switch is not validated for these indications.

• After completing IV benzylpenicillin for neurosyphilis: Some experts recommend a single dose of benzathine benzylpenicillin 2.4 million units IM following the 10–14 day IV course to consolidate treatment — discuss with infectious disease specialist.
• Outpatient alternative (neurosyphilis): If IV access is not feasible, procaine penicillin 2.4 million units IM daily + probenecid 500 mg QID for 10–14 days is an accepted alternative under specialist guidance.
• Early syphilis: Single-dose IM benzathine benzylpenicillin — no IV-to-oral transition required.

🤰 Pregnancy

Syphilis in pregnancy is a medical emergency. All Australian states mandate antenatal syphilis screening. Untreated maternal syphilis results in adverse pregnancy outcomes in up to 80% of cases.

• Screening: Syphilis serology (EIA or RPR + TPPA) at first antenatal visit. Repeat testing at 26–28 weeks and again at delivery in high-prevalence areas (Queensland, NT, WA, SA). Some jurisdictions mandate repeat testing at every trimester.
• Treatment: Benzathine benzylpenicillin 2.4 million units IM — only validated treatment for congenital syphilis prevention. A second dose 1 week later is recommended for primary/secondary syphilis in pregnancy by some authorities given higher organism burden.
• Penicillin allergy in pregnancy: Doxycycline is contraindicated. Erythromycin does NOT reliably prevent congenital syphilis. Penicillin DESENSITISATION is mandatory — refer urgently.
• Jarisch-Herxheimer reaction: Warn patient. May cause uterine contractions and fetal heart rate changes. Monitor in labour and delivery unit if >20 weeks gestation after first dose.
• Congenital syphilis prevention: Treatment ≥30 days before delivery is optimal. Treatment within 30 days of delivery may be inadequate to prevent congenital syphilis — neonatal assessment and treatment may be required regardless.
• Fetal assessment: Ultrasound to detect signs of fetal syphilis (hydrops, hepatomegaly, placentomegaly, ascites) in all pregnant women treated for syphilis.

👶 Paediatrics / Congenital Syphilis

Congenital syphilis requires immediate neonatal evaluation and treatment. Any neonate born to a mother with syphilis needs assessment regardless of maternal treatment history.

• Neonatal evaluation: RPR from neonate (not cord blood), full physical exam, CSF analysis, long bone X-rays, FBC, LFTs, ophthalmology review.
• Confirmed/probable congenital syphilis: IV benzylpenicillin 50,000 units/kg every 12 hours (first 7 days), then every 8 hours for 10 days total. Or procaine penicillin 50,000 units/kg IM daily for 10 days if CNS not involved.
• Acquired syphilis in children: Any STI diagnosis in a pre-adolescent child mandates child protection notification and forensic assessment for sexual abuse.
• Adolescents: Treat with adult regimens. Ensure appropriate consent processes.

🛡️ Immunocompromised (HIV-positive)

HIV co-infection increases risk of accelerated syphilis progression, neurosyphilis, and treatment failure.

• Treatment: Same regimens as HIV-negative for most stages. Some clinicians use 3 doses benzathine penicillin for early syphilis in HIV-positive patients with RPR ≥1:32 — discuss with specialist.
• CSF examination: Consider LP in HIV-positive patients with syphilis (any stage) if RPR ≥1:32, CD4 <350, or any neurological/ocular symptoms.
• Serological monitoring: More frequent follow-up — RPR at 3, 6, 9, 12, 24 months. Unusual serological responses possible.
• ART interaction: No significant interactions between penicillin or doxycycline and most antiretroviral regimens.

🫘 Renal Impairment

Penicillin dose adjustments are required for neurosyphilis regimens in renal impairment; benzathine benzylpenicillin single-dose IM requires no adjustment.

• IV benzylpenicillin (eGFR <30): Reduce dose and/or extend interval — consult pharmacist. Risk of penicillin encephalopathy (seizures) with high doses in renal failure.
• Doxycycline: No dose adjustment required. Safe in renal impairment.
• Probenecid: Avoid in eGFR <30 mL/min (ineffective and accumulates). If procaine penicillin + probenecid regimen needed, use IV benzylpenicillin instead.

• No antimicrobial resistance: T. pallidum has not developed resistance to penicillin — it remains the gold-standard treatment after over 70 years of use. Penicillin allergy should be confirmed before prescribing alternatives.
• Avoid azithromycin for syphilis: Macrolide resistance in T. pallidum (A2058G and A2059G mutations) is prevalent in Australian isolates. Azithromycin must NOT be used to treat syphilis in Australia — treatment failures are documented.
• Correct staging before treatment: Treatment regimen (single vs. 3 doses; IM vs. IV) depends on stage. Thorough history, serology interpretation, and clinical assessment are required before prescribing.
• Epidemiological treatment: Contacts of confirmed infectious syphilis cases (within 90 days of primary/secondary or 12 months of early latent) should be treated epidemiologically without waiting for serology results. This is a key outbreak control measure.
• Mandatory notification: All syphilis diagnoses must be notified to the relevant state/territory health authority. Notification triggers contact tracing and outbreak monitoring.