1.1 Organism Characteristics

Microbiology:

Gram-negative spirochaete (slender, tightly coiled, corkscrew morphology); too thin to be visualised by standard light microscopy: requires darkfield microscopy or immunofluorescent staining of lesion material; cannot be cultured on standard laboratory media (requires animal passage models or specialised co-culture), making serology the cornerstone of diagnosis
Obligate human pathogen with no animal reservoir; transmitted exclusively human-to-human
Three pathogenic subspecies: T. pallidum subsp. pallidum (venereal syphilis: the focus of this section), pertenue (yaws), and endemicum (bejel)
Extremely limited metabolic capacity: encodes virtually no biosynthetic pathways of its own, relying entirely on host cell machinery for lipids, amino acids, and other metabolic substrates; this biological dependency explains why it cannot be cultured independently and why penicillin remains the sole recommended treatment (without the selective pressure of an organism capable of transmitting resistance plasmids under routine in vitro conditions)
Uniquely among spirochaetes, does not possess classical lipopolysaccharide: outer membrane is unusually protein-sparse, a key immune evasion strategy allowing the organism to evade antibody-mediated killing during early dissemination

1.2 Typical Disease Patterns

Syphilis follows a remarkably well-defined, multi-stage natural history if untreated, each stage carrying distinct clinical features, diagnostic profiles, and treatment implications:

Stage hierarchy:

Primary syphilis: localised at the inoculation site
Secondary syphilis: haematogenous dissemination with systemic manifestations
Latent syphilis: asymptomatic seroreactive phase (early latent <2 years; late latent ≥2 years or unknown duration)
Tertiary syphilis: late destructive complications (gummatous, cardiovascular, neurological): now uncommon in the antibiotic era but carrying severe morbidity
Congenital syphilis: transplacental transmission causing multi-system fetal/neonatal disease

1.3 Epidemiologic Factors: EXAM-CRITICAL CURRENT AUSTRALIAN DATA

Syphilis is currently one of the most significant communicable disease challenges in Australia. This is active, ongoing, and exam-examinable public health emergency:

5,960 notifications of infectious syphilis in Australia in 2024 (RANZCOG/Australian ACDC 2025 data), including 1,025 cases among women of reproductive age (15–44 years): the highest annual notification count in the modern surveillance era
The Australian Chief Medical Officer declared syphilis a Communicable Disease Incident of National Significance on 7 August 2025: one of the highest-level public health declarations available under Australian frameworks, reflecting the sustained failure of existing control measures to arrest transmission, particularly among women of reproductive age and in Aboriginal and Torres Strait Islander communities
34 infant deaths attributable to congenital syphilis over the past decade (Kirby Institute 2024 Annual Surveillance Report); congenital syphilis notifications have more than doubled since 2015: a direct consequence of inadequate screening/treatment of infectious syphilis in women of reproductive age
Aboriginal and Torres Strait Islander people are disproportionately affected at a rate 7× higher than non-Indigenous Australians (ACDC 2025), driven by concentrated outbreaks in remote communities across northern/central Australia, inadequate access to timely screening and treatment, social determinants (housing crowding, poverty), and historically under-resourced primary healthcare infrastructure in these communities
A concurrent transmission shift has been occurring: syphilis was historically concentrated in MSM in urban settings; the epidemic has now expanded significantly into heterosexual networks, particularly in remote communities and among women of reproductive age: a critical epidemiological shift with direct implications for congenital syphilis risk
Transmission: predominantly sexual (direct contact with infectious lesions/mucosal surfaces); also transplacental (any stage of pregnancy); rarely via blood transfusion or non-sexual direct contact

1.4 Characteristics of Predisposed Host

MSM/GBMSM: historically the dominant transmission network in urban Australia; HIV co-infection substantially increases syphilis susceptibility and vice versa (syphilitic ulcers increase HIV transmission efficiency approximately 2–5×, and HIV alters both the clinical presentation and serological response to syphilis)
Women of reproductive age in remote and very remote communities: the rapidly growing and most clinically consequential risk group in the Australian epidemic given the direct link to congenital syphilis
Pregnancy: confers no protection against acquiring syphilis but dramatically raises the stakes of any infection given transplacental transmission risk
HIV co-infection: associated with more severe primary syphilis, higher rates of neurosyphilis, more rapid progression through stages, and atypical serological responses (false-negative reactions possible in high-titre primary infection)
Prior syphilis infection does not confer protective immunity: reinfection is entirely possible and common in exposed populations

1.5 Incubation and Infectivity Periods

Primary chancre appears typically 10–90 days (mean approximately 3 weeks) after exposure
Most infectious during primary and secondary stages, when spirochaete burden in lesions and mucosal secretions is highest: a key Australian study (Towns et al., Lancet Infectious Diseases 2021) demonstrated that T. pallidum is detectable by PCR in non-lesion sites (oropharynx, rectum) in men with early syphilis, and that mucosal shedding peaks during secondary syphilis, including in the saliva: an important epidemiological finding supporting oral transmission as an underappreciated route
Latent syphilis is generally considered non-infectious sexually, though transplacental transmission can occur even from late latent infection (though risk is lower than in infectious stages)
Notifiable in all Australian states and territories; sexual contacts within the preceding 3 months (primary), 6 months (secondary), or 12 months (early latent) should be tested and empirically treated

1.6 Clinical Presentation

Primary syphilis:

Chancre: painless (classically), indurated, clean-based ulcer at the inoculation site (glans/shaft in males, vulva/vagina/cervix in females, rectum, oropharynx, or finger depending on exposure type); single lesion classically, though multiple chancres occur; associated with non-tender regional lymphadenopathy
EXAM POINT: painless ulcer is the key distinguishing feature from herpes simplex virus (painful, vesicular/ulcerative, tender) and chancroid (Haemophilus ducreyi, painful, soft/undermined edge, tender lymphadenopathy); in practice, overlap occurs and co-infection with HSV is common
Spontaneously resolves in 3–6 weeks without treatment: the disappearance of the chancre does not imply resolution of infection

Secondary syphilis (6–8 weeks after primary chancre, if untreated):

Diffuse, non-pruritic maculopapular rash: characteristically involving the palms and soles (a classic distinguishing examination finding; very few other rashes involve palms/soles: also seen in Rocky Mountain spotted fever); may be subtle or florid
Condylomata lata: moist, flat, warty-appearing papules in moist/intertriginous areas (perineum, perianal region, axillae); highly infectious
Constitutional symptoms: fever, malaise, pharyngitis, generalised lymphadenopathy, headache
Mucous patches: shallow, painless ulcers on oral/genital mucosa
Alopecia (moth-eaten pattern), hepatitis, uveitis, meningitis: less common but recognised manifestations of secondary syphilis

Latent syphilis: no clinical manifestations by definition; detected by serology; distinguished into early (<2 years) and late (≥2 years or unknown) latent on epidemiological/clinical grounds, as this determines both infectiousness and treatment duration

Neurosyphilis:

Can occur at any stage of syphilis: early neurosyphilis (meningitis, uveitis, cranial nerve palsy) may accompany primary or secondary stages; late neurosyphilis (meningovascular, parenchymatous) manifests years to decades after primary infection
Classic late neurosyphilis syndromes (now rare, pre-antibiotic era language but still examined): tabes dorsalis (posterior column degeneration: lightning pains, ataxia, loss of proprioception, Charcot joints, Argyll Robertson pupils); general paresis of the insane (cortical dementia, psychiatric features, seizures)
Argyll Robertson pupils (small, irregular pupils that accommodate but do not react to light ("prostitute's pupil") accommodates but doesn't react); classically associated with syphilis and an often-examined sign

Tertiary syphilis (10–30 years after primary infection, if untreated):

Gummatous syphilis: granulomatous lesions in skin, bone, viscera; destructive but usually not immediately life-threatening
Cardiovascular syphilis: ascending aortic aneurysm (resulting from endarteritis obliterans of the vasa vasorum), aortic regurgitation, coronary ostial stenosis

Congenital syphilis:

Early congenital syphilis (<2 years): hepatosplenomegaly, jaundice, osteochondritis/periostitis (causing "pseudoparalysis" (the infant refuses to move a limb), rhinitis ("snuffles") persistent serosanguineous nasal discharge), maculopapular/vesiculobullous rash, anaemia, thrombocytopenia, stillbirth/neonatal death
Late congenital syphilis (>2 years): Hutchinson's teeth, interstitial keratitis, eighth nerve deafness, saddle-nose deformity, saber shins: the "stigmata" of late congenital syphilis
>50% of untreated maternal infections lead to adverse outcomes (stillbirth, neonatal death, or major malformation in the liveborn)

1.7 Diagnostic Tools and Approach

Syphilis diagnosis combines serology with clinical context: no single test is sufficient, and the interpretation requires understanding both treponemal and non-treponemal antibody kinetics:

Non-treponemal tests (NTT):

RPR (Rapid Plasma Reagin) and VDRL (Venereal Disease Research Laboratory): detect antibodies against cardiolipin-lecithin-cholesterol antigen (a surrogate for T. pallidum infection); quantitative (titres correlate with disease activity, fall with successful treatment, and should become negative or low-titre after adequate therapy); used for treatment monitoring
False-positive NTT: important; occur in conditions generating antiphospholipid antibodies: pregnancy, autoimmune conditions (SLE, antiphospholipid antibody syndrome), other infections (HIV, EBV, hepatitis, TB, malaria), IV drug use
EXAM POINT: "prozone phenomenon": paradoxically false-negative RPR/VDRL in very high titres of antibody (typically secondary syphilis) due to antibody excess preventing lattice formation: laboratories dilute the sample if high-treponemal load is clinically suspected but NTT is negative

Treponemal tests (TT):

TPPA (Treponema pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody absorption), ELISA/CIA-based treponemal IgG: detect specific anti-treponemal antibodies; highly sensitive and specific; remain positive for life after infection regardless of treatment: cannot be used to distinguish active from previously treated disease
Modern Australian laboratories typically perform a "reverse algorithm": treponemal ELISA first (automated, high throughput) → if positive, confirm with quantitative RPR → if RPR negative, confirm with a second treponemal test (TPPA): an important methodological point for interpreting laboratory results

PCR:

T. pallidum PCR on primary lesion material, CSF, or placental tissue: highly sensitive for diagnosing active infection at the site of sampling; increasingly available in Australian reference laboratories and sexual health services; particularly useful for congenital syphilis diagnosis and for primary lesions where serology may be negative (too early for antibody response)

CSF analysis for neurosyphilis:

LP indicated in: neurological/ocular/auditory symptoms at any stage; treatment failure; HIV co-infection with late latent syphilis; evidence of tertiary disease
CSF VDRL: highly specific but insensitive for neurosyphilis; a positive result is essentially diagnostic; a negative result does not exclude neurosyphilis
CSF FTA-ABS: more sensitive but less specific; a negative result is useful to exclude neurosyphilis in low-pretest-probability settings

Screening in pregnancy:

Antenatal syphilis serology is recommended at first antenatal visit for all pregnant women in Australia, with repeat screening at 26–28 weeks gestation and again at delivery for women in high-risk areas or with ongoing risk: critically, even a single missed screening test, or failure to treat a newly acquired infection before delivery, can result in congenital syphilis; the 2024 MJA cohort analysis found that a substantial proportion of congenital syphilis cases in Australia occurred in women who had been screened but had acquired syphilis between a negative screen and delivery without rescreening

1.8 Effective Antimicrobial and Adjunctive Therapy; Resistance Patterns

Resistance epidemiology: T. pallidum remains universally susceptible to penicillin: no penicillin resistance has ever been documented. This remarkable stability reflects the organism's extremely limited genome and biosynthetic capacity (no penicillin resistance genes can be acquired via the horizontal gene transfer mechanisms that operate in more metabolically complex bacteria), and means that benzathine benzylpenicillin G remains the gold-standard treatment across all stages: the same antibiotic used since syphilis was first treated with penicillin in the 1940s.

Treatment by stage (Australian guidelines):

Stage	First-line treatment	Alternative (penicillin allergy)
Primary, secondary, early latent	Benzathine benzylpenicillin G 1.8g (2.4 million units) IM single dose	Doxycycline 100mg oral BD × 14 days
Late latent or unknown duration	Benzathine benzylpenicillin G 1.8g IM weekly × 3 doses (total 3 weeks)	Doxycycline 100mg oral BD × 28 days
Neurosyphilis	Benzylpenicillin 1.8g IV 4-hourly × 10–14 days	Ceftriaxone 2g IV daily × 10–14 days (limited evidence)
Congenital syphilis	Benzylpenicillin IV/IM, dose and duration by severity per neonatal guidelines	–

EXAM POINTS:

Jarisch-Herxheimer reaction: fever, rigors, headache, myalgia, and transient worsening of rash occurring within 2–8 hours of the first dose of antibiotic therapy (not subsequent doses), caused by rapid spirochaete killing and cytokine release; self-limiting, typically resolves within 24 hours; managed with antipyretics; in pregnancy, can precipitate preterm labour or fetal distress: women must be warned and delivered in a monitored setting if possible; is NOT an allergic reaction and is NOT a reason to stop penicillin
Penicillin desensitisation should be pursued for pregnant women with penicillin allergy requiring syphilis treatment: doxycycline does NOT cross the placenta reliably enough to treat the fetus, so penicillin is essential for congenital syphilis prevention regardless of maternal penicillin allergy history
Serological follow-up after treatment is mandatory: NTT (RPR) titres should fall ≥4-fold within 6–12 months for primary/secondary syphilis; failure to respond should prompt LP to exclude neurosyphilis and consideration of re-treatment

1.9 Expected Morbidity and Mortality

Untreated primary and secondary syphilis is rarely directly fatal but carries substantial long-term morbidity through progression to neurosyphilis and cardiovascular syphilis (10–30 year latency to tertiary complications)
Congenital syphilis is entirely preventable with effective antenatal screening and timely treatment: its ongoing occurrence in Australia (34 infant deaths over the past decade, rising notifications) represents a preventable public health failure, directly reflecting inadequate screening coverage and treatment access for women at risk, particularly in Aboriginal and Torres Strait Islander communities
Neurosyphilis, when it occurs, can cause irreversible neurological damage even with appropriate treatment: early recognition and treatment before irreversible parenchymal damage is the key determinant of outcome
HIV co-infection substantially complicates both the natural history (more rapid/severe disease progression) and serological interpretation

Spirochaetes

1Spirochaetes