syphilis

Canada is in an ongoing syphilis outbreak with rising congenital syphilis. Diagnosis is serological: treponemal test (EIA/CMIA) + quantitative RPR, with TP-PA to resolve discordance. Treat by stage: early (primary, secondary, early latent <1 year) → benzathine penicillin G 2.4 MU IM × 1; late latent/unknown duration or tertiary (non-CNS) → weekly × 3. Neurosyphilis, ocular, or otic syphilis → IV penicillin G 10–14 days. Penicillin is the only acceptable treatment in pregnancy — desensitise if allergic.

do not miss

ocular or otic syphilis (uveitis, vision loss, sudden hearing loss, tinnitus) → treat as neurosyphilis with IV penicillin, urgent ophthalmology/ENT, even with normal CSF
syphilis in pregnancy → penicillin only; screen at first visit, 28–32 weeks, and delivery where risk is ongoing

stages

stage	timing	features
primary	~3 weeks (10–90 days)	painless indurated chancre, regional lymphadenopathy; often unnoticed (rectal, oral, cervical)
secondary	2–12 weeks after chancre	rash including palms/soles, mucous patches, condylomata lata, patchy alopecia, lymphadenopathy, hepatitis, nephrotic syndrome, uveitis, meningitis
early latent	seroreactive, asymptomatic, acquired <1 year	infectious
late latent / unknown duration	≥1 year or unknown	not sexually infectious; vertical transmission still possible
tertiary	years	gummas; cardiovascular (aortitis, aortic regurgitation, root aneurysm)
neurosyphilis	any stage	early: meningitis, cranial neuropathies, stroke (meningovascular); late: general paresis, tabes dorsalis (Argyll Robertson pupils)

testing

treponemal tests (EIA/CMIA, TP-PA, FTA-ABS) stay positive for life → diagnose infection, not activity
non-treponemal (RPR, VDRL) → titre reflects activity; used to stage response and detect reinfection
Canadian labs use either the traditional (RPR first) or reverse (treponemal first) algorithm

EIA	RPR	TP-PA	interpretation
+	+	+	current or recent syphilis (or treated with persistent titre) — stage clinically
+	−	+	very early primary, late latent/tertiary, or previously treated — check history; treat if no prior treatment
+	−	−	likely false-positive EIA
−	+	−	biological false-positive RPR (pregnancy, autoimmune, HIV, IDU)

chancre: PCR or darkfield of lesion; serology may be negative early → treat on clinical suspicion and repeat serology in 2–4 weeks
screen all sexually active people with new/multiple partners; GBMSM, people with HIV, and people with multiple partners every 3–6 months; every pregnancy at first visit, repeat at 28–32 weeks and delivery in outbreak areas or with ongoing risk
test everyone with syphilis for HIV, gonorrhoea, chlamydia

lumbar puncture — indications

neurological, ocular, or otic symptoms/signs (ocular/otic → treat as neurosyphilis regardless of CSF)
tertiary syphilis
serological treatment failure
consider in HIV with RPR ≥1:32 or CD4 ≤350 — older data, practice varies

CSF: lymphocytic pleocytosis, raised protein; CSF-VDRL specific but insensitive; negative CSF FTA-ABS makes neurosyphilis unlikely.

treatment

stage	preferred	penicillin allergy (non-pregnant)
primary, secondary, early latent	benzathine penicillin G 2.4 MU IM × 1	doxycycline 100 mg PO BID × 14 days; ceftriaxone 1 g IV/IM daily × 10 days (exceptional)
late latent, unknown duration, tertiary (non-CNS)	benzathine penicillin G 2.4 MU IM weekly × 3	doxycycline 100 mg PO BID × 28 days
neurosyphilis, ocular, otic	aqueous penicillin G 3–4 MU IV q4h × 10–14 days	ceftriaxone 2 g IV daily × 10–14 days, or desensitise — ID
pregnancy (any stage)	benzathine penicillin per stage; some give a second early-stage dose 1 week later in the third trimester	desensitise — no acceptable alternative

missed weekly dose in late latent: non-pregnant — an interval up to 10–14 days is acceptable; pregnancy — any missed dose → restart the full series (CDC)
benzathine penicillin shortage: follow PHAC interim guidance — reserve for pregnancy and their partners, and for infectious syphilis where oral adherence is doubtful; doxycycline for others
HIV coinfection: same regimens; closer serological follow-up
contacts: offer epidemiological treatment (benzathine × 1) to partners within 90 days of an infectious case; trace back 3 months (primary), 6 months (secondary), 1 year (early latent)
report to public health

post-treatment febrile reaction

Jarisch–Herxheimer reaction: fever, rigors, myalgia, headache within ~2–24 h of the first dose — most common in secondary syphilis. Antipyretics; not an allergy; in pregnancy can trigger preterm labour or foetal distress → monitor.

follow-up

stage	RPR at	adequate response
primary	3, 6, 12 months	4-fold fall by 6 months, 8-fold by 12
secondary	3, 6, 12 months	8-fold fall by 6 months, 16-fold by 12
early latent	3, 6, 12 months	4-fold fall by 12 months
late latent, tertiary	12, 24 months	stable or falling
HIV coinfection	3, 6, 12, 24 months, then yearly	as above

inadequate response or 4-fold rise → reinfection vs treatment failure → LP, HIV status, retreat
serofast: low stable titre after adequate treatment and response — no retreatment if no new exposure

doxycycline PEP

doxycycline 200 mg PO within 72 h after condomless sex (max 200 mg per 24 h) — NAC-STBBI conditional recommendation for cisgender GBMSM and transgender women at high STI risk
reduces syphilis and chlamydia substantially; gonorrhoea benefit smaller (tetracycline resistance)
off-label in Canada; pair with 3-monthly STI screening

traps

treating a positive EIA with negative RPR as a false positive without checking treatment history or TP-PA
missing ocular/otic syphilis because meningism is absent
using doxycycline in pregnancy — penicillin desensitisation instead
mistaking a Jarisch–Herxheimer reaction for penicillin allergy
restarting treatment for a serofast low titre without new exposure
failing to test for HIV and other STIs at diagnosis