Syphilis

Syphilis is a bacterial infection caused by Treponema pallidum, spread by direct contact with a syphilis sore during vaginal, anal or oral sex, and from a pregnant person to the fetus.

Why it matters now

Syphilis is not a historical disease. CDC recorded 209,253 syphilis cases in the United States in 2023 — the highest count since 1950 — including 3,882 cases of congenital syphilis, a more than tenfold rise over the preceding decade. UKHSA reported 9,513 infectious syphilis diagnoses in England in 2023, the highest since 1948.

Stages

• Primary (about 3 weeks after exposure; range 10–90 days). A single firm, round, usually painless sore (chancre) at the site of infection. Because it is painless and can be inside the vagina, rectum or mouth, it is frequently missed. It heals on its own in 3–6 weeks whether or not it is treated — healing is not cure.
• Secondary (weeks to months later). A non-itchy rash that characteristically includes the palms and soles, mucous patches, patchy hair loss, fever, swollen lymph nodes. Also resolves without treatment.
• Latent. No symptoms; detectable only by blood test. Early latent (<1 year) is still transmissible.
• Tertiary (years to decades, in roughly 15–30% of untreated infections). Cardiovascular and gummatous disease.
• Neurosyphilis, ocular and otosyphilis can occur at any stage, including early — presenting as vision change, hearing loss, or headache and confusion. This is an urgent presentation.

Testing

Blood tests. Most services use a treponemal test (EIA/CLIA) first, confirmed by a second test, with RPR/VDRL titres used to gauge activity and monitor treatment. The window period is up to 12 weeks; BASHH advises a repeat test at 12 weeks after a specific risk even if an earlier test was negative. Treponemal antibodies usually stay positive for life, so past treated infection is distinguished by titres, not by a positive/negative result.

Treatment

Benzathine penicillin G by intramuscular injection is the treatment of record and has never developed resistance:

• Early syphilis (primary, secondary, early latent): a single injection of 2.4 million units.
• Late latent or unknown duration: three weekly injections.
• Neurosyphilis: intravenous penicillin in hospital.

Doxycycline for 14 days is an alternative for non-pregnant people with penicillin allergy. In pregnancy, penicillin is the only adequate treatment — allergic patients are desensitised and treated with penicillin, because nothing else reliably treats the fetus.

A Jarisch–Herxheimer reaction (fever, chills, headache within 24 hours of the first dose) occurs in roughly 10–35% of people treated for early syphilis. It is expected, self-limiting, and not an allergy.

Follow-up RPR titres at 3, 6 and 12 months confirm cure; a fourfold drop indicates response.

Congenital syphilis

Untreated maternal syphilis causes stillbirth, prematurity, neonatal death or congenital infection in up to 50–80% of pregnancies. It is fully preventable by testing and penicillin. CDC's 2023 review found that around 88% of congenital syphilis cases could have been prevented by timely testing and treatment. Antenatal syphilis screening is routine in the UK and recommended at the first prenatal visit — and again in the third trimester in higher-incidence areas — in the US.

Prevention

Condoms reduce but do not eliminate risk, because sores may sit outside the covered area. Doxy-PEP substantially reduces syphilis incidence in specific groups (see the doxy-PEP article). Regular testing — 3-monthly for people with multiple partners, and for anyone on HIV PrEP — catches infection in the silent stages.

When to see a clinician

Any new painless genital, anal or oral sore; any rash involving palms or soles; sudden vision or hearing change with a possible syphilis exposure (same-day care).

Sources

• CDC, STI Surveillance 2023; STI Treatment Guidelines, 2021.
• UKHSA, Sexually transmitted infections in England, 2024 report.
• BASHH, UK national guidelines on the management of syphilis, 2024 update.
• WHO, Guidelines for the treatment of Treponema pallidum, 2016.
• Hook EW, The Lancet, 2017, "Syphilis" (seminar review).