Syphilis: Why It's Making a Comeback in 2025

Syphilis has returned. After being close to elimination in many Western countries in the late 1990s, it has been rising steadily for two decades and has now more than doubled in a five-year period in the US. The infection is curable, the test is simple, and the treatment is inexpensive. Yet cases continue to climb, congenital syphilis is reaching alarming levels, and the neurological and cardiovascular complications of late-stage disease are being seen again in clinical settings that had not encountered them for a generation.

• US syphilis cases more than doubled between 2018 and 2023

• Congenital syphilis — babies born with syphilis from infected mothers — rose over 750% between 2012 and 2022

• Syphilis progresses through distinct stages, each with different manifestations and treatment urgency

• The infection can remain latent for years without symptoms while continuing to cause damage

• A single injection of penicillin G cures early syphilis; later stages require longer treatment

Why Syphilis Is Coming Back

The resurgence has multiple drivers, none of which are unique to syphilis. Reduced investment in public sexual health services has created gaps in testing and contact tracing. Inconsistent condom use, particularly in populations that have shifted to PrEP for HIV protection without maintaining condom use for other STIs, has contributed. The rise of dating apps has changed sexual networks in ways that can accelerate transmission. In the US, healthcare access disparities — particularly in rural and Southern states with limited prenatal care — are driving the congenital syphilis crisis. And syphilis’ own clinical subtlety works in its favour: the painless primary sore is frequently missed, the rash of secondary syphilis is often attributed to other causes, and latent syphilis has no symptoms at all.

The Stages of Syphilis

Primary syphilis

The first sign is a chancre — a firm, round, painless sore at the site where Treponema pallidum entered the body. It appears 10←–90 days after exposure (average 3 weeks) on the genitals, anus, lips, or fingers. Because it is painless, and often located inside the vagina, rectum, or under the foreskin where it is not easily visible, it is frequently unnoticed. It heals without treatment in 3–6 weeks, but the bacteria remain active in the body.

Secondary syphilis

If primary syphilis is untreated, systemic infection follows. The classic presentation is a rough, reddish-brown rash on the palms of the hands and soles of the feet — a distinctive combination rarely seen in other conditions — appearing 2–10 weeks after the primary sore heals. The rash may also affect the trunk, face, and limbs. Mucous patches (sores in the mouth, vagina, or anus), condylomata lata (flat, moist wart-like lesions in skin folds), and flu-like symptoms (fever, swollen lymph nodes, fatigue, sore throat) may accompany the rash. Secondary syphilis is highly infectious. Like the chancre, the rash resolves without treatment — but the infection progresses.

Latent syphilis

After secondary syphilis resolves, the infection enters a latent phase. Early latent syphilis (within the first year) may still cause relapses of secondary symptoms and remains highly infectious. Late latent syphilis (after 12 months) has no symptoms but bacteria remain active in the body. Late latent syphilis is less infectious to sexual partners but can still be transmitted from mother to foetus during pregnancy.

Tertiary syphilis

In approximately 30% of people with untreated syphilis, the infection progresses to tertiary disease years or decades later. Tertiary syphilis can damage the heart (aortic aneurysm, aortic valve disease), the nervous system (neurosyphilis, tabes dorsalis, general paresis), the eyes (ocular syphilis), and virtually any organ through gummatous lesions. Neurosyphilis can cause memory loss, personality changes, tremors, and cognitive decline — manifestations that can be mistaken for Alzheimer’s disease or other neurological conditions. The damage caused by tertiary syphilis may be irreversible even after treatment.

Ocular Syphilis: An Emerging Concern

Ocular syphilis — syphilitic infection of the eyes — has been specifically flagged by the CDC as an emerging clinical concern, with documented outbreaks in several US cities. It can occur at any stage of infection and causes uveitis, retinitis, and optic neuritis, potentially leading to blindness if untreated. Any eye symptoms (pain, redness, vision changes) in a person with known or suspected syphilis should be treated as an emergency.

Testing and Treatment

Syphilis is diagnosed by blood tests: non-treponemal tests (RPR, VDRL) detect antibodies produced in response to infection, and treponemal tests (TPPA, TPHA, FTA-ABS) detect antibodies specifically to Treponema pallidum. Initial screening is usually with a treponemal test, with reactive results confirmed by a non-treponemal test that also allows monitoring of treatment response. The window period is 3–6 weeks after exposure.

Treatment is with penicillin G: a single intramuscular injection for primary, secondary, and early latent syphilis; three weekly injections for late latent syphilis; and intravenous penicillin for neurosyphilis and tertiary disease. Penicillin remains the only reliably effective treatment — doxycycline is used in penicillin-allergic patients but requires careful follow-up. All recent sexual partners should be tested and treated. A follow-up blood test at 6 and 12 months confirms treatment response.

Congenital Syphilis: A Preventable Crisis

Congenital syphilis occurs when an infected mother transmits syphilis to her baby during pregnancy. It can cause stillbirth, premature birth, severe bone and organ damage, blindness, and developmental problems. Every case is preventable with routine prenatal syphilis screening and treatment. The current epidemic of congenital syphilis in the US reflects failures of prenatal care access, particularly in rural areas and for women who enter prenatal care late or not at all. Pregnant women who test positive for syphilis and receive adequate treatment in time protect their babies entirely.

Tips for Prevention and Early Detection

• Get tested for syphilis annually if you have new or multiple sexual partners, and at the first prenatal visit if pregnant.

• Know the appearance of a chancre — a painless sore on the genitals, anus, or lips that heals on its own does not mean the infection has cleared.

• Do not dismiss the secondary syphilis rash — a rash on the palms of the hands and soles of the feet is highly characteristic and warrants immediate testing.

• Tell your clinician about any eye symptoms in the context of syphilis risk — ocular syphilis requires urgent assessment.

• Use condoms — consistently, particularly with new or casual partners.

Frequently Asked Questions

Can syphilis be cured at any stage?

Yes, with antibiotics — but the treatment complexity and outcome differ by stage. Early syphilis is easily cured with a single penicillin injection. Late syphilis requires more intensive treatment. Damage already caused by tertiary syphilis — to the heart, nerves, or eyes — may not be reversible even after the bacteria are eliminated. This is why early detection and treatment matter so much.

What is the difference between primary and secondary syphilis in terms of transmission risk?

Both are highly infectious. Primary syphilis is most infectious at the chancre site — direct contact with the sore transmits the bacteria. Secondary syphilis is broadly infectious because bacteria are circulating in the bloodstream and present in skin lesions and mucous patches throughout the body. Latent syphilis is significantly less sexually transmissible but not completely non-infectious.

If I was tested for syphilis and it came back negative, do I need to test again?

Yes, if you had a potential new exposure after the negative test, or if you tested before the window period had passed (within 3–6 weeks of exposure). A negative test is only valid at the time it was taken and does not cover exposures that occurred after the test.

Can syphilis affect the brain even without obvious neurological symptoms?

Yes. Asymptomatic neurosyphilis — syphilitic infection of the central nervous system without clinically obvious symptoms — can occur at any stage. It is detectable by cerebrospinal fluid analysis and is typically treated with intravenous penicillin. Routine CSF examination is not performed in all syphilis cases but is recommended when neurological symptoms are present or when standard treatment has not produced the expected response.

Is the syphilis resurgence connected to the decline in condom use among people on PrEP?

This is part of the picture. Some studies have found higher syphilis rates among people on PrEP who have reduced condom use — PrEP protects against HIV but not against syphilis. However, the resurgence predates widespread PrEP use and reflects broader systemic factors including reduced public health infrastructure. PrEP is an important HIV prevention tool; the appropriate response is to maintain syphilis testing every 3 months as part of the required PrEP monitoring programme, not to forego PrEP.

Get Tested Today

Syphilis is curable — but only if it is detected. If you have been sexually active and have not been tested for syphilis recently, now is the time. Fast, confidential blood testing is available at sexual health clinics and online.

Related reading: Syphilis: Early Symptoms, Testing and Treatment · STI Epidemic 2025 · STDs and Eye Symptoms · The Most Common STDs in the US