Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. It usually starts with a firm, painless sore called a chancre where the germ entered the body, then a rash that often covers the palms of the hands and the soles of the feet. After that, it can hide for years without symptoms before damaging the brain, eyes, ears, heart or blood vessels. It spreads through vaginal, anal or oral sex and from a pregnant person to the baby.
The good news: syphilis is curable. A blood test finds it even when you feel fine, and one injection of benzathine penicillin G cures most early infections.
Syphilis is common again in the United States. CDC counted 190,242 cases of all stages in 2024 and 3,941 babies born with syphilis, the twelfth yearly rise in a row.
Key takeaways
- Syphilis goes through stages: primary (painless sore), secondary (rash, often on palms and soles), latent (no symptoms) and tertiary (organ damage years later).
- It can reach the nervous system, eyes or ears at any stage. Sudden vision or hearing changes with a positive test are an emergency.
- Diagnosis needs two kinds of blood tests: a nontreponemal test (RPR or VDRL) and a treponemal test (TP-PA, EIA, CIA or FTA-ABS).
- Benzathine penicillin G is the treatment of choice: one shot for early syphilis, three weekly shots for late or unknown-duration syphilis.
- Every pregnant person should be tested early in pregnancy; many experts now advise retesting in the third trimester and at birth.
What is syphilis?
Syphilis is a bacterial infection caused by Treponema pallidum, a thin, corkscrew-shaped bacterium called a spirochete. It enters through small breaks in the skin or the moist lining of the genitals, anus, rectum or mouth. It then spreads through the blood to the whole body.
The World Health Organization estimates that 8 million adults aged 15 to 49 acquired syphilis worldwide in 2022. In the United States, cases climbed for years: according to a 2025 JAMA review, they rose 61% from 2019 to 2023, with a 112% increase among females and a 106% increase in congenital syphilis. Primary and secondary cases then fell 22% in 2024, but the total stays far above its 2020 level.
Syphilis is part of a standard STI serology panel.
How syphilis spreads and who is at risk
CDC explains that you get syphilis through direct contact with a syphilis sore during vaginal, anal or oral sex. The moist sores of the primary and secondary stages are the most contagious. A pregnant person can also pass the infection to the fetus through the placenta.
You cannot catch it from toilet seats or swimming pools, and having had syphilis once does not protect you.
Groups at higher risk include:
- People who have condomless sex with several or new partners.
- Gay, bisexual and other men who have sex with men; they made up 32.7% of men with primary and secondary syphilis in 2023.
- People living with HIV or taking HIV pre-exposure prophylaxis (PrEP).
- People with another recent STI, such as gonorrhea or chlamydia.
WHO notes that syphilis roughly doubles the risk of getting HIV, so an HIV blood test is part of every syphilis workup.
Syphilis symptoms by stage
Untreated syphilis moves through stages that can overlap. Many people notice nothing, especially when sores are hidden inside the vagina, rectum or mouth.
Primary syphilis: the chancre
The first sign usually appears about 3 weeks after exposure, with a range of 10 to 90 days. It is a chancre: a round, firm sore that is often painless. Nearby lymph nodes may swell. The chancre heals by itself in about 3 to 6 weeks, with or without treatment, but the infection stays in the body.
Painful recurring blisters point more to herpes (see folliculitis or herpes), but any new genital sore deserves a test.
Secondary syphilis: the rash
Secondary syphilis usually begins 2 to 24 weeks after the chancre heals. The classic sign is a rash that often appears on the trunk, the palms of the hands and the soles of the feet. It usually does not itch.
- Mucous patches: sores in or around the mouth, vagina or penis.
- Condylomata lata: moist, wart-like patches on the genitals or in skin folds; mucous patches or condylomata occur in about one in four patients.
- Fever, sore throat, tiredness, swollen lymph nodes and patchy hair loss.
These signs fade in about 3 months on average (1 to 12 months), and in up to 25% of untreated people they come back during the first years. A rash that does not itch on the palms or soles is a strong reason to get tested.
Latent syphilis: no symptoms
After the secondary stage, the infection becomes silent and only a blood test finds it. Treatment depends on its timing:
- Early latent: infection acquired within the past 12 months.
- Late latent: infection acquired more than 12 months ago.
- Unknown duration: the date cannot be determined; it is treated like late latent syphilis.
In up to two thirds of untreated people, syphilis stays latent for life and never progresses.
Tertiary syphilis
Rare but serious, it appears 10 to 30 years or more after infection. It can cause aortic aneurysms, gummas (destructive masses in skin, bone or organs) and late neurosyphilis such as tabes dorsalis (damaged spinal nerves) and general paresis (dementia).
Neurosyphilis, ocular syphilis and otosyphilis
CDC stresses that syphilis can invade the nervous system, eyes or inner ear at any stage, including the first months.
- Neurosyphilis: early forms include meningitis, cranial nerve problems, stroke and sudden confusion.
- Ocular syphilis: often panuveitis (inflammation inside the whole eye), with vision changes or a red, painful eye. It can cause permanent blindness. Learn how uveitis differs from conjunctivitis.
- Otosyphilis: ringing in the ears, vertigo and hearing loss that can be sudden, one-sided or both-sided, and progress quickly.
Congenital syphilis
Congenital syphilis happens when the infection passes from a pregnant person to the baby. It can cause miscarriage, stillbirth, premature birth, low birth weight and newborn death. Babies may look healthy at birth, then develop bone, liver, blood, eye, hearing or brain problems within weeks. According to the 2025 JAMA review, up to 40% of fetuses exposed to syphilis in the womb are stillborn or die from the infection in infancy.
It is almost entirely preventable. A CDC analysis of the 3,761 congenital cases of 2022 (including 231 stillbirths and 51 infant deaths) found that missing or late testing and inadequate treatment during pregnancy contributed to 88% of them.
Syphilis tests: how diagnosis works
Diagnosis rests on blood tests, your history and an exam. A sore can also be tested directly by darkfield microscopy or PCR.
Nontreponemal tests: RPR and VDRL
These tests detect antibodies against lipids from damaged cells, not the bacterium itself. They give a titer, the highest dilution that still reacts, such as 1:4, 1:16 or 1:64. Titers fall after successful treatment, so these tests are used for follow-up. Our RPR test guide covers this test in detail.
Treponemal tests: TP-PA, EIA, CIA and FTA-ABS
These tests detect antibodies aimed at T. pallidum itself. They usually stay positive for life, even after cure: only 15% to 25% of people treated in the primary stage become negative within 2 to 3 years. A positive treponemal test therefore says "syphilis at some point," not "syphilis now."
Traditional versus reverse sequence algorithm
No single test is enough; CDC requires one test of each type. Laboratories use one of two orders:
- Traditional algorithm: an RPR or VDRL first; if reactive, a treponemal test confirms it.
- Reverse sequence algorithm: an automated treponemal immunoassay (EIA or CIA) first; if reactive, the lab runs a quantitative RPR; if the RPR is negative, a second, different treponemal test (usually TP-PA) settles the question.
The reverse order finds more old or treated infections but also more false-positive screens (0.6% in CDC data from 2006 to 2010).
Titers and the fourfold rule
A fourfold change equals two dilution steps, for example from 1:16 to 1:4 (improvement) or 1:8 to 1:32 (worsening). Compare titers only from the same test (RPR with RPR), ideally in the same laboratory: RPR titers often run slightly higher than VDRL titers.
Prozone, false positives and the serofast state
- Prozone: when antibody levels are extremely high, an undiluted RPR can look falsely negative; diluting the sample fixes it.
- Biologic false positive: a reactive RPR with a negative treponemal test. It occurs in about 0.2% to 0.8% of people, linked to other infections (HIV, malaria), recent vaccination, autoimmune disease, injection drug use, pregnancy or older age. Autoimmune diseases such as lupus are one cause (see the ANA test).
- Serofast state: after successful treatment, the RPR may stay weakly positive, usually at 1:8 or less, for years. It is most common after late treatment or several infections.
Reading your syphilis test results
How CDC guidance reads common combinations (your history always matters):
| Result combination | Most likely meaning | Usual next step |
|---|---|---|
| Screen nonreactive (RPR or EIA/CIA) | No sign of syphilis, unless infection is very recent | Repeat if exposure in the past weeks or a sore; test the sore directly |
| RPR reactive + treponemal reactive, no past treatment | Current syphilis | Stage the infection, treat, test for HIV, notify partners |
| RPR reactive + treponemal reactive, treated in the past | Old infection with a residual titer, or reinfection | Compare with past titers: a fourfold rise suggests reinfection |
| RPR reactive + treponemal nonreactive | Biologic false positive (0.2% to 0.8% of people) | No treatment; look for a cause if it persists |
| EIA/CIA reactive + RPR nonreactive + TP-PA reactive | Past treated syphilis, or untreated latent syphilis | If never treated: treat as late latent syphilis; if treated: nothing unless new exposure (repeat RPR in 2 to 4 weeks) |
| EIA/CIA reactive + RPR nonreactive + TP-PA nonreactive | Probable false-positive screen | No action if risk is low; retest if risk is high or pregnant |
| RPR titer falls fourfold or more after treatment (e.g., 1:32 to 1:8) | Adequate response | Continue scheduled follow-up |
| RPR titer rises fourfold or more for over 2 weeks | Reinfection or treatment failure | Retreat, repeat HIV test, consider spinal fluid testing |
Syphilis treatment
Penicillin, which blocks the proteins bacteria use to build their cell wall, remains the backbone of treatment. CDC's 2021 guidelines recommend:
- Primary, secondary and early latent syphilis: benzathine penicillin G 2.4 million units in one intramuscular injection.
- Late latent syphilis or unknown duration: 7.2 million units in total, given as three weekly injections of 2.4 million units. In pregnancy, a gap of more than 9 days between doses means restarting the series.
- Neurosyphilis, ocular syphilis and otosyphilis: aqueous crystalline penicillin G 18 to 24 million units per day through a vein (3 to 4 million units every 4 hours) for 10 to 14 days.
If you are allergic to penicillin
For nonpregnant adults, doxycycline 100 mg twice daily works as an alternative: 14 days for early syphilis, 28 days for late or unknown-duration syphilis. Ceftriaxone 1 g daily for 10 days is another option, though the best dose is not defined. Azithromycin should not be used, because resistance mutations have caused treatment failures. Many people labeled allergic can be tested (see penicillin allergy). In pregnancy, there is no substitute: allergic patients are desensitized in hospital, then given penicillin.
The Jarisch-Herxheimer reaction
Within 24 hours of treatment, some people develop fever, headache and muscle aches. It is not an allergy; fever reducers help. In pregnancy it can trigger early labor or fetal distress, so call your obstetric team if you notice contractions, but it is never a reason to delay treatment.
The penicillin shortage
Bicillin L-A, the main U.S. brand of benzathine penicillin G, has been in short supply since a recall on July 10, 2025. The FDA allows temporary imports of equivalent products, Extencilline and Lentocilin. In April 2026, CDC reported that full recovery is not expected before late 2027 and asked clinics to reserve benzathine penicillin for pregnant patients first.
Follow-up after treatment
Cure is checked with the same nontreponemal test (RPR or VDRL):
- Primary or secondary syphilis: at 6 and 12 months; with HIV, at 3, 6, 9, 12 and 24 months.
- Latent syphilis: at 6, 12 and 24 months.
The goal is a fourfold drop. CDC notes that 10% to 20% of people in trials do not reach this drop within 12 months even though treatment worked, so a slow response calls for more follow-up, not panic. Signs of reinfection or failure are returning symptoms or a sustained fourfold rise.
Partners: testing and treatment
CDC advises that anyone who had sex with you within 90 days before a diagnosis of primary, secondary or early latent syphilis should be treated right away, even if their blood test is negative. Partners are traced back 3 months plus symptom duration (primary), 6 months plus symptom duration (secondary) or 1 year (early latent). Your clinic or health department can help you reach partners.
Prevention and screening
- Condoms and dental dams, used correctly every time, lower the risk, but they do not cover every sore.
- Screening: the USPSTF recommends it for everyone at increased risk; the 2025 JAMA review advises testing all sexually active people aged 15 to 44 at least once, and at least yearly if at increased risk. CDC suggests every 3 to 6 months for men who have sex with men with ongoing risk, including those on PrEP or living with HIV.
- Doxycycline post-exposure prophylaxis (doxy-PEP): since 2024, CDC recommends offering 200 mg of doxycycline taken within 72 hours after sex to gay and bisexual men and transgender women who had a bacterial STI in the past 12 months. STI testing continues every 3 to 6 months.
HPV and hepatitis B vaccines add protection against other STIs.
Pregnancy, HIV and newborns
Pregnancy
The USPSTF reaffirmed in 2025 that all pregnant people should be screened early in pregnancy, or at the first available opportunity (grade A). The American College of Obstetricians and Gynecologists (ACOG) advised in 2024 to retest everyone in the third trimester and at birth. It is part of standard blood tests during pregnancy. Only penicillin is proven to protect the baby, ideally started at least 30 days before delivery.
People living with HIV
Blood tests work normally in most people with HIV. Treatment uses the same penicillin doses, but follow-up is closer, and a neurologic, eye and ear exam is recommended at diagnosis. See our guide to HIV and AIDS.
Newborns
A newborn's test can be positive simply because the mother's antibodies crossed the placenta. Doctors compare the baby's RPR with the mother's and review her treatment. Confirmed or highly probable congenital syphilis is treated with intravenous aqueous crystalline penicillin G, 100,000 to 150,000 units/kg per day for 10 days.
When to see a doctor
See a clinician or a sexual health clinic soon if you have:
- A new sore on the genitals, anus or mouth, even if it is painless or has healed.
- A rash on the palms or soles, mouth patches or patchy hair loss.
- A partner who tells you they have syphilis or another STI.
- A pregnancy without a syphilis test yet.
Get care the same day if you have a positive or past syphilis test and new eye symptoms (vision changes, eye pain or redness), hearing loss, ringing in the ears or vertigo. Call 911 for a stiff neck with fever, sudden weakness or numbness on one side, trouble speaking, severe confusion or a seizure.
Latest scientific advances in syphilis
One injection is enough for early syphilis, even with HIV
A 2025 U.S. trial randomized 249 people with early syphilis, 61% living with HIV. At 6 months, 76% responded after one dose and 70% after three doses: one injection was not inferior. A 2026 meta-analysis of 8 studies in people with HIV found the same. For you: fewer injections, and penicillin saved during the shortage.
Doxy-PEP: strong against syphilis, but not for everyone
In the DoxyPEP trial (2023), 200 mg of doxycycline after sex cut the risk of syphilis by 87% among participants taking PrEP. A 2025 meta-analysis of 4 trials and 1,727 participants concluded doxy-PEP reduces syphilis by 77%, with high certainty. But a trial in 449 young Kenyan women showed no significant benefit, partly because hair tests found the drug in only 29% of samples. CDC therefore limits its advice to men who have sex with men and transgender women.
Searching for oral alternatives to penicillin
The Spanish Trep-AB trial (2024) tested linezolid 600 mg for 5 days: only 70% responded versus 100% with penicillin, so this regimen should not be used. In a small Czech trial (2025), cefixime 400 mg twice daily for 14 days gave a 93.3% response at 12 months versus 96.8% with penicillin, promising but small.
Oral treatment for newborns
The CONSISTENT trial (NCT07457385), set to start in November 2026 at 11 sites, will compare oral amoxicillin with benzathine penicillin in 374 newborns.
Home tests and the long road to a vaccine
In August 2024, the FDA authorized the first over-the-counter home syphilis test, which reads antibodies in a drop of blood in about 15 minutes. A positive result needs lab confirmation. No syphilis vaccine exists yet; researchers are developing combined (chimeric) antigens.
Which tests can help?
These tests usually appear on your report:
- RPR or VDRL with a titer: screening, staging help and treatment follow-up.
- Treponemal tests (TP-PA, EIA, CIA, FTA-ABS): confirmation.
- HIV test and hepatitis B and C serology (see our hepatitis blood test guide).
- Gonorrhea and chlamydia tests from urine or swabs; see our chlamydia rash guide.
- Spinal fluid tests (CSF-VDRL, cell count, protein) when neurosyphilis is suspected.
Glossary
- Treponema pallidum: the spiral bacterium that causes syphilis.
- Nontreponemal test: RPR or VDRL, measures activity with a titer.
- Treponemal test: TP-PA, EIA, CIA or FTA-ABS, confirms exposure; usually positive for life.
- Titer: the highest dilution of blood that still reacts (1:32 is higher than 1:4).
- Serofast: a low RPR titer that stays positive after successful treatment.
- Jarisch-Herxheimer reaction: fever and aches within 24 hours of treatment.
Frequently asked questions
Is syphilis curable?
Yes. The right antibiotic, usually benzathine penicillin G, cures syphilis at every stage. It cannot reverse damage already done, and you can catch syphilis again.
Can syphilis cause rashes on the palms of the hands?
Yes. A rash on the palms and soles is a hallmark of secondary syphilis. It usually does not itch and deserves a blood test.
Can syphilis mimic psoriasis or dermatitis?
It can. The secondary rash may be scaly, raised or spotty, and look like psoriasis, eczema, a drug rash or another skin condition.
What are syphilis symptoms in females?
The signs are the same as in males, but a chancre inside the vagina is often painless and unseen. Many women first notice the rash or learn of it from a prenatal test.
What is congenital syphilis?
It is syphilis passed from a pregnant person to the baby. Testing during pregnancy and penicillin treatment prevent most cases.
How soon after exposure will a syphilis test turn positive?
Blood tests can be negative in the first weeks, while the chancre appears about 3 weeks after exposure (10 to 90 days). After a risky exposure, test now and again a few weeks later; recent partners (past 90 days) of a person with early syphilis are treated even with a negative test.
Will my syphilis test stay positive forever?
The treponemal test usually does. The RPR or VDRL should fall at least fourfold after treatment and often becomes negative, though a low stable titer (serofast) can remain. Keep a copy of your results and treatment dates.
Sources
- Workowski KA et al. — STI Treatment Guidelines, 2021 — MMWR Recomm Rep, 2021 — doi.org
- Papp JR et al. — CDC Laboratory Recommendations for Syphilis Testing, 2024 — MMWR Recomm Rep, 2024 — doi.org
- Chevalier FJ et al. — Syphilis: A Review — JAMA, 2025 — doi.org
- US Preventive Services Task Force — Screening for Syphilis in Nonpregnant Adults — JAMA, 2022 — doi.org
- US Preventive Services Task Force — Screening for Syphilis During Pregnancy — JAMA, 2025 — doi.org
- McDonald R et al. — Missed Opportunities for Preventing Congenital Syphilis, 2022 — MMWR, 2023 — doi.org
- Hook EW 3rd et al. — One Dose versus Three Doses of Benzathine Penicillin G in Early Syphilis — N Engl J Med, 2025 — doi.org
- Cevallos-Cueva M et al. — One vs Three Doses of Benzathine Penicillin G in Early Syphilis in People with HIV: Meta-Analysis — Sex Transm Dis, 2026 — doi.org
- Luetkemeyer AF et al. — Postexposure Doxycycline to Prevent Bacterial STIs — N Engl J Med, 2023 — doi.org
- Molina JM et al. — Doxycycline prophylaxis to prevent bacterial STIs (ANRS 174 DOXYVAC) — Lancet Infect Dis, 2024 — doi.org
- Stewart J et al. — Doxycycline Prophylaxis to Prevent STIs in Women — N Engl J Med, 2023 — doi.org
- Sokoll PR et al. — Efficacy of Doxy-PEP in reducing STIs: systematic review and meta-analysis — Sex Transm Infect, 2025 — doi.org
- Bachmann LH et al. — CDC Guidelines on Doxycycline Postexposure Prophylaxis, 2024 — MMWR Recomm Rep, 2024 — doi.org
- Ubals M et al. — Oral linezolid vs benzathine penicillin G for early syphilis (Trep-AB) — Lancet Infect Dis, 2024 — doi.org
- Klementová T et al. — Cefixime versus benzathine penicillin G for early syphilis: randomized trial — J Antimicrob Chemother, 2025 — doi.org
- Liu A et al. — New Pathways in Syphilis Vaccine Development — Sex Transm Dis, 2024 — doi.org
- University of Alabama at Birmingham — CONSISTENT trial, amoxicillin vs benzathine in neonates (NCT07457385) — ClinicalTrials.gov, 2026 — clinicaltrials.gov
- CDC — STI Surveillance, 2024 (Provisional) — CDC, 2025 — cdc.gov
- CDC — About Syphilis — CDC, 2025 — cdc.gov
- CDC — Availability of STI Treatment Products — CDC, 2026 — cdc.gov
- ACOG — Screening for Syphilis in Pregnancy (Practice Advisory) — ACOG, 2024 — acog.org
- FDA — Marketing authorization of the first at-home syphilis test — FDA, 2024 — fda.gov
- World Health Organization — Syphilis (fact sheet) — WHO, 2025 — who.int
- MedlinePlus — Syphilis — NLM, 2024 — medlineplus.gov
Further reading
- RPR test: what a positive result really means
- Serology test: what an STI panel detects
- HIV blood test: how to read your results
- HBsAg positive: what your result really means
- Hepatitis C antibody test: what positive means
- Autoimmune disease symptoms and lab tests
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