Syphilis
The Resurgence, Stages, Congenital Stakes, and Why It Is Back
Evidence grade 5 of 5, Settled. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- Penicillin G is FDA-approved and remains first-line per CDC 2021 guidelines
Reference only. Not medical advice.
What can go wrong
Untreated syphilis can cause neurosyphilis (including stroke-like events, dementia, and tabes dorsalis), ocular syphilis (which can cause blindness), otosyphilis, and cardiovascular syphilis (aortitis, aneurysm). Congenital syphilis can cause stillbirth, neonatal death, and severe lifelong disability. Syphilitic ulcers also increase the risk of acquiring and transmitting HIV. Treatment is effective but staging-dependent: late or unknown-duration latent syphilis requires three weekly penicillin injections, and neurosyphilis requires intravenous therapy. Penicillin-allergic patients with neurosyphilis or in pregnancy may require desensitization because alternatives are inferior.
This is something to take to a clinician. The Atlas can tell you what is known about syphilis in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
Syphilis is caused by the spirochete Treponema pallidum and is undergoing a substantial resurgence in many high-income countries, including the United States, with large increases in primary, secondary, and congenital cases over the past decade. It progresses through stages: a painless primary chancre, a secondary stage with rash (classically involving palms and soles) and systemic symptoms, a latent stage with no symptoms, and a tertiary stage with cardiovascular and gummatous disease; neurosyphilis and ocular syphilis can occur at any stage. It is called the great imitator for its protean presentations. Benzathine penicillin G remains first-line per the CDC 2021 guidelines. The congenital stakes are severe, which is why screening in pregnancy and partner notification matter.
An ancient infection roaring back, still cured by penicillin, still able to imitate almost any disease.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
Treponema pallidum penetrates intact mucous membranes and abraded skin, disseminates rapidly via blood and lymph, and provokes an obliterative endarteritis that underlies many of its lesions. It cannot be cultured routinely, so diagnosis relies on serology and, where available, direct detection. Penicillin is treponemicidal; the organism has not developed clinically meaningful penicillin resistance, which is why the same drug used in the 1940s remains first-line. The Jarisch-Herxheimer reaction, a transient febrile response after treatment, results from the release of treponemal components as organisms are killed.
Why syphilis is resurgent
The resurgence is multifactorial: reduced public-health funding and contact-tracing capacity, increased condomless sex in some networks (including in the context of HIV PrEP and the U=U era, where HIV-specific fear has fallen), substance use including methamphetamine, dating-app-facilitated partner change, and disruptions to clinics during the COVID-19 pandemic. Congenital syphilis has risen sharply in parallel, driven by gaps in prenatal screening and treatment, and is largely preventable. The infection disproportionately affects MSM in some surveillance data, but heterosexual and congenital transmission have both increased.
What people get wrong
Often saidSyphilis is a disease of the past
ActuallySyphilis is resurgent, with sharply rising primary, secondary, and congenital cases over the past decade in many countries.
Often saidA painless sore is harmless
ActuallyThe painless chancre is the primary stage of syphilis and is highly infectious; without treatment the infection progresses through serious later stages.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
At a glance
- Organism
- Treponema pallidum (spirochete)
- Primary lesion
- Painless chancre
- Classic secondary sign
- Rash on palms and soles
- First-line treatment
- Benzathine penicillin G
- Nickname
- The great imitator
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about Syphilis. A short entry is not a safe entry.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- How it compares. We have not set it against the alternatives.
- Children and teenagers. We have not checked what is known about younger people.
- Where we land. We have not taken a position on this yet.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
CDC STI Surveillance Reports2018-2023
Documented sustained increases in primary, secondary, and congenital syphilis in the US
CDC STI Treatment Guidelines2021
Reaffirmed benzathine penicillin G as first-line and detailed neurosyphilis/ocular syphilis management
Doxy-PEP trials (e.g., Luetkemeyer et al., NEJM)2023
Doxycycline post-exposure prophylaxis reduced syphilis and chlamydia incidence in MSM and transgender women on PrEP or with HIV