While often thought of as a disease of the past, syphilis is surging with alarming force, as starkly evidenced by the record 207,255 cases reported in the United States in 2022 alone.
Key Takeaways
- In 2022, the United States reported a total of 207,255 syphilis cases (all stages), marking a 68.0% increase since 2018
- Globally, an estimated 7 million new syphilis infections occur annually among adults aged 15–49 years
- In 2021, the syphilis rate in the US reached 68.9 cases per 100,000 population, the highest since 1950
- Syphilis is transmitted primarily through direct contact with a syphilis sore (chancre) during vaginal, anal, or oral sex, occurring in 30-60% of cases during primary stage
- Risk of syphilis transmission per unprotected sexual act with infectious partner is 10-60% for penile ulcers
- MSM engaging in condomless receptive anal sex have 4-6 times higher syphilis acquisition risk than insertive sex
- The primary chancre of syphilis appears 10–90 days (average 21 days) after exposure, painless ulcer with clean base
- Secondary syphilis rash occurs in 70-80% of cases, typically maculopapular on palms/soles, non-pruritic
- Latent syphilis divided into early (infectious, <1 year post-infection) and late (non-infectious, >1 year)
- Darkfield microscopy sensitivity 74-100% for chancre diagnosis
- Nontreponemal tests (RPR/VDRL) sensitivity 78-86% primary syphilis, 100% secondary
- Treponemal tests (TP-PA, FTA-ABS) >95% sensitivity all stages post-primary
- Benzathine penicillin G 2.4 million units IM single dose cures 97.8% early syphilis at 6 months
- Late latent syphilis requires 3 weekly benzathine penicillin 2.4MU doses, cure rate >95%
- Neurosyphilis treatment: aqueous crystalline penicillin G 18-24MU IV daily x10-14 days, 98% CSF normalization
Syphilis infections are rising sharply worldwide to alarming and historically high levels.
Diagnosis and Testing
- Darkfield microscopy sensitivity 74-100% for chancre diagnosis
- Nontreponemal tests (RPR/VDRL) sensitivity 78-86% primary syphilis, 100% secondary
- Treponemal tests (TP-PA, FTA-ABS) >95% sensitivity all stages post-primary
- Reverse sequence algorithm: treponemal first, then nontreponemal confirmatory, used by 45% US labs
- CSF-VDRL specificity 99.1% for neurosyphilis, sensitivity 30-70%
- PCR on chancre swabs sensitivity 82-95%, specificity 100% for T. pallidum
- RPR titer ≥1:32 suggests active infection, <1:4 post-treatment often serofast
- IgM-FTA-ABS for congenital syphilis, sensitivity 70% newborns
- Serofast state (low titer persistent) in 20-25% after treatment, not failure
- Dual HIV/syphilis testing: 4-fold increase in syphilis detection in high-risk clinics
- Point-of-care RDTs (e.g., DPP) sensitivity 84.2% nontreponemal, 92.1% treponemal
- Fourfold RPR decline by 6-12 months post-treatment indicates cure in early syphilis (expected 75%)
- FTA-ABS CSF test sensitivity 70% neurosyphilis but specificity lower
- Multiplex PCR detects T. pallidum in 95% primary lesions
- Prenatal syphilis screening uptake 95% US, but 50% treatment completion
- NAATs on blood/swabs emerging for non-chancre diagnosis, sensitivity 50-70%
- Traditional algorithm (nontreponemal first) false-positive rate 1-2%
- TPPA specificity 100%, used for confirmatory in reverse screening
- Quantitative RPR essential for monitoring, titer rise ≥4-fold suggests reinfection
- Congenital diagnosis: elevated cord IgM or 19S(IgM) FTA-ABS in 60-80%
- Biologic false-positive nontreponemal in 0.2-0.8% healthy, higher in pregnancy/Lupus
- Dried blood spot cards for syphilis testing sensitivity 91% in remote areas
- Whole blood RPR POC test accuracy 91% vs. lab
- Algorithm discordance (treponemal+/nontreponemal-) in 15-20% reverse screening, needs history
- CSF WBC >5 or protein >45 mg/dL indicates neurosyphilis in 40-50% HIV+
- Rapid plasma reagin slide test titers correlate 95% with tube test
- Serologic response slower in late syphilis, only 50% 4-fold decline by 2 years
- T. pallidum particle agglutination (TPPA) >99% specific confirmatory
- Self-collected swabs PCR sensitivity 89% for extragenital syphilis
Diagnosis and Testing Interpretation
While diagnosing syphilis is a medical detective story where we have a brilliant array of imperfect clues—from a darkfield microscope spotting only 74-100% of guilty parties in a chancre lineup, to CSF tests that are 99% sure but only 30-70% sure they’re looking at neurosyphilis, all while 20-25% of treated patients forever whisper a low-titer "serofast" alibi and our best blood tests bicker in 15-20% of reverse screenings—the real plot twist is that even with 95% prenatal screening, only half the mothers complete treatment, proving our most sensitive tool is still a functional human system that follows through.
Prevalence and Incidence
- In 2022, the United States reported a total of 207,255 syphilis cases (all stages), marking a 68.0% increase since 2018
- Globally, an estimated 7 million new syphilis infections occur annually among adults aged 15–49 years
- In 2021, the syphilis rate in the US reached 68.9 cases per 100,000 population, the highest since 1950
- Primary and secondary (P&S) syphilis cases in the US totaled 59,088 in 2022, up 12.3% from 2021
- Among US men, the P&S syphilis rate was 37.5 per 100,000 in 2022, compared to 2.5 per 100,000 among women
- Congenital syphilis cases in the US reached 3,755 in 2022, a record high with a rate of 95.9 per 100,000 live births
- In Europe, 37,125 syphilis cases were reported in 2021, with an EU/EEA rate of 8.5 per 100,000 population
- Australia's notified syphilis cases increased to 6,714 in 2022, with a rate of 25.3 per 100,000
- In Canada, 5,392 syphilis cases were reported in 2022, rate of 13.5 per 100,000, highest among MSM
- UK saw 8,995 syphilis diagnoses in 2022, rate 15 per 100,000, up 32% from 2021
- In China, syphilis incidence rose to 37.86 per 100,000 in 2020, with 557,000 estimated cases
- South Africa's syphilis prevalence among pregnant women was 4.2% in 2022 antenatal surveys
- In India, estimated 6.3 million syphilis cases in 2016 among 15-49 year olds
- Brazil reported 115,000 syphilis cases in 2021, with congenital syphilis at 54.4 per 100,000 live births
- In the US, MSM accounted for 82% of P&S syphilis cases among men in 2022
- Syphilis rates among Black/African American US males were 68.7 per 100,000 in 2022 P&S
- Hispanic US males had P&S syphilis rate of 33.8 per 100,000 in 2022
- Nevada had the highest US state P&S syphilis rate of 49.5 per 100,000 in 2022
- Congenital syphilis rate among American Indian/Alaska Native was 380.5 per 100,000 live births in 2022
- Globally, 661,000 adverse birth outcomes due to syphilis in 2022, including 425,000 fetal deaths/stillbirths
- In 2020, WHO estimated 8 million incident syphilis cases worldwide
- US syphilis cases among women increased 73% from 2016-2022 to 17,678 cases
- P&S syphilis notifications in MSM in Western Australia reached 1,364 cases in 2022, rate 1,040 per 100,000
- In 2021, syphilis seroprevalence among US adults was 0.79% based on NHANES data
- Russia reported 30,288 syphilis cases in 2021, incidence 20.7 per 100,000
- In Kenya, syphilis prevalence among antenatal clinic attendees was 1.2% in 2022
- Mexico's syphilis cases totaled 13,455 in 2021, with rate 10.5 per 100,000
- In 2022, California's congenital syphilis cases were 1,047, rate 202.2 per 100,000 live births
- Global syphilis incidence rate declined 36% from 1990 to 2021, but absolute cases rose due to population growth
- In 2022, New York City reported 2,338 P&S syphilis cases, rate 26.9 per 100,000
Prevalence and Incidence Interpretation
This alarming resurgence of syphilis worldwide, from the American epidemic to global millions, tragically proves that a disease we nearly eradicated is beating us because we keep forgetting our own public health history.
Symptoms and Stages
- The primary chancre of syphilis appears 10–90 days (average 21 days) after exposure, painless ulcer with clean base
- Secondary syphilis rash occurs in 70-80% of cases, typically maculopapular on palms/soles, non-pruritic
- Latent syphilis divided into early (infectious, <1 year post-infection) and late (non-infectious, >1 year)
- Tertiary syphilis affects 15-30% untreated cases after 10-30 years, involving gummas, cardiovascular, neurosyphilis
- Neurosyphilis symptoms include headache, stiff neck, cranial nerve dysfunction in 40% of early neurosyphilis
- Congenital syphilis early manifestations: snuffles (rhinitis) in 40%, hepatosplenomegaly in 50%
- Secondary syphilis mucous patches/oral lesions in 20-30%, highly infectious
- Alopecia in secondary syphilis (moth-eaten hair loss) occurs in 3-7%
- Late congenital syphilis includes Hutchinson teeth (notched incisors) in 30-40% untreated
- Cardiovascular syphilis (aortic regurgitation, aneurysms) in 10% of tertiary cases
- Ocular syphilis (uveitis, retinitis) reported in 4% of US cases 2014-2015
- Jarisch-Herxheimer reaction post-treatment in 10-50% early syphilis, fever/chills/rigors within 24h
- Condyloma lata (broad moist plaques) in secondary syphilis intertriginous areas, 15%
- Gummatous syphilis: destructive granulomas in skin/bone in 7-10% tertiary
- Asymptomatic neurosyphilis found in 10-20% early syphilis via CSF exam
- Congenital syphilis pseudoparalysis (painful osteochondritis) in 20% infants
- Secondary syphilis constitutional symptoms (fever, malaise, lymphadenopathy) in 50-60%
- Tabes dorsalis (neurosyphilis): lightning pains, ataxia, Argyll Robertson pupils in <1% tertiary
- Primary chancre average size 1-2 cm diameter, single in 80%, multiple 20%
- Late neurosyphilis general paresis: dementia, psychiatric symptoms in 5% untreated
- Rash relapse in secondary syphilis occurs in 25% within months untreated
- Congenital syphilis rash (copper-colored macules) on palms/soles in 39% newborns
- Aortitis in cardiovascular syphilis leads to 30% mortality if untreated
- Meningovascular syphilis stroke risk peaks 5-12 years post-infection
- Syphilis serology positive in 70% primary stage (darkfield for definitive)
- Bone pain/osteitis in early congenital syphilis affects 60%
- Hyperkeratotic palmar/plantar lesions unique to secondary syphilis
- Gumma ulceration heals with scarring, typical of tertiary skin disease
- CSF pleocytosis (WBC >5) in 50% symptomatic neurosyphilis
- Primary syphilis heals spontaneously in 3-6 weeks without treatment
Symptoms and Stages Interpretation
Syphilis is the master of hide-and-seek, starting with a quiet, painless introduction before launching a decades-long, multi-system siege that can quietly ruin your heart, brain, and bones if left untreated.
Transmission and Risk Factors
- Syphilis is transmitted primarily through direct contact with a syphilis sore (chancre) during vaginal, anal, or oral sex, occurring in 30-60% of cases during primary stage
- Risk of syphilis transmission per unprotected sexual act with infectious partner is 10-60% for penile ulcers
- MSM engaging in condomless receptive anal sex have 4-6 times higher syphilis acquisition risk than insertive sex
- HIV-positive individuals have 2-5 fold higher syphilis incidence rates than HIV-negative, due to higher-risk behaviors and immune factors
- Vertical transmission of syphilis from mother to fetus occurs in 70-100% of untreated primary/secondary stage pregnancies
- Oral sex accounts for 10-20% of syphilis transmissions in MSM populations
- Multiple sexual partners increase syphilis risk exponentially; odds ratio 3.5 for >5 partners/year
- Geographic proximity to sex work venues associated with 2.3 times higher syphilis incidence in urban MSM
- Substance use, particularly methamphetamine, linked to 3.8-fold increase in syphilis acquisition among MSM
- Transgender women have syphilis prevalence up to 20% in some US cities, 10-fold higher than general population
- Non-injection drug use associated with OR 2.1 for syphilis in heterosexual men
- Incarceration history increases syphilis risk by 1.8 times due to high-prevalence networks
- PrEP use among MSM not associated with increased syphilis risk when adjusted for sexual behavior (aOR 1.1)
- Group sex participation raises syphilis odds by 2.4 in multivariable models for MSM
- Syphilis transmission from blood transfusion rare post-2000 screening, <1 per million units
- Breastfeeding transmits syphilis only if nipple lesions present, risk <1% otherwise
- Chemsex (sex under drug influence) linked to 4.5-fold syphilis risk in European MSM
- Low socioeconomic status associated with OR 1.7 for syphilis seropositivity
- Partner concurrency increases syphilis transmission probability by 2-3 fold
- Travel to high-prevalence areas raises acquisition risk 1.5-2 times for MSM
- Untreated syphilis patients remain infectious for up to 2 years in latent stage if active lesions recur
- Heterosexual transmission risk higher in women (60%) than men (20-30%) per partnership with primary syphilis
- Online dating app use associated with 1.6-fold syphilis incidence in young MSM
- Black race/ethnicity independently associated with 2.2 OR for syphilis after behavior adjustment
- Primary syphilis chancre autoinoculates to other sites in 4-10% of cases via fomites
- Age 25-34 years peak risk group for syphilis, OR 2.8 vs. <25
- Urban residence increases syphilis odds by 1.4 compared to rural
Transmission and Risk Factors Interpretation
While syphilis is equal-opportunity in its transmission, your odds of catching it skyrocket not from a single lapse but from a constellation of modern vices—from condomless chemsex and multiple app-sourced partners to geographic hotspots and social inequities—proving that the most effective barrier to this ancient scourge is, tragically, still just thoughtful human behavior.
Treatment and Outcomes
- Benzathine penicillin G 2.4 million units IM single dose cures 97.8% early syphilis at 6 months
- Late latent syphilis requires 3 weekly benzathine penicillin 2.4MU doses, cure rate >95%
- Neurosyphilis treatment: aqueous crystalline penicillin G 18-24MU IV daily x10-14 days, 98% CSF normalization
- Doxycycline 100mg BID x14 days alternative for penicillin-allergic early syphilis, 95% success
- Congenital syphilis <1 year: procaine penicillin 50,000 U/kg IM daily x10 days
- Jarisch-Herxheimer reaction managed with NSAIDs, occurs 60% early syphilis treatment day 1
- HIV/syphilis co-infection: same regimen, but 20% serologic failure vs. 10% HIV-
- Azithromycin 2g single dose early syphilis efficacy 88%, high resistance 50% globally
- Penicillin desensitization required for allergy, anaphylaxis risk 0.02% per dose
- Post-exposure prophylaxis (PEP) with benzathine penicillin prevents 80% incubating syphilis
- Serologic cure (4-fold titer decline) by 12 months: 72% primary, 56% secondary syphilis
- Tetracycline 500mg QID x14 days 90% effective non-pregnant early syphilis alternative
- Stillbirth prevention: maternal treatment before 18 weeks gestation 96% effective
- Ceftriaxone 1-2g IM/IV daily x10-14 days 89-100% neurosyphilis cure HIV+
- Retreatment needed in 10-20% early syphilis if no titer decline by 6 months
- Partner management: 50-70% partners infected if index early syphilis, expedited therapy key
- Procaine penicillin G 2.4MU IM daily x10-14 days for neurosyphilis alternative
- Pregnancy syphilis: penicillin only, 82% perinatal transmission reduction if treated
- Serofast low titers persist in 25%, no progression if stable 2 years
- Benzathine penicillin allergy in pregnancy: desensitize, no alternatives safe
- Late neurosyphilis stabilization 90%, but neurologic sequelae in 20% pre-existing damage
- Doxycycline failure rate 5% early syphilis vs. <1% penicillin
- Congenital treatment response: clinical improvement 90% within 1 week
- HIV+ neurosyphilis: 70% CSF pleocytosis resolution at 6 months post-penicillin
- Mass treatment campaigns reduced syphilis prevalence 79% in communities
Treatment and Outcomes Interpretation
While penicillin remains the sharpest sword in our arsenal against syphilis, its precision depends heavily on the stage of the battle, the patient's own defenses, and a vigilant watch for both the enemy's retreat and the friendly fire of allergic or Herxheimer reactions.
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