Syphilis

Importance Syphilis is an infectious disease caused by Treponema pallidum , a gram-negative, spirochete bacterium. Worldwide, an estimated 8 million adults aged 18 to 49 years acquired syphilis in 2022. From 2019 to 2023, US syphilis cases increased by 61% overall, with diagnoses among females increasing by 112% and congenital syphilis cases increasing by 106%. Observations Syphilis is transmitted via contact with infectious lesions during vaginal, anal, or oral sex or via the placenta during pregnancy. Individuals at increased risk for syphilis include people with HIV, those engaging in condomless sex with multiple partners, and men who have sex with men (MSM)—who comprised one-third (32.7%) of all males with primary and secondary syphilis in 2023. Early syphilis is defined as syphilis in the first year after infection and includes symptomatic (primary and secondary) and asymptomatic (early latent) stages. Primary syphilis is characterized by painless anogenital lesions. Secondary syphilis is associated with a diffuse rash, mucocutaneous lesions, and lymphadenopathy. Syphilis diagnosed more than a year after infection is referred to as late syphilis and includes asymptomatic (late latent) and symptomatic (tertiary) stages. Neurosyphilis, which can occur at any stage, can lead to meningitis, uveitis, hearing loss, or stroke. In pregnancy, up to 40% of fetuses with in-utero exposure to syphilis are stillborn or die from their infection during infancy. The diagnosis of syphilis relies on serologic reactivity along with a clinical history and presentation consistent with active or latent syphilis infection. The recommended treatment for syphilis is benzathine penicillin G administered as intramuscular doses of 2.4 million units: a single injection for early stage and 3 weekly injections for late latent stage syphilis. Strategies to identify and prevent syphilis infections include (1) screening of sexually active people aged 15 to 44 years at least once and at least annually for those at increased risk, (2) screening 3 times in pregnant individuals (at the first prenatal visit, during the third trimester, and at delivery), (3) counseling about condom use, and (4) offering doxycycline postexposure prophylaxis (200-mg doxycycline taken within 72 hours after sex as postexposure prophylaxis) to MSM and transgender women with a history of a sexually transmitted infection in the past year. Conclusions and Relevance Syphilis infections, including congenital syphilis, have increased in the US and worldwide over the past decade. First-line treatment for syphilis is benzathine penicillin G. Routine syphilis screening of all pregnant patients and all sexually active people aged 15 to 44 years and use of doxycycline postexposure prophylaxis in individuals at risk for syphilis infection are recommended strategies to decrease syphilis transmission.