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Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients

Charles B Hicks, MD
Meredith Clement, MD
Section Editor
Noreen A Hynes, MD, MPH, DTM&H
Deputy Editor
Jennifer Mitty, MD, MPH


Syphilis is an infection caused by the bacterium Treponema pallidum. Most new cases of syphilis are sexually acquired. The clinical manifestations depend upon the stage of disease. Studies performed in the pre-antibiotic era permit a relatively complete understanding of the natural history of untreated syphilis. Information about the natural history of untreated syphilis in humans derives from data collected from several sources:

In the late 19th century, a Norwegian physician described the evolution of infection in more than 1400 patients with primary and secondary syphilis. Because he believed that the available therapies at the time were highly toxic and of little benefit, patients received no treatment [1].

Additional data were collected from a study of 382 adults with syphilis who underwent autopsies between 1917 and 1941 [2]. This compilation provided pathologic confirmation of the late manifestations of syphilis.

Finally, the infamous Tuskegee study conducted between 1932 and 1972 collected data on 431 black men whose syphilis was untreated [3].

The epidemiology, pathogenesis, and clinical manifestations of syphilis will be reviewed here. Discussions of the diagnosis and treatment of syphilis, as well as syphilis in special populations are found elsewhere:


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Literature review current through: Sep 2016. | This topic last updated: Aug 1, 2016.
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