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Syphilis is a systemic sexually transmitted infection (STI) characterized by infectious stages and periods of latency. This ancient disease, known as the Great Pox and the “great imitator,” has captivated clinicians, scientists, poets, and authors for millennia.1 Though documented by clinicians and artists for centuries, the origins of syphilis, while debated, remain a mystery. Prior to the technological advances of the late 1800s and discovery of the causative organism for gonorrhea in 1879, most doctors assumed the clinical presentations of syphilis and gonorrhea represented a single disease entity.2 It was not until 1905 that scientists identified the causative organism for syphilis, the spirochete bacterium, Treponema pallidum subspecies pallidum.3 Left untreated, syphilis infection can be lifelong. Additionally, clinical management of syphilis is complex due to the various stages and limitations of the diagnostic tests. While typically associated with disease in adults, syphilis at any stage can be vertically transmitted and is one of the oldest recognized congenital infections, first described in the fifteenth century.4 Public health providers need to understand the pathogenesis, natural history, and clinical manifestations of syphilis in order to design effective syphilis prevention and control programs.


As an obligate human parasite, there are no animal or environmental reservoirs for T. pallidum subspecies pallidum. Therefore, humans are the only natural host for syphilis. It is believed that during sexual contact, the bacteria in infectious lesions penetrate the skin or mucosal surfaces of a sexual partner through macro- or microscopic abrasions5,6 Of note, the other pathogenic treponemes of humans [i.e., the causative agents of yaws, endemic syphilis (bejel), and pinta] share a common mode of transmission (direct skin-to-skin contact with an infectious lesion), albeit usually during infancy or childhood and not by sexual skin to skin or mucosal contact.7 They also share similar clinical appearances and immune responses. Within hours to days after inoculation, T. pallidum spreads throughout the body via the lymphatics and blood stream, involving most organ systems, including the central nervous system (CNS).8

It is thought that replication of this slow growing organism (generation time ~ 30–33 hours)9 at the site of inoculation leads to the development of the lesions at the primary stage of syphilis within weeks of infection. Replication after widespread dissemination leads to the signs and symptoms of secondary syphilis within months and years later, tertiary syphilis. The most infectious syphilitic lesions are the ulcerative lesions of the primary stage and the mucous membrane lesions of the secondary stage, such as condyloma lata and mucous patches. The highest concentration of spirochetes with the characteristic morphology and motility of T. pallidum seen on darkfield examination10 is from fluid obtained from condyloma lata lesions. This has led to the assumption that condyloma lata lesions are the most infectious lesions of syphilis, followed by the primary-stage chancre.

Over the course ...

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