Reexamining Syphilis: An Update on Epidemiology, Clinical Manifestations, and Management

Molly E Kent, PharmD; Frank Romanelli, PharmD MPH BCPS


The Annals of Pharmacotherapy. 2008;42(2):226-236. 

In This Article


The causative organism of syphilitic disease is Treponema pallidum subsp. pallidum, a member of the order Spirochaetales, family Spirochaetaceae, and genus Treponema.[1] Three other members of the genus Treponema are pathogenic to humans: T. pallidum subsp. pertenue, which causes yaws; T. pallidum subsp. endemicum, which causes nonvenereal endemic syphilis (bejel); and T. carateum, which causes pinta. These pathogenic treponemes are closely related antigenically and result in seropositive outcomes in patients infected with any of these subtypes. Morphologically, T. pallidum is a slender, tightly coiled, unicellular, helical cell measuring 6-15 µm long and 0.14-0.2 µm wide.[1,13] Its size makes it invisible on light microscopy and it is usually identified using darkfield microscopy by its distinctive undulating movements at its center that distinguish it from other pathogenic treponemes.

As T. pallidum has severely limited biosynthetic abilities and requires multiple nutrients from its host, it cannot survive without its only known natural reservoir, humans.[14]T. pallidum has an innate ability to evade the host's immune system. Studies of the outer membrane show only a small number of integral proteins, leaving the immune system few immunogenic transmembrane targets.[15,16,17] Treponeme first enters the host through compromised skin or by invading through intact mucosa.[18] The primary mode of syphilis transmission is sexual contact.[2] Unlike other sexually transmitted diseases (eg, HIV), syphilis is readily transmissible by oral sex and kissing at or near an infectious lesion in addition to vaginal and anal intercourse. The second most common mode of transmission is in utero transmission. Additionally, transmission can occur at delivery if the newborn comes in contact with a contagious lesion.[19] Other possible modes of transmission include receipt of blood products from a donor with syphilis, although this risk has been significantly reduced secondary to serologic testing.[20] The risk from needle sharing is unclear but appears to be low.[13,21] Nonsexual cutaneous transmission has been reported among healthcare workers and laboratory personnel whose unprotected hands have come in contact with the treponeme.[1,18]


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