Syphilis in the Modern Era: An Update for Physicians

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Key points

  • Syphilis is common among men who have sex with men and is associated with HIV acquisition.

  • Syphilis can cause a wide range of systemic manifestations.

  • Penicillin G remains the treatment of choice for all stages of syphilis.

  • Syphilis partner services and presumptive treatment of contacts based on exposure history is essential to prevent syphilis reinfection and control the spread of disease.

Etiology and pathogenesis

Syphilis is caused by infection with the spirochetal bacterium Treponema subspecies pallidum. T pallidum is a highly motile coiled organism with tapering ends and 6 to 14 spirals. Of uniform cylindrical shape, the bacteria measure approximately 6 to 15 μm in length and 0.25 μm in width. T pallidum is a slowly metabolizing organism with an average multiplication time of approximately 30 hours. Humans are the only host for the organism.1 Most cases of syphilis are transmitted by sexual contact

Epidemiology

Infectious syphilis reached a historic low in the United States in 2000, with only 9756 primary and secondary cases (2.1 per 100,000 persons) compared with approximately 100,000 cases (71 per 100,000 persons) in 1946.9 In response to declining syphilis incidence, the Centers for Disease Control and Prevention released “The National Plan to Eliminate Syphilis from the United States” in 1999.10 However, starting in 2001, rates of primary and secondary syphilis have continued to rise, with an

Historical perspective

Current understanding of the natural course of syphilis infection among untreated individuals is largely based on historical data from the preantibiotic era. The Oslo Study was a large prospective natural history study in which Boeck observed approximately 2000 patients with primary and secondary syphilis admitted to the Oslo Clinic from 1891 to 1910.32 From 1932 to 1972 in Macon County, Alabama, the US Public Health Service conducted the infamous Tuskegee Syphilis Study to observe untreated

Early Syphilis

Early syphilis, which includes the primary, secondary, and early latent stages of infection, is defined as syphilis of less than 1 year’s duration. That designation is based on the observation that infectivity declines after the first year.

Diagnosis

Treponema pallidum cannot be cultivated in artificial media, is too slender to be observed by light microscopy, and fails to take up traditional Gram stains. It can be visualized using darkfield microscopy, which uses refracted light on a darkened background to identify the spirochete in clinical specimens; however, this technique is not widely available in clinical practice. Although polymerase chain reaction has been used to amplify genetic elements of T pallidum in clinical specimens, there

Treatment

Penicillin G remains the treatment of choice for all stages of syphilis. The treatment regimen (route of administration and duration) depends on the stage of disease (Table 1). Early syphilis (ie, primary, secondary, or early latent) can be treated with a single injection of 2.4 million units of intramuscular penicillin G benzathine; patients coinfected with HIV do not require additional doses of penicillin.37, 45, 46, 47 A nontreponemal antibody test should be obtained on the day of treatment

Follow-up

Patients with early stage syphilis, particularly those with high titer secondary syphilis, should be counseled about the possibility that they may experience a Jarisch-Herxheimer reaction after treatment. This immune-mediated process occurs within 2 to 24 hours of receiving penicillin G and is characterized by the acute onset of fever, headache, and myalgias. Peripheral leukocytosis and transaminitis can also occur. It occurs in 50% to 75% of patients with primary and secondary syphilis, is

Pregnancy and congenital syphilis

Pregnant women with syphilis who are allergic to penicillin should be desensitized and treated with penicillin according to the guidelines listed previously.37 In pregnant women the Jarisch-Herxheimer reaction can precipitate uterine contractions, fetal distress, or premature labor; thus, pregnant women should be treated in a monitored setting.2, 64 Treatment of neonates with proved or probable congenital syphilis should be done in consultation with a pediatric infectious diseases specialist.

Public health response: management of sex partners

Providers can work together with local health departments to prevent the spread of syphilis. Presumptive and confirmed cases of syphilis should be reported within 1 working day of diagnosis. Staff in public health departments are then able to contact and notify sex partners, and provide testing and treatment as appropriate. Internet partner notification (ie, using email and chat room “handles” to notify partners) can augment syphilis case management and is an important tool in the modern

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    Disclosures: J. Engelman has nothing to disclose. S.E. Cohen has received research support from the US National Institutes of Health. In the past year, S. Philip has received research support from Roche Diagnostics, SeraCare Inc, Abbott Diagnostics, and Cepheid Inc. J.D. Klausner has received educational and research support from Hologic Gen-Probe Inc, Cepheid Inc, Standard Diagnostics, Inc, and the US National Institutes of Health.

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