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Hot Topics in Sexually Transmitted Infections and Associated Conditions

(Published November 2013)


  • Key facts about infection
    • Syphilis is caused by the spiral-shaped bacterium Treponema pallidum.
    • The clinical course is divided into four stages, which may overlap.

Table 15: Four Stages of Syphilis9

Stage Major Manifestations Duration (Untreated)
Primary stage Ulcer or chancre at infection site, regional lymphadenopathy; onset typically 2–4 weeks after exposure 1–3 months
Secondary stage May occur at any stage: early (1–12 months) usually meningovascular, with meningitis, stroke, altered mental status, cranial nerve deficits, and eye involvement; late (1–30 years) may include dementia, gait disturbances, and death Months to years
Tertiary stage Cardiac or gummatous lesions, typically of the skin, bones, or liver  
    • Patients may also present without symptoms (i.e., diagnosed via serology), which is defined as latent infection.
    • Early syphilis refers to primary syphilis, secondary syphilis, and latent syphilis of less than 1 year’s duration.
    • The incidence of infection is increasing among MSM, who now account for more than 70 percent of all cases; up to 4 percent of HIV-infected MSM acquire syphilis annually.13
    • The risk of acquiring HIV is two to five times higher among individuals with syphilis infection.71
  • Screening and diagnosis
    • Treponema pallidum cannot be cultured in the laboratory, which makes diagnostic testing for syphilis challenging.
    • Direct testing
        • Includes dark-field microscopy examination and tests to detect T. pallidum in lesion exudate or biopsied tissue.
        • Direct testing is the main method for diagnos­ing syphilis with mucocutaneous lesions (primary syphilis, occasional secondary syphilis).
    • Serologic testing
        • Serologic testing can be used to make presumptive diagnosis, based on the detection of antibodies to the bacterium.
        • A newly positive serology is strong evidence for infection with syphilis. Thus, it is helpful to know whether a patient has been tested previously and determine the results of prior testing if possible.
        • The use of two types of tests is necessary because each type has limitations, including false positive results.

Table 16: Serologic Testing for Syphilis9

Test Type Examples Comments
Nontreponemal tests Rapid Plasma Reagin; Venereal Disease Research Laboratory test Sensitive but nonspecific (risk of false positive results); all positives need confirmation by a treponemal test; titer (strength of positive result) indicates disease activity, declines with effective treatment and used to follow success of therapy
Treponemal tests Fluorescent treponemal antibody-absorbed test;
T. pallidum particle agglutination assay and others;
enzyme immunoassay;
chemiluminescence immunoassays
Once positive, usually remain positive for life and thus cannot be used to assess treatment response; when used for initial screening, follow-up testing should be performed by a nontreponemal test so treatment response can be followed
  • Treatment and management
    • Penicillin is the preferred antibiotic for all stages of syphilis.9 The formulation and dose depend on the stage and duration of infection and whether the central nervous system is involved.
      • For adults with early syphilis: benzathine penicillin G 2.4 million units IM in a single dose.
      • Alternative for severely penicillin-allergic patients: Doxycycline 100 mg orally twice daily for 2 weeks.
      • For treatment of other stages and of pregnant women, children, or individuals with penicillin allergy, see CDC treatment guidelines.