Syphilis Serology Tests


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Subject: Syphilis Serology Tests

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  • Syphilis is an STD caused by the bacterium Treponema pallidum. Symptoms of infection are often subtle and easily confused with other STDs such as genital herpes infection. Syphilis is passed from person to person through direct contact with infectious exudates from obvious or concealed, moist, early lesions of skin and mucous membranes of infected people during sexual contacts. Exposure almost always occurs during oral, anal, or vaginal intercourse. A pregnant woman with the disease can pass it to her newborn child.

  • The diagnosis of syphilis is most commonly made by serologic testing and is typically performed in two settings: screening of patients at increased risk and evaluation of patients with suspected disease.

  • There are two types of serologic tests for syphilis: nontreponemal tests such as the rapid plasma reagin (RPR) test and Venereal Disease Research Laboratory (VDRL) test, and specific treponemal tests such as the Treponema pallidum particle agglutination assay (TP-PA), fluorescent treponemal antibody absorption (FTA-ABS) test, and the microhemagglutination test for antibodies to Treponema pallidum (MHA-TP).

  • Normal range: Negative.


  • An aid in the diagnosis of active or past T. pallidum infection. Nontreponemal tests are based upon the reactivity of serum from patients with syphilis to a cardiolipin–cholesterol–lecithin antigen. These tests measure IgG and IgM antibodies and are used as the screening test for syphilis in most settings. Positive tests are usually reported as a titer of antibody, and they can be used to follow the response to treatment in many patients. Treponemal tests are more complex and are usually used as confirmatory tests when the nontreponemal tests are reactive. These tests all use T. pallidum antigens and are based upon the detection of antibodies directed against treponemal cellular components. These tests are qualitative and are reported as reactive or nonreactive.



  • A nonreactive result does not totally exclude a recent (within the last 2–3 weeks) T. pallidum infection. Therefore, results need to be interpreted with caution.

  • Detection of treponemal antibodies may indicate recent, past, or successfully treated syphilis infections and, therefore, cannot be used to differentiate between active and cured cases.

  • False-positive tests for syphilis can occur with both nontreponemal and treponemal tests. A false-positive test result may be identified by a reactive nontreponemal test followed by a nonreactive treponemal test. It is estimated that 1–2% of the US population has false-positive nontreponemal test results. False-positive tests are particularly common during pregnancy.

  • The syphilis serology tests may be reactive with sera from patients with yaws (T. pallidum subspecies pertenue) or pinta (Treponema carateum).

  • With nontreponemal tests, biologic false-positive reactions have been reported in diseases such as infectious mononucleosis, leprosy, malaria, SLE, vaccinia, narcotic addiction, autoimmune diseases, and viral pneumonia.

  • Despite active syphilis serologic tests may be negative in severely immune-compromised patients.

  • CDC recommends standard (traditional) testing algorithm where initial screening with a nontreponemal test such as the RPR; a reactive specimen is then confirmed as a true positive with a treponemal test such as the TP-PA test. When results are reactive to both treponemal and RPR tests, persons should be considered to have untreated syphilis unless this is ruled out by treatment history. Persons who were treated in the past are considered to have a new syphilis infection if quantitative testing on an RPR test (or another nontreponemal test) reveals a fourfold or greater increase in titer.

  • Nontraditional testing algorithm: When reverse sequence screening (Figure 17-2) is used, all appropriate reflexing criteria should be used. FTA-ABS test should not be used to confirm discordant treponemal screening results.

Figure 17–2
Nontraditional algorithm for syphilis testing.

RPR, rapid plasma reagin (test); TP-PA, Treponema pallidum particle agglutination (test).

Figure 17–2
Nontraditional algorithm for syphilis testing.

RPR, rapid plasma reagin (test); TP-PA, Treponema pallidum particle agglutination (test).

Suggested Reading

Discordant results of reverse sequence syphilis screening-Five laboratories; United States 2006–2010. MMWR Morb Mortal Wkly Rep.  2011;60:133.