Syphilis serology


 * Common serologic tests used routinely include:
 * Venereal Disease Research Laboratory (VDRL),
 * Rapid plasma reagin (RPR), or
 * Recombinant antigen test


 * Sensitivity of serologic tests vary with the disease stage.
 * 78-86% sensitivity for primary syphilis
 * 100% sensitivity for secondary syphilis
 * 95-98% sensitivity for tertiary syphilis


 * Specificity is aprroximately 85-99%


 * False positives on the rapid tests can be seen in viral infections (Epstein-Barr, hepatitis, varicella, measles), lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease, pregnancy, intravenous drug abuse, or contamination. As a result, these two screening tests should always be followed up by a more specific treponemal test.

Nontreponemal test

 * Nontreponemal test antibody titers may correlate with disease activity, and results should be reported quantitatively.


 * A fourfold change in titer, equivalent to a change of two dilutions (e.g., from 1:16 to 1:4 or from 1:8 to 1:32), is considered necessary to demonstrate a clinically significant difference between two nontreponemal test results that were obtained using the same serologic test.


 * Sequential serologic tests in individual patients should be performed using the same testing method (e.g., VDRL or RPR), preferably by the same laboratory.


 * The VDRL and RPR are equally valid assays, but quantitative results from the two tests cannot be compared directly because RPR titers frequently are slightly higher than VDRL titers.


 * Nontreponemal test titers usually decline after treatment and might become nonreactive with time; however, in some persons, nontreponemal antibodies can persist for a long period of time: a response referred to as the serofast reaction.


 * Most patients who have reactive treponemal tests will have reactive tests for the remainder of their lives, regardless of treatment or disease activity. However, 15%-25% of patients treated during the primary stage revert to being serologically non-reactive after 2-3 years.


 * Treponemal test antibody titers should not be used to assess treatment response.

Treponemal test

 * Some clinical laboratories and blood banks have begun to screen samples using treponemal tests, typically by ELISA or chemiluminescence immunoassays. This strategy will identify both persons with previous treatment for syphilis and persons with untreated or incompletely treated syphilis. The positive predictive value for syphilis associated with a treponemal screening test result might be lower among populations with a low prevalence of syphilis.


 * Persons with a positive treponemal screening test should have a standard non-treponemal test with titer performed reflexively by the laboratory to guide patient management decisions.


 * If the non-treponemal test is negative, then the laboratory should perform a different treponemal test (preferably one based on different antigens than the original test) to confirm the results of the initial test.


 * If a second treponemal test is positive, persons with a history of previous treatment will require no further management unless sexual history suggests likelihood of re-exposure. Those without a history of treatment for syphilis should be offered treatment. Unless history or results of a physical examination suggest a recent infection, previously untreated persons should be treated for late latent syphilis.


 * If the second treponemal test is negative, further evaluation or treatment is not indicated.

Serologic test: HIV-infected persons

 * For most HIV-infected persons, serologic tests are accurate and reliable for the diagnosis of syphilis and for following a patient's response to treatment.


 * However, atypical syphilis serologic test results (i.e., unusually high, unusually low, or fluctuating titers) can occur in HIV-infected persons.

Serologic inconclusive
When serologic tests do not correspond with clinical findings suggestive of early syphilis, use of other tests (e.g., biopsy and darkfield microscopy) should be considered.

Resources

 * Sexually transmitted diseases treatment guidelines, 2010


 * Association of Public Health Laboratories (APHL). Laboratory Diagnostic Testing for Treponema pallidum. Expert Consultation Meeting Summary Report, January 13--15, 2009, Atlanta, GA


 * CDC: Guidelines for the laboratory diagnosis of gonorrhea, chlamydia and syphilis