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.[1] 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

References

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