College of American Pathologists
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  For syphilis screening, a new reflex
  testing algorithm






August 2007
Feature Story

CAP TODAY published an article in November 2000 about Nancy Cornish, MD, director of microbiology, Methodist Hospital and Children’s Hospital, Omaha, who is working to improve physician test-ordering. She teaches Methodist’s physicians about lab tests through periodic clinical briefs, which she writes and distributes. The response of CAP TODAY readers to Dr. Cornish’s work was so enthusiastic and the requests for copies of her briefs so numerous that we asked her to share the clinical briefs she writes as they become available. Here, this month, is her word on syphilis screening.

The laboratory will no longer be using the rapid plasma reagin, or RPR, test as the screening test for syphilis. The RPR will be replaced with the syphilis IgG EIA test. Please order syphilis IgG when syphilis screening is needed. RPR and FTA (fluorescent treponemal antibodies) will remain available for treatment followup and reflex purposes only. VDRL (Venereal Disease Research Laboratory) remains the test of choice for cerebrospinal fluid, or CSF.

The laboratory will be switching to an enzyme immunoassay, or EIA, method that will detect IgG antibodies against Treponema pallidum, the spirochete that causes syphilis. This test has equal sensitivity to and greater specificity for T. pallidum than RPR, which detects anticardiolipin antibodies and has a high false-positive rate. The syphilis IgG test remains positive for many years after the disease has been eradicated. Therefore, the RPR remains essential to demonstrate active disease, monitor therapy, and detect treatment failure and reinfection. The qualitative VDRL remains the screening test for CSF.

There are two categories of tests for syphilis: nontreponemal tests and treponemal tests. A positive test for syphilis is not diagnostic of the disease, because false-positives occur with all currently available laboratory tests.

Nontreponemal tests: The RPR and the VDRL do not directly test for syphilis antibodies. They detect anticardiolipin antibodies and can have a high rate of false-positives, especially in a low-prevalence population of patients. False-positive results are usually, but not always, of low titer (=1:8) and occur because of autoimmune disease, drug addiction, acute viral infections, recent immunizations, and age. (Ten percent of people over 80 years of age have false-positive test results).

Treponemal tests: FTA-ABS (fluorescent treponemal antibodies absorption) and syphilis IgG detect specific antitreponemal antibodies to antigens found in pathogenic and nonpathogenic treponemes indicating exposure during the patient’s life. A positive test does not mean the patient has currently untreated syphilis. Although the tests are sensitive and specific, false-positives occur, especially in low-prevalence populations.

Special circumstances: Pregnancy—May result in an increase in RPR titers in women who have been adequately treated for syphilis. The increase is usually one or two dilutions and raises the question of whether or not to treat or re-treat these women for active disease.

Neonatal syphilis screening—Newborn infants should not be discharged from the hospital without determination of the mother’s serologic status for syphilis. Testing of the infant’s blood is inadequate for screening because false-negative and false-positive results can occur. Passive transfer of maternal antibodies across the placenta occurs and, therefore, a positive syphilis IgG or FTA test is not conclusive of active syphilis infection; the RPR on the infant must be positive as well. The tests performed on the infant should be the same as those performed on the mother to enable the titer results to be compared. A pediatric infectious disease consult is strongly recommended in these cases.

In summary, presumptive diagnosis of syphilis is possible using a combination of nontreponemal and treponemal tests. The use of only one type of test when positive, with no confirmatory test performed, is not sufficient for diagnosis because of false-positive test results owing to different medical conditions. All test results must be interpreted carefully, together with the patient’s clinical history and symptoms, to arrive at a clinical diagnosis.


  1. Pope V. Use of treponemal tests to screen for syphilis. Infect Med. 2004; 21(8):399–404.
  2. Jurado RL. Syphilis serology: a practical approach. Infectious Disease in Clinical Practice. 1996;5:351–358.
  3. RedBook, 2006 Report of the Committee on Infectious Diseases. American Academy of Pediatrics.
  4. A Manual of Tests for Syphilis. 9th ed. American Public Health Association; 1998.

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