Laboratory Testing for Syphilis and Screening for Congenital Syphilis

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  • Laboratory Testing for Syphilis and Screening for Congenital Syphilis

Treponema pallidum is the causative agent of syphilis, a sexually transmitted disease that, as previously discussed, has been showing increasing activity in the United States.  Traditionally, screening for syphilis involved testing using a nontreponemal assay with positive  cases confirmed by use of a treponemal immunoassay.  Today in many laboratories, a “reverse algorithm” is being used with the screening being performed by a treponemal assay and, if positive, results confirmed by a nontreponemal test. 


  • Nontreponemal Assays


    These assays detect antibodies to nonspecific antigens produced in most patients with syphilis infection.  An example of a non-specific antigen nontreponemal assays detect is cardiolipin. 

    Examples of nontreponemal tests include rapid plasma regain (RPR) and the venereal research laboratory (VDRL) assays.

    These tests have a low sensitivity in early and late disease and they generally become negative after treatment.  There is a problem with false negatives early in the disease and this is one reason the treponemal assays are becoming more widely used as first testing option in syphilis diagnosis.

    False positive results are not uncommon. 

    Positive results with these assays must be confirmed using a treponemal assay. 

  • Treponemal Assays


    These assays detect antibodies specifically against T. pallidum.

    Examples of treponemal assays are the T. pallidum particle agglutination test (TP-PA) and the fluorescent treponemal antibody test (FTA).

    In addition to these tests there are multiple ELISA assays widely used in clinical laboratories.  The convenience of these ELISA assays and the fact that many can be automated has led to the use of the reverse algorithm i.e. detection of antibodies against T. pallidum being used as initial screening tests with confirmation using nontreponemal testing.

    False negative results are far less likely to occur with these assays as opposed to the nontreponemal tests.

    False positive results can occur so it is required that a positive result be confirmed with a nontreponemal test.

    Reactivity to the treponemal antibody test lasts a lifetime so it is necessary that in rescreening follow up, a nontreponemal assay be used.

  • Pregnancy and Syphilis

    Congenital syphilis, which has shown a significant increase in occurrence over the past several years, needs constant attention.  Untreated maternal syphilis can be associated with stillbirth, neonatal death, bone deformities and neurologic impairment. 

    The CDC recommendation is all pregnant women be tested for syphilis at the first prenatal visit.  CDC and ACOG also recommend repeat screening in the third trimester in women at high risk for acquiring syphilis and again at the time of delivery.  High risk is generally defined as living in communities with high syphilis prevalence, patients infected with HIV, and those with a history of incarceration, commercial sex work or multiple sexual partners.


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About the author

Dr. John Daly

John T. Daly, M.D. received his MD degree at Weill Cornell University Medical College, performed his internship and residency in Anatomic and Clinical pathology at Duke University Medical Center and a residency in Forensic Pathology at the Office of the Chief Medical Examiner in Chapel Hill, N.C. He is board certified in anatomic, clinical and forensic pathology. Through the course of his career, Dr. Daly has had extensive experience directing and advising laboratories of all sizes including physician office practices, Federal Health Clinics, surgical centers, Community Hospitals and the integrated academic health system clinical laboratories of Duke Medicine. He retired as Director of Laboratories of Duke Medicine, and continues his affiliation as a member of the emeritus staff.


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