What is the recommended screening test for syphilis?

Recommended Screening Test for Syphilis

The recommended screening test for syphilis is a nontreponemal test such as Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test, followed by confirmation with a treponemal-specific test if the initial screening is positive. 1

Traditional Screening Algorithm

The traditional and most widely used approach to syphilis screening follows this sequence:

1. Initial screening: Nontreponemal test (RPR or VDRL)

   • These tests detect antibodies to cardiolipin, a component released during Treponema pallidum infection
   • RPR has shown slightly higher sensitivity compared to VDRL in some studies 1
   • Sensitivity varies by disease stage:
     • Primary syphilis: 62-78% sensitive 1
     • Secondary syphilis: 97-100% sensitive 1
     • Early latent syphilis: 85-100% sensitive 1
     • Late latent syphilis: 61-75% sensitive 1

2. Confirmatory testing: If nontreponemal test is positive, a treponemal-specific test is performed

   • Options include:
     • T. pallidum particle agglutination (TP-PA)
     • Fluorescent treponemal antibody absorption (FTA-ABS)
     • Enzyme immunoassay (EIA)
     • Chemiluminescent immunoassay

Reverse Sequence Algorithm

Some laboratories have adopted a reverse sequence algorithm:

1. Initial screening: Treponemal-specific test (EIA or chemiluminescent immunoassay)
2. Confirmatory testing: If positive, a quantitative nontreponemal test (RPR or VDRL) is performed
3. Additional testing: If treponemal test is positive but nontreponemal test is negative, a different treponemal test is used to resolve discrepancies

This approach may identify more cases of previously treated syphilis or very early infection 1.

Special Considerations

Pregnancy

• All pregnant women should be screened at their first prenatal visit 2
• High-risk pregnant women should be retested in the third trimester and at delivery 2
• A positive RPR with confirmatory positive treponemal antibody test confirms the diagnosis 2

HIV Co-infection

• HIV infection does not significantly change the performance of standard tests for syphilis diagnosis 1
• False-positive nontreponemal tests may be more common in HIV-infected persons 1
• Responses to nontreponemal tests might be atypical (higher, lower, or delayed) in HIV-infected persons 1

Common Pitfalls and Caveats

1. False-negative results:

   • Can occur in very early primary syphilis before antibody development
   • Prozone phenomenon (excess antibody preventing flocculation reaction) in secondary syphilis
   • If clinical suspicion remains high despite negative serology, consider:
     • Repeat testing in 1-2 weeks
     • Direct detection methods (darkfield microscopy, PCR)

2. False-positive nontreponemal tests:

   • Can occur in various conditions including pregnancy, autoimmune diseases, viral infections
   • Always confirm with treponemal-specific tests 2

3. Biological false-positive reactions:

   • More common in HIV-infected persons 1
   • Can occur in hepatitis and systemic lupus erythematosus 3

4. Interpretation challenges:

   • A single positive serologic test is not diagnostic
   • Diagnosis requires both treponemal and nontreponemal test results along with clinical evaluation 1
   • Previously treated individuals may remain serofast (persistent low-titer positive)

Point-of-Care Testing

For resource-limited settings, point-of-care tests are available:

• Dual treponemal/nontreponemal rapid tests can provide both screening and confirmation 4
• These tests have shown good concordance with laboratory-based tests (>95% for both treponemal and nontreponemal components) 4

Remember that the choice of screening approach may depend on laboratory capabilities, population characteristics, and local epidemiology, but the traditional algorithm starting with a nontreponemal test remains the standard recommendation in most clinical settings.