What is the recommended test for diagnosing syphilis?

Recommended Testing for Syphilis Diagnosis

The diagnosis of syphilis requires both a nontreponemal test (VDRL or RPR) and a treponemal test (FTA-ABS or TP-PA), as using only one type of test is insufficient for accurate diagnosis. 1

Diagnostic Testing Algorithm

Primary Testing Strategy

• Perform both nontreponemal and treponemal tests for complete diagnosis 1
  • Nontreponemal tests: VDRL (Venereal Disease Research Laboratory) or RPR (Rapid Plasma Reagin)
  • Treponemal tests: FTA-ABS (Fluorescent Treponemal Antibody Absorbed) or TP-PA (T. pallidum Particle Agglutination)

Definitive Methods for Early Syphilis

• Darkfield examinations and direct fluorescent antibody tests of lesion exudate or tissue are the definitive methods for diagnosing early syphilis 1
• When lesions are present, these direct detection methods should be prioritized 1

Serologic Testing Characteristics

• Nontreponemal tests (VDRL/RPR):

  • Correlate with disease activity and should be reported quantitatively 1
  • Usually become nonreactive after treatment, though some patients may remain "serofast" with persistent low titers 1
  • False positives can occur with various medical conditions, necessitating confirmation 1

• Treponemal tests (FTA-ABS/TP-PA):

  • Remain reactive for life in most patients regardless of treatment or disease activity 1
  • 15-25% of patients treated during primary stage may revert to nonreactive after 2-3 years 1
  • Poor correlation with disease activity; should not be used to assess treatment response 1

Special Considerations

Testing Sequence Options

• Traditional algorithm: Screen with nontreponemal test (VDRL/RPR) followed by treponemal test confirmation 2
• Reverse sequence: Some laboratories now screen with treponemal EIA/CIA first, followed by nontreponemal testing 2
  • Note: In low-prevalence populations, reverse sequence testing may yield more false positives 2

Monitoring Treatment Response

• Sequential serologic tests should use the same testing method (VDRL or RPR), preferably by the same laboratory 1
• A fourfold change in titer (two dilutions) indicates clinically significant difference 1
• Quantitative results from VDRL and RPR cannot be directly compared (RPR titers often slightly higher) 1

HIV Co-infection

• Some HIV-infected patients may have atypical serologic test results (unusually high, low, or fluctuating titers) 1
• When serologic tests and clinical presentation don't align, consider additional testing (biopsy, direct microscopy) 1
• For most HIV-infected patients, standard serologic tests remain accurate and reliable 1

Neurosyphilis Diagnosis

• No single test can diagnose neurosyphilis 1
• VDRL-CSF is highly specific but insensitive 1
• Diagnosis typically requires combinations of:
  • Reactive serologic test results
  • Abnormal CSF cell count (>5 WBCs/mm³) or protein
  • Reactive VDRL-CSF (with or without clinical manifestations) 1
• Some specialists recommend CSF FTA-ABS testing, which is highly sensitive but less specific than VDRL-CSF 1

Test Performance

• Recent evaluation shows high performance for both test types 3:

  • VDRL: 97.9% sensitivity, 100% specificity
  • FTA-ABS: 96.3% sensitivity, 99.5% specificity
  • Treponemal ELISA: 100% sensitivity, 100% specificity

• For primary syphilis specifically, TP-PA as first-line test showed higher sensitivity (86%) compared to traditional algorithm using VDRL/RPR first (71%) 4

Common Pitfalls

• Using only one type of test can lead to misdiagnosis 1
• Failure to report nontreponemal test results quantitatively limits ability to monitor treatment response 1
• Comparing titers between different test types (VDRL vs RPR) can lead to incorrect conclusions 1
• Not considering the possibility of false-positive nontreponemal tests in various medical conditions 1
• Relying on treponemal tests to assess treatment response is inappropriate 1