What is the recommended laboratory diagnosis for a case of syphilis?

Laboratory Diagnosis for Syphilis

The recommended laboratory diagnosis for syphilis requires both treponemal and non-treponemal tests, with initial screening using either a non-treponemal test (traditional approach) or a treponemal test (reverse sequence approach), followed by confirmation with the other test type. 1

Diagnostic Approaches

Traditional Screening Approach

• Initial screening with non-treponemal tests:
  • Rapid Plasma Reagin (RPR)
  • Venereal Disease Research Laboratory (VDRL)
• Confirmation with treponemal tests:
  • T. pallidum particle agglutination (TP-PA)
  • Enzyme immunoassay (EIA)
  • Chemiluminescent immunoassay (CIA) 2, 1

Reverse Sequence Approach

• Initial screening with treponemal tests (EIA or CIA)
• Confirmation of active disease with quantitative non-treponemal tests (RPR or VDRL) 2, 1

Test Characteristics

Non-treponemal Tests (RPR, VDRL)

• Primary Syphilis: Sensitivity 62-78% 2
  • RPR: 62.5-92.7% sensitive
  • VDRL: 50-78.4% sensitive 2, 1
• Secondary Syphilis: Sensitivity 97-100% 2
  • RPR: 97-100% sensitive
  • VDRL: 100% sensitive 2, 1
• Early Latent Syphilis:
  • VDRL: 82.1-100% sensitive 2, 1

Treponemal Tests

• Higher sensitivity (95-100%) and specificity (95-100%) compared to non-treponemal tests 1
• Include:
  • FTA-ABS (Fluorescent Treponemal Antibody Absorption)
  • TP-PA (T. pallidum Particle Agglutination)
  • EIA (Enzyme Immunoassay)
  • CIA (Chemiluminescent Immunoassay) 1

Test Interpretation

RPR/VDRL Result	Treponemal Test Result	Interpretation
Positive	Positive	Confirmed syphilis (current or past)
Positive	Negative	Likely false-positive RPR/VDRL
Negative	Positive	Possible very early infection, previously treated syphilis, or late-stage syphilis
Negative	Negative	No evidence of syphilis [1]

Special Testing Considerations

• Direct detection methods may be useful for primary syphilis:

  • Darkfield microscopy of lesion exudate
  • PCR testing of lesion material 3

• Neurosyphilis diagnosis requires:

  • Lumbar puncture with CSF analysis
  • CSF-VDRL (high specificity but limited sensitivity)
  • CSF treponemal tests (interpreted in clinical context) 1

• Point-of-care testing:

  • Rapid immunochromatographic tests can detect both treponemal and non-treponemal antibodies simultaneously
  • Useful in resource-limited settings or when follow-up is uncertain 4

Common Pitfalls and Caveats

• False-positive non-treponemal tests can occur in:

  • Pregnancy
  • Autoimmune diseases
  • Viral infections
  • Advanced age
  • Malaria
  • HCV infection
  • Drug use 1

• Prozone phenomenon: False-negative results in high-titer specimens due to antibody excess; dilution of specimen resolves this issue

• Serofast state: Persistent low-titer positive non-treponemal tests despite adequate treatment; does not indicate treatment failure

• Window period: Early primary syphilis may be seronegative; direct detection methods should be used if clinical suspicion is high

Follow-up Testing

• Monitor treatment response with quantitative non-treponemal testing at 3,6,9, and 12 months
• A fourfold decline in titer within 6 months indicates successful treatment for primary/secondary syphilis
• Failure to achieve fourfold decline may indicate treatment failure
• A fourfold increase after initial decline suggests reinfection 1

The complexity of syphilis serology often requires the expertise of reference laboratories and clinical specialists for proper interpretation, particularly in challenging cases 5.