What test is used for syphilis confirmation?

Syphilis Confirmation Testing

For syphilis confirmation, a treponemal test such as the TP-PA (Treponema pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody absorbed), or treponemal immunoassay should be used following a reactive nontreponemal test (RPR or VDRL). 1

Diagnostic Algorithm for Syphilis

Traditional Algorithm

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

   • If reactive → Proceed to confirmation
   • If non-reactive → No syphilis (except very early primary)

2. Confirmation: Treponemal test (TP-PA, FTA-ABS, or treponemal immunoassay)

   • If reactive → Confirms syphilis diagnosis
   • If non-reactive → Initial test was likely a false positive

Reverse Algorithm (Increasingly Used)

1. Initial Screening: Treponemal test (automated EIA/CIA)

   • If reactive → Proceed to nontreponemal test
   • If non-reactive → No syphilis

2. Secondary Testing: Nontreponemal test (RPR or VDRL)

   • If reactive → Active syphilis confirmed
   • If non-reactive → Proceed to step 3

3. Confirmation: Second treponemal test (different from initial test)

   • If reactive → Likely treated or very early/late syphilis
   • If non-reactive → Initial test was likely a false positive

Performance of Diagnostic Tests

Nontreponemal Tests (RPR, VDRL)

• Primary syphilis: 62-78% sensitivity 2
• Secondary syphilis: 97-100% sensitivity 2
• Early latent syphilis: 85-100% sensitivity 2
• Specificity: 95-100% 1

Treponemal Tests

• TP-PA, FTA-ABS: 95-100% sensitivity and specificity 1
• Automated immunoassays: High sensitivity and specificity (comparable to manual treponemal tests) 3

Important Clinical Considerations

• Treponemal antibodies typically remain positive for life after infection, even after successful treatment, making them unsuitable for monitoring treatment response 1

• Nontreponemal tests (RPR, VDRL) should be used for monitoring treatment response with expected fourfold decline in titers within 6 months for primary/secondary syphilis 1

• False positive nontreponemal tests are more common in:

  • Women (0.27% vs 0.20% in men)
  • Patients over 60 years (0.34% vs 0.25% in younger patients)
  • Conditions like pregnancy, autoimmune diseases, and certain infections 1

• For primary syphilis with visible lesions, darkfield microscopy provides direct visualization of spirochetes and should be used when available 4

• For neurosyphilis diagnosis, CSF-VDRL has high specificity but limited sensitivity; CSF treponemal tests may be helpful but should be interpreted in clinical context 5

Pitfalls to Avoid

1. Relying solely on nontreponemal tests in primary syphilis - These tests have limited sensitivity (62-78%) in early infection and may yield false negatives 2

2. Misinterpreting persistent treponemal reactivity - A positive treponemal test may indicate past treated infection rather than current disease 1

3. Failing to confirm discordant results - When using reverse sequence screening, discordant results (treponemal reactive/nontreponemal nonreactive) require additional treponemal testing to rule out false positives, especially in low-prevalence populations 6

4. Inadequate follow-up testing - Quantitative nontreponemal testing should be performed at 3,6,9, and 12 months after treatment to ensure adequate response 1

5. Missing neurosyphilis - Patients with late latent syphilis, CD4 count <350 cells/mm³ with high-titer VDRL (>1:32), or treatment failure should be evaluated for neurosyphilis with lumbar puncture 1