What is the best test for diagnosing syphilis?

Best Test for Syphilis Diagnosis

The optimal approach to syphilis diagnosis requires both a nontreponemal test (RPR or VDRL) AND a treponemal test (such as FTA-ABS, TP-PA, or treponemal EIA), as neither test alone is sufficient for complete diagnosis. 1, 2

Definitive Diagnosis When Lesions Are Present

• Darkfield microscopy and direct fluorescent antibody testing of lesion exudate or tissue are the definitive diagnostic methods for early syphilis and should be prioritized when mucocutaneous lesions are present. 2
• These direct detection methods provide immediate confirmation without waiting for antibody development 2

Serologic Testing Algorithm

Nontreponemal Tests (RPR or VDRL)

• RPR and VDRL are the primary screening tests that detect antiphospholipid antibodies and correlate with disease activity. 3, 2
• Sensitivity varies by stage: 88.5% in primary syphilis, 97-100% in secondary syphilis, 85-100% in early latent, but drops to 61-75% in late latent syphilis 3, 1
• These tests must be reported quantitatively, as titers are used to monitor treatment response 3, 2
• A fourfold change in titer (two dilutions, e.g., 1:16 to 1:4) represents clinically significant change 3, 1

Treponemal Tests (FTA-ABS, TP-PA, or EIA)

• Treponemal tests confirm the diagnosis and detect antibodies specific to Treponema pallidum. 2
• These tests remain positive for life in most patients (75-85%) regardless of treatment, making them unsuitable for monitoring treatment response 3, 1
• Modern treponemal EIAs demonstrate 100% sensitivity across all stages of syphilis, compared to 93.7-98.7% for FTA-ABS 4
• Treponemal tests alone cannot distinguish active infection from previously treated disease 1

Why Both Tests Are Required

A positive treponemal test alone is insufficient for diagnosis—nontreponemal tests must also be performed to distinguish between active infection and past treated infection. 1

• The combination provides both confirmation of treponemal infection AND assessment of disease activity 2
• Nontreponemal tests can be false-positive in various medical conditions, requiring treponemal confirmation 3
• In late-stage disease, nontreponemal tests may be negative (25-39% of late latent cases) despite positive treponemal tests, representing either treated infection or waning antibody response 1

Testing Algorithm Options

Traditional Algorithm

1. Screen with nontreponemal test (RPR/VDRL)
2. Confirm positive results with treponemal test 2

Reverse Algorithm (Increasingly Common)

1. Screen with treponemal EIA (higher sensitivity, automated)
2. Confirm positive results with nontreponemal test 3
3. This approach may identify more patients with previous treated infection 3

Special Considerations

• Sequential tests should use the same method (RPR vs RPR, not RPR vs VDRL) and preferably the same laboratory, as results are not directly comparable between methods. 3, 1
• HIV-infected patients may have atypical serologic responses (unusually high, low, or fluctuating titers), but standard tests remain accurate for most HIV patients 3
• For suspected neurosyphilis, VDRL-CSF is highly specific when positive, though CSF FTA-ABS has higher sensitivity 3

Common Pitfalls to Avoid

• Never rely on a single test type—both nontreponemal and treponemal tests are required for complete diagnosis. 1, 2
• Do not use treponemal test titers to monitor treatment response, as they correlate poorly with disease activity 3, 1
• Do not compare titers between different test methods (VDRL vs RPR), as they are not interchangeable 3, 1
• If clinical suspicion is high but serologic tests are negative, pursue direct detection methods (darkfield microscopy, biopsy) or repeat serology in 1-2 weeks 3