What is the test for syphilis?

Syphilis Testing

Syphilis diagnosis requires both nontreponemal tests (RPR or VDRL) and treponemal tests performed together, as using only one type is insufficient for accurate diagnosis. 1

Definitive Diagnostic Methods (When Lesions 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, providing immediate confirmation without waiting for antibody development. 2
• These direct detection methods confirm infection immediately and should be pursued if lesions are accessible. 1

Serologic Testing Algorithm

Traditional Algorithm (Preferred in Most Settings)

• Screen with nontreponemal test (RPR or VDRL) first, then confirm all positive results with a treponemal test. 2
• Nontreponemal tests detect antiphospholipid antibodies that correlate with disease activity and must be reported quantitatively as titers. 3
• The primary nontreponemal tests are Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL), with TRUST and unheated serum reagin used less commonly. 3

Reverse Algorithm (Alternative Approach)

• Screen with treponemal enzyme immunoassay (EIA) first, then confirm positive results with nontreponemal test. 2
• This approach may identify more patients with previous treated infection or late-stage disease where nontreponemal antibodies have waned. 2, 4
• The disadvantage is an increased rate of false-positive results requiring additional workup. 4

Test Performance Characteristics by Stage

Nontreponemal Tests (RPR/VDRL)

• Primary syphilis: 88.5% sensitivity 2
• Secondary syphilis: 97-100% sensitivity 2
• Early latent syphilis: 85-100% sensitivity 2
• Late latent syphilis: 61-75% sensitivity 2
• Tertiary syphilis: 47-64% sensitivity 5
• Specificity approaches 100% when performed on serum. 3

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

• Treponemal tests confirm the diagnosis by detecting antibodies specific to Treponema pallidum. 2
• These tests remain positive for life in most patients (75-85% remain reactive permanently), making them unsuitable for monitoring treatment response. 1, 5
• Only 15-25% of patients treated during primary stage may revert to nonreactive after 2-3 years. 1

Critical Testing Principles

• Both test types are required—never rely on a single test type alone. 2
• Nontreponemal test results must be reported quantitatively (as titers like 1:8,1:16, etc.) because titers are used to monitor treatment response. 1, 2
• A fourfold change in nontreponemal titer (two dilutions, such as 1:8 to 1:32) represents clinically significant change. 1
• Sequential tests should use the same testing method (RPR vs RPR, or VDRL vs VDRL), preferably by the same laboratory, as results are not directly comparable between methods. 1, 2

Special Testing Considerations

Neurosyphilis Diagnosis

• VDRL performed on cerebrospinal fluid (VDRL-CSF) is highly specific when positive but has low sensitivity. 1
• No single test is sufficient for neurosyphilis diagnosis—requires combination of reactive serologic tests, abnormal CSF cell count or protein, and reactive VDRL-CSF. 1
• CSF leukocyte count >5 WBCs/mm³ is a sensitive indicator for neurosyphilis. 1

HIV-Infected Patients

• Standard serologic tests remain accurate and reliable for most HIV-infected patients. 1, 2
• Some HIV patients may have atypical serologic responses with unusually low, high, or fluctuating titers. 2, 5
• False-negative serologic tests have been reported in HIV patients with documented infection, so pursue direct detection methods if clinical suspicion is high despite negative serology. 5

Common Pitfalls to Avoid

• Never use treponemal test titers to monitor treatment response—they correlate poorly with disease activity and remain positive regardless of cure. 2, 5
• Never compare titers between different test methods (e.g., VDRL titer vs RPR titer)—they are not directly comparable. 1, 2
• Do not assume a single negative test rules out syphilis in very early infection—antibodies may not yet be detectable in the first 1-4 weeks after exposure. 5
• Recognize that nontreponemal tests can be negative in late-stage disease (25-39% of late latent cases have nonreactive RPR). 5