What are the recommended laboratory tests for treated syphilis?

Laboratory Monitoring for Treated Syphilis

Use nontreponemal tests (RPR or VDRL) with quantitative titers to monitor treatment response in all patients with treated syphilis. 1, 2

Primary Test for Monitoring: Nontreponemal Antibody Tests

The Centers for Disease Control and Prevention recommends using nontreponemal test titers (RPR or VDRL) exclusively for monitoring treatment response, as these correlate with disease activity and decline after successful treatment. 1, 2

Key Testing Principles

• Always use the same test type (either RPR or VDRL) performed by the same laboratory for serial monitoring, as RPR and VDRL titers are not directly interchangeable—only 29% of sera show concordant titers between the two tests. 3

• Report results quantitatively as titers (e.g., 1:8,1:16,1:32) rather than simply reactive/nonreactive, as titer changes define treatment success. 1, 2

• Never use treponemal tests (FTA-ABS, TP-PA, TPHA) to monitor treatment response, as these remain positive for life in most patients regardless of cure and correlate poorly with disease activity. 1

Monitoring Schedule by Stage

For Primary and Secondary Syphilis

• Recheck nontreponemal titers at 6 and 12 months after treatment. 1
• For HIV-infected patients, check at 3,6,9, and 12 months (every 3 months instead of every 6 months). 1

For Late Latent Syphilis or Unknown Duration

• Recheck nontreponemal titers at 6,12,18, and 24 months after treatment. 1
• For HIV-infected patients, check at 3,6,9,12,18, and 24 months. 1

Defining Treatment Success

Treatment success is defined by a fourfold decline in nontreponemal titer (equivalent to a change of two dilutions, e.g., from 1:32 to 1:8). 1, 4

Expected Timeline for Titer Decline

• For early syphilis (primary/secondary): Expect fourfold decline within 6-12 months. 1, 4
• For late latent syphilis: Expect fourfold decline within 12-24 months. 1
• Approximately 15-25% of patients treated during primary syphilis may achieve complete seroreversion (nonreactive test) after 2-3 years. 1

The Serofast State

Many patients remain "serofast" with persistent low-level positive titers (generally <1:8) for extended periods or life, which does not indicate treatment failure. 1, 5

• The clinical significance of the serofast state is unclear but probably does not represent treatment failure. 1
• Do not retreat patients solely based on persistent low titers without other evidence of active infection. 1

Indicators of Treatment Failure or Reinfection

Suspect treatment failure or reinfection if any of the following occur: 1

• Clinical signs or symptoms persist or recur (new chancre, rash, mucocutaneous lesions, neurologic symptoms, ocular symptoms)
• Sustained fourfold increase in nontreponemal titer compared to post-treatment baseline
• Failure of titer to decline fourfold within the expected timeframe (6-12 months for early syphilis, 12-24 months for late latent)

Management of Suspected Treatment Failure

1. Re-evaluate for HIV infection if not previously tested. 1
2. Perform CSF examination to rule out neurosyphilis. 1
3. Re-treat with three additional weekly doses of benzathine penicillin G 2.4 million units IM unless neurosyphilis is confirmed. 1

Test Performance Characteristics

Sensitivity by Stage (Important for Interpretation)

• Primary syphilis: RPR sensitivity 62.5-92.7%, VDRL 50-78.4% 3
• Secondary syphilis: RPR and VDRL sensitivity 91-100% 3
• Early latent syphilis: VDRL sensitivity 85-100% 3
• Late latent syphilis: RPR sensitivity 61%, VDRL 64-75% 3
• Previously treated syphilis: RPR sensitivity drops to only 30.7-56.9% 3, 5

Specificity Considerations

• RPR specificity is generally 94.3-99.8% in healthy populations. 3
• False-positive rates increase in certain populations: 10.7% in HIV-positive patients, 8.3% in hepatitis B-positive patients. 3, 2

Critical Pitfalls to Avoid

• Never switch between RPR and VDRL when monitoring the same patient—titers are not equivalent and cannot be compared directly. 3
• Never use treponemal test results to assess treatment response—they remain positive regardless of cure. 1
• Do not assume persistent low-titer reactivity indicates treatment failure—the serofast state is common and clinically insignificant. 1
• Do not compare titers from different laboratories—inter-laboratory variation can affect results. 1

Special Population: HIV-Infected Patients

HIV-infected patients require more intensive monitoring due to potential atypical serologic responses. 1

• May have unusually low, high, or fluctuating titers 1
• Require follow-up every 3 months instead of every 6 months 1
• Consider CSF examination for late-latent syphilis or syphilis of unknown duration 1
• False-negative serologic tests have been reported, so pursue alternative diagnostics (biopsy, darkfield examination) if clinical suspicion is high despite negative serology 1