Confirmatory Testing After Positive RPR for Syphilis
After a positive Rapid Plasma Reagin (RPR) test for syphilis, a treponemal-specific test such as TP-PA (Treponema pallidum particle agglutination) or FTA-ABS (fluorescent treponemal antibody absorption) should be performed as confirmatory testing. 1
Understanding Syphilis Testing Algorithms
There are two main testing approaches for syphilis:
Traditional Algorithm:
- Starts with a nontreponemal test (RPR or VDRL)
- Positive results are confirmed with a treponemal-specific test
Reverse Sequence Algorithm:
- Starts with a treponemal test
- Positive results are followed by a nontreponemal test
When an RPR is positive, confirmatory testing is essential because nontreponemal tests can yield false-positive results in various conditions.
Recommended Confirmatory Tests
The CDC and clinical guidelines recommend the following treponemal tests for confirmation 1:
TP-PA (Treponema pallidum particle agglutination) - Preferred option due to:
- High sensitivity (95-100%)
- Excellent specificity (100%)
- Superior sensitivity compared to FTA-ABS, especially in primary syphilis
Other acceptable options:
- FTA-ABS (fluorescent treponemal antibody absorption)
- EIA (enzyme immunoassay)
- CIA (chemiluminescence immunoassay)
Test Performance Characteristics
| Test | Sensitivity | Specificity | Notes |
|---|---|---|---|
| RPR/VDRL | 50-92.7% | 95-100% | Nontreponemal tests |
| TP-PA | 95-100% | 100% | Preferred confirmatory test |
| FTA-ABS | 78.2-95% | 95-100% | Less sensitive for primary syphilis |
| EIA/CIA | 94.5-100% | 95-100% | Newer automated methods |
Important Considerations
False-positive RPR results are more common in:
- Women (0.27% vs 0.20% in men)
- Patients over 60 years (0.34% vs 0.25% in younger patients) 1
Test selection matters: FTA-ABS has poor sensitivity (78.2%) for primary syphilis compared to other treponemal tests (94.5-96.4%) 2
Discordant results: When treponemal tests are reactive but nontreponemal tests are nonreactive, additional treponemal testing may be needed to rule out false positives 1
After Confirmation: Treatment and Monitoring
If syphilis is confirmed:
Treatment should be initiated based on disease stage:
- Primary/secondary: Benzathine penicillin G 2.4 million units IM as a single dose
- Late latent/unknown duration: Benzathine penicillin G 2.4 million units IM once weekly for 3 weeks
Monitoring should include:
- Quantitative nontreponemal testing at 3,6,9, and 12 months
- Expected fourfold decline in titers within 6 months for primary/secondary syphilis
- Failure to decline may indicate treatment failure or reinfection 1
Clinical Pitfalls to Avoid
- Don't rely solely on nontreponemal tests for diagnosis due to potential false positives
- Don't use FTA-ABS as first-line confirmatory test due to inferior sensitivity in primary syphilis
- Don't confuse treatment failure with reinfection - a fourfold increase after initial decline may indicate reinfection rather than failure
- Don't forget partner notification and treatment - essential for preventing reinfection and further transmission
Remember that treponemal tests typically remain positive for life even after successful treatment, while nontreponemal tests are used to monitor treatment response.