Confirmatory Testing After Positive RPR for Syphilis
After a positive Rapid Plasma Reagin (RPR) test for syphilis, a treponemal test such as the Treponema pallidum particle agglutination (TP-PA) assay or fluorescent treponemal antibody absorption (FTA-ABS) test should be performed to confirm the diagnosis. 1
Understanding Syphilis Testing Algorithms
Syphilis diagnosis involves two types of tests:
Nontreponemal tests (RPR, VDRL)
- Detect antibodies to cardiolipin
- Can produce false-positive results
- Used for screening and monitoring treatment response
Treponemal tests (TP-PA, FTA-ABS)
- Detect antibodies specific to T. pallidum
- Higher sensitivity (95-100%) and specificity (95-100%)
- Used for confirmation of infection
Traditional Algorithm
- Initial screening with nontreponemal test (RPR)
- If positive, confirm with treponemal test (TP-PA or FTA-ABS)
Reverse Algorithm
- Initial screening with treponemal test
- If positive, follow with nontreponemal test for activity assessment
Confirmatory Treponemal Tests
The CDC recommends the following treponemal tests for confirmation after a positive RPR 2:
- TP-PA (Treponema pallidum particle agglutination) - Highly sensitive and specific
- FTA-ABS (Fluorescent treponemal antibody absorption) - Traditional gold standard
- EIA/CIA (Enzyme/Chemiluminescence immunoassay) - Automated options
Interpreting Results
| RPR Result | Treponemal Test Result | Interpretation |
|---|---|---|
| Positive | Positive | Confirmed syphilis (current or past) |
| Positive | Negative | Likely false-positive RPR |
False-Positive RPR Considerations
- More common in women than men (0.27% vs 0.20%) 1
- Higher in patients over 60 years (0.34%) 1
- More frequent in HIV-infected persons 2
- Can occur in autoimmune diseases, pregnancy, and other infections
Special Situations
Suspected false-negative treponemal test: Consider repeat testing in 1-2 weeks, exclusion of prozone phenomenon, biopsy, darkfield examination, or direct fluorescent antibody staining 2
Discordant results: When initial treponemal test and follow-up nontreponemal test are discordant, additional treponemal testing with a different method may be helpful 1, 3
Suspected neurosyphilis: CSF examination should be performed in persons with neurologic or ocular symptoms, active tertiary syphilis, treatment failure, or HIV-infected persons with late-latent syphilis 2
Newer Testing Options
While traditional treponemal tests remain the standard for confirmation, newer options include:
- Western blot/Immunoblot assays: High sensitivity and specificity, useful for resolving discordant results 4
- Point-of-care dual tests: Simultaneously detect both nontreponemal and treponemal antibodies 5
Key Pitfalls to Avoid
- Don't rely solely on RPR results - False positives occur in 0.2-0.34% of the population 1
- Don't confuse past treated infection with current infection - Treponemal tests typically remain positive for life after infection
- Don't overlook the possibility of neurosyphilis - Consider CSF examination in appropriate cases
- Don't miss early syphilis - Serologic tests may be negative in very early primary syphilis
Remember that while treponemal tests are highly specific for syphilis, they cannot distinguish between current and past treated infections. The nontreponemal test titer is used to monitor disease activity and treatment response.