What test is done after a positive Rapid Plasma Reagin (RPR) test?

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Confirmatory Testing After a Positive RPR

After a positive Rapid Plasma Reagin (RPR) test, a treponemal test such as TP-PA (Treponema pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody-absorbed), or another treponemal immunoassay should be performed to confirm the diagnosis of syphilis. 1

Diagnostic Algorithm for Syphilis

  1. Initial screening with RPR (non-treponemal test)

    • If positive → Proceed to confirmatory treponemal test
    • RPR sensitivity: 50-92.7%, specificity: 95-100% 1
    • Note: RPR has limited sensitivity (62-78%) in primary syphilis 1
  2. Confirmatory testing options (treponemal tests):

    • TP-PA (T. pallidum particle agglutination) - Sensitivity: 95-100%, Specificity: 95-100% 1
    • FTA-ABS (Fluorescent treponemal antibody-absorption) - Sensitivity: 95-100%, Specificity: 95-100% 1
    • Treponemal immunoassays (EIA or chemiluminescent assays) 2

Important Considerations

  • Treponemal tests detect antibodies specific to T. pallidum and remain positive for life in most patients, even after successful treatment 1
  • Non-treponemal tests like RPR measure antibodies to cardiolipin and can be used to monitor treatment response 1
  • 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

Alternative Testing Approach

Some laboratories use a reverse sequence algorithm:

  1. Start with a treponemal test
  2. If positive, follow with a non-treponemal test (RPR)
  3. If discordant results (treponemal reactive/non-treponemal nonreactive), perform a second treponemal test to rule out false positives 1

Special Situations

  • Neurosyphilis evaluation: If late latent syphilis, CD4 count <350 cells/mm³ with high-titer VDRL (>1:32), or treatment failure is present, consider lumbar puncture with CSF-VDRL testing 1
  • CSF testing: For suspected neurosyphilis, both VDRL and treponemal tests (TP-PA or FTA-ABS) may be performed on CSF 2, 3
    • CSF-VDRL has high specificity but limited sensitivity for neurosyphilis 1

Follow-up Testing

After treatment, quantitative non-treponemal tests (RPR or VDRL) should be used to monitor response:

  • Expected fourfold decline in titers within 6 months for primary/secondary syphilis
  • Follow-up testing recommended at 3,6,9, and 12 months after treatment 1

Pitfalls to Avoid

  • Do not rely solely on non-treponemal tests for diagnosis due to their limited sensitivity, especially in primary syphilis
  • Treponemal tests can remain positive for life, so they cannot distinguish between current and past treated infections
  • FTA-ABS, while highly sensitive, can occasionally give equivocal or false-negative results 4
  • Failure to confirm a positive RPR with a treponemal test may lead to misdiagnosis and inappropriate treatment

Remember that proper diagnosis of syphilis requires correlation of laboratory findings with clinical presentation and history of exposure.

References

Guideline

Syphilis Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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