Understanding Treponemal Antibody Tests vs. Syphilis Particle Agglutination Test
The Treponema pallidum particle agglutination (TPPA) test is actually a specific type of treponemal antibody test—not a separate category—and represents one of the most specific and sensitive manual treponemal assays available for syphilis diagnosis. 1, 2
Key Distinction: Test Categories
Syphilis serologic testing is divided into two fundamental categories 3, 4:
Nontreponemal tests: Detect antiphospholipid antibodies (host antibodies made in response to phosphatidylcholine taken up by T. pallidum). Examples include RPR, VDRL, and TRUST 3, 5
Treponemal tests: Detect antibodies specific to Treponema pallidum antigens. Examples include TPPA, FTA-ABS, MHA-TP, and various immunoassays (EIA, CIA, microbead assays) 1, 2
TPPA as a Treponemal Test
TPPA (Treponema pallidum particle agglutination) is classified as a manual treponemal antibody test and demonstrates superior performance characteristics compared to other manual treponemal assays. 1, 2
Performance Characteristics of TPPA:
- Primary syphilis: 94.5-96.4%
- Secondary syphilis: 100%
- Early latent: 95.2-100%
- Late latent: 86.8-98.5%
Comparison to other treponemal tests: TPPA outperforms FTA-ABS in primary syphilis (FTA-ABS sensitivity only 78.2%) and has superior specificity compared to MHA-TP 1, 2
Clinical Applications
Diagnostic Algorithm:
TPPA is the preferred confirmatory treponemal test for adjudicating discordant results in reverse sequence screening algorithms, superior to FTA-ABS due to its higher specificity and better sensitivity in primary syphilis. 2
- Initial screening: Automated treponemal immunoassay (EIA, CIA, or microbead assay) 6, 2
- Confirmatory testing: TPPA for discordant results 2
- Activity assessment: Quantitative nontreponemal test (RPR or VDRL) 4, 5
Neurosyphilis Diagnosis:
CSF TPPA demonstrates similar performance to CSF FTA-ABS for neurosyphilis diagnosis, with CSF TPPA titers ≥1:640 showing specificity comparable to CSF VDRL. 3, 7, 1
- CSF TPPA sensitivity and specificity are limited and must be interpreted with clinical context, additional CSF parameters (cell count, protein), and serum serology 1
Important Clinical Considerations
Treponemal Test Characteristics:
- Remain reactive for life in most patients (85-75%) regardless of treatment or disease activity 4, 5
- Cannot be used to monitor treatment response or distinguish active from past infection 4, 5
- Only 15-25% of patients treated during primary stage revert to non-reactive after 2-3 years 4, 5
Common Pitfall:
Never use TPPA or any treponemal test alone for diagnosis—both nontreponemal and treponemal tests are required for complete syphilis diagnosis. 4 Using only one test type leads to misdiagnosis, as treponemal tests cannot distinguish active infection from treated disease, and nontreponemal tests alone lack specificity 4, 5
Monitoring Treatment:
Use quantitative nontreponemal tests (RPR or VDRL) exclusively for treatment monitoring, with a fourfold change in titer indicating clinically significant response. 4, 5 TPPA and other treponemal tests remain positive despite successful treatment and provide no information about disease activity 4, 5