What does a positive TPHA result indicate and how is it treated?

How to Interpret TPHA Results

What TPHA Positivity Indicates

A positive TPHA (Treponema pallidum hemagglutination) test indicates current or past treponemal infection with Treponema pallidum, the causative agent of syphilis. 1, 2

Key Characteristics of TPHA Testing

• TPHA is a treponemal-specific test with high sensitivity (similar to or exceeding FTA-ABS) in primary, secondary, and treated syphilis 2
• Specificity is high (approximately 88.5-89% in most populations), though false positives can occur in approximately 11-12% of biological false positive (BFP) sera and leprosy patients 1
• TPHA remains positive for life in most patients after treponemal infection, even with successful treatment 3, 4

Clinical Interpretation Algorithm

Step 1: Confirm Active vs. Past Infection

• A positive TPHA alone cannot distinguish between active and treated syphilis 3, 2
• Must correlate with nontreponemal tests (RPR/VDRL) to assess disease activity 2
• If nontreponemal tests are also positive, this suggests active or recent infection requiring treatment 2
• If nontreponemal tests are negative but TPHA is positive, this typically indicates past treated infection or very early primary syphilis 2

Step 2: Rule Out False Positives

• When TPHA is positive but patient has no history or clinical signs of syphilis, perform confirmatory testing with TPI and FTA-ABS 1
• False positive TPHA reactions occur in approximately 11.3% of BFP sera 1
• Consider false positives in patients with leprosy or other chronic inflammatory conditions 1

Step 3: Assess for Neurosyphilis (if indicated)

• In HIV-infected patients with latent syphilis and positive TPHA, consider lumbar puncture if serum RPR ≥1:32 or CD4 ≤350 cells/µL 5
• CSF TPHA index (ratio of CSF to serum TPHA accounting for blood-brain barrier permeability) can help identify intrathecal antibody production, supporting neurosyphilis diagnosis 6
• A positive TPHA index indicates intrathecal antitreponemal antibody production and provides stronger evidence for active neurosyphilis in patients with CSF abnormalities but nonreactive CSF VDRL 6
• CSF TPPA (similar test) at titers ≥1:640 has specificity similar to CSF VDRL for neurosyphilis diagnosis 5

Treatment Implications

Treatment decisions should be based on:

• Stage of syphilis determined by clinical findings, history, and nontreponemal titer levels 5
• Presence of symptoms (neurologic, ocular, or otic manifestations) 5
• HIV status (though treatment regimens for early syphilis are similar regardless of HIV status) 5

TPHA Response to Treatment

• TPHA titers do not reliably decrease after treatment in most cases of primary and early latent syphilis 3
• In secondary syphilis, some patients show significant and rapid fall in TPHA titer with treatment, but this is inconsistent 3
• Post-treatment TPHA titer does not necessarily reflect the stage at which disease was arrested 3
• Therefore, TPHA should NOT be used to monitor treatment response—use nontreponemal tests (RPR/VDRL) instead 3, 4

Common Pitfalls to Avoid

• Do not use TPHA alone for screening—combine with VDRL/RPR for optimal sensitivity and to distinguish active from past infection 2
• Do not rely on TPHA for treatment monitoring—it remains positive indefinitely in most patients 3
• Do not assume negative CSF VDRL excludes neurosyphilis—CSF VDRL sensitivity is only 49-87%, and CSF TPHA index may provide additional diagnostic value 5, 6
• Do not dismiss positive TPHA in asymptomatic patients—correlate with clinical history, nontreponemal tests, and risk factors 1, 2