What is the clinical significance of a TPHA (Treponema pallidum hemagglutination) titre value in diagnosing and monitoring syphilis?

Clinical Significance of TPHA Titre Values

TPHA titres have minimal clinical utility for diagnosis, treatment monitoring, or assessing disease activity because they remain persistently elevated for life after infection regardless of treatment success, unlike nontreponemal tests (RPR/VDRL) which should be used for these purposes. 1

Diagnostic Role of TPHA

• TPHA serves exclusively as a confirmatory test to distinguish true syphilis infection from biological false-positive nontreponemal tests (RPR/VDRL), not as a quantitative marker of disease activity 1, 2
• The test detects both IgM and IgG treponemal antibodies, with IgM predominating in early infection and IgG persisting indefinitely 3
• TPHA demonstrates excellent sensitivity (99.2-100%) and specificity (97.8-99.3%) for confirming syphilis when used as a second-line test after positive RPR/VDRL 2

Why TPHA Titres Should NOT Be Used for Monitoring

• Treponemal tests including TPHA remain reactive for life in 75-85% of patients regardless of treatment or cure, making serial titres meaningless for assessing treatment response 1, 4
• In a study of 61 early syphilis cases, none of the 55 patients with positive pre-treatment TPHA became consistently negative after successful treatment 5
• While some secondary syphilis cases show rapid titre decline with treatment, this does not reliably reflect disease stage or treatment success 5
• The post-treatment TPHA titre does not necessarily reflect the stage at which disease was arrested 5

Correct Tests for Treatment Monitoring

• Nontreponemal tests (RPR or VDRL) are the only appropriate tests for monitoring treatment response, as their titres correlate with disease activity and should decline fourfold within 6-12 months after successful treatment 1
• Sequential monitoring must use the same nontreponemal test method (RPR vs VDRL) preferably by the same laboratory, as titres are not interchangeable between methods 1

Limited Exception: TPHA Index in Neurosyphilis

• The TPHA index (comparing CSF to serum TPHA titres) can identify intrathecal antitreponemal antibody production in HIV-infected patients with suspected neurosyphilis when CSF VDRL is nonreactive 6
• In one study, 12.5% of HIV-infected patients with abnormal CSF findings but negative CSF VDRL had positive TPHA indices, supporting active neurosyphilis diagnosis 6
• This specialized calculation requires paired CSF and serum samples and is distinct from routine TPHA titre interpretation 6

Critical Pitfalls to Avoid

• Never use TPHA titres to assess treatment success or failure – this is the most common misuse of treponemal testing 1
• Do not compare TPHA titres over time to determine if infection is active or adequately treated 1, 5
• Do not assume a high TPHA titre indicates active disease or that a declining titre indicates cure 5, 7
• Remember that 15-25% of patients treated during primary syphilis may eventually revert to negative treponemal tests after 2-3 years, but this is unpredictable and should not guide management 1

Practical Algorithm for Syphilis Serology Interpretation

For diagnosis:

• Use RPR/VDRL as screening test, confirm positive results with TPHA (or other treponemal test) 1
• Both tests must be positive to diagnose syphilis 1

For treatment monitoring:

• Use only quantitative RPR or VDRL titres (e.g., 1:4,1:16,1:64) 1
• Expect fourfold decline within 6-12 months for early syphilis, 12-24 months for late syphilis 1
• Ignore TPHA results entirely for monitoring purposes 1

Special consideration:

• In HIV-infected patients with suspected neurosyphilis and negative CSF VDRL, calculate TPHA index to detect intrathecal antibody production 6