I have a patient with an equivocal treponemal test result and I don’t see an option to order the Treponema pallidum particle agglutination assay (TP‑PA); what should I do next?

Order an Alternative Treponemal Confirmatory Test

When TP-PA is unavailable and you have an equivocal treponemal test result, order the fluorescent treponemal antibody-absorbed (FTA-ABS) test as your confirmatory treponemal assay. 1

Understanding the Diagnostic Algorithm

The 2018 IDSA/ASM guidelines specify that when the initial treponemal screening test (typically an EIA or chemiluminescence immunoassay) is reactive but the follow-up RPR is negative, you must perform a different treponemal-specific test to guide management decisions. 1 The guideline explicitly names FTA-ABS as the recommended alternative when TP-PA is not available. 1

Why This Matters for Your Patient

• Your patient has an equivocal treponemal result, which creates diagnostic uncertainty that cannot be resolved by repeating the same test. 1
• The reverse algorithm (treponemal test first, then RPR) identifies persons previously treated for syphilis, those with late latent disease, and can yield false positives in low-risk patients. 1
• Without a second, different treponemal test, you cannot distinguish between true infection and a false-positive result. 1, 2

Specific Testing Strategy

First-Line Alternative: FTA-ABS

• FTA-ABS has 82-91% sensitivity and serves as the traditional gold standard for confirming syphilis when TP-PA is unavailable. 3
• This test uses a different antigenic target and methodology than the initial screening EIA/CLIA, providing independent confirmation. 1
• The CDC explicitly recommends FTA-ABS as the alternative confirmatory treponemal test in the reverse algorithm. 1

Second-Line Alternative: Treponemal Line Immunoassay (INNO-LIA)

• If FTA-ABS is also unavailable, request syphilis line immunoassay (INNO-LIA) as a more sensitive confirmatory treponemal test. 3
• INNO-LIA may be particularly useful for resolving equivocal results, with studies showing it can confirm 14% of unconfirmed EIA-positive cases as true latent syphilis. 4

Critical Interpretation Points

If the Second Treponemal Test is Positive

• Both treponemal tests reactive + negative RPR = likely late latent syphilis, previously treated syphilis, or very early primary syphilis. 1, 3
• Review the patient's treatment history: if no documented adequate penicillin regimen exists, treat as late latent syphilis with benzathine penicillin G 2.4 million units IM weekly for 3 weeks. 3
• Nontreponemal tests have reduced sensitivity in late disease (only 61-75% in late latent, 47-64% in tertiary syphilis). 3

If the Second Treponemal Test is Negative

• Initial treponemal reactive + confirmatory treponemal negative + RPR negative = likely false-positive initial screening test; no treatment indicated. 3
• However, if clinical suspicion remains high (new chancre, rash, high-risk exposure), consider direct detection methods (darkfield microscopy, DFA, PCR from lesion) or repeat serology in 2-4 weeks. 3, 5

Common Pitfalls to Avoid

Do Not Order Repeat Testing with the Same Method

• Repeating the same treponemal EIA/CLIA that gave the equivocal result will not resolve diagnostic uncertainty. 1
• The guidelines specifically require a different treponemal test using a different antigenic target. 1

Do Not Rely on RPR Alone

• In very early primary syphilis (first 1-4 weeks), RPR sensitivity is only 62-78%, so a negative RPR does not exclude infection. 3, 5
• In late latent disease, 25-39% of cases have non-reactive RPR despite active infection. 3

Do Not Assume Treponemal Tests Indicate Active Infection

• Treponemal tests (FTA-ABS, TP-PA, EIA) remain positive for life in 75-85% of patients regardless of treatment or disease activity. 3
• These tests cannot distinguish between current infection, past treated infection, or remote untreated infection. 3

Immediate Clinical Actions While Awaiting Results

Assess for Clinical Manifestations

• Examine for primary syphilis: painless genital, oral, or rectal ulcer (chancre). 3
• Examine for secondary syphilis: diffuse maculopapular rash involving palms/soles, mucocutaneous lesions, generalized lymphadenopathy. 3
• Screen for neurosyphilis symptoms: headache, vision changes, hearing loss, cranial nerve palsies, confusion. 3
• Screen for ocular syphilis: eye pain, photophobia, vision changes, uveitis. 3

Obtain HIV Testing

• The CDC recommends HIV testing for all patients with reactive syphilis serology, as HIV co-infection alters monitoring frequency (every 3 months vs. every 6 months), increases neurosyphilis risk, and may cause atypical serologic responses. 3, 6

Consider Empiric Treatment in High-Risk Scenarios

• If the patient has high-risk sexual exposure in the past 90 days plus clinical signs suggestive of syphilis, treat empirically with benzathine penicillin G 2.4 million units IM while awaiting confirmatory testing. 3
• If the patient is likely to be lost to follow-up, treat empirically rather than risk missing active infection. 5
• If the patient is pregnant, treat immediately based on any reactive treponemal test, as only penicillin prevents congenital syphilis. 3

Laboratory Communication

Contact your laboratory directly and specify: "I need a confirmatory treponemal test different from the initial screening assay—please perform FTA-ABS or, if unavailable, INNO-LIA to resolve an equivocal treponemal result." 1 Clarify that you are following the CDC reverse algorithm guidance for discrepant treponemal/nontreponemal results. 1