Should treatment for syphilis be started if the Treponema Pallidum Assay (TPA) test is positive?

Should Treatment Be Started for a Positive TPA Test?

A positive treponemal test (TPA) alone is insufficient to initiate treatment—you must obtain a nontreponemal test (RPR or VDRL) to distinguish between active infection requiring treatment and past treated infection that needs no further therapy. 1

Why TPA Positivity Alone Cannot Guide Treatment

• Treponemal tests (including TPA, FTA-ABS, TP-PA, TPHA) remain positive for life after infection, regardless of whether the patient received adequate treatment or achieved cure 1, 2
• Only 15-25% of patients treated during primary syphilis will eventually revert to treponemal-negative status after 2-3 years, meaning the vast majority remain permanently positive 1
• Treponemal tests correlate poorly with disease activity and cannot be used to monitor treatment response or determine if active infection is present 1

The Critical Next Step: Obtain a Nontreponemal Test

• You must perform an RPR or VDRL test to determine if active infection is present 1
• Nontreponemal test titers correlate directly with disease activity and are the appropriate tests for distinguishing active from past infection 1
• If the nontreponemal test is reactive (positive), this indicates either active infection or recent treatment, and clinical evaluation is needed to determine the stage and appropriate treatment 1, 3
• If the nontreponemal test is non-reactive (negative) with a positive treponemal test, this typically represents past treated infection that requires no further therapy 1

Treatment Algorithm Based on Combined Test Results

TPA Positive + RPR/VDRL Positive = Active Infection

• Determine the stage of syphilis through clinical examination and history 1
• For primary or secondary syphilis: benzathine penicillin G 2.4 million units IM as a single dose 4, 1
• For early latent syphilis (infection <12 months): benzathine penicillin G 2.4 million units IM as a single dose 1
• For late latent syphilis or unknown duration: benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks 1, 3

TPA Positive + RPR/VDRL Negative = Past Treated Infection

• No treatment is indicated in most cases 1
• However, nontreponemal tests have reduced sensitivity in late-stage disease (only 61-75% sensitive in late latent syphilis) 1
• Screen for symptoms of neurosyphilis (headache, vision changes, hearing loss, confusion) or tertiary syphilis (cardiovascular or gummatous manifestations) 1
• If any concerning symptoms are present despite negative nontreponemal test, consider direct detection methods (darkfield microscopy, biopsy) or CSF examination 1

Critical Exceptions and Red Flags

• If new clinical signs or symptoms suggestive of syphilis are present (chancre, rash, mucocutaneous lesions, neurologic symptoms, ocular symptoms), reassess for active infection even with discordant serology 1
• HIV-infected patients may have atypical serologic responses with unusually low, high, or fluctuating titers, and false-negative serologic tests have been reported 1
• In HIV-infected patients with high clinical suspicion and negative serology, pursue other diagnostic procedures such as biopsy or darkfield examination 1

Essential Concurrent Actions

• All patients with confirmed syphilis must be tested for HIV infection 4, 1, 3
• Evaluate and treat sexual contacts appropriately based on timing of exposure 4
• Use the same nontreponemal test method (RPR or VDRL) from the same laboratory for all follow-up testing to ensure accurate comparison 1

Common Pitfalls to Avoid

• Never initiate treatment based solely on a positive treponemal test without obtaining nontreponemal test results 1
• Do not compare titers between different nontreponemal test types (VDRL vs RPR) as they are not directly comparable 1
• Do not use treponemal test titers to assess treatment response—they remain positive regardless of cure 1
• Do not assume persistent low-titer nontreponemal reactivity necessarily indicates treatment failure or reinfection (this may represent a "serofast" state) 1, 5