Treatment Decision for Positive TPA Test
A positive Treponema Pallidum Assay (TPA) test alone is insufficient to initiate treatment—you must obtain a confirmatory nontreponemal test (RPR or VDRL) to establish active infection before treating. 1, 2
Diagnostic Algorithm Required Before Treatment
The diagnosis of syphilis requires both treponemal and nontreponemal tests working together 2:
If TPA is positive but nontreponemal test (RPR/VDRL) is negative: This likely represents either previously treated syphilis or a false-positive treponemal test, and treatment is generally not indicated 2
If TPA is positive AND nontreponemal test is reactive: This confirms active syphilis requiring immediate treatment 1, 2
Critical caveat: Treponemal tests like TPA remain positive for life regardless of treatment status, making them useless for determining current infection status alone 2, 3
Immediate Actions When TPA is Positive
Before initiating treatment, you must:
Obtain quantitative nontreponemal testing (RPR or VDRL) immediately to confirm active disease 1, 2
Perform thorough physical examination specifically looking for chancres (primary syphilis), rash, lymphadenopathy, condyloma latum (secondary syphilis), or neurologic/ocular signs 1, 3
Obtain detailed sexual history including timing of potential exposure to determine disease stage 1
Test for HIV in all patients with confirmed syphilis due to high co-infection rates 4, 5
Treatment Initiation Criteria
Treatment should be started when:
Both treponemal (TPA) AND nontreponemal tests are reactive 1, 2
Nontreponemal titers are quantified to establish baseline for monitoring treatment response 2
Disease stage is determined (primary, secondary, early latent, late latent, or tertiary) as this dictates treatment duration 1, 2
Specific Treatment Regimens by Stage
Once active infection is confirmed:
Primary, secondary, or early latent syphilis: Benzathine penicillin G 2.4 million units IM as a single dose 4, 1, 6, 7
Late latent or unknown duration syphilis: Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks 1, 2
Neurosyphilis: Aqueous crystalline penicillin G 18-24 million units daily IV (administered as 3-4 million units every 4 hours) for 10-14 days 2, 6
Exception: When to Treat Presumptively
The only scenario where treatment precedes full confirmation:
Sexual contacts within 90 days of an index case should receive presumptive treatment even if seronegative, as they may be in the incubation period before serologic conversion 1, 5
High clinical suspicion with risk of loss to follow-up: If the patient has clinical signs consistent with syphilis and may not return for confirmatory testing, treatment should not be delayed 1
Common Pitfalls to Avoid
Never use treponemal test results alone to make treatment decisions—they remain positive after successful treatment and cannot distinguish active from past infection 2, 8
Never monitor treatment response with treponemal tests—only nontreponemal titers (RPR/VDRL) should be used for follow-up 1, 2
Do not delay treatment in pregnant women once diagnosis is confirmed, as untreated syphilis causes severe fetal complications including stillbirth 4, 9
Pregnant women with penicillin allergy require desensitization—there are no acceptable alternatives to penicillin in pregnancy 4, 2, 9
Follow-Up After Treatment
Once treatment is initiated based on confirmed active infection:
Monitor nontreponemal titers at 3,6,9,12, and 24 months after treatment 1
Expect fourfold decline in titers within 6-12 months as evidence of adequate treatment response 1, 2, 3
Treatment failure is defined by: Persistent/recurrent symptoms, sustained fourfold increase in nontreponemal titers, or failure of titers to decline fourfold by 6 months 4, 2