What does a reactive Rapid Plasma Reagin (RPR) test with a titer of 1:16 and a reactive Treponema test indicate in a patient?

Interpretation of Syphilis Serology Results

Your patient has confirmed syphilis infection—either active disease requiring treatment or past treated infection—as indicated by both reactive nontreponemal (RPR) and treponemal tests. 1

What These Results Mean

• Both tests being reactive confirms true syphilis infection, distinguishing this from a biological false-positive result that would show only RPR reactivity with negative treponemal testing. 1, 2

• The RPR titer of 1:16 is clinically significant and essentially rules out a false-positive result, as false-positive RPR results are extremely rare at titers ≥1:8. 1

• The treponemal test remains positive for life in most patients regardless of treatment or disease activity, so this alone cannot distinguish between active infection and past treated disease. 1

• The RPR titer of 1:16 suggests either active infection or recent infection that may require treatment, as nontreponemal test titers correlate with disease activity. 1

Immediate Clinical Assessment Required

You must determine the stage of infection and treatment history through:

• Review prior medical records to determine if the patient received appropriate penicillin treatment for syphilis in the past. 1

• Assess for symptoms of primary syphilis: presence of chancre or ulcer at infection site. 1

• Assess for symptoms of secondary syphilis: rash, mucocutaneous lesions, or adenopathy. 1

• Screen for neurosyphilis symptoms: headache, vision changes, hearing loss, confusion, or ocular symptoms. 1

• Screen for tertiary syphilis manifestations: cardiovascular or gummatous disease. 1

• Obtain sexual history to determine timing of exposure and identify contacts from the past 6 months who require notification and treatment. 1, 3

Treatment Decision Algorithm

If No Prior Treatment or Treatment History Unknown:

• Treat as late latent syphilis with benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units). 1, 3

• Exception: If symptoms suggest primary or secondary syphilis (infection <1 year), treat with benzathine penicillin G 2.4 million units IM as a single dose. 1, 3

If Previously Treated:

• Compare current RPR titer to prior titers using the same test method (RPR vs VDRL are not interchangeable). 1

• Treatment success is indicated by a fourfold decline in titer within 6-12 months for early syphilis or 12-24 months for late latent syphilis. 1

• Treatment failure or reinfection is suggested by a sustained fourfold increase in titer compared to post-treatment baseline. 1

• Serofast state (persistent low titers <1:8 that remain stable) is common and does not necessarily indicate treatment failure, but a titer of 1:16 is above this threshold and warrants careful evaluation. 1

Essential Concurrent Actions

• Test for HIV infection immediately, as HIV-positive patients require more frequent monitoring (every 3 months instead of 6 months), have higher risk of neurosyphilis, and may have atypical serologic responses. 1, 3

• Consider CSF examination if any of the following are present: neurologic symptoms, ocular symptoms, HIV infection with late latent syphilis, or treatment failure. 1

• Screen for pregnancy in women of childbearing age, as only penicillin regimens are acceptable during pregnancy and treatment prevents congenital syphilis. 1

Follow-Up Monitoring Plan

• Repeat quantitative RPR testing at 6 and 12 months after treatment for early syphilis, or at 6,12,18, and 24 months for late latent syphilis. 1, 3

• Use the same testing method (RPR) at the same laboratory for all follow-up testing to ensure accurate comparison. 1

• A fourfold decline in titer (e.g., from 1:16 to 1:4 or less) indicates successful treatment response. 1, 3

• HIV-positive patients require evaluation every 3 months rather than every 6 months. 1

Critical Pitfalls to Avoid

• Never use treponemal test results to monitor treatment response or assess disease activity—only RPR titers should be used for this purpose. 1

• Do not compare titers between different test types (VDRL vs RPR) as they are not directly comparable. 1

• Do not assume persistent low-titer reactivity necessarily indicates treatment failure, but a titer of 1:16 is above the typical serofast range and requires investigation. 1

• Be aware of the prozone phenomenon in HIV-infected patients or those with very high antibody levels, which can cause falsely nonreactive RPR results; request diluted testing if clinical suspicion is high despite negative RPR. 4