Serological Indicators of Acute Syphilis Infection
Acute syphilis infection is indicated by a positive nontreponemal test (RPR or VDRL) with a high titer AND a positive treponemal test (FTA-ABS or TP-PA), particularly when accompanied by clinical findings of primary or secondary syphilis. 1, 2
Key Serological Patterns in Acute Infection
Primary and Secondary Syphilis (Early Acute Disease)
Both nontreponemal (RPR/VDRL) and treponemal tests become positive during acute infection, with treponemal antibodies appearing 1-4 weeks after infection and nontreponemal antibodies appearing slightly later but reliably positive by 4-6 weeks. 1
Nontreponemal test sensitivity is highest in secondary syphilis at 97-100%, making RPR or VDRL extremely reliable for detecting acute infection during this stage. 1, 3
RPR sensitivity ranges from 88.5% in primary syphilis to 100% in secondary syphilis, confirming that these tests are highly effective for acute disease detection. 1
Nontreponemal tests should be reported quantitatively (e.g., 1:4,1:8,1:16) as titers correlate with disease activity, with higher titers typically indicating more active infection. 2, 3
Critical Diagnostic Algorithm
The CDC recommends performing both nontreponemal and treponemal tests for complete diagnosis, as using only one type of test is insufficient for accurate diagnosis. 2
Darkfield examinations and direct fluorescent antibody tests of lesion exudate or tissue are the definitive methods for diagnosing early syphilis and should be prioritized when lesions are present, particularly before serologic tests become positive. 2
A fourfold change in nontreponemal titer (equivalent to two dilutions) indicates clinically significant disease activity, which is essential for distinguishing new infection from past treated disease. 1, 2
Distinguishing Acute from Past Infection
Treponemal tests remain positive for life in most patients regardless of treatment, making them unsuitable for distinguishing acute from past infection. 1, 2
Only 15-25% of patients treated during primary syphilis may revert to serologically nonreactive after 2-3 years, meaning most will have persistent positive treponemal tests. 1
Nontreponemal test titers correlate with disease activity, making VDRL and RPR the appropriate tests for monitoring treatment response and detecting new infection versus past treated disease. 1
Special Considerations for HIV-Infected Patients
HIV-infected patients may have atypical serologic responses with unusually low, high, or fluctuating titers, though standard serologic tests remain accurate for most HIV patients. 4, 1, 2
Concomitant uveitis and meningitis might be more common among HIV-infected patients with syphilis, requiring heightened clinical suspicion even with typical serologic patterns. 4
False-negative serologic tests have been reported among HIV-infected patients with documented T. pallidum infection, so if clinical suspicion is high and serologic tests are negative, pursue other diagnostic procedures such as biopsy or darkfield examination. 4
Common Pitfalls to Avoid
Never rely on treponemal tests alone to diagnose acute infection, as they cannot distinguish between active and past treated infection. 1, 2
Do not compare titers between different test types (VDRL vs. RPR), as they are not directly comparable and sequential tests should use the same method, preferably by the same laboratory. 1, 2
A positive treponemal test with negative nontreponemal test does NOT indicate acute infection but rather suggests either past treated infection, late-stage disease with waning antibodies, or false-positive treponemal test. 2, 3