Timing of Treponemal Test Positivity After Chancre Appearance
Treponemal tests become positive approximately 1-4 weeks after the appearance of a chancre in primary syphilis, and modern treponemal immunoassays demonstrate 94.5%-96.4% sensitivity even in early primary disease. 1
Expected Timeline for Serologic Conversion
Treponemal antibodies typically appear 1-4 weeks after initial infection, which often coincides with or shortly follows chancre development. 2
By the time a chancre is clinically apparent, treponemal tests are positive in the vast majority of cases, with modern immunoassays (CIA, EIA, TPPA) showing 94.5%-96.4% sensitivity for primary syphilis. 1
Traditional FTA-ABS testing has lower sensitivity (78.2%) in primary syphilis compared to newer treponemal immunoassays and TPPA, making it less reliable for early detection. 1
Important Clinical Context
Nontreponemal tests (RPR/VDRL) lag behind treponemal tests, appearing slightly later but becoming reliably positive by 4-6 weeks in primary syphilis. 2
In approximately 16% of patients with PCR-confirmed primary syphilis (T. pallidum DNA detected in chancre specimens), both treponemal and nontreponemal serology may still be negative at the time of presentation, particularly in very early infection. 3
The CDC case definition for probable primary syphilis requires both a clinically compatible chancre AND reactive serologic testing (either nontreponemal or treponemal), acknowledging that serology should be positive when a chancre is present. 4
Critical Diagnostic Considerations
Direct detection methods (darkfield microscopy, DFA-TP, or PCR) remain the gold standard for diagnosing primary syphilis when a chancre is present, as they can confirm infection before serologic conversion. 4, 5, 3
If clinical suspicion is high but initial serology is negative, repeat testing in 1-2 weeks is recommended to capture seroconversion, or pursue direct detection from the lesion. 2
Once positive, treponemal tests remain reactive for life in 75-85% of patients regardless of treatment, making them unsuitable for monitoring treatment response. 2
Common Pitfalls to Avoid
Do not assume negative serology rules out primary syphilis in a patient with a suspicious chancre—direct detection should be pursued, and serologic testing should be repeated if initially negative. 3
Do not delay treatment waiting for serologic confirmation if clinical presentation is highly suggestive of primary syphilis and the patient is at risk for loss to follow-up. 6
Recognize that the "window period" between chancre appearance and serologic positivity is typically brief (days to 1-2 weeks), but can occasionally extend longer in very early presentations. 3, 1