Guidelines for Syphilis Testing

Syphilis diagnosis requires both treponemal and nontreponemal tests, as using only one type of test is insufficient for accurate diagnosis. 1, 2

Diagnostic Testing Algorithm

Darkfield examinations and direct fluorescent antibody tests of lesion exudate or tissue are the definitive methods for diagnosing early syphilis when lesions are present 3, 1
Two main testing approaches are recommended:
- Traditional algorithm: Screen with nontreponemal test (VDRL or RPR), followed by treponemal test confirmation (FTA-ABS, TP-PA) if reactive 2
- Reverse algorithm: Screen with treponemal-based enzyme immunoassay (EIA) or chemiluminescent immunoassay, followed by nontreponemal test for confirmation of active disease 2, 4
When using reverse sequence screening, discordant results (reactive treponemal test with nonreactive nontreponemal test) require additional treponemal testing with TP-PA or FTA-ABS 4

Correlate with disease activity and should be reported quantitatively 3, 1
A fourfold change in titer (equivalent to two dilutions, e.g., from 1:16 to 1:4) indicates a clinically significant difference in disease activity or treatment response 3, 2
Sensitivity varies by stage of infection:
- Primary syphilis: 75-78% 3
- Secondary syphilis: 92-94% 3
- Latent syphilis: 94-99% 3
- Late syphilis: 84% 3
False-positive results can occur in various medical conditions, requiring confirmation with treponemal tests 3, 5

Remain reactive for life in most patients (75-85%) regardless of treatment or disease activity 3, 1
May revert to nonreactive in 15-25% of patients treated during the primary stage 1
Recent data shows high sensitivity (96-100%) across all stages of syphilis 5
The syphilis recombinant ELISA test has shown excellent performance with 100% sensitivity across primary, secondary, and latent syphilis 5

Standard serologic tests remain accurate and reliable for most HIV-infected patients 3
Some patients may have abnormal serologic test results (unusually high, unusually low, or fluctuating titers) 3
Consider additional testing methods (biopsy and direct microscopy) for HIV patients with clinical syndromes suggestive of early syphilis 3

No single test is sufficient for diagnosing neurosyphilis 3, 1
Diagnosis typically requires:
- Reactive serologic test results
- Abnormal CSF cell count (>5 WBCs/mm³) or protein
- Reactive VDRL-CSF (standard serologic test for CSF) 3
CSF FTA-ABS is less specific but highly sensitive; some experts believe a negative CSF FTA-ABS test excludes neurosyphilis 3

All infants born to seroreactive mothers should be evaluated with a quantitative nontreponemal test on infant serum (not cord blood) 3
Thorough physical examination for evidence of congenital syphilis is essential 3
Pathologic examination of the placenta or umbilical cord using specific fluorescent antitreponemal antibody staining is recommended 3

Using only one type of test can lead to misdiagnosis 3, 1
Comparing titers between different test types (e.g., VDRL and RPR) can lead to incorrect conclusions, as RPR titers are often slightly higher than VDRL titers 3
Relying on treponemal tests to assess treatment response is inappropriate as they typically remain reactive for life 3, 1
In low-prevalence populations, reverse sequence screening may yield a higher percentage of false-positive results 4
Failure to perform sequential serologic tests using the same testing method and preferably the same laboratory can lead to inaccurate assessment of treatment response 3, 1

All sexually active people aged 15-44 years should be screened at least once 6
Annual screening for those at increased risk (people with HIV, those engaging in condomless sex with multiple partners, men who have sex with men) 6
Pregnant individuals should be screened three times: at first prenatal visit, during third trimester, and at delivery 6