Syphilis Screening and Diagnosis

Screening Algorithm and Performance

The American Academy of Pediatrics recommends that chemiluminescent microparticle immunoassay (CMIA) is an acceptable treponemal screening test for syphilis that can be used as the first-line screening method in high-volume laboratories, but all reactive results must be confirmed with a nontreponemal test (RPR or VDRL) to assess disease activity, and discordant results require additional treponemal testing 1, 2, 3
The traditional algorithm for syphilis screening involves initial screening with a nontreponemal test (RPR or VDRL), followed by confirmation with a treponemal test (TP-PA, enzyme immunoassay, or CMIA) if the initial test is reactive, as recommended by the American College of Physicians 4, 5, 3
The reverse sequence algorithm (CMIA-based) involves initial screening with a treponemal test (CMIA or enzyme immunoassay), followed by quantitative nontreponemal testing (RPR or VDRL) on all reactive specimens, as recommended by the American Academy of Pediatrics 1, 2, 3

A single positive serologic test is never diagnostic of syphilis—diagnosis requires both treponemal AND nontreponemal test results plus comprehensive clinical evaluation, as emphasized by the American Academy of Pediatrics and the Centers for Disease Control and Prevention 1, 2, 6
Treponemal tests (including CMIA) remain positive for life regardless of treatment and cannot distinguish active from past infection, whereas nontreponemal tests (RPR/VDRL) correlate with disease activity and titers decline with successful treatment, as noted by the Centers for Disease Control and Prevention 6

The American College of Obstetricians and Gynecologists recommends that all pregnant women should be screened for syphilis at the first prenatal visit, with high-risk pregnant women rescreened in the third trimester (28 weeks) and at delivery 4, 5, 6
The Centers for Disease Control and Prevention recommends targeted screening (at least annually) for men who have sex with men (MSM), commercial sex workers, persons who exchange sex for drugs, adults in correctional facilities, and contacts of persons with infectious syphilis 1, 2

The Centers for Disease Control and Prevention recommends that quantitative nontreponemal tests (RPR or VDRL) are essential for treatment monitoring, and treponemal tests including CMIA should NOT be used for this purpose 6
A fourfold change in titer (two dilutions) represents clinically significant change, and follow-up testing at 6 and 12 months post-treatment is recommended, with a fourfold decline in titer indicating adequate treatment response 6