What is the recommended method for syphilis screening and treatment, including the use of CMIA (Chemiluminescent Microparticle Immunoassay) method?

Syphilis Screening Using CMIA Method

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

Screening Algorithm Options

Two validated approaches exist for syphilis screening:

Traditional Algorithm

• Initial screening: Nontreponemal test (RPR or VDRL) 1
• Confirmation: Treponemal test (TP-PA, enzyme immunoassay, or CMIA) if initial test is reactive 1
• This approach has been the standard for decades and remains widely recommended 1

Reverse Sequence Algorithm (CMIA-Based)

• Initial screening: Treponemal test (CMIA or enzyme immunoassay) 1
• Follow-up: Quantitative nontreponemal test (RPR or VDRL) on all reactive specimens 1
• Additional confirmation: If CMIA positive but RPR/VDRL negative, perform a different treponemal test (TP-PA or FTA-ABS) 1

CMIA Performance Characteristics

CMIA demonstrates excellent sensitivity (99.4-100%) and specificity (99.0-99.8%) for syphilis screening. 2, 3, 4

Signal-to-Cutoff (S/CO) Ratio Interpretation

• S/CO ≥10.4: Specificity approaches 100%; confirmatory treponemal testing may be unnecessary, proceed directly to RPR 5
• S/CO 7.2-10.4: 95% specificity; requires confirmatory testing 5
• S/CO <7.2: Higher false-positive rate; mandatory confirmation with alternative treponemal test 2, 5

Approximately 71% of CMIA-reactive samples have S/CO ratios ≥10.4, potentially eliminating the need for secondary treponemal confirmation in these cases. 5

Critical Diagnostic Principles

A single positive serologic test is never diagnostic of syphilis—diagnosis requires both treponemal AND nontreponemal test results plus comprehensive clinical evaluation. 1, 6

Why Both Test Types Are Required

• Treponemal tests (including CMIA): Remain positive for life regardless of treatment; cannot distinguish active from past infection 6
• Nontreponemal tests (RPR/VDRL): Correlate with disease activity; titers decline with successful treatment 6
• Quantitative nontreponemal titers: Essential for monitoring treatment response; must be reported quantitatively 6

Common Pitfalls and False-Positive Results

CMIA False-Positives

The false-positive rate for CMIA is approximately 0.22%, with highest rates in: 3

• Pregnant women (most common)
• Elderly patients
• Cancer patients
• HIV-infected individuals may show atypical serologic responses 1

Management of Discordant Results

When CMIA is positive but RPR/VDRL is negative: 1

• Perform alternative treponemal test (TP-PA or FTA-ABS)
• If second treponemal test is positive: likely represents treated or late latent syphilis
• If second treponemal test is negative: likely false-positive CMIA result
• Exception: In high-risk patients with S/CO <10.4 and negative TPHA/RPR, consider FTA-ABS for confirmation 5

Screening Recommendations by Population

Universal Screening Indicated

• All pregnant women: Screen at first prenatal visit 1, 6
• High-risk pregnant women: Rescreen in third trimester (28 weeks) and at delivery 1

Targeted Screening (At Least Annually)

• Men who have sex with men (MSM) 1
• Commercial sex workers 1
• Persons who exchange sex for drugs 1
• Adults in correctional facilities 1
• Contacts of persons with infectious syphilis 1

High-Risk MSM

Screen every 3-6 months if: multiple or anonymous partners, sex with illicit drug use, or partners engaging in these activities. 1

Treatment Monitoring

Quantitative nontreponemal tests (RPR or VDRL) are essential for treatment monitoring—treponemal tests including CMIA should NOT be used for this purpose. 6

• Use the same nontreponemal test method throughout follow-up for accurate comparison 1, 6
• A fourfold change in titer (two dilutions) represents clinically significant change 6
• Follow-up testing at 6 and 12 months post-treatment 6
• Fourfold decline in titer indicates adequate treatment response 6

Practical Implementation

For high-volume clinical laboratories, CMIA-based reverse sequence screening is efficient and cost-effective, particularly when S/CO ratios ≥10.4 allow bypassing secondary treponemal confirmation. 2, 5, 3 However, laboratories must establish clear protocols for managing discordant results and ensure quantitative nontreponemal testing is available for all reactive specimens to assess disease activity. 1