What is the CDC algorithm for syphilis diagnosis and treatment?

CDC Algorithm for Syphilis Diagnosis and Treatment

Diagnostic Testing Algorithms

The CDC recommends two acceptable serologic testing algorithms for syphilis diagnosis: the traditional algorithm (screening with nontreponemal test followed by treponemal confirmation) and the reverse sequence algorithm (screening with treponemal test followed by nontreponemal confirmation), with both requiring use of both test types for accurate diagnosis. 1, 2

Traditional Algorithm (Conventional Approach)

• Screen with nontreponemal test (VDRL or RPR) 3
• If reactive: Confirm with treponemal test (FTA-ABS or TP-PA) 3
• Advantage: Identifies active disease directly through quantitative titers 1
• Limitation: May miss late latent or early primary syphilis when nontreponemal antibodies are low or absent 4

Reverse Sequence Algorithm (Increasingly Common)

• Screen with treponemal immunoassay (EIA or chemiluminescent immunoassay) 1, 5
• If reactive: Perform nontreponemal test (RPR or VDRL) to assess disease activity 1, 5
• If treponemal positive but nontreponemal negative: Perform second treponemal test (TP-PA or FTA-ABS) for confirmation 1, 5
• Advantage: Increased sensitivity for late latent and early primary syphilis; allows laboratory automation 4, 5
• Limitation: May increase false-positive results requiring additional testing 4

Direct Detection Methods

When lesions are present, darkfield microscopy or direct fluorescent antibody testing of lesion exudate provides definitive diagnosis of early syphilis and should be prioritized over serologic testing alone. 3, 1, 2

Interpretation of Serologic Results

Nontreponemal Tests (VDRL, RPR)

• Report quantitatively to monitor disease activity and treatment response 3, 1, 2
• Fourfold change in titer (two dilutions, e.g., 1:16 to 1:4) indicates clinically significant difference 3, 1
• Use same test method (VDRL or RPR) and preferably same laboratory for sequential testing 3
• Cannot compare VDRL and RPR titers directly as RPR titers are often slightly higher 3

Treponemal Tests (FTA-ABS, TP-PA)

• Remain reactive for life in most patients regardless of treatment 3, 1, 2
• Cannot be used to assess treatment response or distinguish active from past infection 1, 2
• 15-25% may revert to nonreactive after treatment during primary stage 3, 2

Special Pattern: Treponemal Positive/Nontreponemal Negative

• Represents late latent syphilis, treated syphilis, or false-positive treponemal test 2
• Treat as late latent syphilis with benzathine penicillin G 2.4 million units IM weekly for 3 weeks if no documented adequate prior treatment 2

Treatment Recommendations

General Principles

Parenteral penicillin G is the preferred treatment for all stages of syphilis, with preparation, dosage, and duration determined by disease stage. 1

Early Syphilis (Primary, Secondary, Early Latent <1 year)

• Benzathine penicillin G 2.4 million units IM as single dose 1, 6

Late Latent Syphilis (>1 year duration or unknown duration)

• Benzathine penicillin G 2.4 million units IM weekly for 3 weeks (total 7.2 million units) 1, 2, 6

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units daily (administered as 3-4 million units IV every 4 hours) for 10-14 days 1

Penicillin Allergy

• Non-pregnant patients without neurosyphilis: Doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) 1, 7
• Pregnant patients: Penicillin desensitization is mandatory, as no safe alternative exists 3, 1

HIV-Infected Patients

• Use same treatment regimens as HIV-negative patients 3, 1
• Closer follow-up recommended to detect treatment failures 3
• Standard serologic tests remain accurate though atypical responses may occur 3, 2

Follow-Up and Monitoring

Serologic Monitoring

• Clinical and serologic evaluation at 6 and 12 months after treatment 1
• Fourfold decline in nontreponemal titers indicates adequate treatment response 1
• Use same nontreponemal test for all follow-up testing to ensure comparability 3

Treatment Failure Indicators

• Persistent or recurrent signs/symptoms 1
• Sustained fourfold increase in nontreponemal titer 1
• Failure of nontreponemal titer to decline fourfold by 6-12 months 1

Pregnancy-Specific Recommendations

Screening Intervals

• All pregnant women at first prenatal visit 3
• High-risk women: repeat in third trimester and at delivery 3
• Universal screening substantially reduces congenital syphilis 3

Treatment in Pregnancy

• Benzathine penicillin G is the only proven effective treatment to prevent congenital syphilis 3
• Penicillin-allergic pregnant women must undergo desensitization 3, 1

Critical Pitfalls to Avoid

• Never use only one type of serologic test (either treponemal or nontreponemal alone) for diagnosis 3, 1, 2
• Never compare titers between different test methods (VDRL vs RPR) 3, 2
• Never use treponemal tests to monitor treatment response 1, 2
• Never fail to report nontreponemal results quantitatively 3, 1
• Never use alternatives to penicillin in pregnant women without desensitization 3, 1