What is the recommended approach for syphilis testing and treatment?

Syphilis Testing and Treatment: Recommended Approach

Initial Screening Strategy

All patients should be screened for syphilis at baseline, with sexually active individuals screened at least annually and high-risk populations (MSM, multiple partners, HIV-infected persons) screened every 3-6 months. 1, 2

Testing Algorithm Options

Two acceptable approaches exist for syphilis screening:

Traditional Algorithm (Preferred by CDC):

• Screen with nontreponemal test (RPR or VDRL) first 2, 3
• Confirm reactive results with treponemal test (FTA-ABS, TP-PA) 2, 3
• Report nontreponemal tests quantitatively (e.g., 1:8,1:16) 3

Reverse Sequence Algorithm (Used by Some Automated Labs):

• Screen with treponemal EIA/chemiluminescence assay first 2, 3
• Follow reactive results with quantitative nontreponemal test 2, 3
• Critical caveat: This approach identifies 56.7% of patients who are treponemal-positive but RPR-negative, and 31.6% of these discordant results represent false-positives, particularly in low-prevalence populations 4

Diagnostic Interpretation

Active Infection Indicators

• Both treponemal AND nontreponemal tests reactive = active or past infection 2, 3
• Nontreponemal titers correlate with disease activity 3
• A fourfold change in titer (two dilutions, e.g., 1:8 to 1:32) represents clinically significant change 2, 3

Special Diagnostic Considerations

• For visible lesions: Darkfield microscopy or direct fluorescent antibody testing of lesion exudate provides definitive diagnosis 1, 3
• Treponemal tests remain positive for life in 75-85% of treated patients, regardless of cure 2
• 15-25% of patients treated during primary syphilis may become seronegative after 2-3 years 2
• False-positive nontreponemal tests (typically low titer <1:8) occur more commonly in HIV-infected persons and injection drug users 1

Treatment Recommendations by Stage

Primary and Secondary Syphilis

Benzathine penicillin G 2.4 million units IM as a single dose 2, 3, 5

Early Latent Syphilis (<1 year duration)

Benzathine penicillin G 2.4 million units IM as a single dose 2, 3

Late Latent Syphilis or Unknown Duration

Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units) 2, 3, 5

Neurosyphilis

Aqueous crystalline penicillin G 18-24 million units per day (administered as 3-4 million units IV every 4 hours or continuous infusion) for 10-14 days 2, 3

Penicillin Allergy

• Non-pregnant patients without neurosyphilis: Doxycycline 100 mg orally twice daily for 14 days (early syphilis) 2, 3
• Pregnant patients or neurosyphilis: Penicillin desensitization is mandatory 2, 3

Indications for Lumbar Puncture

CSF examination should always be performed in the following situations: 1, 2

• Any neurologic or ocular symptoms/signs 1, 2
• Late latent syphilis (≥1 year duration) 1
• Serologic treatment failure (no fourfold titer decline within 6-12 months) 1
• HIV-infected patients: Some experts recommend CSF examination when nontreponemal titer >1:32 or CD4 count <350 cells/mm³, regardless of stage 1

Important caveat: CSF interpretation is challenging because elevated protein and lymphocytic pleocytosis can occur from HIV infection itself, and CSF VDRL has low sensitivity 1

Follow-Up Monitoring

Early Syphilis (Primary, Secondary, Early Latent)

Clinical and serologic evaluation at 6 and 12 months after treatment 2, 3

• Expected response: Fourfold decline in nontreponemal titer within 6-12 months 2, 3
• HIV-infected patients require more frequent monitoring at 3,6,9,12, and 24 months 2

Late Latent Syphilis

Clinical and serologic evaluation at 6,12, and 24 months after treatment 2

• Expected response: Fourfold decline in titer within 12-24 months 2

Treatment Failure Indicators

• No fourfold decrease in titer within 6-12 months for early syphilis 2
• Persistent or recurrent clinical signs/symptoms 2
• Sustained fourfold increase in titer above baseline 2

Critical Pitfalls to Avoid

Do not compare titers between different test methods (VDRL vs RPR are not interchangeable) - always use the same test from the same laboratory for serial monitoring 2, 3

Do not assume persistent low-titer reactivity indicates treatment failure - many patients remain "serofast" with stable low titers (typically <1:8) indefinitely, which does not represent treatment failure 2

Do not rely on treponemal tests alone for diagnosis - they cannot distinguish active from past treated infection 2

Do not overlook the prozone phenomenon - in secondary syphilis with very high antibody titers, undiluted serum can produce false-negative RPR results in <1% of cases 6

Special Populations

HIV-Infected Patients

• Use same treatment regimens as HIV-uninfected patients 3
• Monitor more frequently (every 3 months instead of 6 months) 2
• Consider CSF examination for late latent syphilis or syphilis of unknown duration 1, 2
• May have atypical serologic responses (higher, lower, or delayed titers) 1

Pregnant Patients

• Screen at first prenatal visit, 28 weeks gestation, and delivery in high-risk populations 1, 5
• Penicillin is the only acceptable treatment 1
• Penicillin desensitization required if allergic 2, 3
• Up to 40% of fetuses with in-utero exposure result in stillbirth or neonatal death without treatment 5