Syphilis Diagnostic Tests and Treatment Options
The diagnosis of syphilis requires both treponemal and non-treponemal test results, along with a comprehensive clinical evaluation, with benzathine penicillin G being the preferred treatment for all stages of syphilis. 1
Diagnostic Tests for Syphilis
Serologic Testing Algorithms
Traditional Algorithm:
Reverse Sequence Algorithm:
Test Characteristics
| Test Type | Examples | Sensitivity | Specificity | Notes |
|---|---|---|---|---|
| Non-treponemal | RPR, VDRL | 50-92.7% | 95-100% | Correlate with disease activity; can be used to monitor treatment response [1] |
| Treponemal | FTA-ABS, TP-PA | 95-100% | 95-100% | Remain positive for life in most cases; cannot be used to assess treatment response [1] |
Direct Detection Methods
- Dark-field microscopy: Examination of material from lesions for visualization of T. pallidum; useful for primary syphilis diagnosis 4, 3
- Molecular detection: PCR-based methods for detecting T. pallidum DNA 3
Special Considerations
- Neurosyphilis diagnosis: Requires CSF evaluation with VDRL-CSF (highly specific but insensitive), CSF cell count (typically >5 WBCs/mm³), and protein levels 2
- False-negative results: More common in HIV-infected individuals, requiring clinical correlation 1
- False-positive non-treponemal tests: Can occur with various medical conditions, requiring treponemal confirmation 2
Treatment Options
Primary, Secondary, and Early Latent Syphilis (≤1 year)
- First-line: Benzathine penicillin G 2.4 million units IM as a single dose 1, 4
- Alternative for penicillin-allergic patients (non-pregnant):
Late Latent Syphilis (>1 year) or Latent Syphilis of Unknown Duration
- First-line: Benzathine penicillin G 2.4 million units IM weekly for 3 weeks 1
- Alternative for penicillin-allergic patients (non-pregnant):
- Doxycycline 100 mg orally twice daily for 28 days 1
Neurosyphilis
- First-line: Aqueous crystalline penicillin G 18-24 million units IV daily (3-4 million units every 4 hours) for 10-14 days 1
- Alternative: Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg orally four times daily, both for 10-14 days 1
Special Populations
- Pregnant women: Penicillin is the only recommended treatment; desensitization is required for penicillin-allergic patients 1, 5
- HIV-infected patients: Same regimens as HIV-negative patients but require more frequent monitoring 1
Post-Treatment Monitoring
Follow-up serologic testing with quantitative non-treponemal tests at:
- 3,6,9, and 12 months after treatment for primary and secondary syphilis
- 6,12,18, and 24 months for late latent or syphilis of unknown duration 1
Treatment success: Four-fold decline in non-treponemal test titers (e.g., from 1:16 to 1:4) within 6-12 months 2, 1
HIV-infected patients: More frequent monitoring at 3,6,9,12, and 24 months 1
Common Pitfalls and Caveats
Serofast reaction: Some patients maintain low-positive non-treponemal titers despite adequate treatment 2
Prozone phenomenon: False-negative results in high-titer specimens; dilution of serum may be necessary 6
Jarisch-Herxheimer reaction: Acute febrile reaction that can occur within 24 hours of treatment; more common in early syphilis 4
Drug interactions: Bacteriostatic antibiotics (chloramphenicol, erythromycins, sulfonamides, tetracyclines) may antagonize the bactericidal effect of penicillin 5
Macrolide resistance: Azithromycin is no longer recommended as empiric therapy due to widespread resistance 7
Penicillin remains the only proven effective treatment for syphilis during pregnancy and neurosyphilis 1, 5