What is the recommended test and treatment for syphilis?

Recommended Testing and Treatment for Syphilis

The diagnosis of syphilis requires both nontreponemal (RPR or VDRL) and treponemal (FTA-ABS or TP-PA) tests, followed by treatment with parenteral penicillin G as the first-line therapy for all stages of syphilis. 1

Diagnostic Testing Algorithm

Initial Testing

1. Two-test approach required:

   • Nontreponemal tests: VDRL (Venereal Disease Research Laboratory) or RPR (Rapid Plasma Reagin)
   • Treponemal tests: FTA-ABS (Fluorescent Treponemal Antibody Absorbed) or TP-PA (T. pallidum Particle Agglutination)

2. Traditional screening sequence:

   • Start with nontreponemal test (VDRL or RPR)
   • If positive, confirm with treponemal test (FTA-ABS or TP-PA)

3. Reverse screening sequence (increasingly common):

   • Start with automated treponemal test
   • If positive, perform nontreponemal test to assess disease activity
   • If treponemal positive but nontreponemal negative, confirm with a second treponemal test 2

Diagnostic Considerations

• Darkfield microscopy or direct fluorescent antibody tests of lesion exudate/tissue are definitive methods for diagnosing early syphilis 1
• Nontreponemal test results should be reported quantitatively (e.g., 1:32)
• A fourfold change in titer (equivalent to two dilutions) indicates significant difference in disease activity 1
• False-positive nontreponemal tests can occur with various medical conditions 1
• Sequential serologic tests should use the same testing method by the same laboratory 1

Special Situations

• Neurosyphilis diagnosis:

  • No single test can diagnose neurosyphilis
  • Requires combination of reactive serologic tests, CSF abnormalities (cell count, protein), and reactive VDRL-CSF 1
  • CSF leukocyte count >5 WBC/mm³ suggests active neurosyphilis 1

• HIV co-infection:

  • May cause atypical serologic results (unusually high, low, or fluctuating titers)
  • Consider additional testing (biopsy, direct microscopy) when serologic tests don't match clinical presentation 1

Treatment Protocol

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

• First-line: Benzathine penicillin G 2.4 million units IM in a single dose 1

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 (total 7.2 million units) 1

Neurosyphilis

• First-line: Aqueous crystalline penicillin G 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1

Alternative Regimens (for non-pregnant, non-neurosyphilis patients with penicillin allergy)

• Doxycycline 100 mg orally twice daily for 14 days (primary, secondary, early latent) or 28 days (late latent) 3
• Tetracycline 500 mg orally four times daily for 14 days (primary, secondary, early latent) or 28 days (late latent) 3

Special Populations

• Pregnant women: Only penicillin effectively treats maternal infection and prevents congenital syphilis
• Penicillin allergy in pregnancy or neurosyphilis: Desensitization required before penicillin treatment 3
• HIV co-infection: Same treatment regimens as HIV-negative patients, but closer follow-up may be needed 1

Post-Treatment Monitoring

• Quantitative nontreponemal tests should be obtained at treatment initiation
• Titers should decline fourfold within:
  • 6 months for primary/secondary syphilis
  • 12-24 months for latent/late syphilis 3
• Clinical and serological evaluation recommended at 6,12, and 24 months after treatment 1

Common Pitfalls to Avoid

1. Using only one type of test: Single test is insufficient for diagnosis 1
2. Comparing results from different test types: RPR titers are often slightly higher than VDRL titers 1
3. Using treponemal tests to monitor treatment response: These tests typically remain positive for life regardless of treatment success 1
4. Inadequate follow-up: Treatment failure or reinfection can occur; serial monitoring is essential
5. Jarisch-Herxheimer reaction: Patients should be advised about this potential acute febrile reaction occurring within 24 hours of treatment 1

Proper diagnosis and treatment of syphilis are critical to prevent progression to late-stage disease with potentially irreversible complications affecting multiple organ systems, particularly the cardiovascular and central nervous systems.