What is the recommended approach for investigating syphilis?

Recommended Approach for Investigating Syphilis

The recommended approach for investigating syphilis involves a dual testing strategy using both treponemal and nontreponemal tests, with interpretation based on the combined results to guide treatment decisions. 1

Diagnostic Testing Algorithm

Initial Screening Options

1. Traditional Algorithm:

   • Start with nontreponemal test (RPR or VDRL)
   • If positive, confirm with treponemal test (TP-PA, FTA-ABS, EIA, or chemiluminescent immunoassay)
   • Advantages: Lower false-positive rate, cost-effective for low-prevalence settings 2, 1

2. Reverse Algorithm:

   • Start with automated treponemal test (EIA or chemiluminescent immunoassay)
   • If positive, perform nontreponemal test for confirmation
   • If discordant (treponemal positive, nontreponemal negative), perform second treponemal test
   • Advantages: Higher sensitivity for early primary and late latent syphilis, automation capability 1, 3

Test Interpretation

Nontreponemal Result	Treponemal Result	Interpretation
Positive	Positive	Confirmed syphilis (current or past)
Positive	Negative	Likely false-positive nontreponemal test
Negative	Positive	Possible very early infection, previously treated syphilis, or late-stage syphilis
Negative	Negative	No evidence of syphilis [1]

Special Testing Considerations

Neurosyphilis Evaluation

• Perform CSF examination when:

  • Neurologic or ocular symptoms present
  • Evidence of active tertiary syphilis
  • Treatment failure
  • HIV-infected patients with late latent syphilis or unknown duration
  • HIV-infected patients with CD4 <350 cells/μL and RPR ≥1:32 2, 1

• CSF findings suggestive of neurosyphilis:

  • Reactive CSF-VDRL (specific but not sensitive)
  • CSF WBC >10 cells/μL
  • Elevated protein (>40 mg/dL) 2

Congenital Syphilis

• For infants born to mothers with reactive syphilis tests:
  • Perform quantitative nontreponemal test on infant serum (not cord blood)
  • Examine thoroughly for clinical evidence of congenital syphilis
  • Consider darkfield microscopy of suspicious lesions
  • Treatment decisions based on maternal treatment adequacy and infant evaluation 2

HIV Co-infection

• Same serologic tests used for diagnosis
• False-positive nontreponemal tests may be more common
• Consider more intensive follow-up due to higher risk of treatment failure
• Lower threshold for CSF examination 2, 1

Test Performance Characteristics

• Nontreponemal tests (RPR, VDRL):

  • Sensitivity varies by stage: 50-92.7% in early infection, 97-100% in secondary, 61-75% in late stages
  • Specificity: 95-100%
  • May be negative in very early primary or late latent syphilis 1, 4

• Treponemal tests (FTA-ABS, TP-PA, EIA):

  • Sensitivity: 95-100%
  • Specificity: 95-100%
  • Become positive earlier than nontreponemal tests 1, 4

Post-Treatment Follow-up

• Recommended follow-up schedule for quantitative nontreponemal tests:

  • 3,6,9,12, and 24 months after treatment
  • Clinical evaluation at 6 and 12 months 1

• Treatment success indicated by fourfold (2 dilution) decline in nontreponemal titer within:

  • 6 months for primary/secondary syphilis
  • 12 months for late syphilis 1

• Treatment failure criteria:

  • Persistent or recurring clinical symptoms
  • Sustained fourfold increase in titer after initial reduction
  • Failure to achieve fourfold decrease in titer within appropriate timeframe 1

Common Pitfalls and Caveats

• False-positive nontreponemal tests can occur with:

  • Pregnancy
  • Autoimmune diseases
  • Viral infections
  • Advanced age 1, 5

• Prozone phenomenon: False-negative results in high-titer specimens due to antibody excess; consider diluting samples when clinical suspicion is high 2

• Serofast state: Persistent low-titer reactivity despite adequate treatment; not indicative of treatment failure 1

• Interpretation challenges with reverse algorithm: Increased detection of previously treated cases or very early infections, requiring clinical correlation 3, 6

By following this systematic approach to syphilis investigation, clinicians can accurately diagnose and appropriately manage this re-emerging infection, ultimately reducing morbidity and mortality associated with untreated disease.