What is the recommended method for diagnosing HSV 2 infection?

Diagnosis of HSV-2 Infection

Nucleic acid amplification testing (NAAT/PCR) from active lesions is the gold standard for diagnosing HSV-2 infections, offering superior sensitivity (>90%) and specificity (>90%) compared to other available methods. 1

Diagnostic Testing Algorithm for HSV-2

1. For Patients with Active Lesions:

• First-line test: NAAT/PCR from lesion specimen

  • Provides highest sensitivity and specificity
  • Can differentiate between HSV-1 and HSV-2
  • Should be collected during the active phase of lesions 2

• Alternative if NAAT unavailable: Viral culture

  • Less sensitive than PCR but acceptable alternative
  • Sensitivity decreases as lesions heal 2

• Last resort options: Antigen detection tests

  • Direct immunofluorescence assay (DIF) or enzyme immunoassay (EIA)
  • Only if PCR and culture are unavailable
  • HSV type determination remains important 2

• NOT recommended:

  • HSV direct immunofluorescence assay and Tzanck smear (lack sensitivity) 2
  • Testing asymptomatic sites (low yield due to intermittent shedding) 2

2. For Patients without Active Lesions:

• Type-specific serologic testing:
  • Tests for antibodies to HSV glycoprotein G-1 (gG-1) or glycoprotein G-2 (gG-2)
  • Wait at least 12 weeks after suspected exposure (window period) 1
  • Sensitivity for HSV-2: approximately 92% 2
  • Specificity varies based on index values:
    • Index values 1.1-2.9: only 39.8% specificity
    • Index values ≥3.0: 78.6% specificity 2

Interpretation of Serologic Results

• For positive HSV-2 serologic results with low index values (<3.0):

  • Confirmation with a second test using a different gG antigen is necessary
  • Biokit HSV-2 rapid assay or Western blot can be used as confirmatory tests 1, 3
  • Confirmatory testing increases positive predictive value from 80.5% to 95.6% 3

• For positive HSV-2 serologic results with high index values (≥3.0):

  • May be sufficient for diagnosis without further confirmatory testing 1
  • However, false positives have been reported even with high index values

• Special considerations:

  • Persons with HSV-1 infection are more likely to have false-positive HSV-2 test results with low index values 2
  • HSV-1 serologic tests lack sensitivity (approximately 70.2%) 2

Recommended Testing Populations

• Type-specific serology should be used for:

  • Detecting asymptomatic infections
  • Testing pregnant women at risk of acquiring HSV infection close to delivery
  • Men who have sex with men
  • People who are HIV positive 2

• NOT recommended:

  • Widespread screening for HSV antibodies 2, 1
  • Testing in the absence of clinical suspicion 1

Quality Control Considerations

• Ensure proper internal positive controls and negative controls are used in laboratory testing 2, 1
• Non-validated diagnostic tests should be validated against a recommended, approved gold standard test 2
• Consider referral to specialized laboratories for Western blot testing in cases where diagnosis remains uncertain despite repeated testing 1

By following this evidence-based approach to HSV-2 testing, clinicians can achieve accurate diagnosis while minimizing false positive and false negative results, ultimately improving patient care and appropriate management of genital herpes infections.