What is the recommended testing method for diagnosing genital herpes via blood work, specifically to detect Human Simplex Virus (HSV) -1 and HSV-2 antibodies?

Recommended Testing Method for Diagnosing Genital Herpes via Blood Work

For diagnosing genital herpes via blood work, type-specific serologic tests that detect antibodies to HSV glycoprotein G-1 (gG-1) or glycoprotein G-2 (gG-2) should be used when direct testing of lesions is not possible. 1

Primary Diagnostic Approach

When Lesions Are Present

1. First-line testing: NAAT/PCR from lesion specimen

   • Highest sensitivity and specificity
   • Can differentiate between HSV-1 and HSV-2
   • FDA-approved tests typically have >90% sensitivity and specificity 2, 1
   • Preferred over blood tests when lesions are present

2. Alternative if NAAT unavailable: Viral culture

   • Less sensitive than NAAT/PCR
   • Sensitivity decreases as lesions heal 2, 1

When No Lesions Are Present (Blood Work)

1. Type-specific serologic testing:
   • Tests for antibodies to HSV glycoprotein G-1 (gG-1) or glycoprotein G-2 (gG-2)
   • Methods include enzyme immunoassay (EIA) or chemiluminescent immunoassay (CLIA) 2, 1
   • Sensitivity for HSV-2 is approximately 92% 1
   • Specificity varies based on index values:
     • Index values ≥3.0: 78.6% specificity
     • Index values 1.1-2.9: 39.8% specificity 1

Interpretation of Serologic Results

• Wait period: Test at least 12 weeks after suspected exposure 1
• Index values ≥3.0: May be sufficient for diagnosis without further testing
• Index values <3.0: Should be confirmed with a second test using a different gG antigen 1
• False negatives: Commercial type-specific antibody assays may be false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions 3

Recommended Use of Type-Specific Serology

Type-specific serology is particularly recommended 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, 1

Important Considerations and Pitfalls

• Avoid widespread screening: Not recommended by WHO and the American College of Physicians 1
• Window period: Directly after infection, there is a 'window' in which testing for antibodies will give a negative result 2
• HSV-1 assay limitations: HSV-1 serologic tests lack sensitivity (as low as 70.2% in some studies), which can result in false-negative diagnoses 2
• HSV-2 assay limitations: HSV-2 serologic tests may lack specificity, particularly with low index values 2, 1
• Multiple test approach: Using more than one test can improve detection rates. Among patients with confirmed HSV-1 or HSV-2 genital herpes, 88.2% of HSV-1 and 90.1% of HSV-2 cases were detected when using multiple antibody tests 3

Quality Control Considerations

• Internal positive controls and negative controls are essential for reliable results 2, 1
• Non-validated diagnostic tests should be validated against a recommended, approved gold standard test 2, 1
• Western blot/immunoblot is considered the gold standard for HSV serologic testing but is typically only available in specialized laboratories 2, 1

Remember that serologic tests alone cannot determine the anatomical site of infection and cannot definitively establish the etiology of a presenting genital lesion 2. Direct testing of lesions via NAAT/PCR remains the preferred diagnostic approach when lesions are present.