Should a patient undergo Herpes Simplex Virus (HSV) 1 and 2 antibody (Ab), Immunoglobulin G (IgG) testing?

HSV-1 and HSV-2 IgG Antibody Testing: When to Order

HSV serologic testing should NOT be routinely ordered for asymptomatic patients, but is indicated for specific high-risk populations including pregnant women at risk of acquiring HSV near delivery, HIV-positive individuals, and partners of HSV-2 infected persons considering suppressive therapy to reduce transmission risk. 1, 2

When HSV Serology IS Indicated

High-Risk Populations Warranting Testing

• HIV-positive patients: Routine type-specific HSV-2 serologic testing should be performed due to significant HIV-HSV-2 interactions and need for potential suppressive therapy 3
• Pregnant women at risk: Testing is appropriate for women at risk of acquiring HSV infection close to delivery 2
• Discordant couples: HSV-2 seronegative individuals should consider having partners tested with type-specific serology before initiating sexual activity, as suppressive therapy in the infected partner reduces transmission by 48-50% 3
• Men who have sex with men: This population warrants type-specific serologic testing 1

Clinical Scenarios Where Serology May Help

• Suspected genital herpes with negative PCR/culture: When lesions have healed and molecular testing is negative, serology obtained ≥12 weeks after exposure can confirm or exclude HSV-2 infection 1
• Asymptomatic partners of newly diagnosed patients: These individuals may benefit from evaluation to determine their HSV status 1

When HSV Serology Should NOT Be Ordered

General Population Screening

• Widespread screening is explicitly discouraged: The US Preventive Services Task Force recommends against screening asymptomatic adolescents and adults for HSV-2 infection 2
• Asymptomatic immunocompetent individuals: Routine testing is not indicated unless they fall into one of the high-risk categories above 3

Active Lesion Diagnosis

• Never use serology to diagnose active genital ulcers: HSV molecular assays (PCR) or viral culture from lesion swabs are the appropriate tests for symptomatic patients 1, 2
• Serology cannot determine if current lesions are HSV-related: Type-specific antibodies indicate past or current infection but do not establish causation of present symptoms 1, 2

Critical Limitations of HSV Serology

Test Performance Issues

HSV-2 IgG testing has serious specificity problems that can lead to false-positive diagnoses:

• Index values 1.1-2.9 have only 39.8% specificity compared to Western blot 1
• Index values ≥3.0 have 78.6% specificity 1
• Low positive results (index <3.0) should be confirmed with a second assay using different methodology 1
• Patients with HSV-1 infection are more likely to have false-positive HSV-2 results with low index values 1

HSV-1 IgG testing lacks sensitivity:

• Sensitivity for detecting HSV-1 antibodies is only 70.2%, resulting in frequent false-negative results 1

Timing Considerations

• Window period: False-negative results occur during the first 12 weeks after infection 1
• Do not repeat negative serology until ≥12 weeks post-exposure to allow adequate time for antibody development 1

Proper Diagnostic Approach by Clinical Scenario

Patient WITH Active Genital Lesions

1. First-line: PCR/NAAT from lesion base or vesicle fluid (>90% sensitivity and specificity) 1, 2
2. Second-line: Viral culture if PCR unavailable (lower sensitivity, especially in healing lesions) 1, 2
3. Never use: Direct immunofluorescence or Tzanck smear (inadequate sensitivity) 1, 2
4. Serology role: Only if lesions have healed and PCR/culture negative, wait 12 weeks then test 1

Patient WITHOUT Active Lesions (Asymptomatic)

1. Determine if testing indicated: Review high-risk criteria above
2. If indicated: Order type-specific HSV-2 IgG (and HSV-1 IgG if desired)
3. Interpret cautiously: Low positive HSV-2 results require confirmatory testing 1
4. Counsel appropriately: Positive serology indicates infection but not necessarily disease requiring treatment 3

Common Pitfalls to Avoid

• Ordering serology for active lesion diagnosis: This cannot determine if current ulcers are HSV-related 2
• Accepting low-positive HSV-2 results without confirmation: Index values <3.0 have poor specificity and need second assay 1
• Testing during window period: Wait 12 weeks after exposure for accurate results 1
• Initiating treatment based solely on positive serology without symptoms: Asymptomatic immunocompetent individuals do not require routine antiviral treatment 3
• Using non-type-specific assays: Only type-specific tests that differentiate HSV-1 from HSV-2 should be used 1