What tests are available to diagnose HSV (Herpes Simplex Virus) 1 and 2 in a young adult with a history of cold sores?

Testing for HSV-1 and HSV-2

Yes, multiple tests are available to diagnose HSV-1 and HSV-2, with the optimal test depending on whether you have active lesions (use PCR/NAAT) or no current symptoms (use type-specific serology). 1

When Active Lesions Are Present

PCR/NAAT testing from the lesion is the preferred diagnostic method, with >90% sensitivity and specificity. 1

• Swab the base of the lesion and send for HSV PCR/NAAT that differentiates HSV-1 from HSV-2 1
• As of 2019,17 FDA-approved HSV NAAT/PCR assays are available for clinical use 1
• PCR remains highly accurate even as lesions begin healing, though sensitivity decreases as ulcers heal completely 1
• Viral culture is an alternative if PCR is unavailable due to cost or laboratory limitations, but it is significantly less sensitive than PCR 1
• Do not use Tzanck smear or direct immunofluorescence assay—these lack adequate sensitivity and are not recommended 1

When No Active Lesions Are Present

Type-specific HSV serology testing IgG antibodies to glycoprotein G is the appropriate test when lesions are absent. 1, 2

• Request type-specific HSV-1 and HSV-2 IgG antibody tests using enzyme immunoassay (EIA) or chemiluminescent immunoassay (CLIA) 1, 2
• These tests detect antibodies that develop within several weeks of infection and persist for life 2
• Do not swab in the absence of lesions—intermittent viral shedding makes this approach insensitive 1

Critical Limitations of Serology Testing

HSV-1 Serology Issues

• HSV-1 antibody tests have only 70.2% sensitivity, resulting in frequent false-negative results 1, 3
• Commercial tests may miss 12-30% of true HSV-1 infections 4

HSV-2 Serology Issues

• HSV-2 serology has serious specificity problems that depend heavily on the index value reported 1, 2, 3
• Index values 1.1-2.9 have only 39.8% specificity (meaning 60% are false positives) 1, 2
• Index values ≥3.0 have improved specificity of 78.6% 1, 2
• False-positive HSV-2 results are more common in people who have HSV-1 infection, especially at low index values 1, 2, 3

Confirmation Strategy for Low-Positive Results

• For HSV-2 results with index values between 1.1-2.9, confirm with a second test using a different glycoprotein G antigen 2, 3
• Using the Biokit HSV-2 rapid assay as confirmation improves specificity from 93.2% to 98.7% 2, 3
• Western blot is the gold standard but has limited availability 1, 2

Timing Considerations

• If testing after a potential recent exposure, wait at least 12 weeks before serology testing to avoid false-negative results during the "window period" 2, 5
• Antibodies develop within several weeks but may not be detectable immediately after infection 1, 2

Clinical Context for Your History of Cold Sores

• Your history of cold sores indicates likely HSV-1 infection, which can be confirmed with HSV-1 IgG serology 5
• HSV-1 can cause both oral cold sores and genital herpes through oral-genital contact 5
• If you develop genital lesions, PCR/NAAT testing is essential to determine whether they are caused by HSV-1 or HSV-2, as this affects prognosis and counseling 1
• HSV-2 causes more frequent genital recurrences and subclinical shedding compared to HSV-1 genital infections 2

Common Pitfalls to Avoid

• Never accept a low-positive HSV-2 result (index 1.1-2.9) without confirmatory testing—this leads to false diagnoses with significant psychological consequences 2, 3
• Do not use serology to diagnose active genital lesions when PCR/NAAT is available 1, 3
• Do not test too early after exposure—wait the full 12 weeks 2, 5
• Widespread screening of asymptomatic individuals is not recommended 2, 3