Optimal Testing for Herpes Simplex Virus
Nucleic acid amplification tests (NAATs), specifically PCR, are the preferred diagnostic method for herpes testing when active lesions are present, while type-specific serological tests should be used when no lesions are present. 1
Testing Based on Clinical Presentation
When Active Lesions Are Present:
First-line test: PCR (NAAT)
- Superior sensitivity compared to viral culture (11-71% more sensitive) 1
- Can detect and type HSV in a single reaction tube
- Faster results (approximately two hours)
- Remains positive longer in lesions (average 6.8 days vs 2.6 days for culture) 2
- Less strict sample transportation requirements
- Increases overall HSV detection rate by 24-27% compared to culture 3, 4
Alternative: Viral culture
Not recommended:
- Direct immunofluorescence assay
- Tzanck smear (lack sensitivity) 1
When No Active Lesions Are Present:
- Type-specific serological tests (based on glycoprotein G)
Sampling Sites and Methods
| Clinical Situation | Sampling Site | Preferred Method |
|---|---|---|
| Visible lesions | Vesicular rash on skin/mucosa | NAAT or antigen detection |
| Male patients | Urethra | NAAT or antigen detection |
| Female patients | Cervix/urethra | NAAT or antigen detection |
| Eye symptoms | Conjunctiva | NAAT or antigen detection |
| No visible lesions | Venous blood | Serological assays (EIAs) |
Important Considerations
- Timing matters: PCR sensitivity decreases as lesions heal, but remains detectable longer than culture 2
- Type differentiation: Always use assays that differentiate between HSV-1 and HSV-2 to provide accurate information about expected natural history 1
- False negatives: May occur with healing lesions; consider serological testing if clinical suspicion remains high despite negative PCR 1
- Serological limitations:
- HSV-1 assays may lack sensitivity, resulting in false negatives
- Not useful for determining the site of infection (oral vs. genital)
- Cannot distinguish between recent and old infections
Clinical Pearls
- First-episode infections typically show higher viral quantities (median 4.2 × 10^5 copies) compared to recurrent infections (1.0 × 10^4 copies) 4
- HSV-1 is more commonly the cause of first-episode genital infections (72%), while HSV-2 more commonly causes recurrent and atypical genital manifestations (73%) 4
- PCR testing becomes negative when lesions re-epithelialize 2
- Do not obtain swabs in the absence of genital ulcers due to the intermittent nature of HSV shedding 1
By following this evidence-based testing algorithm, you can ensure accurate diagnosis of herpes infections, which is crucial for appropriate treatment, counseling, and prevention of transmission.