What is the recommended test and treatment for Herpes Simplex Virus (HSV) infection, particularly for genital herpes?

Diagnostic Testing for Genital Herpes Simplex Virus

For patients with active genital lesions, nucleic acid amplification testing (NAAT/PCR) is the first-line diagnostic test due to its superior sensitivity and specificity, and viral culture should only be used when NAAT is unavailable. 1

Diagnostic Approach for Active Lesions

First-Line Testing: NAAT/PCR

• NAAT/PCR is 11-71% more sensitive than viral culture and should be the primary diagnostic test for all patients presenting with active genital lesions. 1
• PCR allows simultaneous detection and typing of HSV-1 and HSV-2 in a single reaction, which is essential for prognosis and counseling. 1, 2
• NAAT permits less strict sample transportation conditions compared to viral culture, making it more practical for clinical use. 1

Sample Collection Technique

• Sample fluid from intact vesicles or the base of ulcers by opening vesicles with a sterile needle and collecting content with a swab. 3, 1
• For males without visible lesions: obtain urethral swabs by inserting a cotton-wool or Dacron swab 0.5-2 cm into the external urethral meatus. 3, 1
• For females without visible lesions: obtain cervical swabs by inserting a swab 2 cm into the cervical canal, or vaginal swabs from the posterior vaginal wall. 3, 1

Second-Line Testing: Viral Culture

• Viral culture should only be used when NAAT is unavailable, as it has significantly lower sensitivity. 3, 1
• Samples for viral culture must be transported on ice and processed within 24 hours to maintain viability. 1

Tests to Avoid

• Do not use direct immunofluorescence assay or Tzanck smear due to lack of sensitivity. 1
• Never rely on clinical diagnosis alone without laboratory confirmation, as clinical differentiation from other causes of genital ulceration (syphilis, chancroid, Crohn's disease, Behçet syndrome) is unreliable. 3

Serological Testing Strategy

When to Order Type-Specific HSV-2 Serology

Type-specific serology should be reserved for specific clinical scenarios and is NOT recommended for widespread screening of asymptomatic populations. 3, 4

Appropriate Indications:

• Patients with genital symptoms suggestive of herpes but negative NAAT/culture results. 3
• Patients told they have genital herpes without virologic confirmation. 3
• Sexual partners of persons with confirmed HSV-2 infection. 3, 4
• Pregnant women at risk of acquiring HSV infection close to delivery. 1, 4
• Men who have sex with men. 1, 4
• HIV-positive individuals. 1, 4

Algorithmic Approach to Serologic Testing

Step 1: Order type-specific HSV-2 IgG test using glycoprotein G-based EIA or CLIA 4

Step 2: Interpret based on index value:

• Index <0.9: Negative 4
• Index 0.9-1.1: Indeterminate, repeat in 2-4 weeks 4
• Index 1.1-2.9: Low positive - REQUIRES CONFIRMATION 4
• Index ≥3.0: Positive (specificity 78.6%, may still consider confirmation in low-prevalence populations) 3, 4

Step 3: For low-positive results (1.1-2.9), confirm with second assay using different glycoprotein G antigen 4

• This improves specificity from 93.2% to 98.7% and positive predictive value from 80.5% to 95.6%. 3, 4
• The Biokit HSV-2 rapid assay is recommended as the confirmatory test. 3

Critical Limitations of Serologic Testing

• HSV-1 antibody testing has only 70.2% sensitivity, resulting in frequent false-negative results and should not be used to diagnose genital herpes. 4
• HSV-2 serology has serious specificity problems at low index values: only 39.8% specificity for index values 1.1-2.9. 4
• Patients with HSV-1 infection are significantly more likely to have false-positive HSV-2 results, especially at low index values. 4
• Allow 12 weeks after exposure before testing, as antibodies may not be detectable earlier. 4
• Serology cannot determine the anatomic site of infection or whether a current lesion is caused by HSV. 1

Common Clinical Pitfalls to Avoid

1. Never order serology when active lesions are present - this misses the opportunity for definitive NAAT/PCR diagnosis that can type the virus and confirm active infection. 4

2. Never report low-positive HSV-2 results (index 1.1-2.9) without confirmatory testing - this leads to false-positive diagnoses with significant psychological and relationship consequences. 4

3. Never use HSV-1 serology to diagnose genital herpes - it cannot distinguish oral from genital infection and has poor sensitivity. 4

4. Never screen asymptomatic general populations - the U.S. Preventive Services Task Force recommends against this practice. 3, 1

5. Never use HSV molecular assays in the absence of genital ulcers - testing should be directed by clinical presentation. 1

Why HSV Typing Matters

• Up to 50% of first-episode genital herpes cases are caused by HSV-1. 1
• Recurrences and subclinical viral shedding are significantly less frequent with genital HSV-1 than HSV-2. 1
• HSV-2 carries greater stigma and requires different counseling regarding transmission risk and recurrence patterns. 3
• The same antiviral medication dosages are recommended for both HSV-1 and HSV-2 genital infections. 1