What are the recommended diagnostic tests and treatment options for Herpes Simplex Virus (HSV) infection?

Diagnostic Tests and Treatment Options for Herpes Simplex Virus (HSV) Infection

Nucleic acid amplification tests (NAATs) are the gold standard for diagnosing active HSV lesions, while type-specific serological testing should be used for asymptomatic individuals or those with suspected infection but no active lesions. 1

Diagnostic Testing for HSV

Testing for Active Lesions

1. First-line testing:

   • NAAT/PCR - Highest sensitivity (11-71% superior to culture) and specificity (>90%) 1
   • Sample collection from vesicular rash, ulcers, or mucosal surfaces
   • Allows for HSV typing (HSV-1 vs HSV-2) in a single test
   • Requires less strict sample transportation conditions than culture

2. Alternative tests (if NAAT unavailable):

   • Viral culture - Traditional method but less sensitive than NAAT, especially for healing lesions 1
   • Antigen detection - Direct immunofluorescence (DIF) or enzyme immunoassay (EIA) 1

3. Not recommended:

   • HSV direct immunofluorescence assay and Tzanck smear (lack sensitivity) 1

Testing for Individuals Without Active Lesions

1. Type-specific serological assays:

   • Detect HSV glycoprotein G antibodies to differentiate HSV-1 from HSV-2
   • Sensitivity ~97%, specificity ~98% 1
   • Window period may be up to 12 weeks after infection 1

2. Interpretation cautions:

   • HSV-2 specificity is highly dependent on index value (values 1.1-2.9 have only 39.8% specificity) 1
   • HSV-1 assays lack sensitivity (approximately 70.2%) 1
   • IgM detection is a poor indicator of recent infection 1

Recommended Sampling Sites and Methods 1

• Vesicular lesions: NAAT or antigen detection
• Urethra (male): NAAT or antigen detection
• Cervix/urethra (female): NAAT or antigen detection
• Conjunctiva: NAAT or antigen detection
• Urine: NAAT
• Spinal cord fluid: NAAT
• Venous blood: Serological assays

Treatment Options for HSV

Oral Treatment for Episodic Therapy 1

1. First-line options:

   • Valacyclovir: Better bioavailability than acyclovir
   • Acyclovir: Synthetic nucleoside analogue active against HSV-1, HSV-2, and VZV 2
   • Famciclovir: Alternative option with similar efficacy

2. Dosing for orolabial lesions:

   • Treatment for 5-10 days 1

3. Dosing for genital HSV:

   • Treatment for 5-14 days 1
   • Short-course therapy (1-3 days) should not be used in immunocompromised patients 1

Treatment for Severe Infections

• Intravenous acyclovir - First-line for severe mucocutaneous HSV lesions 1
• May switch to oral therapy after lesions begin to regress
• Continue until lesions have completely healed

Suppressive Therapy

• Consider for patients with frequent recurrences
• Options include:
  • Acyclovir 400 mg twice daily
  • Valacyclovir 500 mg daily
  • Famciclovir 250 mg twice daily 1

Treatment in Special Populations

• Immunocompromised patients:

  • May require longer treatment courses
  • Higher risk of complications including disseminated and visceral infections 3
  • Consider prophylaxis in high-risk patients 3

• HIV-infected patients:

  • Type-specific serology recommended for detecting asymptomatic HSV-2 1
  • Consider suppressive therapy to reduce risk of HIV transmission 1

Clinical Pearls and Pitfalls

1. HSV typing is crucial:

   • HSV type determination is important for counseling and prognosis 1
   • HSV-2 is almost always associated with genital disease, while HSV-1 can cause both oropharyngeal and genital disease 1

2. Common diagnostic pitfalls:

   • Relying solely on clinical diagnosis (laboratory confirmation is essential) 4
   • Using non-type-specific serological tests 5
   • Testing too early in the course of infection (false negatives) 1
   • Misinterpreting low index values in HSV-2 serological testing 1

3. Treatment considerations:

   • Antiviral resistance may develop, especially in immunocompromised patients 2, 6
   • Monitor renal function in patients receiving high-dose IV acyclovir 1
   • Widespread screening for HSV antibodies is not recommended 1

4. When to repeat testing:

   • If initial HSV PCR is negative but clinical suspicion remains high (especially with temporal lobe involvement on neuroimaging), repeat lumbar puncture within 3-7 days 1

By following these evidence-based diagnostic and treatment approaches, clinicians can effectively manage HSV infections and reduce associated morbidity and transmission risk.