What is the best initial test for acute genital herpes simplex infection?

Optimal Testing for Acute Genital Herpes Simplex Infection

Nucleic acid amplification tests (NAATs), particularly PCR, are the first-line diagnostic test for acute genital herpes simplex infection due to their superior sensitivity and specificity compared to other methods. 1, 2

Diagnostic Test Hierarchy

• First choice: Nucleic Acid Amplification Tests (NAATs)/PCR

  • Offers highest sensitivity (11-71% superior to viral culture) 1
  • Allows simultaneous detection and typing of HSV-1 and HSV-2 in a single reaction 1
  • Remains positive longer in lesions (average 6.8 days) compared to viral culture (average 2.6 days) 3
  • Most FDA-approved tests have >90% sensitivity and specificity 1
  • Requires less strict sample transportation conditions than viral culture 1

• Second choice: Viral Culture

  • Use only if NAAT/PCR is unavailable 1, 2
  • Less sensitive than NAAT/PCR, especially for healing lesions 1
  • Samples must be transported to the laboratory on ice and processed within 24 hours 2
  • Allows virus typing and antiviral sensitivity testing 1

• Not recommended:

  • Direct immunofluorescence assay and Tzanck smear (lack sensitivity) 1, 2

Optimal Sampling Technique

• For vesicular lesions:

  • Open vesicles with a sterile needle 1
  • Collect vesicular fluid with a swab 1
  • Place in appropriate transport medium for NAAT or viral culture 1

• For ulcerative lesions:

  • Sample the base of ulcers 1
  • PCR detects HSV DNA in ulcerative lesions more effectively than viral culture (15/17 days vs. 3/17 days) 3

• For male patients:

  • Clean external urethral opening with saline-moistened swab 1
  • Insert cotton-wool or Dacron swab into urethral meatus (0.5-2 cm depth) 1

• For female patients:

  • Clean introitus with sterile gauze 1
  • Insert swab into urethra (0.5 cm depth) or cervical canal (2 cm depth) 1
  • Alternatively, collect from vaginal wall 1

Important Clinical Considerations

• HSV typing is essential for counseling and prognosis as HSV-1 and HSV-2 have different clinical courses 1, 2

  • Up to 50% of first-episode genital herpes cases are caused by HSV-1 2
  • Recurrences and subclinical viral shedding are less frequent with genital HSV-1 than HSV-2 2

• Timing matters:

  • The yield of testing decreases as lesions heal 1
  • PCR becomes negative when lesions re-epithelialize 3
  • First-episode infections show higher viral quantities than recurrent infections 4

• Differential diagnosis:

  • Consider other causes of genital ulceration (Treponema pallidum, Haemophilus ducreyi) 1
  • Non-infectious causes include inflammatory bowel disease, Behçet syndrome, or fixed drug eruption 1

Common Pitfalls and Caveats

• Do not rely solely on clinical diagnosis without laboratory confirmation 2

  • Clinical differentiation of genital HSV from other causes of genital ulceration is difficult 1

• Do not use HSV molecular assays in the absence of genital ulcers 1, 2

  • Due to intermittent nature of HSV shedding, swabs obtained without visible lesions lack sensitivity 1

• Serological testing limitations:

  • Cannot determine the etiology of a presenting genital lesion with certainty 1, 2
  • Not recommended for widespread screening 2, 5
  • Consider only for detecting asymptomatic infections in high-risk individuals 2

• Quality control for NAAT:

  • Each DNA extraction and analysis should include internal positive control and negative control 1
  • Be aware of test characteristics of HSV NAATs used in your clinical setting 1