What is the recommended diagnostic approach for a female patient suspected of having herpes simplex virus (HSV) type 1 or 2?

How to Test for Herpes in a Female

For symptomatic females with active genital lesions, obtain a swab from the lesion and send for nucleic acid amplification testing (NAAT/PCR), which is the first-line diagnostic test due to its superior sensitivity (11-71% better than viral culture) and ability to simultaneously type HSV-1 versus HSV-2. 1

Diagnostic Approach Based on Clinical Presentation

For Symptomatic Patients (Active Lesions Present)

Specimen Collection Technique:

• Vesicles (if intact): Open vesicles with a sterile needle and collect fluid with a swab for NAAT testing 2, 1
• Ulcers: Swab the base of the ulcer vigorously to obtain cellular material 2, 1
• Cervical lesions: Insert speculum (moistened with warm water), clean cervical opening with sterile gauze, then insert cotton or Dacron swab 2 cm into cervical canal 2
• Vaginal lesions: Insert swab through hymen to collect material from posterior vaginal wall 2
• Urethral involvement: Clean introitus with sterile gauze, then carefully insert swab 0.5 cm into urethra 2

Testing Priority:

1. First choice: NAAT/PCR - highest sensitivity and specificity, allows HSV typing in single reaction 1, 3
2. Second choice: Viral culture (if NAAT unavailable) - lower sensitivity but acceptable alternative 1
3. Third choice: Direct immunofluorescence or enzyme immunoassay for antigen detection (only if culture/NAAT unavailable) - must include HSV typing 2
4. Never use: Tzanck smear or direct immunofluorescence assay as primary tests due to poor sensitivity 1

Critical Pitfall: Clinical diagnosis alone leads to both false positives and false negatives; laboratory confirmation is mandatory 2, 4

For Asymptomatic Patients or Those Without Active Lesions

Use type-specific HSV-2 serology (glycoprotein G-based assays) only in specific populations: 1, 5

• Pregnant women at risk of acquiring HSV near delivery
• Women who are HIV-positive
• Sexual partners of individuals with known genital herpes
• Women with history suggestive of genital herpes but negative direct testing 6

Serology Testing Details:

• Collect venous blood sample 5
• Sensitivity ~97%, specificity ~98% for HSV-2 antibodies 5
• Important limitation: Cannot determine if current lesion is HSV-related 1, 5
• Window period: Negative result within 12 weeks of exposure may be false negative; repeat after 12 weeks if recent acquisition suspected 5
• Confirmatory testing needed: If index value <3.0, confirm with second test using different glycoprotein G antigen 5

Do NOT perform: Widespread screening for HSV antibodies in general asymptomatic population 2, 1, 5

Why HSV Typing Matters

HSV-1 versus HSV-2 differentiation is essential because: 1

• Up to 50% of first-episode genital herpes is caused by HSV-1 1
• Genital HSV-1 has fewer recurrences and less subclinical shedding than HSV-2 1
• Different prognostic implications affect counseling 4, 7
• Same treatment dosages apply to both types 1

Sample Handling Requirements

• NAAT samples: Less strict transportation requirements, more forgiving 1
• Viral culture samples: Must transport on ice and process within 24 hours 1
• Patient should avoid urinating for at least 2 hours before sampling if urine collection needed 2

Common Diagnostic Pitfalls to Avoid

• Never rely on clinical appearance alone - HSV can mimic other STIs (syphilis, chancroid) or non-infectious causes (Crohn's disease, Behçet syndrome, drug eruptions) 2
• Do not use HSV molecular assays in absence of genital ulcers - inappropriate test selection 1
• Avoid IgM testing - approximately one-third of recurrent HSV-2 cases show IgM responses, making it unreliable 5
• Do not assume anatomic location indicates HSV type - oro-genital practices mean HSV-1 commonly causes genital disease 2