What are the recommended methods for testing a patient suspected of having genital herpes, including physical examination, medical history, and laboratory tests?

Testing for Genital Herpes

PCR (nucleic acid amplification testing) from swabs of active genital lesions is the preferred diagnostic test for genital herpes, offering superior sensitivity and specificity compared to viral culture, with results available in approximately 2 hours and the ability to simultaneously type HSV-1 versus HSV-2. 1, 2

When to Test

Laboratory confirmation should always be obtained because clinical diagnosis alone leads to both false positive and false negative results 3, 2. Test patients with:

• Vesicular or ulcerative lesions on genitals, buttocks, or thighs 3
• Mucous or purulent vaginal discharge 3
• History of recurrent genital lesions 3
• Sexual contact with a confirmed HSV case 3
• Concurrent STI screening 3
• Persistent dysuria after treatment for gonorrhea or nongonococcal urethritis 3

Optimal Sample Collection Technique

For Vesicular Lesions (Highest Yield)

• Open vesicles with a sterile needle 3, 1
• Collect vesicular fluid with cotton-wool or Dacron swab 3, 1
• Vigorously swab the base of the lesion to obtain epithelial cells 2
• Detection rates reach 90% with viral culture and even higher with PCR 1

Critical pitfall: Do not sample crusted lesions—detection rates plummet to only 27% even with viral culture 1. Collect specimens as early as possible in the disease course 2.

For Male Patients

• Clean external urethral opening with saline-moistened swab 3
• Retract prepuce to avoid contamination 3
• Insert cotton-wool or Dacron swab 0.5-2 cm into urethral meatus to collect exudates 3, 1
• Consider urethral sampling if discharge present (HSV isolated from urethra in 28% of first-episode infections) 2

For Female Patients

• Clean introitus with sterile gauze 3
• Insert swab 0.5 cm into urethra for urethral exudates 3
• After inserting speculum, clean cervical canal opening and insert swab 2 cm deep 3, 1
• Collect from vaginal wall using cotton-wool or Dacron swab on aluminum shaft 3, 1
• HSV can be isolated from cervix and vaginal wall in 88% of women with first-episode genital herpes 2

Laboratory Testing Methods

First-Line: PCR/NAAT with HSV Typing

• Provides highest sensitivity and specificity (>90%) 2, 4
• Simultaneously detects and types HSV-1 versus HSV-2 in single reaction 1
• Results available in approximately 2 hours 1
• Less strict transportation requirements than viral culture 1
• Always request HSV typing because 12-month recurrence rates differ dramatically: HSV-2 (90%) versus HSV-1 (55%) 2

Alternative: Viral Culture

• Significantly lower sensitivity than PCR, particularly for ulcerative lesions (70% detection) or crusting lesions (27% detection) 1
• Requires refrigeration during transport 1
• Takes 24-72 hours for results 5
• Being replaced by PCR as the gold standard 4, 6

Alternative: Antigen Detection

• Immunofluorescence or enzyme immunoassay can be used for symptomatic patients 1
• Less sensitive than PCR 1
• Can provide HSV type determination 4

Type-Specific Serologic Testing

Use glycoprotein G-based type-specific serology (approximately 97% sensitivity, 98% specificity) for: 1

• Asymptomatic individuals with history suggestive of genital herpes 7
• Patients with atypical presentations 1
• When lesions have healed and PCR/culture was not obtained 2
• Evaluating discordant couples 7
• Pregnant women whose partners have genital herpes history 7

Critical pitfalls with serology:

• HSV-1 EIA/CLIA assays have only 70.2% sensitivity, resulting in frequent false-negatives 2
• HSV-2 EIA/CLIA assays with index values 1.1-2.9 have only 39.8% specificity 2
• Do NOT use HSV-specific IgM testing—approximately one-third of patients with recurrent HSV-2 have IgM responses, making it a poor indicator of recent infection 1

Differential Diagnosis Considerations

Always consider and test for other causes of genital ulceration: 3, 2

• Treponema pallidum (syphilis)—can occasionally be recovered from same lesion as HSV 3
• Haemophilus ducreyi (chancroid) 3
• Non-infectious causes: Crohn disease, Behçet syndrome, fixed drug eruption 3

Methods to Avoid

Never rely on: 1

• Tzanck smears—low sensitivity and specificity
• Cytological examinations—inadequate diagnostic accuracy
• Clinical diagnosis alone—unreliable for confirming HSV infection