What are the methods for diagnosing genital herpes?

Testing for Genital Herpes

PCR (nucleic acid amplification test) from swabs of active genital lesions is the preferred initial diagnostic test for genital herpes, offering superior sensitivity and specificity compared to all other methods. 1

Optimal Diagnostic Approach

When active lesions are present, always obtain PCR testing with HSV typing (HSV-1 vs HSV-2 differentiation) as your first-line diagnostic test. 1, 2 This single test provides both detection and typing simultaneously, with results available in approximately 2 hours. 1 The distinction between HSV-1 and HSV-2 is clinically critical because 12-month recurrence rates differ dramatically: HSV-2 recurs in 90% of patients versus only 55% for HSV-1. 2

Critical Sampling Technique

For vesicular lesions, open the vesicles with a sterile needle and collect the vesicular fluid with a cotton-wool or Dacron swab, then vigorously swab the base of the lesion. 1, 2 This technique yields the highest detection rates—90% for viral culture and even higher for PCR. 1 Timing matters significantly: collect specimens as early as possible in the disease course, as vesicular lesions yield substantially higher positivity rates than ulcerative or healing lesions. 2

Never sample from crusted lesions—detection rates plummet to only 27% even with viral culture. 1

Site-Specific Collection Methods

For males with genital lesions:

• Clean the external urethral opening with a saline-moistened swab 3
• If urethral involvement is present, insert a cotton-wool or Dacron swab 0.5-2 cm into the urethral meatus to collect exudates 1, 2
• HSV can be isolated from the urethra in 28% of men with first-episode infection 2

For females with genital lesions:

• Collect from the cervical canal (insert swab 2 cm depth) using cotton-wool or Dacron swab on aluminum shaft 1
• Also collect from the vaginal wall 1
• HSV can be isolated from the cervix in 88% of women with first-episode genital herpes 2

Alternative Testing Methods (When PCR Unavailable)

Viral culture can serve as an alternative but has significantly lower sensitivity, particularly for ulcerative lesions (70% detection) or crusting lesions (27% detection). 1 Antigen detection methods (immunofluorescence or enzyme immunoassay) are less sensitive than PCR and should only be considered for symptomatic patients when PCR is unavailable. 1

Serologic Testing: Limited Role

Type-specific serologic testing based on glycoprotein G should be reserved for specific situations only:

• Asymptomatic individuals or those with atypical presentations 1
• When lesions have healed and PCR/culture was not obtained 2
• To distinguish between HSV-1 and HSV-2 in patients with a history of genital herpes but no current lesions 2

Type-specific serology has approximately 97% sensitivity and 98% specificity. 1 However, be aware that HSV-1 EIA/CLIA assays have only 70.2% sensitivity (frequent false-negatives), and HSV-2 EIA/CLIA assays lack specificity, particularly with index values 1.1-2.9 (only 39.8% specificity). 2

Critical Pitfalls to Avoid

Never rely on clinical diagnosis alone—laboratory confirmation should always be sought. 3, 2 Clinical differentiation of genital HSV infection from other causes of genital ulceration (syphilis, chancroid, Crohn disease, Behçet syndrome, fixed drug eruption) is unreliable and leads to both false positive and false negative diagnoses. 3

Never use Tzanck smears or cytological examinations—they have low sensitivity and specificity. 1

Never use HSV-specific IgM testing to diagnose recent infection. 1 Approximately one-third of patients with recurrent HSV-2 have IgM responses, making it a poor indicator of acute infection. 1

Transportation and Handling

PCR samples tolerate less strict transportation conditions compared to viral culture. 1 If using viral culture, samples require refrigeration during transport to maintain viability. 1

Who Should Be Tested

Testing is indicated for:

• Males with vesicular/ulcerative lesions on penis, buttocks, or perineum 3
• Females with vesicular/ulcerative lesions on genitals, buttocks, or thighs 3
• Anyone with dysuria following treatment for gonorrhea/nongonococcal urethritis 3
• Patients with history of recurrent vesicular/ulcerative genital lesions 3
• Sexual contacts of proven genital herpes cases 3
• Patients being examined for other sexually transmitted infections 3