What is the recommended testing and treatment for a patient suspected of having an active Herpes Simplex Virus (HSV) 1 infection?

HSV-1 Testing: Diagnostic Approach

For suspected active HSV-1 infection, obtain nucleic acid amplification testing (NAAT/PCR) directly from lesions as the first-line diagnostic test, as it provides >95% sensitivity and specificity and is far superior to viral culture or other methods. 1

Testing Strategy for Active Lesions

Primary Diagnostic Test

• Collect samples directly from vesicular or ulcerative lesions using cotton-wool or Dacron swabs for HSV NAAT/PCR testing 2
• For vesicular lesions, pierce the vesicle and collect fluid; for ulcerative lesions, swab the base vigorously 2
• Request testing that differentiates HSV-1 from HSV-2, as this provides critical prognostic information (HSV-1 recurs less frequently than HSV-2 in genital locations) 1, 2
• PCR results are typically available within 2 hours, compared to 24-72 hours for viral culture 2

Alternative Testing When PCR Unavailable

• If NAAT/PCR is unavailable due to cost or laboratory limitations, viral culture is acceptable but recognize it has significantly lower sensitivity (11-71% less sensitive than PCR) 2, 3
• Do not use direct immunofluorescence assay or Tzanck smear, as they lack adequate sensitivity 1

Testing for Suspected HSV Encephalitis

CSF Testing Protocol

• All patients with suspected viral encephalitis should have CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses, as this identifies 90% of cases due to known viral pathogens 1
• CSF PCR for HSV between days 2-10 of illness has >95% sensitivity and specificity for HSV encephalitis in immunocompetent adults 1
• If initial CSF PCR is negative but clinical suspicion remains high, obtain a second lumbar puncture 24-48 hours later 1

Late Presentation Testing

• For patients presenting after day 10-12 of illness where initial CSF was not tested by PCR, send CSF and serum samples (taken approximately 10-14 days after illness onset) for HSV-specific IgG antibody testing to detect intrathecal antibody synthesis 1
• Intrathecal HSV-specific IgG antibodies normally appear after 10-14 days, peak at one month, and can persist for years 1

Serological Testing Approach

When to Use Serology

• Use type-specific HSV serologic testing when lesions have healed and direct testing was not performed, or when recurrent episodes occur but direct testing has been negative 1, 2
• Consider routine type-specific serologic testing for HSV-2 in persons seeking HIV care 1
• Pre-transplant recipient serology should be obtained for HSV-1, HSV-2, and VZV 1

Interpreting Serologic Results

• FDA-approved EIA/CLIA tests have significant limitations: HSV-1 assays have only 70.2% sensitivity (high false-negative rate), while HSV-2 assays lack specificity with only 57.4% specificity compared to Western blot 1
• For HSV-2 EIA results, index values of 1.1-2.9 have only 39% positive predictive value; values >3.5 are more reliable 1
• Western blot/immunoblot is the gold standard for HSV serologic testing but is not widely available 1
• Allow at least 12 weeks after exposure before serologic testing, as antibodies may not be detectable earlier 4

Special Populations

Immunocompromised Patients

• In immunocompromised patients with suspected encephalitis, test CSF for HSV-1, HSV-2, VZV, EBV, CMV, and HHV-6/7 1
• Consider more aggressive diagnostic evaluation including early biopsy in immunocompromised patients with atypical presentations 2
• Extensive, deep, nonhealing ulcerations are more common in patients with CD4+ counts <100 cells/µL 1

Ancillary Testing

• When indicated, obtain throat swabs, rectal swabs, and vesicle samples for PCR/culture to establish systemic infection, though these do not necessarily confirm CNS disease 1
• For patients with herpetic lesions, send vesicle samples for electron microscopy, PCR, and culture 1

Common Pitfalls to Avoid

• Do not obtain HSV molecular assays in the absence of lesions to diagnose genital herpes, as intermittent shedding makes this approach insensitive; use serology instead 1
• Do not delay testing as viral yield decreases as lesions heal; healing lesions may become PCR-negative 1
• Do not rely on clinical diagnosis alone, as clinical differentiation of HSV from other causes of ulceration is unreliable and laboratory confirmation should always be sought 2
• Be aware that intrathecal immune responses may be delayed or absent when antiviral therapy is started early in encephalitis cases 1