Herpes Simplex Virus Infection Diagnostics

Last updated: 06 October 2025

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Laboratory Tests and Ancillaries

Virological Tests

 

Sources of specimens for viral culture include skin, mucocutaneous lesions, blood, cerebrospinal fluid, urine, stool, oropharynx or conjunctiva. A positive viral culture will show cytopathic effect, characteristic of herpes simplex virus replication. Viral culture provides rapid results (within 7 days). It is sensitive and allows discrimination between HSV-1 and HSV-2. It is also the preferred diagnostic method for virus isolation for drug susceptibility testing. However, it has low sensitivity in recurrent and healing lesions and is less sensitive than polymerase chain reaction (PCR) for the detection of herpes simplex virus.

 

Examples of antigen detection tests include immunoperoxidase tests, immunofluorescence, and enzyme immunoassay. These tests detect herpes simplex virus antigens. They are rapid but do not allow for the discrimination between HSV-1 and HSV-2.

 

PCR provides virologic confirmation via herpes simplex virus DNA detection. It is the most sensitive method to confirm both primary and recurrent herpes simplex virus infection using clinical specimens from mucocutaneous sites, including oral and genital ulcers. It is also the test of choice for herpes simplex virus infection in the CNS and systemic infections.

 

Type-specific Serological Tests

 

Type-specific serological tests include complement fixation tests, enzyme-linked immunosorbent assay, and Western blot. These tests do not distinguish anogenital from orolabial infection. IgG antibody indicates past infection while IgM antibody suggests recent infection. However, it must be noted that IgM antibody detection lacks sensitivity especially for recurrent infections. Furthermore, type-specific serological tests may be used to diagnose herpes simplex virus infection in the absence of genital lesions. They can also be used to screen for HSV-1 or HSV-2 infection in asymptomatic pregnant women to mitigate potential transmission to the infant due to viral shedding at the time of the delivery.

 

Tzanck Smear

 

A Tzanck preparation (Wright-Giesma or Papanicolaou stain) may show multinucleated giant cells or intranuclear inclusions from the scrapings from the base of freshly ruptured lesions. However, it cannot reliably differentiate herpes simplex virus from varicella-zoster virus.