Herpes Simplex Virus 2

Herpes Simplex Virus 2 (HSV-2) is a double-stranded DNA virus that causes lifelong genital infections with episodes of reactivation and viral shedding.

Transmitted primarily through sexual contact, HSV-2 often remains asymptomatic but can lead to complications, including recurrent outbreaks, complications in pregnancy, and increased risk of HIV acquisition.

What is Herpes Simplex Virus 2 (HSV-2)?

HSV-2 is a double-stranded DNA virus from the Herpesviridae family that primarily causes genital herpes. 

Unlike HSV-1, which commonly causes oral lesions, HSV-2 is typically transmitted through sexual contact and establishes lifelong infection with intermittent reactivation. 

After the initial infection, HSV-2 becomes dormant in sensory neurons and reactivates over time, often causing recurrent genital outbreaks.

When is HSV-2 Testing Relevant?

Testing should be considered in the following scenarios:

Symptomatic Individuals 

Individuals with genital blisters, ulcers, itching, or painful urination should be tested for HSV-2 infection.

Sexual Contact with HSV-2 Positive Partner

Testing should occur in these individuals, even in the absence of symptoms.

Pregnancy 

Pregnant people should be considered for HSV-2 screening for HSV-2 to assess the risk of neonatal herpes, particularly if there is a history or concern for new infection. 

The CDC recommends asking about HSV history and an examination at labor, but does not recommend routine HSV-2 serologic screening in pregnancy.

Evaluation of Genital Ulcers

HSV-2 is a key cause of genital ulcer disease and must be included in the differential.

Types of HSV-2 Tests

The following types of HSV-2 tests are available:

Polymerase Chain Reaction (PCR)

Due to its high sensitivity, this is the preferred diagnostic method for active lesions. Detects HSV-2 DNA from lesion swabs or body fluids.

Viral Culture

A viral culture of fluid from active lesions is less sensitive than PCR (culture has about 50% sensitivity) and best used early in lesion development.

Antibody (Serologic) Testing

This testing detects past or present infection by measuring HSV-2-specific antibodies in the blood. It is useful in asymptomatic individuals or for partner testing, although it may not detect early infection as antibodies take time to develop.

HSV-2 Testing Procedure

Genital HSV-2 infections are diagnosed using PCR, viral culture, or serology. 

PCR is the most sensitive test and can detect HSV DNA even after lesions begin healing. Swabs from fresh genital lesions should be placed in viral transport medium and kept cold during transport.

Viral culture, once the gold standard, is highly specific but less sensitive, especially for older or recurrent lesions. Results may take several days. Shell vial culture offers faster turnaround but is slightly less sensitive.

DFA testing (a type of antibody testing) detects HSV antigens from lesion smears and provides quicker results than culture, though it’s less sensitive than PCR.

Serologic tests, another antibody test, identify past or current infection using a blood sample. These tests are helpful when lesions are absent or other tests are negative. They can distinguish between HSV-1 and HSV-2 but not the site of infection.

For best results, collect samples early, avoid alcohol on lesions, and use appropriate swabs and transport methods.

Interpreting HSV-2 Test Results

The following findings may have these clinical implications:

• Positive PCR or Culture: Confirms active infection and the presence of viral shedding at the tested site.
• Positive Antibody Test: Indicates current or past infection. Cannot determine timing or activity of infection.
• Negative PCR or Culture: Suggests no active shedding at the time of testing but does not rule out HSV-2.
• Negative Antibody Test: Suggests no previous infection, but recent exposure may not yet produce detectable antibodies.

What Does the Absence of HSV-2 Mean?

A negative PCR and antibody testing result generally indicates no HSV-2 infection.

However, recent exposure or a false negative serologic test must be considered in the appropriate clinical context.

Clinical Features

The clinical features of HSV-2 often include:

• Initial Outbreak: Painful vesicles or ulcers, fever, myalgias, lymphadenopathy, and dysuria. Symptoms last 2–3 weeks.
• Recurrent Episodes: Milder and shorter, often preceded by a prodrome of itching or tingling. Triggered by stress, illness, or menstruation.
• Asymptomatic Shedding: Common, and contributes to transmission—most people are unaware of their infection.

Management and Treatment

• First Episode: Oral antivirals for 7–10 days (e.g., acyclovir 400 mg TID or valacyclovir 1 g BID).
• Episodic Therapy: For recurrences—short course at symptom onset.
• Suppressive Therapy: Daily antivirals reduce outbreak frequency and lower transmission risk. Indicated for:
  
  • Frequent or severe recurrences
  • Discordant couples (one person is HSV-2 positive and the other is HSV-2 negative)
  • Immunocompromised patients (e.g., HIV+)

Complications

HSV-2 infections can pose distinct complications:

• Neurologic: Aseptic meningitis, urinary retention.
• Pregnancy: Primary infection in late pregnancy poses the greatest risk of neonatal herpes.
• HIV Risk: HSV-2 triples the risk of HIV acquisition and worsens outcomes in coinfected patients.

Counseling and Prevention

The following points should be discussed with patients:

• Condom Use: Reduces but does not eliminate transmission risk.
• Abstain During Outbreaks: Essential to reduce transmission.
• Suppressive Antiviral Therapy: Lowers the risk of spread to partners.
• Routine STI Screening: Particularly HIV testing in individuals with HSV-2.

Conclusion

HSV-2 is a lifelong, often asymptomatic infection with significant implications for sexual and reproductive health. 

PCR is the most reliable diagnostic tool for active disease, while antibody testing aids in identifying past exposure. 

Antiviral therapy effectively reduces symptoms and transmission; ongoing patient education is vital to management.