What is the role of herpes antibody testing in diagnosing and managing herpes infections?

Role of Herpes Antibody Testing in Diagnosing and Managing Herpes Infections

Nucleic acid amplification tests (NAATs) such as PCR are the first-line diagnostic test for herpes simplex virus (HSV) detection in patients with active genital lesions, while type-specific serologic testing should be reserved for specific clinical scenarios including asymptomatic high-risk individuals, partners of HSV-infected persons, and patients with recurrent symptoms but negative PCR results. 1

Diagnostic Testing for Active Lesions

First-Line Testing

• PCR/NAAT is the gold standard for diagnosing active herpes infections, offering 11-71% higher sensitivity than viral culture and allowing simultaneous detection and typing of HSV-1 and HSV-2 1
• Samples should be collected from fluid in intact vesicles or the base of ulcers for optimal results 1
• NAAT allows less strict sample transportation conditions compared to viral culture 1

Alternative Testing Options

• Viral culture is the second-choice diagnostic method if NAAT is unavailable, but has lower sensitivity 1
• Direct immunofluorescence assay and Tzanck smear are not recommended due to their lack of sensitivity 1
• For male patients, urethral swabs can be used for NAAT or antigen detection 1
• For female patients, cervical/urethral swabs are recommended for NAAT or antigen detection 1

Serologic Testing

Appropriate Use of Type-Specific Serology

• Type-specific serology should be used for: 2, 3
  • Detecting asymptomatic infections in high-risk individuals
  • Testing pregnant women at risk of acquiring HSV close to delivery
  • Men who have sex with men
  • People who are HIV positive
  • Partners of HSV-infected individuals
  • Patients with recurrent genital symptoms but negative PCR results

Limitations of Serologic Testing

• Commercial HSV-2 serologic tests using enzyme immunoassay (EIA) have significant specificity limitations, especially at lower index values 2
• Index values of 1.1-2.9 have only 39.8% specificity, while values ≥3.0 have improved specificity of 78.6% 2
• False positives are more common in individuals with HSV-1 infection, especially with low index values 2
• For low positive results (index value <3.0), confirmation with a second test using a different glycoprotein G antigen is recommended 2
• Serological tests alone cannot determine the etiology of a presenting genital lesion with certainty 2
• Commercial type-specific gG HSV-1 or HSV-2 antibody assays can be false negative in 12-30% of patients with recurrent HSV DNA positive genital lesions 4

When Not to Use Serologic Testing

• Widespread screening for HSV antibodies is discouraged 1, 2
• The US Preventive Services Task Force recommends against screening for HSV-2 infection among asymptomatic adolescents and adults 3

Clinical Significance of HSV Typing

• HSV typing is essential for counseling and prognosis 1
• HSV-2 is primarily associated with genital herpes, with higher rates of symptomatic recurrences and subclinical viral shedding compared to HSV-1 genital infections 2
• Up to 50% of first-episode genital herpes cases are caused by HSV-1 1
• Recurrences and subclinical viral shedding are less frequent with genital HSV-1 than HSV-2 1

Management Implications Based on Testing Results

• Positive HSV-2 antibody indicates past exposure and ongoing latent infection, with antibodies persisting indefinitely 2
• Patients with genital herpes should be counseled about:
  • The natural history of the disease
  • Potential for recurrent episodes
  • Asymptomatic viral shedding
  • Sexual transmission risk 3
• Patients should be advised to abstain from sexual activity while lesions are present 3
• Condom use should be encouraged during all sexual exposures 3
• Treatment options include episodic therapy for outbreaks or suppressive therapy to reduce recurrences and transmission risk 2
• The same medication dosages are recommended for both HSV-1 and HSV-2 genital infections 3

Special Considerations

• A negative serologic result within 12 weeks of potential exposure may represent the "window period" and should be repeated after 12 weeks if recent acquisition is suspected 2
• Type-specific testing can identify asymptomatic HSV-2 infections, which is important as many cases are transmitted during asymptomatic periods 3, 5
• In HIV-infected persons, intermittent or suppressive therapy with oral acyclovir may be needed at increased dosages 3