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Genital Herpes: Laboratory Support of Diagnosis and Management

Genital Herpes: Laboratory Support of Diagnosis and Management

Clinical Focus

Genital Herpes

Laboratory Support of Diagnosis and Management

  

Contents

Clinical Background

Table: Disease Recurrence and Risks Associated with Herpes Simplex Virus Infection

Figure 1: Pathogenesis of Primary HSV-2 Infection

Individuals Suitable for Testing

Test Availability and Selection

Figure 2: Diagnosis of Genital Herpes

Test Interpretation

Appendix: Herpes Tests

References
 

Clinical Background [return to contents]

Infection with either herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) is common in the United States, with a seroprevalence of 58% for HSV-1 and 17% for HSV-2 among people 14 to 49 years old.1 HSV-1 most often causes oral herpes and HSV-2 most often causes genital herpes, although HSV-1 is responsible for an increasing proportion of primary genital infections.2

Genital infections may be associated with small, painful lesions affecting the genitals and surrounding areas as well as generalized symptoms such as fever, muscle aches, and malaise. However, most genital herpes infections are transmitted by individuals who do not know they are infected, as symptoms are often mild or absent.2

Genital HSV-1 and HSV-2 infections can also cause neonatal herpes, especially among women who acquire genital herpes near the time of delivery.2 If genital herpetic lesions are present at the onset of delivery, cesarean delivery should be considered to prevent neonatal infection. Newborns exposed to HSV during birth should be followed closely with consideration of antiviral therapy.2

Diagnosing infection and determining HSV type can indicate risk of disease recurrence, transmission risks, and prognosis (Table). However, the pathogenesis of herpes infections can make diagnosis difficult: antibodies and nucleic acids are measurable at different points of pathogenesis (Figure 1). Many laboratory test methods, such as viral culture, polymerase chain reaction (PCR), and antibody (serologic) testing, are available to address this difficulty. This Clinical Focus discusses the testing options available for the diagnosis and management of HSV infections.

Table. Disease Recurrence and Risks Associated with Herpes Simplex Virus Infection2,3

 

Rate of  Recurrence After Symptomatic Genital Herpesa

Risks Associated With Genital Herpes

HSV-1

First year of infection: 1 per year
After 1 year: rare

Transmission to sexual partner
Maternal transmission to newborn

HSV-2

First year of infection: 4 per year
After 1 year: slowly decreasing

Transmission to sexual partner
Maternal transmission to newborn
Increased risk of acquiring HIV infection

HSV, herpes simplex virus; HIV, human immunodeficiency virus.

a

Recurrent infections are characterized by type-specific HSV detection in the presence of the same antibody type.

Figure 1. Pathogenesis of Primary HSV-2 Infection

Individuals Suitable for Testing [return to contents]

Viral culture or PCR testing may be appropriate for:

  • Individuals with clinically suspected genital herpes infection or suspicious mucocutaneous lesions

Serologic testing may be appropriate for:

  • Individuals who have recurrent genital symptoms
  • Individuals who have a prior diagnosis of genital herpes without laboratory confirmation
  • Individuals who have a partner with genital herpes
  • Individuals at increased risk of HSV infection should be considered for testing (eg, those presenting for an evaluation for a sexually transmitted disease, those with multiple sex partners or HIV infection, or men who have sex with men)

Screening of the general population for HSV-1 or HSV-2 antibodies is NOT indicated2

Test Availability and Selection [return to contents]

Quest Diagnostics offers a variety of viral culture, PCR, and serologic tests for HSV (Appendix).

Diagnosis

Diagnosis of genital herpes based on medical history and physical examination is insensitive and nonspecific; clinical indications such as lesions may not be present in infected individuals. Thus, the Centers for Disease Control and Prevention (CDC) recommends laboratory confirmation of infection in appropriate individuals (see Individuals Suitable for Testing section).2 The appropriate test depends largely on the presence or absence of lesions (Figure 2).

Figure 2. Diagnosis of Genital Herpes

Viral Culture and PCR Testing

When genital or mucocutaneous lesions are present, viral culture or PCR tests are recommended.2 However, viral culture has low sensitivity that decreases as lesions heal; sensitivity is especially low for recurrent lesions. PCR tests are 1.5- to 4-times more sensitive.3 In the absence of a lesion, both assays depend on viral shedding, which is intermittent. A negative result in these assays does not necessarily indicate absence of infection, and serologic assays may be helpful.2 

Serologic Testing

When lesions are absent, type-specific serologic tests are recommended.2 Because antibodies to HSV persist for life, serologic assays can detect infection even in the absence of lesions. However, antibody detection occurs an average of 2 to 3 weeks after primary infection and cannot determine the site of infection.5

Testing for immunoglobin G (IgG) antibody seroconversion is the recommended method for identifying primary HSV infections.2,4 The CDC recommends against using immunoglobin M (IgM) testing for HSV due to multiple drawbacks: IgM tests 1) can be positive during infection with other herpes family viruses (eg, cytomegalovirus [CMV]); 2) cannot distinguish between primary HSV infections and recurrent genital or oral episodes2; and 3) cannot differentiate HSV types.

Differentiation of HSV-1 and HSV-2 Infections

In addition to its role in diagnosis of HSV infection, laboratory testing can help distinguish the type of HSV, which has important implications for prognosis and patient management and can indicate risk of disease recurrence and transmission (Table). For example, HSV-2 infection suggests a stronger likelihood of recurrent genital outbreaks and asymptomatic viral shedding than HSV-1 infection. Thus, genital HSV-2 infection poses a higher risk than HSV-1 for transmission to sex partners and vertical transmission from mothers to neonates. In addition, genital HSV-2 infection is associated with an increased risk of acquiring HIV infection.2 Type-specific testing is recommended by the CDC to confirm any clinical diagnosis of genital herpes.2

Test Interpretation [return to contents]

Viral Culture and PCR Testing

A “detected” result for viral culture or PCR tests supports the diagnosis of HSV infection. If HSV is detected, the type of HSV should be identified. The CDC recommends offering HIV testing to individuals diagnosed with laboratory-confirmed genital HSV infection.2

A “not detected” result does not exclude the possibility of HSV infection. In the absence of a lesion, viral shedding is intermittent. Viral culture can also have lower sensitivity if the sample is collected from healing ulcers or is improperly collected. Furthermore, PCR tests of blood products can be performed, but less than a quarter of immunocompetent patients with primary or recurrent genital HSV infection will have detectable viremia.6

Serologic Testing

A positive result indicates the presence of detectable antibody to the corresponding virus (HSV-1 or HSV-2), which indicates current or previous exposure to the virus; however, it does not indicate the site of infection. False-positive results can be seen in persons who have never had symptoms, which is one reason that screening of asymptomatic persons is not recommended. False-positive HSV-2 results may occur when index values are low (1.1-3.5); confirmatory testing, such as inhibition testing, is recommended in these cases.2 The CDC recommends offering HIV testing to individuals diagnosed with laboratory-confirmed genital HSV infection.2

A negative result suggests absence of infection. However, a negative result does not rule out infection; antibodies often are not detected during early infection (within 4 weeks of infection). If clinical suspicion of genital HSV infections is high, then repeat antibody testing should be considered 4 to 6 weeks later.

Appendix. Herpes Testsa 

Test Code

Test Name

Specimen Type

Clinical Indication

HSV-1

3636

Herpes Simplex Virus 1 (IgG), Type-Specific Antibody 

Serum

Diagnose HSV-1 infection when lesions are absent

HSV-2

3640

Herpes Simplex Virus 2 (IgG), Type-Specific Antibody 

Serum

Diagnose HSV-2 infection when lesions are absent

17170b

Herpes Simplex Virus 2 (IgG), with Reflex to HSV-2 Inhibition

Serum

Diagnose and confirm HSV-2 infection when lesions are absent

HSV-1/2

2692

Herpes Simplex Virus Culture

Swab: lesion (vesicle) aspirate, endocervical, vaginal, oral, urethral, or rectal mucosa (without feces)b

Diagnose HSV infection when lesions are present

2649c

Herpes Simplex Virus Culture with Reflex to Typing

Swab: lesion (vesicle) aspirate, endocervical, vaginal, oral, urethral, or rectal mucosa (without feces)b

Diagnose HSV infection when lesions are present; determine HSV type

34257d

Herpes Simplex Virus, Type 1 and 2 DNA, Qualitative, Real-Time PCR 

Lesion swabe

Diagnose HSV infection when lesions are present; determine HSV type

90569e

Herpes Simplex Virus, Type 1 and 2 DNA, Real-Time PCR, Pap Vial

Vaginal swab (Pap vial)

Diagnose HSV infection when lesions are present; determine HSV type

90570e,g

SureSwab®, Herpes Simplex Virus, Type 1 and 2 DNA, Real-Time PCR

Vaginal swab (SureSwab); genital lesion

Diagnose HSV infection when lesions are present; determine HSV type

6447

Herpes Simplex Virus 1/2 (IgG), Type-Specific Antibodies

Serum

Diagnose HSV infection when lesions are absent; determine HSV type

17169c

Herpes Simplex Virus 1 and 2 (IgG), with Reflex to HSV-2 Inhibition

Serum

Diagnose HSV infection when lesions are absent; determine HSV type; confirm positive result of HSV-2 antibody test

a

Viral culture and PCR tests are not available for individual HSV-1 and HSV-2 types.

b

This test can also be used to test nasal/nasopharyngeal and eye swabs.

c

Reflex tests are performed at an additional charge and are associated with additional CPT codes.

d

This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the U.S. Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

e

Polymerase chain reaction (PCR) is performed pursuant to a license agreement with Roche Molecular Systems, Inc.

f

This test can also be used to test CSF, serum, and plasma specimens.

g

For men, test code 90570 can be used if the Unisex Collection device is used.

References [return to contents]

  1. Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. Jama. 2006;296:964-973.

  2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.

  3. Bulletins—Gynecology. ACoP. ACOG practice bulletin: Clinical management guidelines for obstetrician-gynecologists, number 57, November 2004. Gynecologic herpes simplex virus infections. Obstet Gynecol. 2004;104:1111-1118.

  4. Hot Topics in Sexually Transmitted Infections and Associated Conditions. 2013; http://www.arhp.org/Publications-and-Resources/Quick-Reference-Guide-for-Clinicians/Sexually-Transmitted-Infections-and-Associated-Conditions. Accessed July 26, 2017.

  5. Strick LB, Wald A. Diagnostics for herpes simplex virus: is PCR the new gold standard? Mol Diagn Ther. 2006;10:17-28.

  6. Brice SL, Stockert SS, Jester JD, et al. Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis. J Am Acad Dermatol. 1992;26:594-598.
     

Content reviewed 08/2017

 
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