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  • /Epstein-Barr Virus (EBV), Real-Time PCR

Diseases (2)

Diagnostic Testing (2)

Note:

EBV can be detected from formalin fixed paraffin-embedded tissue. However, PCR on fresh tissue can give faster results, and a quantitative viral load where clinically indicated.

Overview

The Epstein-Barr virus (EBV) is a member of the herpes virus family, and is responsible for many disorders including infectious mononucleosis, and other lymphoproliferative disorders. Herpes viruses are leading causes of viral infections worldwide, second only to the influenza and cold viruses. These viruses are important because they establish latency in B lymphocytes (a type of white blood cell or WBC), meaning they are never truly eliminated from the body and can pose a risk of reactivation under certain conditions. Reactivation of latent viruses is especially important in patients that have compromised or suppressed immune systems, such as immunodeficient patients (e.g., chemotherapy, HIV, organ transplant patients etc). In addition, two types of human cancers, Burkitt’s lymphoma and nasopharyngeal carcinoma, have been associated with EBV infection. There is no cure available for latent infections.

EBV infection is via exposure to oral secretions, usually by kissing, sharing food or utensils, or coughing. It can also be spread through blood transfusions and organ transplants. It does not survive outside the host and has not been recovered from any environmental sources. In the very young, EBV infections are generally asymptomatic. In adolescents the primary initial infection may be asymptomatic; however, the most common manifestation in this age group is infectious mononucleosis. In immunocompromised/ immunosuppressed patients, especially solid-organ transplant patients, there is a risk of developing a potentially fatal disorder called post-transplant lymphoproliferative disorder (PTLD). Although less common than in solid-organ recipients, EBV associated PTLD is also seen in bone marrow and blood stem cell transplant patients. In these populations, active EBV infection can result in high morbidity and mortality if left untreated.

Patients presenting with primary infection are generally diagnosed using serology testing. In normal, healthy individuals, once EBV has been identified as the causative agent, no further testing is required. Immunocompromised individuals, however, may not produce an appropriate serological response, and require testing using other methods. It is this population where EBV testing by molecular methods is beneficial. Also, once EBV has been identified in this population, either through primary infection or reactivation, it is important to know the amount of virus circulating in the patient in order to monitor disease progression and treatment outcome. Determining the amount of circulating virus is known as the “viral load.”

This assay detects the number of circulating EBV viral particles using polymerase chain reaction (PCR). This assay is not intended for diagnostic purposes in healthy individuals. Specimen types include serum, plasma, whole blood, and cerebral spinal fluid (CSF).

Clinical Utility

  • Diagnosis of an active EBV infection in transplant patients (solid-organ, bone marrow, blood stem cell)
  • Diagnosis of an active EBV infection in AIDS patients
  • Therapy treatment monitoring

Interpretation

Positive in:

  • Active EBV infection in transplant patients and AIDS patients
  • Infectious mononucleosis
  • Lymphoproliferative disease
  • Chronic fatigue syndrome
  • Burkitt’s lymphomas
  • Nasopharyngeal carcinoma

Negative in:

  • Past EBV infection
  • Uninfected individuals

Reference Ranges

Negative (Not detected)
 

 

Methodology

Polymerase Chain Reaction (PCR), Real-time PCR, PCR chip array technology, (qualitative or quantitative).

Specimen Collection

Serum (Red), Whole blood or Plasma EDTA (Lavander) or CSF

Stability:

  • Ambient: 48 hours
  • Refrigerated: 8 days
  • Frozen: Unacceptable

Additional Testing

EBV serology, CMV by PCR, HSV 1 and 2 by PCR, Herpes virus 8 (HHV8), Viral Culture.

Turnaround Time

1-3 days.

CPT

87798
87799

LOINC

ICD10

A83Mosquito-borne viral encephalitis
A84Tick-borne viral encephalitis
A85Other viral encephalitis, not elsewhere classified
A85.0Enteroviral encephalitis
A85.1Adenoviral encephalitis
A85.2Arthropod-borne viral encephalitis, unspecified
A85.8Other specified viral encephalitis
A86Unspecified viral encephalitis
B00.4Herpesviral encephalitis
C77Secondary and unspecified malignant neoplasm of lymph nodes
C83.7Burkitt lymphoma
C83.70Burkitt lymphoma, unspecified site
C83.79Burkitt lymphoma, extranodal and solid organ sites
C85.88Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites
C85.90Non-Hodgkin lymphoma, unspecified, unspecified site

References

  • Virus Res. 2002 Jan 30;82(1-2):109-13. [PMID:11885937]
  • Am Fam Physician. 2004;70:1279.[PMID:15508538]
  • Annu Rev Pathol. 2006;1:375-404. [PMID:18039120]
  • Lancet Infect Dis. 2003 Mar;3(3):131-40. [PMID:12614729]
  • Am J Med. 2007 Oct;120(10):911.e1-8. [PMID:17904463]
  • In Vivo. 2007 Sep-Oct;21(5):707-13. [PMID:18019402]
  • Clin Otolaryngol Allied Sci. 2001 Feb;26(1):3-8. [PMID:11298158]
  • Stevens, Christine Dorresteyn. Clinical Immunology & Serology A Laboratory Perspective 3rd edition. Philadelphia: F.A. Davis Company. 2010.
  • EBV early antigen (EA) ELISA II package insert. Wampole laboratories ref. 425000CE 06/2005