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.

CPT
87798$35.09
87799$42.84

ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
A83 - Mosquito-borne viral encephalitis
A84 - Tick-borne viral encephalitis
A85 - Other viral encephalitis, not elsewhere classified
A85.0 - Enteroviral encephalitis58710, 58720, 58726, 58747, 58761
A85.1 - Adenoviral encephalitis58710, 58720, 58726, 58747, 58761
A85.2 - Arthropod-borne viral encephalitis, unspecified58710, 58720, 58726, 58747, 58761
A85.8 - Other specified viral encephalitis58710, 58720, 58726, 58747, 58761
A86 - Unspecified viral encephalitis58710, 58720, 58726, 58747, 58761
B00.3 - Herpesviral meningitis58710, 58720, 58726, 58747, 58761
B00.4 - Herpesviral encephalitis58710, 58720, 58726, 58747, 58761
B00.82 - Herpes simplex myelitis
B01 - Varicella [chickenpox]
B01.0 - Varicella meningitis58710, 58720, 58726, 58747, 58761
B01.1 - Varicella encephalitis, myelitis and encephalomyelitis
B01.11 - Varicella encephalitis and encephalomyelitis58710, 58720, 58726, 58747, 58761
B02.1 - Zoster meningitis58710, 58720, 58726, 58747, 58761
B02.2 - Zoster with other nervous system involvement
B10 - Other human herpesviruses
B10.0 - Other human herpesvirus encephalitis
B10.01 - Human herpesvirus 6 encephalitis58710, 58720, 58726, 58747, 58761
B10.09 - Other human herpesvirus encephalitis
B10.81 - Human herpesvirus 6 infection
B27.11 - Cytomegaloviral mononucleosis with polyneuropathy
B27.12 - Cytomegaloviral mononucleosis with meningitis58710, 58720, 58726, 58747, 58761
B27.82 - Other infectious mononucleosis with meningitis58710, 58720, 58726, 58747, 58761
B27.92 - Infectious mononucleosis, unspecified with meningitis
C77 - Secondary and unspecified malignant neoplasm of lymph nodes
C83 - Non-follicular lymphoma
C83.7 - Burkitt lymphoma
C83.70 - Burkitt lymphoma, unspecified site
C83.71 - Burkitt lymphoma, lymph nodes of head, face, and neck
C83.72 - Burkitt lymphoma, intrathoracic lymph nodes
C83.73 - Burkitt lymphoma, intra-abdominal lymph nodes
C83.74 - Burkitt lymphoma, lymph nodes of axilla and upper limb
C83.75 - Burkitt lymphoma, lymph nodes of inguinal region and lower limb
C83.76 - Burkitt lymphoma, intrapelvic lymph nodes
C83.77 - Burkitt lymphoma, spleen
C83.78 - Burkitt lymphoma, lymph nodes of multiple sites
C83.79 - Burkitt lymphoma, extranodal and solid organ sites
C85.88 - Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites
C85.90 - Non-Hodgkin lymphoma, unspecified, unspecified site
G89 - Pain, not elsewhere classified
G89.3 - Neoplasm related pain (acute) (chronic)
Z51 - Encounter for other aftercare and medical care
Z51.0 - Encounter for antineoplastic radiation therapy
Z51.1 - Encounter for antineoplastic chemotherapy and immunotherapy
Z51.11 - Encounter for antineoplastic chemotherapy58710, 58720, 58726, 58747, 58761
Z51.12 - Encounter for antineoplastic immunotherapy
Z79 - Long term (current) drug therapy
Z85.72 - Personal history of non-Hodgkin lymphomas

Additional ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
A17.82 - Tuberculous meningoencephalitis
A32.1 - Listerial meningitis and meningoencephalitis
A32.12 - Listerial meningoencephalitis58710, 58720, 58726, 58747, 58761
A39.81 - Meningococcal encephalitis58710, 58720, 58726, 58747, 58761
A42.82 - Actinomycotic encephalitis
A50.42 - Late congenital syphilitic encephalitis
A52.14 - Late syphilitic encephalitis
A81.1 - Subacute sclerosing panencephalitis
A83.0 - Japanese encephalitis
A83.1 - Western equine encephalitis
A83.2 - Eastern equine encephalitis
A83.3 - St Louis encephalitis
A83.4 - Australian encephalitis
A83.5 - California encephalitis
A83.6 - Rocio virus disease
A83.8 - Other mosquito-borne viral encephalitis
A83.9 - Mosquito-borne viral encephalitis, unspecified
A84.0 - Far Eastern tick-borne encephalitis [Russian spring-summer encephalitis]
A84.1 - Central European tick-borne encephalitis
A84.8 - Other tick-borne viral encephalitis
A84.81 - Powassan virus disease
A84.89 - Other tick-borne viral encephalitis58710, 58720, 58726, 58747, 58761
A84.9 - Tick-borne viral encephalitis, unspecified58710, 58720, 58726, 58747, 58761
A85.0 - Enteroviral encephalitis58710, 58720, 58726, 58747, 58761
A85.1 - Adenoviral encephalitis58710, 58720, 58726, 58747, 58761
A85.2 - Arthropod-borne viral encephalitis, unspecified58710, 58720, 58726, 58747, 58761
A85.8 - Other specified viral encephalitis58710, 58720, 58726, 58747, 58761
B01.0 - Varicella meningitis58710, 58720, 58726, 58747, 58761
B01.1 - Varicella encephalitis, myelitis and encephalomyelitis
B01.11 - Varicella encephalitis and encephalomyelitis58710, 58720, 58726, 58747, 58761
B01.12 - Varicella myelitis
B01.2 - Varicella pneumonia
B01.8 - Varicella with other complications
B01.81 - Varicella keratitis
B01.89 - Other varicella complications
B01.9 - Varicella without complication
B10.0 - Other human herpesvirus encephalitis
B10.01 - Human herpesvirus 6 encephalitis58710, 58720, 58726, 58747, 58761
B10.09 - Other human herpesvirus encephalitis
B10.8 - Other human herpesvirus infection
B10.81 - Human herpesvirus 6 infection
B10.82 - Human herpesvirus 7 infection
B10.89 - Other human herpesvirus infection
C77.0 - Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck
C77.1 - Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes
C77.2 - Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes
C77.3 - Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes
C77.4 - Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes
C77.5 - Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes
C77.8 - Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions

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