EBV Viral Load

Useful For

Follow-up of D+R- patients; follow-up of D-R- patients with primary EBV infection; ruling out PTLD.

Aid in diagnosing and monitoring chronic active EBV infection; X-linked lymphoproliferative disorder; Nasopharyngeal carcinoma.

 

Indications for Testing

Transplant Recipients

  1. Follow-up of D+R- patients
    1. Frequency: 1st or 2nd week post transplant; then every 2 weeks for 3 months; then every  month for 3 months; then every 3 to 6 months for duration of 1 to 2 years.
  2. Follow-up of D-R- patients who acquire primary infection after transplantation
    1. Frequency: 1st or 2nd week post transplant; then every 2 weeks for 3 months; then every  month for 3 months; then every 3 to 6 months for duration of 1 to 2 years.
  3. Ruling out the presence of PTLD; typically when lymphadenopathy or other mass lesion, organ dysfunction, fever, malaise or other signs and symptoms suggestive of PTLD occur.

 

Nontransplant Patients

  1. Chronic active EBV infection
  2. X-linked lymphoproliferative disorder
  3. Nasopharyngeal carcinoma
  4. Hodgkin and non-Hodgkin lymphomas
  5. HIV-associated primary brain lymphoma

 

Method Name

Real-time quantitative polymerase chain reaction (PCR)

 

Reporting Name

EBV Viral Load

 

Aliases

EBV

Epstein-Barr Virus

Post transplantation Lymphoproliferative Disease

PTLD

Lymphoma

Specimen Required

Plasma (promptly separate plasma from cells)

Container/Tube: EDTA (Lavender)

Specimen Volume: 5 mL of whole blood

Specimen Minimum Volume: 0.3 mL

 

Cerebral spinal fluid (CSF)

Container: Sterile screw cap

Specimen Volume: 1 mL

Specimen Minimum Volume: 0.3 mL

 

Transport Temperature

Specimen Room temperature Refrigerated Frozen
Plasma NO YES* YES**
CSF NO YES* YES**

*The samples should be stored for not more than 2 days at 2-8°C.

**For longer delay, freeze at -20°C or below and transport on dry ice.

 

Reject Due To

Specimens other than Serum & CSF
Anticoagulants other than EDTA REJECT

Useful For

Follow-up of D+R- patients; follow-up of D-R- patients with primary EBV infection; ruling out PTLD.

Aid in diagnosing and monitoring chronic active EBV infection; X-linked lymphoproliferative disorder; Nasopharyngeal carcinoma.

 

Clinical Information

In the setting of alogenic transplantation when immunosupression is used to prevent graft rejection, an unintended consequence is failure to suppress active EBV infection, which is accompanied by a hightened risk of developing posttransplant lymphoprofilerative disorder (PTLD). EBV DNA normally lies dormant inside circulating B lymphocytes, whereas patients with active infection or EBV-related PTLD additionally have detectable viral DNA in plasma. In nasopharyngeal carcinoma, the infected malignant epithelial cells are not seen in circulating blood, and the EBV that is measureable in plasma is naked DNA emanating from dying tumor cells. EBV viral load, as measured by quantitative molecular analysis of the viral genome, serves as a biomarker for predicting and monitoring the course of PTLD.

 

An EBV-specific immunodeficiency, X-linked lymphoproliferative disorder, is caused by a heritable mutation of SH2D1A rendering a child susceptible to fatal primary EBV infection or EBV-related lymphoma. Clinical recognition of this rare syndrome is difficult but important given the divergent therapy required for sepsis, which has similar clinical features in young children.

 

Undifferentiated nasopharyngeal carcinoma is strongly associated with EBV in southeast Asia, where NPC is endemic, and to a lesser extent in western countries, where NPC is rare. The level of circulating EBV DNA in plasma or serum tracks with tumor stage at initial diagnosis and serves as a marker of tumor burden during therapy. EBV viral load in plasma serves as a marker of tumor burden in patients with sporadic EBV-related lymphoma including B cell, T cell, NK cell and Hodgkin subtypes. EBV is found in CSF of patients with HIV-associated primary brain lymphoma.

 

The Epstein-Barr virus (EBV), also known as human herpesvirus 4, belongs to the subfamily Gammaherpesvirinae in the Herpesviridae family. EBV has the morphology of a herpesvirus, with 162 capsomeres in icosahedral arrangement surrounded by a lipid-rich envelope. EBV primarily infects B cells, which carry the receptor for EBV, the CD21 complement receptor. It has the ability to transform precursor and mature human B lymphocytes to lymphoblastoid cell lines. B cells are the site of latency, but epithelial cells, not expressing the receptor, are the main producers of progeny virus. Also monocytes may be productively infected by EBV, and the infection may affect the virus-host interaction.

 

Epstein-Barr virus is a ubiquitous human herpes virus. Infection with EBV is common, worldwide in distribution, and largely subclinical in early childhood. EBV has been established as the causative agent of heterophile-positive infectious mononucleosis, which occurs most frequently in late adolescence or early adulthood.

 

Reference Values

EBV Viral Load: UNDETECTABLE

 

Interpretation

Transplant recipients

Detection of a significant rise in viral load

 

Clinical Reference

Johannsen, E. C., and Kaye, K. M. 2010. Epstein-Barr Virus (Infectious Mononucleosis, Epstein-Barr Virus – Associated Malignant Diseases, and Other Diseases), p. 1989-2010. In Mandell, D., Bennett, J. E., and Dolin, R. Principles and practice of infectious diseases, 7th ed., vol. 2. Churchill Livingstone, Elsevier,Philadelphia,PA.

 

Linde, A., and Falk, K. I. 2007. Epstein-Barr Virus, p. 1564-1573. In Murray, P. R., Baron, E. J., Jorgensen, J. H., Landry, M. L., and Pfaller, M. A. Manual of Clinical Microbiology, 9th ed., vol. 2. ASM Press, American Society for Microbiology,Washington,DC.

 

Gärtner, B. 2011. Varicella-Zoster Virus, p. 1575-1584. In Versalovic, J., Carroll, K. C., Funke, G., Jorgensen, J, H., Landry, M. L., and Warnock, D, W. Manual of Clinical Microbiology, 10th ed., vol. 2. ASM Press, American Society for Microbiology, Washington, DC.

 

Gulley, M. L. and Tang, W. 2008. Laboratory assays for Epstein-Barr virus-related disease. J Mol Diagn. 10(4):279-292.

 

Gulley, M. L. and Tang, W. 2010. Using Esptein-Barr viral load assays to diagnose, monitor, and prevent posttransplant lymphoproliferative disorder. Clin Microbiol Rev. 23(2):350-366.

 

Allen, U., Alfieri, C., Preiksaitis, J., et al. 2002. Epstein-Barr virus infection in transplant recipients: summary of a workshop on surveillance, prevention and treatment. Can J Infect Dis. 3(2):89-99.

Sensitivity: ≤ 50 copies / ml plasma or CSF

Measuring range: 500 – 5 X 106 copies / ml

 

 

EBV Antibody Profile

Status Days Analytic Time Maximum Laboratory Time Specimen Retention
Routine Wed 7h 6 day 2 years

 

Method Description

Quantitative real-time polymerase chain reaction (PCR).

 

 

Performing Laboratory Location

Newfoundland & Labrador Public Health Laboratory

St. John’s

 

 

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