Chapter 101 : Epstein-Barr Virus

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Epstein-Barr virus (EBV) is associated with a wide variety of disease states in immunocompetent and immunosuppressed patients, ranging from infectious mononucleosis (IM) to malignant disorders. Tests for EBV infection diagnosis are used primarily for patients with suspected IM, for which antibody assays are the method of choice. A variety of immunoassays, blots, and flow cytometry tests have been used for EBV serology assays; assays targeting vial capsid antigen (VCA) IgG, VCA IgM, and EBV nuclear antigen 1 (EBNA 1) IgG are favored. Additional assays such as avidity testing or viral load measurement are only rarely necessary to establish the diagnosis of IM. The detection of heterophile antibodies is sometimes useful when a young adult with typical IM symptoms is being tested, but this test often lacks sensitivity and specificity, particularly when testing young children and older adults and when symptoms are atypical. In these settings, EBV-specific assays are preferred. Many EBV antibody-specific point-of-care tests that combine high sensitivity and specificity with rapid detection are currently available. Antibody assays detecting early antigen (EA) are rarely useful because of their heterogeneity with respect to the specific target detected and poor specificity. Assays that measure EBV in peripheral blood using quantitative nucleic acid amplification tests (QNAT) are increasing being used for immunosuppressed hematopoietic stem cell (HSCT) and solid-organ transplant (SOT) recipients and for patients with EBV-associated malignant disorders to prevent and diagnose disease and to monitor response to therapy. In most of these settings, the interpretation of assay results in relationship to patient outcomes is uncertain, and the usefulness of these assays has not been clearly proven. The best evidence exists for EBV DNA monitoring to trigger preemptive therapy for the prevention of early posttransplant lymphoproliferative disorders (PTLD) in high-risk HSCT and SOT patients, as well as for the diagnosis and treatment monitoring of nasopharyngeal carcinoma. Quantitative EBV DNA assays lack standardization, and recently an international reference standard for EBV DNA has been developed that may improve interassay result harmonization. QNAT values that could be used as trigger points for intervention remain undefined and may also vary by specimen type, clinical setting, and patient group. Dynamic changes in viral load, rather than absolute QNAT values alone, may be important in patient management.

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101
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Development of antibodies to EBV antigens following primary infection. While there is marked interpatient and interlaboratory variation in titers, the typical relative development of titers by antibody class and antigen specificity is given. doi:10.1128/9781555817381.ch101.f1

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101
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Image of FIGURE 2

Diagnostic algorithm and interpretation scheme based on EBNA 1 used with microparticle multiplex assays or rapid tests with random access in Europe. Diagnostic procedures and interpretation may start with EBNA 1 IgG. If this parameter is positive, a past infection is proven; if EBNA 1 IgG is negative, a negative VCA IgG results in the diagnosis of seronegative and a positive VCA IgM in the diagnosis of a primary infection. If VCA IgG is positive and the other parameters are negative, supplementary tests should be applied, e.g., avidity testing or blotting using p18 antigen. doi:10.1128/9781555817381.ch101.f2

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101
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Materials and methods to be used for prevention, diagnosis, and monitoring of EBV disease and EBV-associated malignancies

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101
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Overview of commercial products for EBV diagnosis

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101
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Typical EBV serological profiles using the most frequently employed antigens and Ig isotypes

Citation: GÄrtners B, Preiksaitis J. 2015. Epstein-Barr Virus, p 1738-1753. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch101

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