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Description
Epstein-Barr virus (EBV) is an omnipresent member of the human herpesvirus family.1 The virions which make up EBV are hexagonal nucleocapsids, with a complex surrounding envelope.1 EBV is most commonly found in B lymphocytes and also in epithelial cells of the nasopharynx.1 The virus was discovered in 1964 by Drs. Epstein and Barr, after whom it was named.1 EBV is the causative agent of heterophile-positive infectious mononucleosis, which is most commonly seen in young adults or older adolescents.1

Epidemiology & Pathogenesis
EBV antibodies have been isolated in all populations and appear to have no affinity for infecting one sex over the other.1 EBV antibodies are found in 90-95% of virtually all populations by the time they reach adulthood.1 In the US and in Great Britain, approximately 50% of the population seroconverts before the age of 5.1 Between the ages of 10 and 20, a second wave of seroconversion typically occurs.1 Infectious mononucleosis most often manifests itself clinically in individuals who are not exposed to it until their second decade.2

EBV primarily infects B lymphocytes, but has also been seen in epithelial cells,
T lymphocytes, smooth muscle cells and follicular dendritic cells.2 EBV enters the
B lymphocyte and the viral DNA forms a self-replicating circular episome within the cell nucleus.2 B lymphocytes also proliferate, which increases the number of cells available to carry the virus.2 If an individual is immunocompetent, specific
T lymphocytes that are cytotoxic control the amount of B cell proliferation.2 In the immunocompromised patient, a latent EBV infection can reactivate and potentially cause lymphoproliferative disease and even malignancies.2

Childhood primary EBV infections are usually asymptomatic.3 When adults or adolescents experience a primary infection, it takes the form of infectious mononucleosis.3 One of the groups at highest risk is those patients receiving a transplant who are experiencing a primary EBV infection for which they are being treated with immunosuppressive medications.3 Recent studies indicate that individuals who experience lymphoproliferative disease following a transplant have very high EBV viral loads circulating in their peripheral blood.3

Clinical Manifestations
The classic clinical manifestation of EBV is infectious mononucleosis, which occurs in 30-50% of patients, and typically presents with sore throat, fever and lymphadenopathy.1,2 The disease is often self-limiting and lasts approximately 2-3 weeks.2 Immunocompetent individuals usually do not experience additional complications, but some do develop a chronic, persistent strain of the disease, which can involve organ system dysfunctions and last over 6 months.1,2

PTLD
Patients undergoing stem cell transplantation and those who have a solid organ transplant are particularly at risk for EBV-associated lymphoproliferation.4 EBV-induced proliferation may lead to posttransplant lymphoproliferative disorder (PTLD). PTLD represents a spectrum of diseases that makes diagnosis difficult. Clinically, PTLD presents as an infectious-mono like illness, febrile illness with leucopenia, focal organ system involvement, including the gastrointestinal tract, central nervous system and the allograft as well as disseminated disease. Therefore, PTLD may mimic rejection leading to intensified immunosuppression when an actual reduction in immunosuppression is needed. The incidence of PTLD ranges from 1-25% depending on the transplanted allograft. Primary EBV infection in pediatric patients as well as the intensity and duration of immunosuppressive therapy have been shown to be risk factors for the development of PTLD.5 Individuals with risk factors such as an unrelated donor, T-cell—depleted allografts, use of antithymocyte globulin and immunosuppression to prevent graft-versus-host disease (GVHD) can have a risk of up to 20%.4 If lymphoproliferative disease does develop, the prognosis for these patients is quite poor.4 The disease can manifest itself in forms ranging from benign polyclonal hyperplasia to malignant lymphoma.2 HIV patients can also develop non-malignant lymphoproliferative diseases, such as follicular hypoplasia, primary lymphoid hyperplasia and oral hairy leukoplasia, as well as lymphoid, muscular and epithelial cell malignancies.2

Diagnosis
Roughly 90% of people with EBV have heterophile antibodies at some time during the course of the illness.1 Therefore, testing for these bodies has been important to the diagnosis of infectious mononucleosis.2 In some cases of infectious mononucleosis and other EBV-associated illnesses, testing for EBV-specific antibodies has also been shown to be useful.2 Testing methods such as PCR that facilitate early detection of EBV and the beginning of lymphoproliferation may facilitate early therapy and potentially slow down the spread of the disease.3 For these reasons, PCR is considered a valuable option for detecting and monitoring viral loads of active EBV infection. Although both PBMCs and plasma are useful material for EBV-specific Real Time PCR in immunosuppressed patients, the specificity of analysis seems to be higher if plasma is used.5

Treatment
Most cases of infectious mononucleosis require only supportive care, as over 95% of patients will recover without therapy or complications.1 Each individual should limit his or her activity level to that which is comfortably tolerable, and heavy lifting should be avoided for 2-3 weeks, in order to avoid spleen ruptures in those who have splenomegaly.1

The usefulness of antiviral therapy to treat immunocompromised patients with EBV has not been supported by sufficient clinical evidence to become a frequently recommended option.1 Acyclovir has benefited some HIV patients with EBV-related diseases, but results in the literature are mixed.1 Additional agents have been shown to have antiviral activity against EBV, but only in vitro.1 Current experimental approaches that may prove promising include tumor-directed monoclonal antibodies and EBV-specific cytotoxic T cells.1

  1. Schooley RT. Epstein-Barr Virus (Infectious Mononucleosis). In Mandell GL, Bennett JE, Dolin, eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 4th edition, Vol. 2. New York, NY: Churchill Livingstone; 1995:1364-1377.
  2. Miller LE. The Lab and Epstein-Barr Virus Infections. ADVANCE for Medical Laboratory Professionals. 2002:19-21. Available at www.ACVANCEforMLP.com
  3. Rose C, Green M, Webber S, Ellis D, Reyes J et al. Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment. Journal of Clinical Microbiology. 2001;39:1407-1415.
  4. van Esser JWJ, van der Holt B, Meijer E, Niesters HGM, Trenschel R et al. Epstein-Barr virus (EBV) reactivation is a frequent event after allogenic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell depleted SCT. Blood. 2001;98:972-978.
  5. Wagner Hans-Joachim, Wessel M, Jabs W, et al. Patients At Risk For Development Of Posttransplant Lymphoproliferative Disorder: Plasma Versus Peripheral Blood Mononuclear Cells As Material For Quantification Of Epstein-Barr Viral Load By Using Real Time Quantitative Polymerase Chain Reaction. Transplantation, 2001 Vol. 72. 1012-1019.



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