Infectious Mononucleosis, Epstein-Barr Virus Infections

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  • Epstein-Barr virus (EBV) is a member of the herpes virus family; human herpes virus 4 (1)
    • Two subtypes: ST1 predominates in Western Hemisphere, Southeast Asia; ST1 and ST2 equally prevalent in Africa
  • Primary infection typically occurs in childhood; responsible for infectious mononucleosis (IM) (most common); also linked to numerous cancers
  • WHO classified EBV as “tumor virus” (group I carcinogen) due to cancer association (1).


Worldwide, infects >90% of people (antibody positive)

  • Military recruits, college students, and others living in cloistered and crowded populations have highest infection rate. Overall rate in United States is 500/100,000 (2).
  • Predominant age of primary infection is 15 to 24 years; 200 to 800/100,000 affected (2)
    • Primary clinical manifestation is IM.
    • Early childhood infections are usually asymptomatic.
  • Seroconversion occurs later in childhood in developed countries; there is suggestion of race/ethnicity disparity in the United States with higher seroprevalence in non-Hispanic black, Asian, and Hispanic populations (2).

Etiology and Pathophysiology

  • After inoculation, the virus replicates in the nasopharyngeal epithelium with resulting cell lysis, virion spread, and viremia. The reticuloendothelial system is affected, resulting in a host response and the appearance of atypical lymphocytes in the peripheral blood. Viral genome can be detected in the oral cavity 1 week prior to symptoms.
  • A polyclonal B-cell proliferative response follows. Relatively few (<0.1%) of the circulating lymphocytes are infected by EBV in the acute illness.
  • A persistent (asymptomatic) state ensues with the EBV genome invisible to the immune system.
  • During this period, coinfection increases risk for an EBV-associated condition (e.g., malignancy).
  • Either through B-cell stimulation or diminished EBV-specific immune modulation, the previously latent EBV-infected B cells replicate, allowing clinical expression of the EBV genome. The proteins produced may either modify host response to or contribute directly to subsequent malignancy (1,3).
  • Immunosuppression (organ transplant/acquired immune deficiency) can result in transformation and lymphoproliferative disorders.

Risk Factors

  • Age (highest incidence in adolescent, young adults)
  • Socio-hygienic level (“crowded conditions”)
  • Geographic location
  • Close, intimate contact; especially “deep kissing” in adolescents and young adults (4)
  • Immunosuppression

General Prevention

  • Avoid close physical contact with symptomatic EBV/IM patients.
  • Meticulous hand washing and hygiene
  • General precautions with potential blood exposure (EBV can be transmitted via blood contamination as well as hematopoietic cell and solid organ transplant.)
  • EBV vaccines under investigation—limited efficacy

Commonly Associated Conditions

  • IM: Symptomatic primary EBV infection is common in otherwise healthy adolescents and young adults.
    • Clinical features vary in severity and duration: In children age <10 years, generally mild; in adolescents and adults, symptoms can be more severe and protracted.
    • Incubation period is 30 to 50 days.
  • X-linked lymphoproliferative syndrome (XLP—rare, inherited extreme vulnerability to EBV infection)
  • Lymphoproliferative syndromes due to EBV infections in transplant recipients
  • Lymphomas (B-cell lymphoblastic, T cell)
  • Lymphocytic interstitial pneumonitis
  • Hairy leukoplakia of the tongue, leiomyosarcoma, and CNS lymphomas in patients with AIDS
  • Burkitt lymphoma (most common childhood tumor in Africa and Papua New Guinea where malaria is also endemic and may be a cofactor)
  • Nasopharyngeal carcinoma (particularly in SE China)
  • Parotid carcinoma
  • Hodgkin lymphoma (most common EBV-associated malignancy in United States, European Union)
  • Postulated to be associated with multiple sclerosis (2 to 3 times incidence in EBV-positive individuals)
  • Chronic active Epstein-Barr virus (CAEBV) due to loss of host control of viral replication

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