Epstein-Barr Virus (Infectious Mononucleosis)



Epstein-Barr virus (EBV) is a double-stranded DNA virus implicated as a causative agent for infectious mononucleosis by an infected laboratory worker in 1968.


  • Worldwide distribution
  • Humans are the only known reservoir.
  • Transmission occurs through saliva and, occasionally, via blood transfusions and solid organ transplant (SOT).
  • Incubation period is 4 to 7 weeks.
  • Antibodies to EBV are present in up to 90% of adult populations.
  • Areas with a high population density or low socioeconomic status usually become primarily infected within the first 3 years of life.


In developed countries, acquisition of EBV is biphasic.

  • Initial peak in incidence occurs before the age of 5 years.
  • Second peak occurs during adolescence, coinciding with an increased frequency of intimate oral contacts.


>90% of adults have demonstrable EBV titers.

General Prevention

  • No vaccine is clinically available.
  • Standard precautions should be used in the hospitalized patient.
  • Restriction of intimate contact with immunosuppressed individuals may be advisable.
  • Patients with recent EBV infection, either proven or suspected, should not donate blood or solid organs.


  • Enters host via saliva and replicates initially in the oropharyngeal epithelium
  • Selective infection of B lymphocytes occurs.
  • The clinical syndrome of infectious mononucleosis results from proliferation of cells in the tonsils, lymph nodes, and spleen.
  • Nonspecific humoral immune responses include the formation of heterophile antibodies and autoantibodies.
  • Specific antibodies to EBV antigens are produced.
  • Despite humoral responses, cellular immunity is responsible for controlling EBV infection.
  • Latent, lifelong infection of B lymphocytes occurs.
  • Latent virus may be reactivated during periods of immunosuppression or cellular stress.

Commonly Associated Conditions

  • Subclinical infection
    • Most EBV infections in children, and even in adolescents, are clinically inapparent.
    • Mild, nonspecific symptoms may include coryza, diarrhea, and/or fever.
    • Immunologic seroconversion does occur.
  • Infectious mononucleosis (“glandular fever”): most commonly observed with late primary acquisition of EBV. The classically defined illness is characterized by the following:
    • Fatigue
    • Malaise
    • Fever
    • Tonsillopharyngitis (often exudative)
    • Lymphadenopathy
    • Splenomegaly
    • Usually associated with increased atypical lymphocytes in the peripheral blood
  • Rare illnesses of the nervous system have been reported, including the following:
    • Guillain-Barré syndrome
    • Bell palsy
    • Aseptic meningitis
    • Meningoencephalitis
    • Peripheral and/or optic neuritis
  • Hematologic complications have been reported in association with EBV:
    • Aplastic anemia
    • Hemolytic anemia
    • Agranulocytosis
    • Hemophagocytic syndrome
  • Other illnesses associated with EBV in case reports include the following:
    • Hemolytic uremic syndrome
    • Hepatitis
    • Pancreatitis
    • Myocarditis
    • Mesenteric adenitis
    • Orchitis
    • Genital ulcerative disease
  • Lymphoproliferative disorders
    • Burkitt lymphoma
    • Nasopharyngeal carcinoma
    • Lymphoma and non-Hodgkin lymphoma (in immunocompromised children)
    • Lymphomatoid granulomatosis
    • Posttransplant lymphoproliferative disorders (PTLDs)
    • X-linked lymphoproliferative disease (Duncan disease)

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