Epstein-Barr Virus EBV

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Epstein-Barr virus (EBV) is the causative agent of Glandular Fever.

  • Also known as Human Herpesvirus 4 (HHV-4), a member of the Herpes Virus family.
  • It is one of the most prevalent viruses within humans.

Glandular Fever is also known as:

  • Infectious Mononucleosis or "Mono"
  • Pfeiffer's Disease

See also these assocated articles:


  • Prevalence = up to 50% of 5 year olds and 95% of adults are seropositive by age 40 years.
    • Infection during childhood is usually mild or asymptomatic.
    • During adolescence, EBV infection causes Glandular Fever / Infectious Mononucleosis in up to 50%.
  • Age: infection is most prevalent in adolescents and young adults
  • Sex: peak incidence occurs 2 years earlier in females.
  • Ethnicity: people in developing countries tend to be infected with EBV at a younger age. Glandular Fever is therefore very uncommon since most adolescents have already been infected.

Incubation period: 30 - 50 days

Clinical features

EBV infection and Glandular fever is an acute febrile illness though many patients will be asymptomatic.

  • Acute symptoms resolve within 1-2 weeks
  • Fatigue takes longer to improve, usually over 1-2 months and possibly up to 4.

Clinical Features:

  • Fever
  • Headache
  • General malaise
  • Sore throat
  • Palatal petechiae
  • Transient macular rash (occurs in 90% of those given ampicillin / amoxicillin for the sore throat)
  • Cervical lymphadenopathy
    • particularly posterior cervical nodes
  • Splenomegaly
  • Mild hepatitis


  • Splenic rupture (0.2%)
  • Myocarditis
  • Meningitis
  • Encephalitis
  • mesenteric adenitis

Chronic effects: Some patients remain debilitated and depressed for several months following infection.

EBV remains latent in B cells following infection.

  • Reactivation may occur in immunosuppressed patients


EBV should be suspected if atypical mononuclear cells are seen in peripheral blood.

The Paul Bunnell test will be positive in the second week of infection (quantitative).

  • this test detects heterophile antibodies (IgM) which agglutinate sheep erythrocytes.
  • False positives:
    • viral hepatitis
    • Hodgkin's Disease
    • Acute leukaemia

The Monospot Test is a rapid slide agglutination test (qualitative).

Left upper quadrant pain should prompt investigation for splenic rupture.

  • Splenic rupture may be spontaneous or due to mild trauma.
    • Occurs in 0.2% of patients.

Differential Diagnoses

These can be differentiated with serological testing.

  • Cytomegalovirus infection (CMV)
  • Toxoplasmosis


Most cases require no specific treatment and recovery is spontaneous and rapid.

  • Isolation is not indicated due to low transmission rates

Corticosteroids are recommended if there is neurological involvement and when there is marked thrombocytopenia or haemolysis

Contact sports / heavy lifting, etc. should be advised against for at least 2-3 weeks.

  • some people recommend 2 months cautious activity.

Tonsillar enlargement can occasionally threaten the airway.

EBV associated malignancies

EBV is the cause of oral hairy leukoplakia in patients with Acquired Immunodeficiency Syndrome (AIDS).

  • A study by the Centre for Disease Control and Prevention found that EBV did not meet Koch's Postulates as a causative organism.
  • Studies are compounded by the fact that EBV infection is ubiquitous.

EBV is also the main aetiological agent implicated in:

  • post transplant lymphoproliferative disease
  • Burkitt's Lymphoma (a subtype of Non-Hodgkin's Lymphoma)
    • Endemic Burkitt's Lymphoma is the most common childhood tumour in Africa
      • It is associated with EBV when the child is co-infected with Plasmodium Falciparum.
      • P.falciparum stimulates polyclonal B-cell proliferation with EBV infection and also impairs T-cell response to EBV.
  • Non-Hodgkin's Lymphomas
  • Hodgkin's Lymphomas
    • EBV is present in the Reed-Sternberg cell.
  • Nasopharyngeal carcinoma
  • Immunoblastic lymphoma in patients with AIDS.

EBV associated Chronic Fatigue

Some patients remain debilitated and depressed for several months following infection resulting in Glandular Fever. The mechanism for this is uncertain and the timecourse of recovery variable.

EBV has been suggested as a cause of a subset of patients with Chronic Fatigue Syndrome. No mechanism has been elucidated at present.


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