Infectious Mononucleosis


Infectious mononucleosis is an acute self‐limiting disease caused by an orally transmitted herpesvirus, Epstein–Barr virus. The disease typically involves fever, enlarged lymph glands and malaise, with elevated blood lymphocyte counts that reflect an exaggerated cellular immune response to the infection. Epstein–Barr virus is widespread in all human populations and is most often acquired asymptomatically in infancy. However, in affluent societies, primary infection can be delayed until the second or third decade, when 25–50% of those involved may develop symptoms. Hence infectious mononucleosis is typically a disease affecting adolescents or young adults in the Western world. Almost all patients recover completely within a few weeks but rare cases with persistent, even fatal, symptoms do occur and involve those with a pre‐existing immune defect or rare individuals where the virus infection spreads into atypical cell types. There is no obvious association between this virus and so‐called chronic fatigue syndrome.

Key concepts:

  • Infectious mononucleosis is caused by Epstein–Barr virus, an orally transmitted human herpesvirus that is common in all human populations.

  • Most individuals acquire Epstein–Barr virus asymptomatically early in life, then carry the virus for life without undue effect.

  • Only when primary infection has been delayed until adolescence or young adulthood is there a substantial risk of mononucleosis developing; hence, the disease is largely confined to affluent societies where delayed infection is more common.

  • Infectious mononucleosis is self‐limiting and ‘immunopathological’ in nature: that is, the symptoms (fever and malaise) are caused not by the virus infection per se, but by the patient mounting an exaggerated cellular immune response to that infection.

  • Most (but not all) cases with the relevant clinical symptoms and large numbers of atypical mononuclear cells in the blood will be Epstein–Barr virus‐related; however, definite diagnosis requires serological testing for IgM antibodies to Epstein–Barr virus.

  • Cases where severe disease symptoms persist are extremely rare and involve either patients with a pre‐existing immune defect or individuals where the virus infection has spread into atypical cell types.

  • A history of proven infectious mononucleosis brings with it an increased risk of subsequently developing another Epstein–Barr virus ‐associated disease, Hodgkin lymphoma.

Keywords: infectious disease; Epstein–Barr virus; epidemiology; immune response; blood mononuclear cells

Figure 1.

Comparison of the ages at which individuals in different populations become infected with (EBV). In developing countries almost all children have acquired the virus by 2–4 years of age, depending on geographical region. In developed countries with high standards of living and hygiene, the time of infection is delayed for many individuals, more markedly among the affluent than the less well off. Among the very rich, as many as 50% may reach adolescence or young adulthood without having encountered the virus and will undergo delayed primary infection with a high risk that this will be accompanied by the symptoms of infectious mononucleosis.

Figure 2.

Percentage of patients with (IM) showing various clinical features during the course of the disease, and the timing and average duration of each.

Figure 3.

Photomicrographs of peripheral blood films stained by the Giemsa method (×40; insets ×100): (a) from a normal individual, showing four neutrophils (detail in upper inset) and one lymphocyte (arrow and lower inset) among a mass of red cells; (b) from a patient with infectious mononucleosis, showing numerous large atypical mononuclear cells (arrows and insets) in addition to the normal cells; though not illustrated here, when stained for differentiation markers these cells have the phenotype of activated CD8+ cytotoxic T cells. This figure was kindly provided by the late Professor DY Mason, Department of Haematology, John Radcliffe Hospital, Oxford, UK, to whom the authors are most grateful.


Further Reading

Carter RL and Penman HG (eds) (1969) Infectious Mononucleosis. Oxford: Blackwell Scientific.

Diepstra A, Niens M, Vallenga E et al. (2005) Association with HLA class I in Epstein–Barr‐virus‐positive and with HLA class III in Epstein–Barr‐virus‐negative Hodgkin's Lymphoma. Lancet 365: 2216–2224.

Epstein MA and Achong BG (eds) (1979) The Epstein–Barr Virus. Berlin: Springer.

Hislop AD, Taylor GS, Sauce D and Rickinson AB (2007) Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annual Review of Immunology 25: 587–617.

Hjalgrim H, Askling J, Rostgaard K et al. (2003) Characteristics of Hodgkin's Lymphoma after infectious mononucleosis. New England Journal of Medicine 349: 1324–1332.

Hoagland RJ (1955) The transmission of infectious mononucleosis. American Journal of Medical Science 229: 262–272.

McAulay KA, Higgins CD, Macsween KF et al. (2007) HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection. Journal of Clinical Investigation 117: 3042–3048.

Rickinson AB and Kieff E (2007) Epstein–Barr virus. In: Knipe DM and Howley PM (eds) Fields Virology, 5th edn, vol. 2, pp. 2680–2700. Philadelphia: Lippincott Williams and Wilkins.

Schlossberg D (ed.) (1989) Infectious Mononucleosis, 2nd edn. Berlin: Springer.

Sprunt TP and Evans FA (1920) Mononuclear leucocytosis in reaction to acute infections (‘infectious mononucleosis’). Bulletin of the Johns Hopkins Hospital 31: 410–417.

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How to Cite close
Epstein, MA, and Rickinson, AB(Feb 2010) Infectious Mononucleosis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002318.pub2]