Investigations

Screening tests:

• full blood count -
  • leucocytosis of between 10,000 and 20,000 cells/mm3
• blood film - reveals a lymphocytosis with many atypical activated T lymphocytes (mononucleosis cells).
  • peaks in the second or third week of illness (2)
  • usually the diagnosis is likely when atypical lymphocytosis is ≥ 20 % or when atypical lymphocytosis is ≥10 % and ≥ 50 % lymphocytes (1), but the number of atypical lymphocytes may vary between 0-90% of the total lymphocyte count (2)
  • when the cut off point of the abnormal number of lymphocytes is increased the sensitivity of the test decreases (more false negative results) but the specificity increases (less false positive results) (1)
• positive Paul Bunnell reaction - IgM heterophile antibodies that agglutinate sheep erythrocytes.
  • seen in around 90% of cases (2)
  • heterophile antibodies usually peak during the second week and decreases rapidly after the fourth week (2,3)
  • false negative rate is high (25%) when blood is taken in the first week but the rate reduces to 5% if blood is taken in the third week of illness (1)
  • is less sensitive in patients younger than 12 years (detects around 25-50% of infections) (1)
  • repeat testing is done after 5-7 days in patients with a negative initial test (1)
• liver function test – abnormal in around 80% of patients with mild to moderate elevation of transaminases, alkaline phosphatase and bilirubin (2).

Specific tests:

• more sensitive tests include – detection of viral capsid antigen (VCA)-IgG and VCA-IgM (1):
  • useful in patients with typical clinical features of IM but a negative heterophile antibody test (1)
  • IgM antibodies to Epstein Barr viral capsid antigen (VCA) - detectable early in the course of the disease but transient.
  • IgG EBV VCA - appear soon after IgM. They persist for life at a stable or slowly declining level and so may also be used as markers of previous EBV exposure.
  • these tests are useful in diagnosing patients who have negative heterophile antibody test results(1)
  • when the results are negative, these tests are better than heterophile antibody tests in excluding infectious mononucleosis caused by EBV (1)
  • antibodies to EBV nuclear antigen - detectable from about 4 months after infection. Persist throughout life.
• the isolation of EBV is difficult and rarely performed.

Note:

• Hoagland's criteria for the diagnosis of infectious mononucleosis (1):
  • this includes the following features in the presence of fever, pharyngitis, and adenopathy, and confirmed by a positive serologic test
    • at least 50 percent lymphocytes
    • at least 10 percent atypical lymphocytes .
  • these criteria are most useful for research purposes (1)
  • only about 50% of patients with symptoms suggestive of infectious mononucleosis and a positive heterophile antibody test meet all of Hoagland's criteria (1)

Reference:

• (1) Mark H. Ebell. Epstein-Barr Virus Infectious Mononucleosis. Am Fam Physician 2004;70:1279-87,1289-90.
• (2) Charles PGP. Infectious mononucleosis. Australian Family Physician 2003;32(10)
• (3) Center for Disease Control (CDC) 2006. National Center for Infectious Diseases - Epstein-Barr virus and Infectious Mononucleosis