UMHS LOGOUniversity of Michigan
Department of Pediatrics

Evidence-Based Pediatrics Web Site

Accurate Diagnosis of EBV Mono With Rapid Heterophile Latex Agglutination Depends on the Test Used


  • A 15 year old high school football player presents to your clinic with complaints of fatigue, sore throat, and swollen glands.  You are suspicious of mono.  His monospot test is negative. Can he continue to play football? In other words, how accurate is a negative test in this setting?

Clinical Bottom Lines

  1. Rapid latex heterophile agglutination tests have a wide range of sensitivities such that a negative test may not effectively rule out disease in a case of high clinical suspicion.
  2. The rapid latex heterophile agglutination tests in this article have a fairly high level of specificity, indicating that a positive test result effectively rules in the diagnosis of EBV mono.

Summary of Key Evidence

  1.  53 sera with known EBV infection and 47 sera with no EBV infection by IgG and IgM antibodies to EBV VCA were tested on 6 rapid test kits for heterophile antigens.  Sensitivities of the latex agglutination kits ranged from 85-91%, specificities ranged from 96-100%.1
  2.  Ages in the study ranged from 2-83yo.  Half of the non-EBV infected sera were infected with other viral diseases often confused with EBV (CMV, Adeno, HIV, VZV).
  3.  The authors found a sensitivity of 89% in children under age of 13 years. This is contrary to previous evidence of poor heterophile response in small children.
  4.  This study used a gold standard of IgG and IgM antibodies to EBV VCA.  However, in the face of discordant results, they retested serum using a second gold standard of EB virus nuclear antigen 1 (EBNA-1).  No detection of EBNA-1 along with an IgM antibody titer > 1:20 were defined as primary EBV infection.  This is a form of verification or work-up bias.

Additional Comments

  •  According to the manufacturer, the rapid latex heterophile agglutination test used here at the University of Michigan Health System (UMHS) has a sensitivity of 99% and a specificity of 93%.  The sensitivity of our test is much higher indicating a negative test would effectively rule out EBV mono even in a case of high clinical suspicion.
  •  Therefore, it is important to know the sensitivity and specificity of the kit utilized in your lab.
  •  With the lower sensitivities noted in the kits tested in this article, it would be benfecial to follow-up a negative test with serologies for EBV VCA in a case of high clinical suspicion.  A positive test would still be useful in ruling in EBV mono as a cause for this young manís symptoms.


  1. Elgh F, Linderholm M. Evaluation of six commercially available kits using purified heterophile antigen for the rapid diagnosis of infectious mononucleosis compared with Epstein-Barr virus-specific serology. Clinical and Diagnostic Virology 1996; 7:17-21.

CAT Author: Keri A. Lattimore, MD

CAT Appraisers: Robert Schumacher, MD

Date appraised: October 1, 2001

Last updated October 24, 2001
Department of Pediatrics and Communicable Diseases
© 1998-2002 University of Michigan Health System