How is the heterophile antibody test used to differentiate heterophile-negative infectious mononucleosis (mono) and Epstein-Barr virus (EBV) infectious mononucleosis (mono)?

Updated: Sep 20, 2018
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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The heterophile antibody test (eg, the Monospot test) results may be negative early in the course of EBV infectious mononucleosis. Positivity increases during the first 6 weeks of the illness. Patients who remain heterophile negative after 6 weeks with a mononucleosis illness should be considered as having heterophile-negative infectious mononucleosis.

  • Patients with heterophile infectious mononucleosis should be tested for EBV-specific antibodies before definitively diagnosing heterophile-negative infectious mononucleosis.

  • Patients with heterophile- or Monospot-negative infectious mononucleosis should be tested serologically as are patients who present with a mononucleosislike illness who are negative for heterophile antibodies. The heterophile test is less useful in children younger than 2 years, in whom the results are frequently negative.

  • Although virtual 100% specificity exists with the Monospot test, rarely, other disorders have been reported that may produce a false-positive Monospot test result. These causes of false-positive Monospot test results include toxoplasmosis, rubella, lymphoma, and certain malignancies, particularly leukemias and/or lymphomas.

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