What are the diagnostic tests for infectious mononucleosis (mono)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 27, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

The most effective diagnostic approach for infectious mononucleosis (mono) involves a combination of clinical evaluation and laboratory tests, including the monospot test and specific Epstein-Barr virus (EBV) antibody tests, such as IgM and IgG antibodies to viral capsid antigen (VCA) and antibodies to EBV nuclear antigen (EBNA) 1.

Diagnostic Tests

The diagnostic tests for mono can be categorized into several types:

  • Monospot test: a rapid test that detects heterophile antibodies, which can be performed in a doctor's office with results available within minutes 1.
  • EBV antibody tests: specific tests that detect IgM and IgG antibodies to VCA and EBNA, which can provide a more definitive diagnosis 1.
  • Complete blood count (CBC): a useful test that often shows an elevated white blood cell count with atypical lymphocytes 1.

Interpretation of Test Results

The interpretation of test results is crucial in diagnosing mono:

  • A positive monospot test result indicates the presence of heterophile antibodies, which are often associated with EBV infection 1.
  • The presence of VCA IgM antibodies, with or without VCA IgG antibodies, indicates recent primary infection with EBV 1.
  • The presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample and therefore is not likely to implicate EBV as a cause 1.

Clinical Evaluation

A clinical evaluation is essential in diagnosing mono, as it involves assessing symptoms such as:

  • Severe sore throat
  • Fatigue
  • Fever
  • Swollen lymph nodes Early diagnosis helps manage symptoms appropriately and prevents complications, particularly avoiding contact sports due to the risk of splenic rupture during the acute phase of illness 1.

From the Research

Diagnostic Tests for Infectious Mononucleosis

The diagnostic tests for infectious mononucleosis (mono) include:

  • Heterophile antibody test (monospot test) 2, 3
  • Epstein-Barr virus (EBV) antibody tests, such as:
    • IgG antibodies to viral capsid antigen (VCA) 4
    • IgM antibodies to VCA 4, 3
    • Antibodies to early antigen (anti-D) 4
    • Epstein-Barr nuclear antigen (EBNA) antibodies 4
  • Complete blood count (CBC) with differential to assess for lymphocytosis and atypical lymphocytes 3, 5, 6
  • Real-time PCR (RT-PCR) to measure EBV viral load (EBV-VL) in peripheral blood 5

Interpretation of Test Results

The diagnosis of infectious mononucleosis may be made when:

  • IgG-VCA, IgM-VCA, and anti-D antibodies are present and EBNA antibodies are absent 4
  • The heterophile antibody test is positive 2, 3
  • The CBC with differential shows greater than 40% lymphocytes and greater than 10% atypical lymphocytes 3, 6

Limitations of Diagnostic Tests

The diagnostic tests for infectious mononucleosis have some limitations, including:

  • The heterophile antibody test can have a false-negative result in children younger than five years and in adults during the first week of illness 3
  • The EBV antibody tests can be more expensive and take longer to process than the rapid heterophile antibody test 3
  • The interpretation of laboratory findings can be difficult, and the diagnosis must be made with caution and possible sources of error considered 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.