What is the test for infectious mononucleosis (mono)?

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From the Guidelines

The most accurate test for mono is the detection of IgM and IgG directed against the EBV viral capsid antigen (VCA) with negative EBNA1 IgG, as the Paul–Bunnell and monospot tests are suboptimal for diagnosis. When diagnosing mono, it's essential to consider the limitations of various tests. The monospot test, for instance, detects heterophile antibodies but is not as reliable as other methods 1.

Diagnostic Approach

  • The detection of IgM and IgG directed against the EBV viral capsid antigen (VCA) with negative EBNA1 IgG is the preferred method for diagnosing primary EBV infection, which causes mono 1.
  • EBNA1 IgG usually appears weeks or months after the initial infection, making it less useful for early diagnosis.
  • Biopsy diagnosis and classification by a specialist haematopathologist may be necessary to differentiate infectious mononucleosis from other conditions like lymphoproliferative disease, non-Hodgkin's lymphoma, and Hodgkin's disease, and should include EBER in situ hybridisation to detect the presence of EBV 1.

Testing Considerations

  • The Paul–Bunnell and monospot tests are suboptimal for diagnosis and should not be relied upon as the sole diagnostic tool 1.
  • Post-transplant EBV viral load monitoring has a high sensitivity for current or future EBV-associated PTLD in high-risk patients but poor specificity, and its use is limited in the context of mono diagnosis 1.
  • Immunohistochemistry for EBV is not an adequate substitute for EBER in situ hybridisation, as EBV viral proteins like LMP-1 are often not expressed 1.

From the Research

Testing for Mono

The diagnosis of infectious mononucleosis, also known as mono, can be made through various tests, including:

  • The monospot test, which detects serum heterophile antibodies 2
  • Serologic testing for antibodies to viral capsid antigens, recommended when confirmation of the diagnosis is required in patients with a negative mono-spot test 2

Characteristics of Mono

Infectious mononucleosis is characterized by:

  • A triad of fever, tonsillar pharyngitis, and lymphadenopathy 2
  • Fatigue, which may be profound but tends to resolve within three months 2
  • Periorbital and/or palpebral edema, typically bilateral, occurring in one-third of patients 2
  • Splenomegaly and hepatomegaly, occurring in approximately 50% and 10% of cases, respectively 2
  • A skin rash, usually widely scattered, erythematous, and maculopapular, occurring in approximately 10 to 45% of cases 2

Blood Test Results

Peripheral blood leukocytosis is observed in most patients, with:

  • Lymphocytes making up at least 50% of the white blood cell differential count 2
  • Atypical lymphocytes constituting more than 10% of the total lymphocyte count 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

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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.

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