What is the etiology of infectious mononucleosis (Infectious Mononucleosis)?

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Last updated: March 25, 2025View editorial policy

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From the Guidelines

Infectious mononucleosis is primarily caused by Epstein-Barr Virus (EBV), which is responsible for approximately 90% of cases. The diagnosis of infectious mononucleosis typically involves a combination of clinical assessment and laboratory testing, including a complete blood count with differential, heterophile antibody test (Monospot), and specific EBV serologic testing 1.

Key Diagnostic Tests

  • Complete blood count with differential to reveal lymphocytosis with atypical lymphocytes
  • Heterophile antibody test (Monospot), which is positive in 85-90% of adolescents and adults with the condition
  • Specific EBV serologic testing, including EBV viral capsid antigen (VCA) IgM and IgG, and EBV nuclear antigen (EBNA) antibodies, to confirm the diagnosis and determine the stage of infection 1

EBV Serologic Testing

  • The presence of VCA IgM indicates acute infection
  • VCA IgG with negative EBNA suggests recent infection
  • EBNA antibodies indicate infection more than 6 weeks from the time of the sample and are detectable for life 1

Additional Testing

  • Liver function tests to assess for mild transaminitis, which is common in infectious mononucleosis
  • Throat cultures to rule out streptococcal pharyngitis, which can present similarly
  • Abdominal ultrasound to assess splenic size and monitor for potential complications in cases with significant splenomegaly 1

Importance of Accurate Diagnosis

Accurate etiologic diagnosis is crucial for appropriate management and patient counseling, as EBV causes approximately 90% of infectious mononucleosis cases, with cytomegalovirus, toxoplasmosis, and acute HIV infection accounting for most of the remainder 1.

From the Research

Etiology of Infectious Mononucleosis

The etiology of infectious mononucleosis is attributed to the Epstein-Barr virus (EBV) 2, 3, 4.

  • The virus is primarily transmitted through close personal contact with an infected person, particularly through their saliva 3, 4.
  • Infectious mononucleosis most commonly affects adolescents and young adults aged 15 to 24 years 2, 3, 4.
  • The disease is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy, with additional symptoms such as fatigue, periorbital and/or palpebral edema, splenomegaly, and hepatomegaly 3.

Transmission and Risk Factors

  • Transmission of EBV occurs mainly through saliva, making close personal contact a primary risk factor 3, 4.
  • Immunosuppressed populations are at higher risk of severe disease and significant morbidity 4.
  • EBV infection has been linked to various types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, as well as some autoimmune diseases 4.

Diagnosis and Laboratory Testing

  • The diagnosis of infectious mononucleosis can be made through clinical assessment, hematologic and serologic manifestations, and laboratory tests such as the heterophile antibody test and EBV-specific antibody tests 2, 5, 4.
  • The heterophile antibody test has a sensitivity of 87% and specificity of 91%, but can have false-negative results in certain populations 4.
  • More sensitive and specific tests, such as EBV viral capsid antigen-antibody testing, are available but may be more expensive and take longer to process 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and treatment of infectious mononucleosis.

American family physician, 1994

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Infectious Mononucleosis: Rapid Evidence Review.

American family physician, 2023

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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