Can a person contract another strain of infectious mononucleosis (mono) and how would reinfection be diagnosed?

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Last updated: April 6, 2025View editorial policy

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From the Guidelines

You can be infected with different strains of the Epstein-Barr virus (EBV) that causes mono, though reinfection is uncommon in people with healthy immune systems. To test for mono reinfection, doctors typically order specific blood tests including EBV antibody panels that look for different antibody patterns, as recommended by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM) in their 2013 guidelines 1. These tests measure IgM antibodies (indicating recent infection) and IgG antibodies to various EBV antigens like viral capsid antigen (VCA), and Epstein-Barr nuclear antigen (EBNA). Some key points to consider when testing for reinfection include:

  • The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of antibodies to EBNA 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 not likely implicating EBV as a cause 1
  • A reinfection or reactivation would show a specific pattern where IgM antibodies to VCA might be present alongside existing IgG antibodies
  • Your doctor might also order PCR tests to detect active viral DNA in your blood, which can distinguish between a latent infection and active viral replication
  • Additional tests like complete blood count and liver function tests may be ordered to assess your overall health status Reinfection typically occurs in immunocompromised individuals whose immune systems cannot keep the dormant virus in check, allowing either reactivation of the original strain or infection with a new strain 1.

From the Research

Reinfection with Mono

  • It is possible to have another strain of mono, as Epstein-Barr virus (EBV) has multiple strains and reinfection can occur 2.
  • However, the likelihood of reinfection and the severity of symptoms may vary depending on several factors, including the individual's immune response and the specific strain of EBV involved.

Testing for Reinfection

  • The classic test for infectious mononucleosis is the demonstration of heterophile antibodies, which can be detected using the monospot test 3.
  • When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended 3.
  • EBV-specific antibody profiles are the best choice for staging EBV infection and can help determine if an individual has been reinfected with a different strain of EBV 2.

Diagnosis and Management

  • Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy, and diagnosis is typically made based on clinical presentation and laboratory tests 3.
  • Treatment is mainly supportive, with reduction of activity and bed rest as tolerated, and patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present 3.
  • Antiviral drugs have been shown to be effective inhibitors of EBV replication, but their use in clinical practice is limited and none have been approved for treatment of EBV infections 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Infectious Mononucleosis.

Current topics in microbiology and immunology, 2015

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Antiviral Drugs for EBV.

Cancers, 2018

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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