Can you get infectious mononucleosis (mono) twice from the Epstein-Barr virus (EBV)?

Can You Get Mono Twice?

No, you typically cannot get infectious mononucleosis (mono) twice from Epstein-Barr virus (EBV) because after primary infection, you develop lifelong immunity through VCA IgG and EBNA IgG antibodies. 1

Understanding EBV Infection and Immunity

EBV infection follows a predictable serological pattern that helps explain why true second cases of mono are rare:

1. Primary Infection (Mono):

   • Characterized by positive VCA IgM, positive VCA IgG, and negative EBNA IgG 1
   • Presents with the classic triad of fever, tonsillar pharyngitis, and lymphadenopathy 2
   • Often accompanied by fatigue, which may be profound but typically resolves within three months 2

2. Past Infection/Immunity:

   • Marked by negative VCA IgM, positive VCA IgG, and positive EBNA IgG 1
   • These antibodies persist for life, providing immunity against developing mono again

Why People Might Think They Have Mono Twice

Several scenarios might lead someone to believe they've had mono twice:

1. Misdiagnosis of the first episode:

   • Mono-like symptoms can be caused by other infections (cytomegalovirus, toxoplasmosis)
   • Heterophile antibody tests (Monospot) can miss approximately 10% of EBV cases, especially in children under 10 years 1

2. EBV Reactivation:

   • While not causing classic mono, EBV can reactivate from latency, especially in immunocompromised individuals
   • Reactivation typically causes milder symptoms than primary infection
   • Can be distinguished by serological testing showing past infection pattern (VCA IgM negative, VCA IgG positive, EBNA IgG positive) 1

3. Chronic Active EBV Infection:

   • Rare condition where symptoms persist beyond 6 months 1
   • Not a second case of mono but rather a complication of the initial infection

Diagnostic Considerations

If a patient believes they have mono for a second time, comprehensive serological testing is essential:

• Standard EBV antibody panel should include:

  • Viral Capsid Antigen (VCA) IgM
  • Viral Capsid Antigen (VCA) IgG
  • Epstein-Barr Nuclear Antigen (EBNA) IgG 1

• For persistent symptoms, consider:

  • Quantitative EBV viral load by PCR to confirm active viral replication 1
  • Evaluation for chronic active EBV infection if symptoms persist beyond 6 months 1
  • Testing for other infectious causes of mono-like symptoms

Clinical Implications

Understanding that true second cases of mono are extremely rare has important clinical implications:

• For patients with recurrent mono-like symptoms:

  • Look for alternative diagnoses
  • Consider EBV reactivation in immunocompromised patients
  • Monitor for complications like chronic active EBV infection

• For patients with confirmed primary EBV infection:

  • Advise that they will likely have lifelong immunity against developing mono again
  • Explain that EBV remains dormant in the body after primary infection
  • Note that approximately 5-6% of patients may develop post-infectious fatigue syndrome after acute EBV infection 1

Prevention Measures

While you cannot get mono twice, prevention of primary EBV infection includes:

• Frequent handwashing with soap and water
• Avoiding sharing utensils, glasses, toothbrushes, or food
• Avoiding kissing or intimate contact with infected individuals 1

Currently, there is no available vaccine for EBV, although vaccine development efforts are ongoing 3.