What virus causes infectious mononucleosis (mono)?

Epstein-Barr Virus (EBV) Causes Infectious Mononucleosis (Mono)

Infectious mononucleosis (mono) is primarily caused by the Epstein-Barr virus (EBV), which is a ubiquitous human herpesvirus that infects approximately 90% of adults worldwide. 1, 2

Diagnostic Features of EBV-Associated Mononucleosis

EBV infection typically presents with the classic triad of:

• Fever
• Tonsillar pharyngitis
• Cervical lymphadenopathy

Additional common clinical manifestations include:

• Fatigue (may be profound and last up to three months)
• Periorbital/palpebral edema (occurs in about one-third of patients)
• Splenomegaly (approximately 50% of cases)
• Hepatomegaly (approximately 10% of cases)
• Maculopapular rash (10-45% of cases, especially if treated with ampicillin)

Laboratory Findings

Characteristic laboratory findings include:

• Peripheral blood leukocytosis
• Lymphocytosis (≥50% of white blood cell count)
• Atypical lymphocytes (>10% of total lymphocyte count)
• Elevated liver enzymes

Diagnostic Testing

Initial Testing

• Heterophile antibody tests (Monospot test): Most widely used initial test
  • Becomes detectable between 6-10 days after symptom onset
  • Peaks during the second or third week of illness
  • False-negative results occur in approximately 10% of patients, especially in children under 10 years 1

Confirmatory Testing

When the Monospot test is negative but clinical suspicion remains high, EBV-specific antibody testing is recommended:

• EBV antibody profile:
  • VCA (Viral Capsid Antigen) IgM: Indicates recent primary infection
  • VCA IgG: Develops during acute infection and persists for life
  • EBNA (Epstein-Barr Nuclear Antigen) IgG: Develops 1-2 months after primary infection and persists for life 1

The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of EBNA antibodies indicates recent primary EBV infection. The presence of EBNA antibodies indicates infection more than 6 weeks prior 1.

Transmission

EBV is primarily transmitted through oral secretions (saliva), commonly through:

• Deep kissing among adolescents and young adults
• Possibly through sharing food or eating utensils among younger children 3

The incubation period for symptomatic primary EBV infection is unusually long, lasting approximately six weeks 3.

Complications

While generally self-limiting, EBV infection can lead to serious complications:

• Splenic rupture (0.1-0.5% of cases) - most feared acute complication
• Neurological complications (encephalitis, meningitis, Guillain-Barré syndrome)
• Hematologic complications (hemolytic anemia, thrombocytopenia)
• Airway obstruction due to tonsillar hypertrophy
• Chronic fatigue syndrome
• Long-term associations with certain malignancies (nasopharyngeal carcinoma, Burkitt lymphoma, lymphoproliferative disorders in immunocompromised hosts) 2, 4

Management

Treatment is primarily supportive:

• Rest as tolerated
• Adequate hydration
• Analgesics for pain and fever
• Avoidance of contact sports or strenuous exercise for at least 8 weeks or while splenomegaly is present (to prevent splenic rupture)
• Corticosteroids may be considered in cases with significant tonsillar inflammation causing airway obstruction

Prevention

Currently, no vaccine is available for EBV. The most effective prevention would be the development of a safe and effective EBV vaccine that could confer lifelong immunity 2.