What is the diagnostic approach for an 8-year-old child suspected of having infectious mononucleosis (mono) presenting with fatigue?

Diagnostic Testing for Infectious Mononucleosis in an 8-Year-Old Child

Start with a heterophile antibody test (Monospot) as the initial diagnostic test, but be aware that false-negatives are common in children under 10 years old, so proceed directly to EBV-specific serologic testing if clinical suspicion remains high. 1

Initial Laboratory Testing Approach

First-Line Test: Heterophile Antibody (Monospot)

• Order the heterophile antibody test as your initial diagnostic test, which has a sensitivity of 87% and specificity of 91% in the general population 1
• The test typically becomes positive between the sixth and tenth day after symptom onset, so timing matters 1
• Critical caveat for this age group: False-negative heterophile results are common in children younger than 10 years, with an approximate 10% false-negative rate overall 1
• Given this child is 8 years old, you should have a lower threshold to proceed to EBV-specific testing even with a negative Monospot 1

Supportive Laboratory Findings

• Order a complete blood count with differential to look for:
  • Lymphocytosis ≥50% of white blood cell differential 1
  • Atypical lymphocytosis ≥10% of total lymphocyte count 1
• These findings support the diagnosis but are not specific 1, 2

Second-Line Testing: EBV-Specific Serology

When to order: If the heterophile test is negative but clinical suspicion remains high (which is likely in an 8-year-old), proceed immediately to EBV serologic testing 1

Specific Tests to Order

Order the following three EBV antibody tests together 1:

1. IgM antibodies to viral capsid antigen (VCA-IgM)
2. IgG antibodies to viral capsid antigen (VCA-IgG)
3. Antibodies to Epstein-Barr nuclear antigen (EBNA)

Interpretation Algorithm

• Recent primary EBV infection (acute mono): VCA-IgM present (with or without VCA-IgG) AND EBNA antibodies absent 1
• Past infection (>6 weeks ago): EBNA antibodies present 1
• Important note: Over 90% of normal adults have IgG antibodies to VCA and EBNA reflecting past infection, and approximately 5-10% of patients fail to develop EBNA antibodies even after infection 1

Differential Diagnosis Testing

If both heterophile and EBV testing are negative, consider testing for other causes of mononucleosis-like illness 1:

• Cytomegalovirus (CMV) infection
• HIV infection
• Toxoplasma gondii infection
• Adenovirus infection
• Streptococcal pharyngitis (rapid strep test or throat culture)

Common Pitfalls to Avoid

False-Positive Heterophile Results

May occur in patients with 1:

• Leukemia
• Pancreatic carcinoma
• Viral hepatitis
• CMV infection

False-Negative Heterophile Results

Common in 1:

• Children younger than 10 years (this patient!)
• Early in the course of infection (before day 6-10)
• Approximately 10% false-negative rate overall

Testing Too Early

• The heterophile test may be negative if drawn before the sixth day of symptoms 1
• Consider repeating the test after several days if initial test is negative and symptoms persist 1

Clinical Context for This 8-Year-Old

Given the patient's age and presentation with fatigue:

• Start with both heterophile antibody test AND complete blood count with differential simultaneously to avoid delays 1
• Have a very low threshold to order EBV-specific serology given the high false-negative rate of heterophile testing in this age group 1
• Look for the classic findings of lymphocytosis with atypical lymphocytes on the blood smear 1, 2
• Consider that fever, pharyngitis, and cervical lymphadenopathy are the classic triad, though fever may not always be prominent 3, 2