Diagnostic Testing for Infectious Mononucleosis (Mono)
The primary diagnostic test for infectious mononucleosis (mono) is serum testing for Epstein-Barr virus (EBV) antibodies, not a throat swab. While throat swabs are essential for diagnosing streptococcal pharyngitis, they are not the recommended method for diagnosing mono.
Recommended Diagnostic Approach for Mono
- The initial test for suspected mono should be a heterophile antibody test (Monospot test) using a blood sample, which has 71-90% accuracy for diagnosing infectious mononucleosis 1
- False-negative Monospot results are common (25%) in the first week of illness, requiring additional testing if clinical suspicion remains high 1
- When the Monospot test is negative but EBV infection is still suspected, EBV-specific antibody testing should be performed on serum samples 2
EBV-Specific Antibody Panel (Gold Standard)
- The most definitive diagnostic approach includes testing for:
- Recent primary EBV infection is indicated by positive VCA IgM (with or without VCA IgG) and negative EBNA antibodies 2
- EBNA antibodies typically appear later (>6 weeks after infection) and persist indefinitely 4
Sample Collection for EBV Testing
- Serum is the preferred specimen for EBV antibody testing, collected in a clot tube and transported at room temperature within 2 hours 5
- For EBV DNA quantification (viral load), plasma or whole blood collected in an EDTA tube is recommended 5
- Cerebrospinal fluid testing is only indicated when neurological symptoms are present 5
Supporting Laboratory Findings
- Complete blood count typically shows:
- Lymphocytosis (lymphocytes ≥50% of white blood cells)
- Atypical lymphocytes >10% of total lymphocyte count 6
- Mono is unlikely if the lymphocyte count is less than 4,000/mm³ 1
Why Throat Swabs Are Not Primary for Mono Diagnosis
- The Infectious Diseases Society of America (IDSA) does not list throat swabs as a diagnostic method for EBV infection 7
- EBV primarily infects B lymphocytes in the bloodstream, making blood-based testing more reliable 2
- While EBV can be detected in throat secretions, this finding does not confirm acute infection as the virus can persist in the throat for weeks to months after infection 7
Common Diagnostic Pitfalls
- Relying solely on clinical presentation without laboratory confirmation can lead to misdiagnosis, as other infections can cause similar symptoms 8
- Testing too early in the disease course may yield false-negative results 1
- Interpreting the presence of EBV in throat samples must be done cautiously, as it may represent prolonged excretion rather than acute infection 7
Clinical Pearls
- Mono should be suspected in patients 15-24 years of age with fever, tonsillar pharyngitis, and lymphadenopathy 6
- Additional suggestive findings include periorbital edema, palatal petechiae, and splenomegaly 6, 1
- Patients with negative heterophile tests may have other infections such as cytomegalovirus, toxoplasmosis, or streptococcal infection 8
By following this evidence-based diagnostic approach, clinicians can accurately diagnose infectious mononucleosis and provide appropriate management to reduce morbidity and prevent complications such as splenic rupture.