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Updated: Jul 20, 2026

Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Clinical inquiries. What test is the best for diagnosing infectious mononucleosis?
Amy Trelease Bell1, Barbara Fortune, Robert Sheeler
1University of Wyoming Family Practice Residency Program at Cheyenne, WY, USA.
Insights
Diagnosing infectious mononucleosis involves trade-offs between test sensitivity, specificity, and cost. Antibody tests are sensitive but costly, while heterophile antibody tests are cheaper but less sensitive, especially early in illness.
Area of Science:
- Infectious Diseases
- Virology
- Immunology
Background:
- Infectious mononucleosis is a common viral illness.
- Accurate diagnosis is crucial for patient management.
- Several diagnostic tests are available, each with varying performance characteristics.
Purpose of the Study:
- To evaluate the sensitivity, specificity, and cost-effectiveness of different diagnostic tests for infectious mononucleosis.
- To provide guidance on selecting the most appropriate diagnostic test based on clinical context.
Main Methods:
- Review of diagnostic tests including antibody tests (Epstein-Barr viral capsid antigen, Epstein-Barr nuclear antigen), heterophile antibody tests, polymerase chain reaction (PCR) for Epstein-Barr virus DNA, and complete blood count (CBC) with lymphocyte differentials.
- Analysis of sensitivity, specificity, and cost data from validating cohort studies.
Main Results:
- Antibody tests for Epstein-Barr viral capsid antigen or Epstein-Barr nuclear antigen offer high sensitivity and specificity but are expensive.
- Heterophile antibody tests are less sensitive, particularly in children or early illness, but are more cost-effective.
- PCR for Epstein-Barr virus DNA is sensitive and specific but also expensive.
- CBC with lymphocyte differentials provides a specific, moderately sensitive, and inexpensive diagnostic option.
Conclusions:
- The choice of diagnostic test for infectious mononucleosis depends on balancing sensitivity, specificity, cost, and the clinical stage of the illness.
- Antibody tests and PCR are highly sensitive and specific but costly, while heterophile antibody tests and CBC offer more affordable alternatives with some limitations in sensitivity.
Abstract:
Tests for antibodies to Epstein-Barr viral capsid antigen or Epstein-Barr nuclear antigen are the most sensitive, are highly specific, and are also the most expensive for diagnosing infectious mononucleosis (strength of recommendation [SOR]: C, based on validating cohort study). Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness (SOR: C, based on validating cohort study). The polymerase chain reaction assay for Epstein-Barr virus DNA is more sensitive than the heterophile antibody test in children, is highly specific, but is also expensive (SOR: C, based on validating cohort study). The percentages of atypical lymphocytes and total lymphocytes on a complete blood count provide another specific and moderately sensitive, yet inexpensive, test (SOR: C, based on validating cohort study).
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