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Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Age-Dependent Clinical Patterns of Primary Epstein-Barr Virus Infection in Children: Insights for Diagnostic Accuracy
Demet Teker-Düztaş1, Ayşe Kaman2, Gönül Tanır2
1Departments of Pediatrics, Dr. Sami Ulus Children's Health and Diseases Training and Research Hospital, 06080 Ankara, Türkiye.
Insights
Primary Epstein-Barr virus (EBV) infection in children varies widely. Specific clinical signs, not just age, predict outcomes, guiding better diagnostic and antibiotic strategies.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Clinical Diagnostics
Background:
- Primary Epstein-Barr virus (EBV) infection in children presents with diverse symptoms, complicating diagnosis and potentially leading to inappropriate antibiotic use.
- Understanding the clinical heterogeneity is crucial for accurate and timely diagnosis in pediatric populations.
Purpose of the Study:
- To analyze the clinical spectrum of primary EBV infection in children.
- To identify key determinants of clinical outcomes and hospitalization.
- To evaluate potential diagnostic tools for improving antimicrobial stewardship.
Main Methods:
- Retrospective analysis of 695 children (0-18 years) diagnosed with primary EBV infection (VCA IgM+, EBNA IgG-).
- Comparison of clinical, laboratory, and ultrasonographic findings by age group (≤4 vs. >4 years) and setting (inpatient vs. outpatient).
- Multivariable logistic regression and ROC analysis for diagnostic markers and risk score derivation.
Main Results:
- Younger children (<4 years) showed more nonspecific symptoms, while older children presented with classic infectious mononucleosis (IM) features (p < 0.001).
- Antibiotics were prescribed in 64.2% and hospitalization occurred in 21.7% of patients.
- Clinical findings (lymphadenopathy, vomiting) and laboratory results (lymphopenia, thrombocytosis) were stronger predictors of outcomes than age alone.
Conclusions:
- Primary EBV infection has an age-related clinical spectrum, but specific clinical and laboratory features are key outcome drivers.
- Age-specific diagnostic strategies and improved antimicrobial stewardship are needed.
- A derived composite risk score shows potential for future validation as a diagnostic aid.
Abstract:
Primary Epstein-Barr virus (EBV) infection in children exhibits substantial clinical heterogeneity, often complicating early diagnosis and leading to unnecessary antibiotic use. This retrospective study evaluated 695 children (0-18 years) diagnosed with primary EBV infection at a tertiary pediatric center between 2010 and 2015, defined by positive viral capsid antigen (VCA) IgM and negative Epstein-Barr nuclear antigen (EBNA) IgG. Clinical, laboratory, and ultrasonographic findings were compared according to age group (≤4 vs. >4 years) and clinical setting (inpatient vs. outpatient). The median age was 3.75 years (IQR: 2-6.25), and more than half of the patients were ≤4 years. Younger children more frequently presented with nonspecific respiratory and gastrointestinal symptoms, whereas older children more commonly exhibited the classic infectious mononucleosis (IM) phenotype, including sore throat, dysphagia, lymphadenopathy, and hepatosplenomegaly (p < 0.001). Antibiotics were prescribed in 64.2% of patients, while 21.7% required hospitalization. Multivariable logistic regression analyses demonstrated that age was not an independent predictor of hospitalization, classic IM phenotype, or antibiotic use. Instead, specific clinical and laboratory findings-such as lymphopenia, lymphadenopathy, vomiting, thrombocytosis, and tonsillar hypertrophy-emerged as the key determinants of clinical outcomes. To enhance diagnostic discrimination, receiver operating characteristic (ROC) analysis of ANC/ALC and AST/ALT ratios was performed, and a composite risk score (0-2) was derived. Although both markers showed modest discriminative ability (AUC 0.607 and 0.575), their high negative predictive values (>90%) suggest potential utility as rule-out tools. The composite score demonstrated a stepwise increase in the probability of classic IM presentation across age groups. In conclusion, primary EBV infection demonstrates a clear age-related clinical spectrum; however, clinical and laboratory features rather than age alone drive key outcomes. These findings highlight the need for age-specific diagnostic strategies and improved antimicrobial stewardship, while the proposed risk score provides a foundation for future validation studies.
