Related Experiment Video
Updated: Jul 19, 2025
Rapid Molecular Detection and Differentiation of Influenza Viruses A and B
Published on: January 30, 2017
Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a
Priyen Shah1, Marie Voice2, Leonides Calvo-Bado2
1Section of Paediatric Infectious Disease, Department of Infectious Diseases, and Centre for Paediatrics and Child Health, Imperial College, London, UK.
Insights
Molecular pathogen detection in febrile children often fails to definitively distinguish bacterial from viral infections. Current methods show low clinical value for guiding antibiotic treatment, necessitating new diagnostic approaches.
Area of Science:
- Pediatric infectious diseases
- Molecular diagnostics
- Clinical microbiology
Background:
- The PERFORM study investigated the causes of febrile illness in children.
- It compared molecular pathogen detection with standard clinical practices across nine European countries.
Purpose of the Study:
- To evaluate the effectiveness of centralized molecular tests (CMTs) in diagnosing infections in febrile children.
- To compare molecular findings with clinical diagnoses and assess their utility in guiding treatment decisions.
Main Methods:
- Recruited febrile children and controls from 2016-2020.
- Assigned diagnostic categories based on clinical and microbiological data.
- Performed CMTs for 19 respiratory and 27 blood pathogens.
Main Results:
- CMTs detected blood bacteria more frequently in definite bacterial infection (DB) cases than definite viral infection (DV) cases.
- Respiratory viruses were common, but less frequent in DB cases compared to DV cases.
- Virus detection poorly ruled out bacterial infection, with low predictive values.
Conclusions:
- Molecular tests supplementing conventional methods do not conclusively differentiate bacterial from viral infections in most febrile children.
- Individual pathogen detection has limited clinical value for treatment decisions.
- Novel strategies are required to determine antibiotic necessity in febrile children.
Background:
The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.
Methods:
Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.
Findings:
Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.
Interpretation:
Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.
Funding:
EU Horizon 2020 grant 668303.
