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The Future Possibilities of Diagnostic Testing for the Evaluation of Febrile Infants

Prashant Mahajan, MD, MPH, MBA1; Octavio Ramilo, MD2; Nathan Kuppermann, MD, MPH3
[+] Author Affiliations
1Department of Pediatrics and Emergency Medicine, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit
2Department of Pediatrics, Nationwide Children’s Hospital and Ohio State University, Columbus
3Department of Emergency Medicine, University of California, Davis School of Medicine, Sacramento
JAMA Pediatr. 2013;167(10):888-898. doi:10.1001/jamapediatrics.2013.2491.
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Fever is one of the most common reasons for childhood visits to emergency departments and primary care practitioners worldwide. Most febrile infants younger than 3 months have nonbacterial causes of fever, and these children are frequently clinically indistinguishable from those with serious bacterial infections (SBIs) (including bacterial meningitis, bacteremia, and urinary tract infections).

The evaluation of well-appearing febrile infants continues to be challenging and controversial for clinicians. This is particularly true for infants younger than 3 months because although the risks of bacteremia and bacterial meningitis are low in those with normal routine screening laboratory test results (eg, complete blood cell counts and urinalyses), the outcomes of bacteremia and meningitis could be devastating.1 The need for performing routine lumbar punctures in well-appearing febrile infants younger than 3 months is also part of the controversy.1 The essence of the controversy is that no definitive clinical criteria or laboratory screening tests reliably exclude SBI, and blood cultures have a not-inconsequential rate of false-positive and false-negative results.2 Clinically apparent viral syndromes such as bronchiolitis reduce but do not exclude the possibility of SBI,3 and although clinical prediction rules can help identify those infants with bacterial meningitis, they are not perfect, particularly in the youngest infants.4

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Gene Expression Patterns Discriminate Viral vs Bacterial Infections

A, Set of 35 genes that discriminates patients with viral infections (influenza A; green) and bacterial infections (Escherichia coli and Streptococcus pneumoniae; red). The discriminative pattern is shown by the gene expression patterns in the heat map (red indicates overexpressed genes; blue, underexpressed genes). B, The diagnostic signature was tested in an independent set of patients that confirmed its accuracy. K-NN indicates nearest neighbor algorithm.

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