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New assay helps differentiate between viral and bacterial infections in children

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This assay shows promise

Being able to accurately determine if a child is suffering from a serious bacterial infection that requires hospitalization or a viral infection that can be treated at home is a difficult decision. Physicians are wary of prescribing antibiotics due to overuse, resulting in poor outcomes for patients, society, and the health care system, but have not had the diagnostic tests to accurately determine infection types in pediatric patients.

The work of Srugo et al. and the development of the ImmunoXpert assay have added another diagnostic tool to help physicians more effectively treat infections in children. When determining the effectiveness of a diagnostic test, the sensitivity and specificity of the test must be scrutinized. Compared with traditional laboratory tests, the ImmunoXpert assay displayed higher specificity and sensitivity and a superior positive likelihood ratio. With a positive likelihood near 10 and a negative likelihood ratio of 0.07, the “test results may be able to be used meaningfully in the management of patients to a degree that currently does not exist.”

Although the ImmunoXpert assay shows promise as a diagnostic tool, confirmatory investigations must be done to determine if the assay will work in a more real world manner, using refrigerated instead of frozen specimens, and testing the assay in children under 3 months of age.

David Kimberlin, MD, is a professor of pediatrics, vice chair for clinical and translational research, as well as the codirector of the division of pediatric infections diseases at the University of Alabama, Birmingham. Claudette L. Poole, MD, is a Dixon Fellow of Infections Diseases at the university. These comments were published in a commentary accompanying the Srugo et al. article in Pediatrics (2017;140[4]:e20171210).



An assay testing the presence of three blood-borne host-proteins shows promise in accurately identifying viral and bacterial infections in febrile children, a validation study found.

The three proteins that the ImmunoXpert assay uses to differentiate between viral and bacterial infections are: viral-induced tumor necrosis factor-related apoptosis–inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and bacterial-induced C-reactive protein (CRP). TRAIL and IP-10 are novel identifiers, while CRP has been used in traditional bacterial detecting assays, Isaac Srugo, MD, and his colleagues reported.

The investigators identified 597 potential stored patient serum samples from patients admitted to multiple pediatric emergency departments and wards in Israel and Switzerland, and ultimately, 361 samples were selected for assay testing (Pediatrics. 2017;140[4]:e20163453).

Of the 361 patients whose samples were selected for testing, the assay identified 209 patients (58%) with a viral infection, 99 patients (27%) with a bacterial infection, and the remaining 53 patients (15%) with an equivocal outcome, according to Dr. Srugo of the Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel, and his colleagues. The 307 patients with a bacterial or viral diagnosis had sensitivity of 93.8% (95% confidence interval, 87.8%-99.8%) and specificity of 89.8% (CI, 85.6%-94.0%). There were 4 false-negative and 21 false-positive findings.

The levels of TRAIL and IP-10 were present in higher levels in children with viral infections than children with bacterial infections. The opposite was true of CRP results, with levels being drastically lower in children with viral infections than in children with bacterial infections.

“Notably, among the indeterminate diagnosis patients without a reference standard, the assay gave a bacterial or viral outcome for 69% of the cases (the rest were equivocal), with half of these yielding a score associated with a particularly high degree of assay diagnostic confidence,” investigators said. “This finding suggests that the assay may be applicable to ‘harder to diagnose’ cases in real-life clinical settings.”

Also, the assay “exhibits consistent performance across a wide range of ages [3 months to 18 years], time from symptom onset, and clinical syndromes,” Dr. Srugo and his associates said.

Dr. Srugo has no relevant financial disclosures. Nine of the investigators are employees of MeMed, receiving salaries as well as stock options. Dr. Robert Cohen has received grants and revenue unrelated to the study from AstraZeneca, GlaxoSmithKline, Merck, Pfizer, and Sanofi Pasteur. All other authors have no relevant financial disclosures.

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