A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study

Abstract

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1–97.9%), specificity 94.3% (95% CI 90.7–98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.Electronic supplementary materialThe online version of this article (10.1007/s10096-018-3261-3) contains supplementary material, which is available to authorized users.

Differential Markers of Bacterial and Viral Infections in Children for Point-of-Care Testing

“…However, it is difficult to say that IL-6 and IL-8 are more sensitive or specific than CRP or PCT because both poorer and better results have been obtained. Recent studies have shown that IL-6 tests are more sensitive and specific for identifying sepsis in children, but in regards to differential diagnosis of bacterial and viral infections in children with respiratory tract infections or fever without a source, CRP tests are more accurate [ 25 , 46. , 47.…”

Diagnosis and Monitoring of Acute Infections with Emphasis on the Novel Biomarker Human Neutrophil Lipocalin

“…Thus, to avoid this, tubes with no additives should be used, but the tube of choice should be tested before any clinical studies are performed. In a recent study HNL in serum and plasma was compared to the 3-biomarker algorithm of TRAIL, IP-10, and CRP (25). In that study serum HNL was clearly inferior to the 3-biomarker algorithm and considerably less powerful as compared to other studies on serum.…”

A Two-Dimensional Affinity Capture and Separation Mini-Platform for the Isolation, Enrichment, and Quantification of Biomarkers and Its Potential Use for Liquid Biopsy

“…A panel of biomarkers should therefore be able to confirm the presence or absence or a microbial infection. It has been reported that isolation and characterization of a panel of host-protein biomarkers yields significantly superior performance for diagnosing bacterial versus viral infections [ 184 ].…”