In the Journals

Immune signature distinguishes bacterial, viral infections

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March 24, 2015

An immune signature may help physicians determine whether patients have acute bacterial or acute viral infections, according to new data.

“A major cause of antibiotic overuse and underuse is the difficulty of distinguishing between bacterial and nonbacterial (mostly viral) etiologies,” researchers wrote in PLoS One. “While routinely used microbiological diagnostic tests such as culture, serology and more recently nucleic acid-based tests can assist the clinician in the etiological determination of the underlying infectious process, several challenges remain. An approach that has the potential to address these challenges relies on monitoring the host’s immune-response to infection, rather than direct pathogen detection.”

Researchers from MeMed Diagnostics conducted bioinformatics screening and identified 600 potential host proteins expressed as a result of infection. Each protein was measured on 20 to 30 patients from a training set, and 86 proteins were evaluated further in another 100 patients. Additional testing determined that the optimal immune signature included three proteins: TNF-related apoptosis-inducing ligand (TRAIL) and interferon gamma-induced protein-10 (IP-10), which were upregulated in viral infections; and C-reactive protein (CRP), which was upregulated in bacterial infections.

The immune signature was evaluated using blood samples from 1,002 patients who were recruited prospectively of which 139 were excluded and 98 had indeterminate diagnoses. Three independent physicians diagnosed each patient using clinical and laboratory testing, and they identified 319 bacterial infections, 334 viral infections and 112 controls. Among this group of 765 patients, the signature was effective at distinguishing bacterial and viral infections (area under the curve [AUC] = 0.94 ± 0.04) and at distinguishing infectious and noninfectious controls (AUC = 0.96 ± 0.02).

In a subcohort of unanimous diagnoses that included 256 bacterial infections, 271 viral infections and 112 controls, the immune signature also was effective at distinguishing bacterial and viral infections (AUC = 0.96 ± 0.02). In a second subcohort of microbiologically confirmed diagnoses, including 68 bacterial infections, 173 viral infections and 112 controls, the immune signature also effectively distinguished viral and bacterial infections (AUC = 0.96 ± 0.04).

Further, the signature surpassed established clinical parameters and laboratory findings, including white blood cell count, absolute neutrophil count, percentage neutrophils, maximal temperature, pulse and respiratory rate, and any combinations of these parameters.

“Despite advances in infectious disease diagnosis, timely identification of bacterial infections remains challenging, leading to antibiotic misuse with its profound health and economic consequences,” the researchers wrote. “Our finding in a large sample size of patients is promising. The translational benefit could have a broad impact on the diagnosis and management of patients with acute infections.” – by Emily Shafer

Disclosure: The study was funded by MeMed Diagnostics. Oved reports being employed or previously employed by MeMed. Please see the full study for a list of all other authors’ relevant financial disclosures.

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