Myxovirus Resistance Protein A as a Marker of Viral Cause of Illness in Children Hospitalized with an Acute Infection

Abstract

ABSTRACT A biomarker for viral infection could improve the differentiation between viral and bacterial infections and reduce antibiotic overuse. We examined blood myxovirus resistance protein A (MxA) as a biomarker for viral infections in children with an acute infection. We recruited 251 children presenting with a clinical suspicion of serious bacterial infection, determined by need for a blood bacterial culture collection, and 14 children with suspected viral infection at two pediatric emergency departments. All children were aged between 4 weeks and 16 years. We classified cases according to the viral, bacterial, or other etiology of the final diagnosis. The ability of MxA to differentiate between viral and bacterial infections was assessed. The median blood MxA levels were 467 (interquartile range, 235 to 812) μg/L in 39 children with a viral infection, 469 (178 to 827) μg/L in 103 children with viral-bacterial coinfection, 119 (68 to 227) μg/L in 75 children with bacterial infection, and 150 (101 to 212) μg/L in 26 children with bacterial infection and coincidental virus finding (P < 0.001). In a receiver operating characteristics analysis, MxA cutoff level of 256 μg/L differentiated between children with viral and bacterial infections with an area under the curve of 0.81 (95% confidence interval [CI] = 0.73 to 0.90), a sensitivity of 74.4%, and a specificity of 80.0%. In conclusion, MxA protein showed moderate accuracy as a biomarker for symptomatic viral infections in children hospitalized with an acute infection. High prevalence of viral-bacterial coinfections supports the use of MxA in combination with biomarkers of bacterial infection. IMPORTANCE Due to the diagnostic uncertainty concerning the differentiation between viral and bacterial infections, children with viral infections are often treated with antibiotics, predisposing them to adverse effects and contributing to the emerging antibiotic resistance. Since currently available biomarkers only estimate the risk of bacterial infection, a biomarker for viral infection is needed in attempts of reducing antibiotic overuse. Blood MxA protein, which has broad antiviral activity and is rapidly induced in acute, symptomatic viral infections, is a potential biomarker for viral infection. In this diagnostic study of 265 children hospitalized because of an acute infection, blood MxA cutoff level of 256 μg/L discriminated between viral and bacterial infections with a sensitivity of 74% and specificity of 80%. MxA could improve the differential diagnostics of febrile children at the emergency department but, because of frequently detected viral-bacterial coinfections, a combination with biomarkers of bacterial infection may be needed.

Keywords

• interferon inducible protein
• myxovirus resistance protein A
• viral infection
• bacterial infection