Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study

Abstract

ObjectiveDiscriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses. MethodsChildren with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls. ResultsMxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 μg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78–99%) sensitivity and 100% (95% CI: 51–100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 μg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 μg/l, interquartile range: 679 to 2489). DiscussionMxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.