Rapid Detection of Powassan Virus in a Patient With Encephalitis by Metagenomic Sequencing

Abstract

We describe a patient with severe and progressive encephalitis of unknown etiology. We performed rapid metagenomic sequencing from cerebrospinal fluid and identified Powassan virus, an emerging tick-borne flavivirus that has been increasingly detected in the United States.

Figure 1.

Clinical data and genome sequencing data. A, Timeline of diagnostic testing, imaging, and procedures. For diagnostic tests, each bar indicates the time between specimen collection and receipt of results. B, Brain imaging and brain biopsy findings. Axial brain MRI images from hospital day 1 show focal T₂-weighted/fluid-attenuated inversion recovery hyperintensities of the bilateral thalamus (panel I, arrowheads) and cortex (panel I, asterisk) and confluent hyperintensities of the cerebellum (panel II, arrowheads). Hematoxylin and eosin staining of a right posterior fossa biopsy performed on hospital day 11 shows extensive lymphocytic infiltration and thickening of dura and diffuse inflammation of the cerebellum (panel III). CD3 staining of the cerebellum reveals a predominantly T-cell lymphocytic infiltrate in the granule cell and molecular layers (panel IV). Scale bar = 100 um. C, Phylogenetic tree of Powassan virus genomes. The partial Powassan virus genomes identified in this study are labeled in pink. These sequences cluster together and with other Powassan virus lineage II genomes isolated from Ixodes ticks in the Northeast United States. A separate cluster of Powassan virus lineage II genomes isolates from Ixodes ticks in the Midwest United States is also demonstrated, and all lineage II branches are labeled in purple. Powassan virus lineage I genomes are included for reference (labeled in blue). Branches are labeled with the location, date, source, and GenBank ID of each Powassan virus genome. Nodes with at least 80% bootstrap support are labeled with percentage of bootstrap support. Ixodes dammini has been renamed Ixodes scapularis. Abbreviations: CRAG, cryptococcal antigen; CSF, cerebrospinal fluid; EBV, Epstein-Barr virus; EEE, Eastern equine encephalitis virus; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; LCMV, lymphocytic choriomeningitis virus; LP, lumbar puncture; MRI, magnetic resonance imaging; PMN, polymorphonuclear leukocyte; RMSF, Rocky Mountain spotted fever; SLE, Saint Louis encephalitis virus; CT, computed tomography; VDRL, Venereal Disease Research Laboratory; VZV, varicella-zoster virus; WNV, West Nile virus.