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.

Capturing diverse microbial sequence with comprehensive and scalable probe design

“…We show that capture with probe sets designed by CATCH improved viral genome detection and recovery, across a range of sample source materials, while accurately preserving sample complexity of the targets. Probe sets we present here have also helped us to assemble genomes of low titer viruses in other patient samples: V ZC for suspected ZIKV cases 7 and V ALL for improving rapid detection of Powassan virus in a clinical case 52 .…”

Tick-Borne Flaviviruses, with a Focus on Powassan Virus

“…Headache and fever up to a temperature of 38.5°C to 41°C are reported by all patients (4,145,157). A fine erythematous morbilliform rash was observed in some cases (138,(223)(224)(225). The prodrome phase lasts approximately 1 to 3 days and precedes CNS manifestations.…”

“…This approach has led to the discovery of numerous novel viruses but has limited value in clinical settings due to the low sensitivity. This low sensitivity was recently demonstrated for a patient with encephalitis of an unknown etiology, whose CSF sample, collected during the acute phase, was found to contain only 10 POWV (lineage II)-specific sequence reads out of 2.4 million total sequence reads generated for the sample (225). Targeted enrichment of possible viral targets by using a mixture of virus-specific capture oligonucleotides has been demonstrated to increase the sensitivity of NGS-based detection of numerous medically important viruses from clinical specimens (255).…”

Powassan virus, a scoping review of the global evidence

“…The immunoassays used in these studies varied over time from haemagglutination inhibition assays, complement fixation, plaque reduction neutralization tests to IgM and IgG enzyme‐linked immunosorbent assays (ELISA). More recently there has been an example of rapid metagenomics sequencing which enabled the identification of POWV approximately 4 weeks earlier than by standard serological testing (Piantadosi et al., ).…”

“…Potential risk factors for humans infected with POWV were reported in 22 studies and included exposure to tick bites (11/22) (Cavanaugh et al., ; El Khoury, Camargo, White, et al., ; Granger, Lopansri, Butcher, Wong, & Tavakoli, ; Johnson, Staples, Sotir, Warshauer, & Davis, ; Piantadosi et al., , ; Raval, Singhal, Guerrero, & Alonto, ; Rossier, Harrison, & Lemieux, ; Smith et al., ; Trépanier, Loungnarath, Gourdeau, Claessens, & Savard, ; Tutolo, Staples, Sosa, & Bennett, ); residing, vacationing, or frequenting wooded areas (12/22) (Ananthan, Shah, Haseer‐Koya, & Patel, ; Choi & Taylor, ; Courtney et al., ; El Khoury, Camargo, White, et al., ; Fitch & Artsob, ; Goldfield, Austin, Black, Taylor, & Altman, ; Harrison, Rossier, & Lemieux, ; Hinten et al., ; Johnson et al., ; Piantadosi et al., , ; Rossier et al., ); owning or being bitten by a cat or dog with POWV antibodies (2/22) (Mahdy, Bansen, & McLaughlin, ; Wilson, Wherrett, & Mahdy, ); owning a cat infested with ticks (1/22) (Mahdy, Wilson, Wherrett, & Dorland, ); having close contact with a dog that frequently chased forest rodents (1/22) (Joshua, ); working in basements with uncertain rodents and bat exposures (1/22) (Piantadosi et al., ); and handling a recently deceased woodchuck (1/22) (Embil, Camfield, Artsob, & Chase, ).…”