Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis.
Fiona McGill, Rafal Tokarz, Emma C Thomson, Ana Filipe, Stephen Sameroff, Komal Jain, Nishit Bhuva, Shirin Ashraf, W Ian Lipkin, Caroline Corless, Chitra Pattabiraman, Barry Gibney, Michael J Griffiths, Anna Maria Geretti, Benedict D Michael, Nicholas J Beeching, David McKee, Ian J Hart, Ken Mutton, Agam Jung, Alastair Miller, Tom Solomon
Author Information
Fiona McGill: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Leeds Teaching Hospitals NHS Trust, Leeds, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. Electronic address: f.mcgill@nhs.net.
Rafal Tokarz: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA.
Emma C Thomson: Institute of infection, immunity and inflammation, University of Glasgow, Glasgow, UK.
Ana Filipe: Institute of infection, immunity and inflammation, University of Glasgow, Glasgow, UK.
Stephen Sameroff: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA.
Komal Jain: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA.
Nishit Bhuva: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA.
Shirin Ashraf: Institute of infection, immunity and inflammation, University of Glasgow, Glasgow, UK.
W Ian Lipkin: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, NY, USA.
Caroline Corless: Liverpool Specialist virology centre, Department of Infection and Immunity, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Chitra Pattabiraman: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute for Mental Health and Neurosciences, Bangalore, India.
Barry Gibney: UK Health Security Agency (previously Public Health England), UK.
Michael J Griffiths: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Alder Hey Children's NHS Foundation Trust, Liverpool, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
Anna Maria Geretti: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Faculty of Medicine, University of Rome Tor Vergata.
Benedict D Michael: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
Nicholas J Beeching: Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Liverpool School of Tropical Medicine, Liverpool, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
David McKee: Central Manchester Foundation Trust, Manchester, UK.
Ian J Hart: Liverpool Specialist virology centre, Department of Infection and Immunity, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Ken Mutton: University of Manchester, Manchester, UK.
Alastair Miller: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Tom Solomon: Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK; National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. Electronic address: tsolomon@liv.ac.uk.
OBJECTIVES: Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis. METHODS: Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing. Patients were categorised as suspected viral meningitis - CSF pleocytosis, no pathogen identified (n = 38), proven viral meningitis - CSF pleocytosis with a pathogen identified (n = 15) or not meningitis - no CSF pleocytosis (n = 20). RESULTS: VirCapSeq-VERT detected virus in the CSF of 16/38 (42%) of those with suspected viral meningitis, including twelve individual viruses. A potentially clinically relevant virus was detected in 9/16 (56%). Unexpectedly Toscana virus, rotavirus and Saffold virus were detected and assessed to be potential causative agents. CONCLUSION: VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach we identified Toscana virus and, for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time. This knowledge can help to reduce antimicrobial use and hospitalisations leading to both patient and health system benefits.
