Metagenomic testing as a means of identifying the pathogens causing encephalitis and meningitis
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Ann Neurol. 2017 Jul;82(1):105-114. doi: 10.1002/ana.24982.
A novel cause of chronic viral meningoencephalitis: Cache Valley virus.
Wilson MR1,2, Suan D3, Duggins A4, Schubert RD1,2, Khan LM5, Sample HA5, Zorn KC5, Rodrigues Hoffman A6, Blick A6, Shingde M7, DeRisi JL5,8.
1Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA.
2Department of Neurology, University of California, San Francisco, San Francisco, CA.
3Department of Clinical Immunology and Allergy, Westmead Hospital, Westmead, New South Wales, Australia.
4Department of Neurology, Westmead Hospital, Westmead, New South Wales, Australia.
5Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA.
6Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX.
7Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales, Australia.
8Chan Zuckerberg Biohub, San Francisco, CA.
Immunodeficient patients are particularly vulnerable to neuroinvasive infections that can be challenging to diagnose. Metagenomic next generation sequencing can identify unusual or novel microbes and is therefore well suited for investigating the etiology of chronic meningoencephalitis in immunodeficient patients.
We present the case of a 34-year-old man with X-linked agammaglobulinemia from Australia suffering from 3 years of meningoencephalitis that defied an etiologic diagnosis despite extensive conventional testing, including a brain biopsy. Metagenomic next generation sequencing of his cerebrospinal fluid and brain biopsy tissue was performed to identify a causative pathogen.
Sequences aligning to multiple Cache Valley virus genes were identified via metagenomic next generation sequencing. Reverse transcription polymerase chain reaction and immunohistochemistry subsequently confirmed the presence of Cache Valley virus in the brain biopsy tissue.
Cache Valley virus, a mosquito-borne orthobunyavirus, has only been identified in 3 immunocompetent North American patients with acute neuroinvasive disease. The reported severity ranges from a self-limiting meningitis to a rapidly fatal meningoencephalitis with multiorgan failure. The virus has never been known to cause a chronic systemic or neurologic infection in humans. Cache Valley virus has also never previously been detected on the Australian continent. Our research subject traveled to North and South Carolina and Michigan in the weeks prior to the onset of his illness. This report demonstrates that metagenomic next generation sequencing allows for unbiased pathogen identification, the early detection of emerging viruses as they spread to new locales, and the discovery of novel disease phenotypes. Ann Neurol 2017;82:105-114.
© 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.