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Nat Med. 2019 Nov;25(11):1748-1752. doi: 10.1038/s41591-019-0613-1. Epub 2019 Oct 21.

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Author information

1
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
3
Chan Zuckerberg Biohub, San Francisco, CA, USA.
4
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
5
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
6
School of Medicine, University of California, San Francisc, San Francisco, CA, USA.
7
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
8
Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
9
Division of Neurology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
10
Department of Laboratory Medicine and Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA.
11
Department of Pediatrics, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA.
12
Department of Pediatric Infectious Diseases, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA.
13
Division of Communicable Disease Control, California Department of Public Health, Richmond, CA, USA.
14
Children's Hospital Colorado and Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
15
Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
16
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
17
Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
18
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. michael.wilson@ucsf.edu.
19
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. michael.wilson@ucsf.edu.

Abstract

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.

PMID:
31636453
DOI:
10.1038/s41591-019-0613-1

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