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      Diagnosis of Neuroinvasive Astrovirus Infection in an Immunocompromised Adult With Encephalitis by Unbiased Next-Generation Sequencing

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          Abstract

          Metagenomic next-generation sequencing (NGS) was used to diagnose an unusual and fatal case of progressive encephalitis in an immunocompromised adult presenting at disease onset as bilateral hearing loss. The sequencing and confirmatory studies revealed neuroinvasive infection of the brain by an astrovirus belonging to a recently discovered VA/HMO clade.

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          Most cited references13

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          Actionable diagnosis of neuroleptospirosis by next-generation sequencing.

          A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.
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            Multiple novel astrovirus species in human stool.

            Diarrhoea remains a significant cause of morbidity and mortality in developing countries where numerous cases remain without identified aetiology. Astroviruses are a recently identified cause of animal gastroenteritis which currently includes two species suspected of causing human diarrhoea. Using pan-astrovirus RT-PCR, we analysed human stool samples from different continents for astrovirus-related RNA sequences. We identified variants of the two known human astrovirus species plus, based on genetic distance criteria, three novel astrovirus species all distantly related to mink and ovine astroviruses, which we provisionally named HMOAstV species A-C. The complete genome of species A displayed all the conserved characteristics of mammalian astroviruses. Each of the now three groups of astroviruses found in human stool (HAstV, AstV-MLB and HMOAstV) were more closely related to animal astroviruses than to each other, indicating that human astroviruses may periodically emerge from zoonotic transmissions. Based on the pathogenic impact of their closest phylogenetic relatives in animals, further investigations of the role of HMOAstV, so far detected in Nigeria, Nepal and Pakistan, in human gastroenteritis are warranted.
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              Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis.

              The etiology of a large proportion of gastrointestinal illness is unknown. In this study, random Sanger sequencing and pyrosequencing approaches were used to analyze fecal specimens from a gastroenteritis outbreak of unknown etiology in a child care center. Multiple sequences with limited identity to known astroviruses were identified. Assembly of the sequences and subsequent reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends generated a complete genome of 6,586 nucleotides. Phylogenetic analysis demonstrated that this virus, named astrovirus VA1 (AstV-VA1), is highly divergent from all previously described astroviruses. Based on RT-PCR, specimens from multiple patients in this outbreak were unequivocally positive for Ast-VA1.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                15 March 2015
                07 January 2015
                07 January 2015
                : 60
                : 6
                : 919-923
                Affiliations
                [1 ]Departmentof Laboratory Medicine, University of California, San Francisco
                [2 ]UCSF-Abbott Viral Diagnostics and Discovery Center , San Francisco, California
                [3 ]Departments of Clinical Hematology
                [4 ]Clinical Microbiology
                [5 ]Neuropathology
                [6 ]Neurology, University College London Hospitals NHS Foundation Trust
                [7 ]Research Department of Infection, Division of Infection and Immunity, University College London , United Kingdom
                [8 ]Department of Medicine, Division of Infectious Diseases, University of California , San Francisco
                Author notes
                Correspondence: Charles Y. Chiu, MD, PhD, Department of Laboratory Medicine, University of California, San Francisco, 185 Berry St, Box 0134, San Francisco, CA 94107 ( charles.chiu@ 123456ucsf.edu ).
                Article
                ciu912
                10.1093/cid/ciu912
                4345816
                25572898
                3d1f023c-306f-4035-bdeb-ea7157f6b849
                © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

                History
                : 17 July 2014
                : 15 September 2014
                Categories
                Brief Reports

                Infectious disease & Microbiology
                va/hmo astrovirus clade,encephalitis,deafness,next-generation sequencing,pathogen discovery

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