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Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

Brown, JR; Bharucha, T; Breuer, J; (2018) Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases. Journal of Infection , 76 (3) pp. 225-240. 10.1016/j.jinf.2017.12.014. Green open access

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Abstract

BACKGROUND: Current estimates suggest that even in the most resourced settings, the aetiology of encephalitis is identified in less than half of clinical cases. It is acknowledged that filling this gap needs a combination of rigorous sampling and improved diagnostic technologies. Next generation sequencing (NGS) methods are powerful tools with the potential for comprehensive and unbiased detection of pathogens in clinical samples. We reviewed the use of this new technology for the diagnosis of suspected infectious encephalitis, and discuss the feasibility for introduction of NGS methods as a frontline diagnostic test. METHODS: A systematic literature review was performed, using MESH and text word searches for variants of "sequencing" and "encephalitis" in Medline and EMbase, and searching bibliographies and citations using the Web of Science database. Two authors independently reviewed, extracted and summarised data. FINDINGS: The review identified 25 articles reporting 44 case reports of patients with suspected encephalitis for whom NGS was used as a diagnostic tool. We present the data and highlight themes arising from these cases. There are no randomly controlled trials to assess the utility of NGS as a diagnostic tool. INTERPRETATION: There is increasing evidence of a role for NGS in the work-up of undiagnosed encephalitis. Lower costs and increasing accessibility of these technologies will facilitate larger studies of these patients. We recommend NGS should be considered as a front-line diagnostic test in chronic and recurring presentations and, given current sample-to-result turn-around times, as second-line in acute cases of encephalitis.

Type: Article
Title: Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jinf.2017.12.014
Publisher version: http://dx.doi.org/10.1016/j.jinf.2017.12.014
Language: English
Additional information: © 2018 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Deep sequencing, Diagnosis, Encephalitis, Infection, Metagenomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10043338
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