Performance of Metagenomic Next-Generation Sequencing for the Diagnosis of Viral Meningoencephalitis in a Resource-Limited Setting.
MinION
meningoencephalitis
metagenomics
nanopore
next-generation sequencing
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
13
12
2019
accepted:
06
02
2020
entrez:
12
3
2020
pubmed:
12
3
2020
medline:
12
3
2020
Statut:
epublish
Résumé
Meningoencephalitis is a devastating disease worldwide. Current diagnosis fails to establish the cause in ≥50% of patients. Metagenomic next-generation sequencing (mNGS) has emerged as pan-pathogen assays for infectious diseases diagnosis, but few studies have been conducted in resource-limited settings. We assessed the performance of mNGS in the cerebrospinal fluid (CSF) of 66 consecutively treated adults with meningoencephalitis in a tertiary referral hospital for infectious diseases in Vietnam, a resource-limited setting. All mNGS results were confirmed by viral-specific polymerase chain reaction (PCR). As a complementary analysis, 6 viral PCR-positive samples were analyzed using MinION-based metagenomics. Routine diagnosis could identify a virus in 15 (22.7%) patients, including herpes simplex virus (HSV; n = 7) and varicella zoster virus (VZV; n = 1) by PCR, and mumps virus (n = 4), dengue virus (DENV; n = 2), and Japanese encephalitis virus (JEV; n = 1) by serological diagnosis. mNGS detected HSV, VZV, and mumps virus in 5/7, 1/1, and 1/4 of the CSF positive by routine assays, respectively, but it detected DENV and JEV in none of the positive CSF. Additionally, mNGS detected enteroviruses in 7 patients of unknown cause. Metagenomic MinION-Nanopore sequencing could detect a virus in 5/6 PCR-positive CSF samples, including HSV in 1 CSF sample that was negative by mNGS, suggesting that the sensitivity of MinION is comparable with that of mNGS/PCR. In a single assay, metagenomics could accurately detect a wide spectrum of neurotropic viruses in the CSF of meningoencephalitis patients. Further studies are needed to determine the value that real-time sequencing may contribute to the diagnosis and management of meningoencephalitis patients, especially in resource-limited settings where pathogen-specific assays are limited in number.
Sections du résumé
BACKGROUND
BACKGROUND
Meningoencephalitis is a devastating disease worldwide. Current diagnosis fails to establish the cause in ≥50% of patients. Metagenomic next-generation sequencing (mNGS) has emerged as pan-pathogen assays for infectious diseases diagnosis, but few studies have been conducted in resource-limited settings.
METHODS
METHODS
We assessed the performance of mNGS in the cerebrospinal fluid (CSF) of 66 consecutively treated adults with meningoencephalitis in a tertiary referral hospital for infectious diseases in Vietnam, a resource-limited setting. All mNGS results were confirmed by viral-specific polymerase chain reaction (PCR). As a complementary analysis, 6 viral PCR-positive samples were analyzed using MinION-based metagenomics.
RESULTS
RESULTS
Routine diagnosis could identify a virus in 15 (22.7%) patients, including herpes simplex virus (HSV; n = 7) and varicella zoster virus (VZV; n = 1) by PCR, and mumps virus (n = 4), dengue virus (DENV; n = 2), and Japanese encephalitis virus (JEV; n = 1) by serological diagnosis. mNGS detected HSV, VZV, and mumps virus in 5/7, 1/1, and 1/4 of the CSF positive by routine assays, respectively, but it detected DENV and JEV in none of the positive CSF. Additionally, mNGS detected enteroviruses in 7 patients of unknown cause. Metagenomic MinION-Nanopore sequencing could detect a virus in 5/6 PCR-positive CSF samples, including HSV in 1 CSF sample that was negative by mNGS, suggesting that the sensitivity of MinION is comparable with that of mNGS/PCR.
CONCLUSIONS
CONCLUSIONS
In a single assay, metagenomics could accurately detect a wide spectrum of neurotropic viruses in the CSF of meningoencephalitis patients. Further studies are needed to determine the value that real-time sequencing may contribute to the diagnosis and management of meningoencephalitis patients, especially in resource-limited settings where pathogen-specific assays are limited in number.
Identifiants
pubmed: 32158774
doi: 10.1093/ofid/ofaa046
pii: ofaa046
pmc: PMC7051036
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofaa046Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204904/Z/16/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Références
Genome Res. 2019 May;29(5):831-842
pubmed: 30992304
Genome Biol. 2016 May 26;17(1):111
pubmed: 27224977
J Infect. 2018 Mar;76(3):225-240
pubmed: 29305150
Nucleic Acids Res. 2005 Apr 07;33(6):e65
pubmed: 15817564
Clin Microbiol Infect. 2019 Oct;25(10):1277-1285
pubmed: 31059795
Open Forum Infect Dis. 2017 Sep 27;4(4):ofx203
pubmed: 29226169
Nucleic Acids Res. 2015 Apr 20;43(7):e46
pubmed: 25586223
Nat Methods. 2015 Jan;12(1):59-60
pubmed: 25402007
J Neurol Sci. 2017 Feb 15;373:250-253
pubmed: 28131199
Lancet. 1999 Oct 9;354(9186):1253-6
pubmed: 10520634
J Virol Methods. 2013 Jan;187(1):138-43
pubmed: 23046990
mBio. 2013 Jun 18;4(3):e00231-13
pubmed: 23781068
Lancet. 2018 Nov 10;392(10159):1736-1788
pubmed: 30496103
Clin Infect Dis. 2006 Dec 15;43(12):1565-77
pubmed: 17109290
mSystems. 2016 Jul 19;1(4):
pubmed: 27822544
Clin Infect Dis. 2003 Mar 15;36(6):731-42
pubmed: 12627357
N Engl J Med. 2019 Jun 13;380(24):2327-2340
pubmed: 31189036
J Infect. 2018 Dec;77(6):509-515
pubmed: 30217659
Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10264-9
pubmed: 23716702
N Engl J Med. 2019 Oct 10;381(15):1444-1457
pubmed: 31597021
J Virol Methods. 2015 Mar;213:139-46
pubmed: 25497414
Open Forum Infect Dis. 2017 Mar 04;4(2):ofx046
pubmed: 28480297
Virol J. 2015 Jun 09;12:85
pubmed: 26050791
Lancet Neurol. 2010 Nov;9(11):1097-105
pubmed: 20965438
PLoS Negl Trop Dis. 2019 Aug 29;13(8):e0007469
pubmed: 31465452
J Med Virol. 2005 Mar;75(3):470-4
pubmed: 15648065
Genome Med. 2015 Sep 29;7:99
pubmed: 26416663
Nat Rev Genet. 2019 Jun;20(6):341-355
pubmed: 30918369
J Clin Microbiol. 2019 Aug 26;57(9):
pubmed: 31217274
Virol J. 2016 Jul 07;13:125
pubmed: 27388326
J Hum Genet. 2020 Jan;65(1):35-40
pubmed: 31582773
PLoS Negl Trop Dis. 2014 Aug 28;8(8):e3127
pubmed: 25165820
Lancet Infect Dis. 2010 Dec;10(12):835-44
pubmed: 20952256