A metagenomics-based diagnostic approach for central nervous system infections in hospital acute care setting
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Abstract
Abstract The etiology of central nervous system (CNS) infections such as meningitis and encephalitis remains unknown in a large proportion of cases partly because the diversity of pathogens that may cause CNS infections greatly outnumber available test methods. Here we present a metagenomic next generation sequencing (mNGS) based approach for broad-range detection of pathogens associated with CNS infections, which is suitable for application in the acute care hospital setting. Using an Illumina MiSeq benchtop sequencer and the IDseq pipeline for identifying pathogens in metagenomic sequence data, we show that the analytical sensitivity of mNGS to detect pathogens is comparable to that of PCR in simulated cerebrospinal fluid (CSF) specimens. We then applied this method for pathogen detection in 74 CSF specimens from patients with suspected CNS infections that were previously tested by culture and/or PCR. Diagnostic accuracy, sensitivity and specificity of mNGS approach with reference to conventional methods were all 95%. Furthermore, confirmatory testing on specimens that gave discrepant results were mostly in favor of the mNGS assay. The clinical application of mNGS holds promise to benefit patients with CNS infections of unknown etiology.
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mNGS has been shown to detect more neuroinvasive viruses accurately.
“A new emerging technique that might be very broad yet highly accurate at detection is the mNGS, which has been shown to detect more neuroinvasive viruses accurately (32, 35).”
From Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay (2020) · cites this paper as [32]
The Results (Clinical validation of mNGS for pathogen detection in CSF; page unavailable) report that mNGS detected pathogens in CSF, but the additional pathogens identified beyond conventional methods were not viruses. The same section says a low-level HSV2 finding could not be verified. The Discussion notes that this DNA-specific method did not detect RNA viruses, so the paper does not establish that it accurately detects more neuroinvasive viruses. (LLM, conf=0.86)
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References 29 · Cited by 37
Research works printed but not linked: 3
- [3]Tunkel AR Beek D Scheld WM Bennett JE Dolin R Blaser MJ Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases 2015 Amsterdam Elsevier Inc. 1097 1137
- [4]Bennett JE Bennett JE Dolin R Blaser MJ Mandell, Douglas, and Bennet’s Principles and Practice of Infectious Diseases 2015 Philadelphia Elsevier 1138 1143
- [5]Beckham JT Tyler KL Bennett JE Dolin R Blaser MJ Mandell, Douglas, and Bennet’s Principles and Practice of Infectious Diseases 2015 Philadelphia Elsevier 1144 1163
- Authors
- Hasan, M. R., Sundararaju, S., Tang, P., Tsui, K.-M., Lopez, A. P., Janahi, M., Tan, R., & Tilley, P.
- Affiliations
- Sidra Medical and Research Center (QA)
- Weill Cornell Medical College in Qatar (QA)
- University of British Columbia (CA)
- Corresponding author
- Hasan, Mohammad Rubayet
- Venue
- Scientific Reports
- Published
- 2020-07-08
- Volume
- 10
- Issue
- 1
- Pages
- 11194-11194
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7343800
- OpenAlex
- W3041603820
- Cited by
- 37
- References
- 29
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 3
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- BC Children's Hospital Foundation (British Columbia Children's Hospital Foundation (KRZ28061)
- Sidra Internal Research Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- central nervous system infection, meningitis, encephalitis, metagenomic next-generation sequencing, cerebrospinal fluid, pathogen detection, diagnostic accuracy
- MeSH terms
- Adolescent, Central Nervous System Infections, Cerebrospinal Fluid, Child, Child, Preschool, DNA, Bacterial, DNA, Viral, Feasibility Studies, Female, Hospitals, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Sensitivity and Specificity, Sequence Analysis, DNA, Computational Biology, Metagenome, Young Adult, Metagenomics, High-Throughput Nucleotide Sequencing, Datasets as Topic
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