Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings
4 affiliations
- 1Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
- 2Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- 3Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
- 4Bioinformatics and Data Centre, University of Gothenburg, Gothenburg, Sweden
Abstract
The primary aim of this study was to determine whether metagenomic next-generation sequencing (mNGS) can identify potential microbial agents responsible for encephalitis of unknown origin in immunocompetent patients, thereby enhancing clinical diagnostics. Cerebrospinal fluid samples from well-characterized patients (n = 17) diagnosed with encephalitis of unknown origin, according to Swedish national guidelines, were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections i.e. HSV-2 meningitis (n = 4), VZV CNS infections (n = 3), enterovirus meningitis (n = 2), JCV CNS infection (n = 2) were used as controls for the methodology (n = 11). No viral agents were detected in 16/17 CSF samples from patients with encephalitis of unknown etiology. 13/17 CSF samples were analysed for the most common autoimmune antibodies and were negative. In one CSF sample from patients with encephalitis of unknown origin a Human pegivirus (HPgV) was detected. In 9/11 control CSF samples from patients with CNS infections, RNA or DNA of the known virus were detected. The main conclusion in this study was that the negative results were related to that the majority of included patients were immunocompetent. The finding of HPgV in a patient with unknown encephalitis was judged as a bystander. However, mNGS might detect more pathogens in other patient cohorts and this study implicates that a close collaboration between the clinical laboratory and the clinicians enables a safe implementation of metagenomics.
Related
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- Plasma and Serum Metagenomic Sequencing of Microbial Cell-Free Nucleic Acids for Suspected Central Nervous System Infection: A Systematic Review
BibTeX
@article{stentoft2026metagenomic,
title = {{Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings}},
author = {Erika Stentoft and Josefin Olausson and Emilio Rudbeck and Marie Studahl and Hedvig E. Jakobsson},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358189},
url = {https://doi.org/10.1371/journal.pone.0358189},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings
AU - Erika Stentoft
AU - Josefin Olausson
AU - Emilio Rudbeck
AU - Marie Studahl
AU - Hedvig E. Jakobsson
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0358189
UR - https://doi.org/10.1371/journal.pone.0358189
AB - The primary aim of this study was to determine whether metagenomic next-generation sequencing (mNGS) can identify potential microbial agents responsible for encephalitis of unknown origin in immunocompetent patients, thereby enhancing clinical diagnostics. Cerebrospinal fluid samples from well-characterized patients (n = 17) diagnosed with encephalitis of unknown origin, according to Swedish national guidelines, were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections i.e. HSV-2 meningitis (n = 4), VZV CNS infections (n = 3), enterovirus meningitis (n = 2), JCV CNS infection (n = 2) were used as controls for the methodology (n = 11). No viral agents were detected in 16/17 CSF samples from patients with encephalitis of unknown etiology. 13/17 CSF samples were analysed for the most common autoimmune antibodies and were negative. In one CSF sample from patients with encephalitis of unknown origin a Human pegivirus (HPgV) was detected. In 9/11 control CSF samples from patients with CNS infections, RNA or DNA of the known virus were detected. The main conclusion in this study was that the negative results were related to that the majority of included patients were immunocompetent. The finding of HPgV in a patient with unknown encephalitis was judged as a bystander. However, mNGS might detect more pathogens in other patient cohorts and this study implicates that a close collaboration between the clinical laboratory and the clinicians enables a safe implementation of metagenomics.
SN - 1932-6203
ER -