The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis
Open accessAbstract
BACKGROUND: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS: In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS: We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS: Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Metagenomic next-generation sequencing (mNGS) to detect microbial cell-free DNA (mcfDNA) in plasma is a promising approach, potentially allowing earlier detection and diagnosis of fungal infections when other blood biomarkers/tests are still negative.23”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [23]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In fact, mNGS was able to identify 16 pathogens that could not otherwise be detected by routine methods (35), attesting to its robustness and sensitivity.”
From Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay (2020) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [35]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform
Katoh, K. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf436 · Cited by 17,027
A clinical approach to diagnosis of autoimmune encephalitis
Graus, F., Titulaer, M. J., Balu, R., Benseler, S. M., Bien, C. G., Cellucci, T., Cortese, I. C. M., Dale, R. C., Gelfand, J. M., Geschwind, M. D., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00401-9 · Cited by 4,580
Self-citationThe Comprehensive Antibiotic Resistance Database
McArthur, A. G., Waglechner, N., Nizam, F., Yan, A., Azad, M. A., Baylay, A. J., Bhullar, K., Canova, M. J., Pascale, G. D., Ejim, L. J., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00419-13 · Cited by 2,287
Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer
Li, M. M., Datto, M., Duncavage, E. J., Kulkarni, S., Lindeman, N. I., Roy, S., Tsimberidou, A. M., Vnencak‐Jones, C. L., Wolff, D. J., Younes, A., et al. (2016) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.10.002 · Cited by 2,113
Granerod, J., Ambrose, H. E., Davies, N. W., Clewley, J. P., Walsh, A. L., Morgan, D., Cunningham, R., Zuckerman, M., Mutton, K. J., Solomon, T., et al. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70222-x · Cited by 1,358
Hepatitis E Virus and Chronic Hepatitis in Organ-Transplant Recipients
Kamar, N., Sèlves, J., Mansuy, J., Ouezzani, L., Péron, J., Guitard, J., Cointault, O., Esposito, L., Abravanel, F., Danjoux, M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706992 · Cited by 1,342
Estimating Maximum Likelihood Phylogenies with PhyML
Guindon, S., Delsuc, F., Dufayard, J.-F., & Gascuel, O. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-251-9_6 · Cited by 843
Simner, P. J., Miller, S., & Carroll, K. C. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/cix881 · Cited by 821
Self-citationBeyond Viruses: Clinical Profiles and Etiologies Associated with Encephalitis
Glaser, C. A., Honarmand, S., Anderson, L. J., Schnurr, D. P., Forghani, B., Cossen, C. K., Schuster, F. L., Christie, L. J., & Tureen, J. H. (2006) · Clinical Infectious Diseases · doi:10.1086/509330 · Cited by 649
Miller, S. A., Naccache, S. N., Samayoa, E., Messacar, K., Arevalo, S., Federman, S., Stryke, D., Pham, E., Fung, B., Bolosky, W. J., et al. (2019) · Genome Research · doi:10.1101/gr.238170.118 · Cited by 593
Self-citationValidation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection
Schlaberg, R., Chiu, C. Y., Miller, S., Procop, G. W., Weinstock, G., the Professional Practice Committee and Committee on Laboratory Practices of the American Society for Microbiology, & the Microbiology Resource Committee of the College of American Pathologists (2017) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2016-0539-ra · Cited by 550
Self-citationNaccache, S. N., Federman, S., Veeraraghavan, N., Zaharia, M., Lee, D., Samayoa, E., Bouquet, J., Greninger, A. L., Luk, K.-C., Enge, B., et al. (2014) · Genome Research · doi:10.1101/gr.171934.113 · Cited by 460
Self-citationGlaser, C. A., Gilliam, S., Schnurr, D. P., Forghani, B., Honarmand, S., Khetsuriani, N., Fischer, M., Cossen, C. K., & Anderson, L. J. (2003) · Clinical Infectious Diseases · doi:10.1086/367841 · Cited by 436
Goldberg, B., Sichtig, H., Geyer, C., Ledeboer, N., & Weinstock, G. M. (2015) · mBio · doi:10.1128/mbio.01888-15 · Cited by 360
Metagenomics: The Next Culture-Independent Game Changer
Forbes, J. D., Knox, N., Ronholm, J., Pagotto, F., & Reimer, A. R. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01069 · Cited by 340
Naccache, S. N., Peggs, K. S., Mattes, F. M., Phadke, R., Garson, J. A., Grant, P., Samayoa, E., Federman, S., Miller, S., Lunn, M. P., et al. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/ciu912 · Cited by 294
Self-citationHIV‐1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment
Edén, A., Fuchs, D., Hagberg, L., Nilsson, S., Spudich, S., Svennerholm, B., Price, R. W., & Gisslén, M. (2010) · The Journal of Infectious Diseases · doi:10.1086/657342 · Cited by 287
Molecular Methods for Diagnosis of Viral Encephalitis
DeBiasi, R. L., & Tyler, K. L. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.4.903-925.2004 · Cited by 274
Self-citationGeno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes
Beerenwinkel, N. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg575 · Cited by 266
Understanding the Direction of Bias in Studies of Diagnostic Test Accuracy
Kohn, M. A., Carpenter, C. R., & Newman, T. B. (2013) · Academic Emergency Medicine · doi:10.1111/acem.12255 · Cited by 247
Burden of encephalitis-associated hospitalizations in the United States, 1988-1997
Khetsuriani, N., Holman, R. C., & Anderson, L. J. (2002) · Clinical Infectious Diseases · doi:10.1086/341301 · Cited by 200
Identification of MW Polyomavirus, a Novel Polyomavirus in Human Stool
Siebrasse, E. A., Reyes, A., Lim, E. S., Zhao, G., Mkakosya, R. S., MANARY, M. J., Gordon, J. I., & Wang, D. (2012) · Journal of Virology · doi:10.1128/jvi.01210-12 · Cited by 196
Ogata, M., Fukuda, T., & Teshima, T. (2015) · Bone Marrow Transplantation · doi:10.1038/bmt.2015.76 · Cited by 122
Chiu, C. Y., Coffey, L. L., Murkey, J. A., Symmes, K., Sample, H. A., Wilson, M. R., Naccache, S. N., Arevalo, S., Somasekar, S., Federman, S., et al. (2017) · Emerging infectious diseases · doi:10.3201/eid2310.161986 · Cited by 92
Self-citationMurkey, J. A., Chew, K. W., Carlson, M., Shannon, C. L., Sirohi, D., Sample, H. A., Wilson, M. R., Vespa, P., Humphries, R. M., Miller, S. A., et al. (2017) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofx121 · Cited by 78
Self-citationIdentifying Neisseria Species by Use of the 50S Ribosomal Protein L6 ( rplF ) Gene
Bennett, J. S., Watkins, E., Jolley, K. A., Harrison, O. B., & Maiden, M. C. J. (2014) · Journal of Clinical Microbiology · doi:10.1128/jcm.03529-13 · Cited by 65
Diagnosis of Neurosyphilis in Patients Infected with Human Immunodeficiency Virus Type 1
Marra, C. M., Gary, D. W., Kuypers, J. M., & Jacobson, M. A. (1996) · The Journal of Infectious Diseases · doi:10.1093/infdis/174.1.219 · Cited by 52
Cited by
Sorted by citations
Desforges, M., Le Coupanec, A., Dubeau, P., Bourgouin, A., Lajoie, L., Dubé, M., & Talbot, P. J. (2019) · Viruses · doi:10.3390/v12010014 · Cited by 1,048
Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids
Gu, W., Deng, X., Lee, M., Sucu, Y., Arevalo, S., Stryke, D., Federman, S., Gopez, A., Reyes, K. R., Zorn, K. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1105-z · Cited by 710
Self-citationMiller, S. A., Naccache, S. N., Samayoa, E., Messacar, K., Arevalo, S., Federman, S., Stryke, D., Pham, E., Fung, B., Bolosky, W. J., et al. (2019) · Genome Research · doi:10.1101/gr.238170.118 · Cited by 593
Self-citationEvaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old
Pantell, R. H., Roberts, K. B., Adams, W. G., Dreyer, B. P., Kuppermann, N., O’Leary, S. T., Okechukwu, K., Woods, C. R., Byington, C. L., Lavelle, J. M., et al. (2021) · PEDIATRICS · doi:10.1542/peds.2021-052228 · Cited by 461
Miller, J. M., Binnicker, M. J., Campbell, S. M., Carroll, K. C., Chapin, K. C., Gonzalez, M. D., Harrington, A., Jerris, R. C., Kehl, S. C., Leal, S. M., et al. (2024) · Clinical Infectious Diseases · doi:10.1093/cid/ciae104 · Cited by 419
Metadata
- Authors
- Wilson, M. R., Sample, H. A., Zorn, K. C., Arevalo, S., Yu, G., Neuhaus, J., Federman, S., Stryke, D., Briggs, B., Langelier, C., Berger, A., Douglas, V., Josephson, S. A., Chow, F. C., Fulton, B. D., DeRisi, J. L., Gelfand, J. M., Naccache, S. N., Bender, J., Dien Bard, J., Murkey, J., Carlson, M., Vespa, P. M., Vijayan, T., Allyn, P. R., Campeau, S., Humphries, R. M., Klausner, J. D., Ganzon, C. D., Memar, F., Ocampo, N. A., Zimmermann, L. L., Cohen, S. H., Polage, C. R., DeBiasi, R. L., Haller, B., Dallas, R., Maron, G., Hayden, R., Messacar, K., Dominguez, S. R., Miller, S., & Chiu, C. Y.
- Affiliations
- University of California, San Francisco (US)
- Children's Hospital Los Angeles (US)
- From the Departments of Neurology (M.R.W., V.D., S.A.J., F.C.C., J.M.G.), Biochemistry and Biophysics (H.A.S., K.C.Z., J.L.D.), Laboratory Medicine (S.A., G.Y., S.F., D.S., B.B., B.H., S.M., C.Y.C.), and Epidemiology and Biostatistics (J.N.), the Department of Medicine, Division of Infectious Diseases (C.L., C.Y.C.), the Department of Medicine, Division of Hospital Medicine (A.B.), and Weill Institute for Neurosciences (M.R.W., V.D., S.A.J., F.C.C., J.M.G.), University of California, San Francisco ...
- University of California, Los Angeles (US)
- Children's National (US)
- San Francisco General Hospital (US)
- St. Jude Children's Research Hospital (US)
- ORCID
- Wilson, Michael R.
- Sample, Hannah A.
- Zorn, Kelsey C.
- Yu, Guixia
- Neuhaus, John
- Federman, Scot
- Briggs, Benjamin
- Langelier, Charles
- Douglas, Vanja
- Josephson, S. Andrew
- Chow, Felicia C.
- Fulton, Brent D.
- DeRisi, Joseph L.
- Gelfand, Jeffrey M.
- Naccache, Samia N.
- Bender, Jeffrey
- Murkey, Jamie
- Vijayan, Tara
- Allyn, Paul R.
- Humphries, Romney M.
- Klausner, Jeffrey D.
- Cohen, Stuart H.
- Polage, Christopher R.
- DeBiasi, Roberta L.
- Dallas, Ronald
- Hayden, Randall
- Messacar, Kevin
- Dominguez, Samuel R.
- Miller, Steve
- Chiu, Charles Y.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-06-13
- Volume
- 380
- Issue
- 24
- Pages
- 2327-2340
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6764751
- OpenAlex
- W2953017819
- Cited by
- 1,067
- References
- 27
- Citations by year
- 2026: 148 · 2025: 152 · 2024: 149 · 2023: 151 · 2022: 164 · 2021: 146 · 2020: 116 · 2019: 39
- FWCI
- 83.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS096117)
- National Heart, Lung, and Blood Institute (HL105704, U54HL119893)
- California Initiative to Advance Precision Medicine
- National Center for Advancing Translational Sciences (UL1TR000004)
- Bowes Foundation
- Charles and Helen Schwab Foundation
- Sandler Foundation
- Rachleff Family Endowment
- Chan Zuckerberg Biohub
- George and Judy Marcus Innovation Fund
- Topics
- Health Sciences › Medicine › Microbiology (medical) › 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
- metagenomic sequencing, cerebrospinal fluid, infectious meningitis, encephalitis, neuroinvasive infection, pathogen detection, clinical microbiology, telemedicine, physician feedback, pediatric patients, intensive care unit admission
- MeSH terms
- Adolescent, Adult, Cerebrospinal Fluid, Child, Child, Preschool, Encephalitis, Female, Humans, Infant, Infections, Length of Stay, Male, Meningitis, Meningoencephalitis, Middle Aged, Myelitis, Prospective Studies, Sequence Analysis, DNA, Sequence Analysis, RNA, Young Adult, Metagenomics, High-Throughput Nucleotide Sequencing, Genome, Microbial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
