Evidence map›Paper›PMID 35354815›Full record

ArticleNature communications2022

Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics.

P S Ramachandran, A Ramesh, F V Creswell, A Wapniarski, R Narendra, C M Quinn, E B Tran, M K Rutakingirwa, A S Bangdiwala, E Kagimu and 21 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
18.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 79 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Metagenomic next-generation sequencing: new horizons in microbiology.Frontiers in cellular and infection microbiology · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Observational
  17. Article
  18. Article
  19. Article
  20. Tuberculosis: An Update for the Clinician.Respirology (Carlton, Vic.) · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 7 institutions in 4 countries.

P S Ramachandran *Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
A Ramesh *Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
F V CreswellClinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.ORCID 0000-0002-5070-532X
A WapniarskiWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9937-2442
R NarendraWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-1292-1336
C M QuinnUniversity of California School of Medicine, San Francisco, CA, USA.
E B TranUniversity of California School of Medicine, San Francisco, CA, USA.
M K RutakingirwaInfectious Diseases Institute, Makerere University, Kampala, Uganda.
A S BangdiwalaUniversity of Minnesota, Minneapolis, MN, USA.
E KagimuInfectious Diseases Institute, Makerere University, Kampala, Uganda.
K T KandoleInfectious Diseases Institute, Makerere University, Kampala, Uganda.
K C ZornUCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA.ORCID 0000-0003-1227-2137
L TugumeInfectious Diseases Institute, Makerere University, Kampala, Uganda.
J KasibanteInfectious Diseases Institute, Makerere University, Kampala, Uganda.
K SsebambuliddeInfectious Diseases Institute, Makerere University, Kampala, Uganda.ORCID 0000-0002-8125-0698
M OkirwothInfectious Diseases Institute, Makerere University, Kampala, Uganda.
N C BahrDivision of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.
A MusubireInfectious Diseases Institute, Makerere University, Kampala, Uganda.
C P SkipperInfectious Diseases Institute, Makerere University, Kampala, Uganda.
C FouassierWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
A LydenChan Zuckerberg Biohub, San Francisco, CA, USA.
P SerpaChan Zuckerberg Biohub, San Francisco, CA, USA.
G CastanedaChan Zuckerberg Biohub, San Francisco, CA, USA.
S CalderaChan Zuckerberg Biohub, San Francisco, CA, USA.
V AhyongChan Zuckerberg Biohub, San Francisco, CA, USA.
J L DeRisiUCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA.
C LangelierChan Zuckerberg Biohub, San Francisco, CA, USA.ORCID 0000-0002-6708-4646
E D CrawfordChan Zuckerberg Biohub, San Francisco, CA, USA.
D R BoulwareUniversity of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-4715-0060
D B MeyaInfectious Diseases Institute, Makerere University, Kampala, Uganda.
M R WilsonWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Michael.wilson@ucsf.edu.ORCID 0000-0002-8705-5084
University of California, San Francisco · USInfectious Diseases Institute · UGChan Zuckerberg Initiative (United States) · USUniversity of Minnesota · USLondon School of Hygiene & Tropical Medicine · GBThe University of Melbourne · AUUniversity of Kansas · US

Funding

NPGH LEADERs YR12: OBSSR (Greenberg, Ngwafong Mukere) & NIBIB (Lee)D43TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI Dibyadyuti Datta, Chandy C. John · 2017 to 2026
$15.2M
Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Redefining Tuberculosis Meningitis with Metagenomics and Host TransciptomicsR01AI145437 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILSON, MICHAEL R · 2019 to 2023
$3.5M
Novel Diagnostic Development for TB Meningitis and HistoplasmosisK23NS110470 · NINDS · UNIVERSITY OF MINNESOTA · PI BAHR, NATHAN · 2019 to 2023
$1.0M
Next-Generation Diagnostics for Acute EncephalitisK08NS096117 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILSON, MICHAEL R · 2017 to 2021
$999k
FIC NIH HHS D43 TW009345NIAID NIH HHS R01 AI145437NINDS NIH HHS K08 NS096117NINDS NIH HHS K23 NS110470NINDS NIH HHS R01 NS086312Wellcome TrustWellcome Trust 210772/Z/18/Z
6 · The paper itself

Abstract

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

Indexed as

MeningitisMycobacterium tuberculosisTuberculosis, MeningealCentral Nervous SystemHumansMetagenomics

Identifiers

PMID35354815
PMCPMC8967864
OpenAlexW4220683490

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.