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, K. T. Kandole, K. C. Zorn, L. Tugume, J. Kasibante, K. Ssebambulidde, M. Okirwoth, N. C. Bahr, A. Musubire, C. P. Skipper, C. Fouassier, A. Lyden, P. Serpa, G. Castaneda, S. Caldera, V. Ahyong, J. L. DeRisi, C. Langelier, E. D. Crawford, D. R. Boulware, D. B. Meya and M. R. Wilson ()
Additional contact information
P. S. Ramachandran: University of California, San Francisco
A. Ramesh: University of California, San Francisco
F. V. Creswell: London School of Hygiene and Tropical Medicine
A. Wapniarski: University of California, San Francisco
R. Narendra: University of California, San Francisco
C. M. Quinn: University of California School of Medicine
E. B. Tran: University of California School of Medicine
M. K. Rutakingirwa: Infectious Diseases Institute, Makerere University
A. S. Bangdiwala: University of Minnesota
E. Kagimu: Infectious Diseases Institute, Makerere University
K. T. Kandole: Infectious Diseases Institute, Makerere University
K. C. Zorn: UCSF Center for Encephalitis and Meningitis
L. Tugume: Infectious Diseases Institute, Makerere University
J. Kasibante: Infectious Diseases Institute, Makerere University
K. Ssebambulidde: Infectious Diseases Institute, Makerere University
M. Okirwoth: Infectious Diseases Institute, Makerere University
N. C. Bahr: University of Kansas
A. Musubire: Infectious Diseases Institute, Makerere University
C. P. Skipper: Infectious Diseases Institute, Makerere University
C. Fouassier: University of California, San Francisco
A. Lyden: Chan Zuckerberg Biohub
P. Serpa: Chan Zuckerberg Biohub
G. Castaneda: Chan Zuckerberg Biohub
S. Caldera: Chan Zuckerberg Biohub
V. Ahyong: Chan Zuckerberg Biohub
J. L. DeRisi: UCSF Center for Encephalitis and Meningitis
C. Langelier: Chan Zuckerberg Biohub
E. D. Crawford: Chan Zuckerberg Biohub
D. R. Boulware: University of Minnesota
D. B. Meya: Infectious Diseases Institute, Makerere University
M. R. Wilson: University of California, San Francisco

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29353-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29353-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29353-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().