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

Autor:	Ramachandran PS; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.; University of Melbourne, Melbourne, VIC, Australia.; UCSF Center for Tuberculosis, San Francisco, CA, USA.; UCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA., Ramesh A; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Creswell FV; Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; Medical Research Council-Uganda Virus Research Institute-LSHTM Uganda Research Unit, Entebbe, Uganda., Wapniarski A; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Narendra R; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Quinn CM; University of California School of Medicine, San Francisco, CA, USA., Tran EB; University of California School of Medicine, San Francisco, CA, USA., Rutakingirwa MK; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Bangdiwala AS; University of Minnesota, Minneapolis, MN, USA., Kagimu E; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Kandole KT; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Zorn KC; UCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA.; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA., Tugume L; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Kasibante J; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Ssebambulidde K; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Okirwoth M; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Bahr NC; Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA., Musubire A; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Skipper CP; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; University of Minnesota, Minneapolis, MN, USA., Fouassier C; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Lyden A; Chan Zuckerberg Biohub, San Francisco, CA, USA., Serpa P; Chan Zuckerberg Biohub, San Francisco, CA, USA., Castaneda G; Chan Zuckerberg Biohub, San Francisco, CA, USA., Caldera S; Chan Zuckerberg Biohub, San Francisco, CA, USA., Ahyong V; Chan Zuckerberg Biohub, San Francisco, CA, USA., DeRisi JL; UCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA.; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Langelier C; Chan Zuckerberg Biohub, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Crawford ED; Chan Zuckerberg Biohub, San Francisco, CA, USA., Boulware DR; University of Minnesota, Minneapolis, MN, USA., Meya DB; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; University of Minnesota, Minneapolis, MN, USA., Wilson MR; Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Michael.wilson@ucsf.edu.; UCSF Center for Tuberculosis, San Francisco, CA, USA. Michael.wilson@ucsf.edu.; UCSF Center for Encephalitis and Meningitis, San Francisco, CA, USA. Michael.wilson@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2022 Mar 30; Vol. 13 (1), pp. 1675. Date of Electronic Publication: 2022 Mar 30.
DOI:	10.1038/s41467-022-29353-x
Abstrakt:	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. (© 2022. The Author(s).)
Databáze:	MEDLINE
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