1. A metagenomics-based diagnostic approach for central nervous system infections in hospital acute care setting
- Author
-
Patrick Tang, Kin Ming Tsui, Sathyavathi Sundararaju, Rusung Tan, Andres Perez Lopez, Mohammad Rubayet Hasan, Peter Tilley, and Mohammad Janahi
- Subjects
Male ,0301 basic medicine ,Hospital setting ,Cns infections ,lcsh:Medicine ,Datasets as Topic ,Central Nervous System Infections ,Acute care ,lcsh:Science ,Child ,Cerebrospinal Fluid ,Multidisciplinary ,High-Throughput Nucleotide Sequencing ,Hospitals ,medicine.anatomical_structure ,Child, Preschool ,Female ,Meningitis ,Encephalitis ,DNA, Bacterial ,medicine.medical_specialty ,Adolescent ,030106 microbiology ,Central nervous system ,Sensitivity and Specificity ,Article ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Clinical microbiology ,Retrospective Studies ,business.industry ,lcsh:R ,Infant, Newborn ,Laboratory techniques and procedures ,Computational Biology ,Infant ,Sequence Analysis, DNA ,medicine.disease ,030104 developmental biology ,Metagenomics ,DNA, Viral ,Etiology ,Feasibility Studies ,Metagenome ,lcsh:Q ,business - Abstract
The etiology of central nervous system (CNS) infections such as meningitis and encephalitis remains unknown in a large proportion of cases partly because the diversity of pathogens that may cause CNS infections greatly outnumber available test methods. We developed a metagenomic next generation sequencing (mNGS)-based approach for broad-range detection of pathogens associated with CNS infections suitable for application in the acute care hospital setting. The analytical sensitivity of mNGS performed on an Illumina MiSeq was assessed using simulated cerebrospinal fluid (CSF) specimens (n = 9). mNGS data were then used as a training dataset to optimize a bioinformatics workflow based on the IDseq pipeline. For clinical validation, residual CSF specimens (n = 74) from patients with suspected CNS infections previously tested by culture and/or PCR, were analyzed by mNGS. In simulated specimens, the NGS reads aligned to pathogen genomes in IDseq were correlated to qPCR CT values for the respective pathogens (R = 0.96; p
- Published
- 2020