The use of metagenomics to enhance diagnosis of encephalitis.

Introduction: Encephalitis has a broad etiology, including infectious and auto-immune causes. In infectious encephalitis, the breadth of causative organisms results in incomplete testing and low diagnostic yields.Metagenomics sequences all DNA and RNA allowing untargeted detection of all organisms in a single specimen; this is of particular use in diagnosis of encephalitis with a broad etiology.

Areas covered: We review the literature and discuss metagenomics workflows, host depletion and pathogen enrichment methods, bioinformatics analysis and potential analysis of the host transcriptome to aid diagnosis. We discuss the clinical use of metagenomics for diagnosis of neurological infection including time to result, cost, quality assurance, patient cohorts in whom metagenomics adds the most value, recommended specimen types, limitations and review published cases in which metagenomics has been used to diagnose encephalitis.

Expert opinion: There is good evidence for the utility of metagenomics to diagnose infection in encephalitis. Due to infections with rare, unexpected or novel pathogens, metagenomics adds most value to diagnosis in immunocompromised patients and the greatest diagnostic yield is in brain biopsies. Technical advances are needed to reduce the complexity, cost and time to result which will enable wider adoption in clinical laboratories and use as a first-line test.