2563. Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Meningitis and Encephalitis
Session: Oral Abstract Session: Novel Diagnostics for Fungi, Parasites, and CNS Infection
Saturday, October 6, 2018: 2:00 PM
Room: S 158

Metagenomic next-generation sequencing (mNGS) of CSF can identify nearly all pathogens in a single test. We previously validated a CSF mNGS assay in a licensed clinical laboratory. To date, the utility of mNGS for infectious disease diagnosis has been described in case reports and small case series, but not in a large-scale clinical trial.


The PDAID (“Precision Diagnosis of Acute Infectious Diseases”) study was a one-year nationwide prospective study across 8 tertiary care hospitals to evaluate the performance and utility of a clinical metagenomic sequencing assay for diagnosis of meningitis, encephalitis, or myelitis from cerebrospinal fluid (CSF) (ClinicalTrials.gov number NCT02910037). We recruited acutely ill hospitalized inpatients lacking a diagnosis at time of enrollment. CSF samples were processed and analyzed by mNGS testing within 1 week of receipt in the clinical microbiology laboratory, with sequencing results reported in the patient medical record and used to make contemporaneous treatment decisions. Weekly clinical microbial sequencing boards were convened to discuss mNGS results with treating physicians, and clinical impact evaluated by surveys, chart review, and direct clinician feedback.


204 patients were enrolled. Patients were severely ill (48% in ICU, average length of stay = 26 days, overall 30-day mortality of 7.4%). 59 neurologic infections were diagnosed in 57 patients (27.9%). mNGS identified 15 (25.4%) infections that were missed by all conventional microbiological tests, including emerging and/or uncommon pathogens such as St. Louis encephalitis virus, hepatitis E virus acquired by lung transplant, and Nocardia farcinica. 12 of the 15 mNGS-only diagnoses (80%) had clinical impact, with 9 of 15 (60%) guiding appropriate treatment. For diagnosis of infections by direct detection CSF testing, mNGS had 79.1% sensitivity and 98.8% specificity, versus 65.1% sensitivity and 99.4% specificity by conventional testing.


A significant proportion of neurologic infections are missed despite extensive diagnostic testing performed in tertiary care hospitals. Clinical metagenomic CSF testing was found to be useful in increasing the number of diagnosed neurologic infections and providing actionable information for physicians.

Michael Wilson, M.D.1, Hannah Sample, B.S.2, Kelsey Zorn, M.P.H.2, Samia N Naccache, Ph.D.3,4, Steve Miller, M.D., Ph.D.4,5 and Charles Y. Chiu, M.D., Ph.D.4,5, (1)Neurology, University of California, San Francisco, San Francisco, CA, (2)Biochemistry, University of California, San Francisco, San Francisco, CA, (3)Laboratory Medicine, University of California, San Francisco, San Francisco, CA, (4)UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, (5)Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA


M. Wilson, None

H. Sample, None

K. Zorn, None

S. N. Naccache, None

S. Miller, None

C. Y. Chiu, None

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