Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections

基因组 DNA测序 计算生物学 生物 中枢神经系统 医学 生物信息学 遗传学 神经科学 基因
作者
Patrick Benoit,Noah Brazer,Mikaël de Lorenzi-Tognon,Emily Kelly,Venice Servellita,Miriam Oseguera,Jenny Nguyen,Jack Tang,Charles Omura,Jessica Streithorst,Melissa Hillberg,Danielle Ingebrigtsen,Kelsey C. Zorn,Michael R. Wilson,Timothy M. Blicharz,Amy P. Wong,Brian D. O’Donovan,Brad Murray,Steve Miller,Charles Y. Chiu
出处
期刊:Nature Medicine [Nature Portfolio]
标识
DOI:10.1038/s41591-024-03275-1
摘要

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection.

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