TY - JOUR T1 - Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System Infections: A Multicentre Prospective Study JF - bioRxiv DO - 10.1101/658047 SP - 658047 AU - Siyuan Fan AU - Xiaojuan Wang AU - Yafang Hu AU - Jingping Shi AU - Yueli Zou AU - Weili Zhao AU - Xiaodong Qiao AU - Chunjuan Wang AU - Jerome H. Chin AU - Lei Liu AU - Lingzhi Qin AU - Shengnan Wang AU - Hongfang Li AU - Wei Yue AU - Weihe Zhang AU - Xiaohua Li AU - Ying Ge AU - Honglong Wu AU - Weijun Chen AU - Yongjun Li AU - Tianjia Guan AU - Shiying Li AU - Yihan Wu AU - Gaoya Zhou AU - Zheng Liu AU - Yushun Piao AU - Jianzhao Zhang AU - Changhong Ren AU - Li Cui AU - Caiyun Liu AU - Haitao Ren AU - Yanhuan Zhao AU - Shuo Feng AU - Haishan Jiang AU - Jiawei Wang AU - Hui Bu AU - Shougang Guo AU - Bin Peng AU - Liying Cui AU - Wei Li AU - Hongzhi Guan Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/10/658047.abstract N2 - Background Infectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen. Metagenomic next-generation sequencing (mNGS) is a high throughput technology that enables the detection of pathogens independent of prior clinical or laboratory information.Methods The present study was a multicentre prospective evaluation of mNGS of cerebrospinal fluid (CSF) for the diagnosis of suspected central nervous system infections.Results A total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an etiologic pathogen in CSF by mNGS was achieved in 101 patients (36.6%). mNGS detected 11 bacterial species, 7 viral species, 2 fungal species, and 2 parasitic species. The five leading positive detections were varicella-zoster virus (17), Mycobacterium tuberculosis (14), herpes simplex virus 1 (12), Epstein-Barr virus (12), and Cryptococcus neoformans (7). False positives occurred in 12 (4.3%) patients with bacterial infections known to be widespread in hospital environments. False negatives occurred in 16 (5.8%) patients and included bacterial, viral and fungal aetiologies.Conclusions mNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections.mNGSmetagenomic next-generation sequencingCSFcerebrospinal fluidCNScentral nervous systemPCRpolymerase chain reactionHSVherpes simplex virusVZVvaricella zoster virusNTC‘no-template’ controlsRPMreads per millionEBVEpstein-Barr virusCMVcytomegalovirusSSRNspecies-specific read number ER -