Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System Infections: A Multicentre Cohort Study

Abstract Background: Infectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen, even if comprehensive conventional diagnostic technologies are applied. 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 in China, where routine PCR was not widely used. Results: A total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an aetiologic 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 leading positive detections were Mycobacterium tuberculosis (14), Listeria monocytogenes (8), Brucella (7), varicella-zoster virus (17), 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: This study shows that mNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections. The result of mNGS should be interpreted with clinical information sometimes.