Pathogen profiles in CSF from patients with acute infectious meningitis or encephalitis: a multicenter study based on multiplex PCR and mNGS in China, 2018–2019

Acute meningitis or encephalitis (AME) is mainly caused by viral and bacterial infections, leading to severe sequelae and even death. However, there is limited systematic research on the spectrum of pathogens causing AME in China. Here, cerebrospinal fluid (CSF) samples from 229 acute meningitis or encephalitis patients (AMEP) excluding Japanese encephalitis virus infections collected from multicenter of China between 2018 and 2019 were analyzed. The pathogen profile was comprehensively characterized using both 43-pathogens multiplex PCR (MPCR) and metagenomic next-generation sequencing (mNGS). MPCR revealed that 73 (31.88%) cases had at least one potential pathogen. mNGS were conducted on 22 randomly selected AMEPs, and the results showed that mNGS reported all the pathogens detected by MPCR. Interestingly, mNGS successfully identified multiple pathogens in cases that were undiagnosed by MPCR. The most frequently detected viruses by MPCR were Human herpesvirus (HHV), Adenovirus, Enterovirus/Rhinovirus (Ev/Rv), and Bocavirus. The most abundant bacteria were Bordetella pertussis, Haemophilus influenzae, and Listeria monocytogenes. Coronavirus and other respiratory viruses could also induce AME. Ev/Rv were significantly enriched in the adolescent cases, and tick-borne encephalitis cases were concentrated in northeastern China. This study systematically characterized the pathogen spectrum and distribution of AME in China. Additionally, it revealed that combining MPCR and mNGS significantly improves the diagnostic rate of pathogens in AME. These findings will provide important support for the diagnosis, treatment, and development of drugs and vaccines for AME.