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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Systems Microbiology

The application value and limitations of metagenomic detection technology based on cerebrospinal fluid samples in suspected central nervous system infection: a retrospective study

Provisionally accepted
Qiujuan  FengQiujuan Feng1Baoyi  LiuBaoyi Liu1Huazhao  LiuHuazhao Liu1Yaqin  FanYaqin Fan1Shanshan  GaoShanshan Gao1Jia  ZhangJia Zhang1Yingjie  KuangYingjie Kuang1Wenshan  WangWenshan Wang1Huiqiang  LiangHuiqiang Liang1Yulan  QiuYulan Qiu1Huamei  WenHuamei Wen1Zize  FengZize Feng1Yanming  HuangYanming Huang1Wanli  ZuoWanli Zuo1Xin  ZhangXin Zhang1Jincheng  ZengJincheng Zeng2Jinhua  WuJinhua Wu1Yuanhao  LiangYuanhao Liang1*Jiyong  GuJiyong Gu1
  • 1Jiangmen Central Hospital, Jiangmen, China
  • 2Guangdong Medical University, Dongguan, China

The final, formatted version of the article will be published soon.

Background: Accurately diagnosing central nervous system (CNS) infections remains challenging. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) in diagnosing suspected CNS infections and its role in facilitating rapid and accurate pathogen identification. Methods: This retrospective study enrolled cerebrospinal fluid specimens from 246 patients with suspected CNS infections and 20 controls with definitively ruled-out infections. Using clinical diagnoses established by an expert panel based on comprehensive criteria as the reference standard, we evaluated the diagnostic performance of mNGS relative to culture and conventional tests. Additionally, we analyzed the therapeutic guidance value of positive mNGS results and risk factors for false negatives. Results: mNGS showed 73.2% (180/246) agreement with clinical diagnosis, superior to culture (54.1%, 133/246) and conventional methods (61.4%, 151/246). For general bacteria and fungi, mNGS showed 61.9% (26/42) concordance with culture. False negatives in mNGS predominantly involved viral missed detection. Age, presence of systemic infection, headache, and cerebrospinal fluid glucose levels were likely key determinants of mNGS performance. mNGS detection of Epstein-Barr virus, Streptococcus spp., Mycobacterium tuberculosis complex, herpes simplex virus type 1, and Staphylococcus spp. suggested high pathogenic potential, whereas Torque teno virus detection more likely indicated carriage or experimental contamination. Conclusions: mNGS holds significant value for the diagnosis, therapeutic management, and prognostic assessment of suspected CNS infections.

Keywords: Central Nervous System Infections, Cerebrospinal Fluid, Conventional testing, culture, metagenomics next generation sequencing

Received: 20 Aug 2025; Accepted: 09 Dec 2025.

Copyright: © 2025 Feng, Liu, Liu, Fan, Gao, Zhang, Kuang, Wang, Liang, Qiu, Wen, Feng, Huang, Zuo, Zhang, Zeng, Wu, Liang and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yuanhao Liang

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