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常规检测漏诊的中枢神经系统感染的宏基因组学检测

Metagenomic detection of central nervous system infections missedby conventional testing.

作者信息

Ferreira Noely Evangelista, Berg Michael G, da Costa Antonio C, Rodgers Mary A, Kallas Esper G, Silveira Cassia G Terrasani, Thomazella Mateus Vailant, de Oliveira Ana Carolina Soares, Honorato Layla, Paião Heuder Go, Domingues Renan Barros, Senne Carlos, Côrtes Marina F, Tozetto-Mendoza Tania R, Gomes Hélio R, Matos Maria Laura Mariano, Ribeiro Geovani de Oliveira, Witkin Steven S, Cloherty Gavin A, Mendes-Correa Maria Cassia

机构信息

Departamento de Infectologia e Medicina Tropical, Faculdade de Medicina, and.

Laboratório de Investigação Médica LIM 52, Instituto de Medicina Tropical, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.

出版信息

JCI Insight. 2025 May 20;10(13). doi: 10.1172/jci.insight.189295. eCollection 2025 Jul 8.

DOI:10.1172/jci.insight.189295
PMID:40392601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12306619/
Abstract

Community-acquired infectious meningoencephalitis is associated with high rates of mortality and morbidity, compounded by limited access to diagnostic resources. The current study assessed acute central nervous system (CNS) infections in patients with meningoencephalitis enrolled in a hospital-based diagnostic surveillance study in São Paulo, Brazil. Cerebrospinal fluid (CSF) was collected from 600 patients between March 2018 and November 2019 and initially screened for a broad range of pathogens according to a local diagnostic algorithm. Standard microbiological and molecular diagnostic methods were applied. Metagenomic sequencing was used as a complementary approach to investigating etiology in instances where no pathogen was initially identified. Standard testing identified infectious etiologies in 292 patients (48.6%), with 227 (77.7%) confirmed as viral infections, predominantly caused by enteroviruses (n = 144) and herpesviruses (n = 40). Nonviral agents were identified in 65 patients (22.3%). Metagenomic sequencing (mNGS) of 277 of 308 undiagnosed patients revealed several additional potential etiologies, including Parvovirus B19, Toxoplasma gondii, Picobirnavirus, other enterovirus species and Vesivirus, the latter being associated with CNS infection for the first time. These findings underscore the complexity of CNS infections and highlight the potential of metagenomics to improve diagnostic accuracy, inform treatment strategies, and support efforts to address future pandemics.

摘要

社区获得性感染性脑膜脑炎死亡率和发病率高,且诊断资源有限,使情况更加复杂。本研究评估了巴西圣保罗一项基于医院的诊断监测研究中,患有脑膜脑炎的患者的急性中枢神经系统(CNS)感染情况。2018年3月至2019年11月期间,从600名患者中采集了脑脊液(CSF),并根据当地诊断算法初步筛查了多种病原体。应用了标准微生物学和分子诊断方法。在最初未鉴定出病原体的情况下,宏基因组测序被用作调查病因的补充方法。标准检测在292名患者(48.6%)中确定了感染病因,其中227例(77.7%)被确认为病毒感染,主要由肠道病毒(n = 144)和疱疹病毒(n = 40)引起。65名患者(22.3%)中鉴定出非病毒病原体。对308名未确诊患者中的277名进行宏基因组测序(mNGS),发现了其他几种潜在病因,包括细小病毒B19、弓形虫、微小双股RNA病毒、其他肠道病毒种类和水疱病毒,后者首次与中枢神经系统感染相关。这些发现强调了中枢神经系统感染的复杂性,并突出了宏基因组学在提高诊断准确性、为治疗策略提供信息以及支持应对未来大流行方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/d7c5b36e24a4/jciinsight-10-189295-g236.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/64a305228958/jciinsight-10-189295-g233.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/1d3467471500/jciinsight-10-189295-g234.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/7922ea8e5c49/jciinsight-10-189295-g235.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/d7c5b36e24a4/jciinsight-10-189295-g236.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/64a305228958/jciinsight-10-189295-g233.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/1d3467471500/jciinsight-10-189295-g234.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/7922ea8e5c49/jciinsight-10-189295-g235.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ce/12306619/d7c5b36e24a4/jciinsight-10-189295-g236.jpg

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本文引用的文献

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