当前位置:科学网首页 > 小柯机器人 >详情
研究利用临床宏基因组测序诊断脑膜炎和脑炎
作者:小柯机器人 发布时间:2019/7/19 12:57:30

加州大学旧金山分校Charles Y. Chiu小组研究了利用临床宏基因组测序诊断脑膜炎和脑炎。相关论文发表在2019年6月13日出版的《新英格兰医学杂志》杂志上。

在一项为期一年的多中心前瞻性研究中,课题组人员研究了脑脊液(CSF)的宏基因组二代测序(NGS)在诊断住院患者感染性脑膜炎和脑炎中的作用。 采用正交试验法,对原基因组NGS的所有病原菌检测均为阳性。通过与临床微生物测序委员会的电话会议和调查,获得医生的反馈。临床疗效采用回顾性图表分析。该研究团队在8家医院登记了204名儿童和成人患者。患者病情严重:48.5%入院重症监护室,所有研究患者30天死亡率为11.3%。其中神经系统感染58例,占57例(27.9%)。在这58例感染中,宏基因组 NGS鉴定出13例(22%)未通过源医院的临床试验鉴定。宏基因组NGS能够诊断其余45例(78%)感染中的19例。在未检出的26例中,11例仅通过血清学检查确诊,7例非脑脊液组织标本诊断,8例由于脑脊液中病原体滴度较低而未检出。仅用宏基因组NGS进行的13项诊断中,有8项可能具有临床疗效,13项中有7项具有指导治疗作用。常规的微生物学检测往往不足以检测出所有的神经侵袭性病原体。在本研究中,从脑膜炎或脑炎患者中获得的CSF宏1基因组NGS改善了对神经感染的诊断,并在某些情况下提供了可操作的信息。

据介绍,脑脊液(CSF)的宏基因组下一代测序(NGS)具有在一次测试中识别广泛的病原体的潜力。

附:英文原文

Title: Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis

Author: Michael R. Wilson, M.D., M.A.S., Hannah A. Sample, B.S., Kelsey C. Zorn, M.H.S., Shaun Arevalo, B.S., C.L.S., Guixia Yu, B.S., John Neuhaus, Ph.D., Scot Federman, B.A., Doug Stryke, B.S., Benjamin Briggs, M.D., Ph.D., Charles Langelier, M.D., Ph.D., Amy Berger, M.D., Ph.D., Vanja Douglas, M.D., S. Andrew Josephson, M.D., Felicia C. Chow, M.D., M.A.S., Brent D. Fulton, Ph.D., Joseph L. DeRisi, Ph.D., Jeffrey M. Gelfand, M.D., M.A.S., Samia N. Naccache, Ph.D., Jeffrey Bender, M.D., Jennifer Dien Bard, Ph.D., D(ABMM), Jamie Murkey, B.S., Magrit Carlson, M.D., Paul M. Vespa, M.D., Tara Vijayan, M.D., Paul R. Allyn, M.D., Shelley Campeau, Ph.D., D(ABMM), Romney M. Humphries, Ph.D., D(ABMM), Jeffrey D. Klausner, M.D., Czarina D. Ganzon, M.D., Fatemeh Memar, B.S., Nicolle A. Ocampo, B.S., Lara L. Zimmermann, M.D., Stuart H. Cohen, M.D., Christopher R. Polage, M.D., M.A.S., Roberta L. DeBiasi, M.D., Barbara Haller, M.D., Ronald Dallas, Ph.D., Gabriela Maron, M.D., Randall Hayden, M.D., Kevin Messacar, M.D., Samuel R. Dominguez, M.D., Ph.D., Steve Miller, M.D., Ph.D., and Charles Y. Chiu, M.D., Ph.D.

Issue&Volume:VOL. 380 NO. 24, 2019

Abstract:

BACKGROUND
Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.
METHODS
In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.
RESULTS
We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.
CONCLUSIONS
Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases.

DOI: DOI: 10.1056/NEJMoa1803396

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1803396

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home