研究利用臨床宏基因組測序診斷腦膜炎和腦炎

研究利用臨床宏基因組測序診斷腦膜炎和腦炎

作者：

小柯機器人

發布時間：2019/7/19 12:57:30

加州大學舊金山分校Charles Y. Chiu小組研究了利用臨床宏基因組測序診斷腦膜炎和腦炎。相關論文發表在2019年6月13日出版的《新英格蘭醫學雜誌》雜誌上。

在一項為期一年的多中心前瞻性研究中，課題組人員研究了腦脊液（CSF）的宏基因組二代測序（NGS）在診斷住院患者感染性腦膜炎和腦炎中的作用。 採用正交試驗法，對原基因組NGS的所有病原菌檢測均為陽性。通過與臨床微生物測序委員會的電話會議和調查，獲得醫生的反饋。臨床療效採用回顧性圖表分析。該研究團隊在8家醫院登記了204名兒童和成人患者。患者病情嚴重:48.5%入院重症監護室，所有研究患者30天死亡率為11.3%。其中神經系統感染58例，佔57例(27.9%)。在這58例感染中，宏基因組 NGS鑑定出13例(22%)未通過源醫院的臨床試驗鑑定。宏基因組NGS能夠診斷其餘45例（78%）感染中的19例。在未檢出的26例中，11例僅通過血清學檢查確診，7例非腦脊液組織標本診斷，8例由於腦脊液中病原體滴度較低而未檢出。僅用宏基因組NGS進行的13項診斷中，有8項可能具有臨床療效，13項中有7項具有指導治療作用。常規的微生物學檢測往往不足以檢測出所有的神經侵襲性病原體。在本研究中，從腦膜炎或腦炎患者中獲得的CSF宏1基因組NGS改善了對神經感染的診斷，並在某些情況下提供了可操作的信息。

據介紹，腦脊液(CSF)的宏基因組下一代測序(NGS)具有在一次測試中識別廣泛的病原體的潛力。

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