宏基因组下一代测序在儿童中枢神经系统感染的病原体检测和转录组分析中的应用
Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections.
作者信息
Ramchandar Nanda, Coufal Nicole G, Warden Anna S, Briggs Benjamin, Schwarz Toni, Stinnett Rita, Xie Heng, Schlaberg Robert, Foley Jennifer, Clarke Christina, Waldeman Bryce, Enriquez Claudia, Osborne Stephanie, Arrieta Antonio, Salyakina Daria, Janvier Michelin, Sendi Prithvi, Totapally Balagangadhar R, Dimmock David, Farnaes Lauge
机构信息
Rady Children's Institute for Genomic Medicine, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego, California, USA.
出版信息
Open Forum Infect Dis. 2021 Mar 6;8(6):ofab104. doi: 10.1093/ofid/ofab104. eCollection 2021 Jun.
BACKGROUND
Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections.
METHODS
We conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis.
RESULTS
We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours.
CONCLUSIONS
Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.
背景
小儿中枢神经系统（CNS）感染可能危及生命，并可能导致严重的发病情况。确定病原体很重要，这在指导治疗管理和判断预后方面都有意义。通过培养和聚合酶链反应进行的常规检测往往无法确定病原体。我们研究了宏基因组下一代测序（mNGS）在检测中枢神经系统（CNS）感染儿童脑脊液（CSF）中的病原体及转录组分析方面的系统应用。
方法
我们进行了一项前瞻性多中心研究，旨在纳入研究期间入住3家三级儿科医院之一的所有脑脊液有细胞增多症且疑似中枢神经系统感染的儿童。在进行常规检测后，将剩余的脑脊液送去进行mNGS和转录组分析。
结果
在为期12个月的招募期内，我们筛查了221名受试者并纳入了70名。通过任何诊断方法，在25名（35.7%）受试者脑脊液中分离出假定病原体。脑脊液样本的宏基因组下一代测序在20名（28.6%）受试者中鉴定出病原体，这些病原体也都通过常规检测鉴定出来了。获得结果的中位时间为38小时。
结论
脑脊液的宏基因组测序有潜力快速鉴定中枢神经系统感染儿童的病原体。
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