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Analysis of the Clinical Value of Metagenomic Next-generation Sequencing in Central Nervous System Infection
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摘要:
目的 探讨宏基因组高通量测序(metagenomic next-generation sequencing，mNGS)技术在中枢神经系统感染性疾病诊断中的临床价值。 方法 依托中国医学科学院北京协和医院感染性疾病宏基因组检测平台，回顾性分析2022年4—12月临床诊断为中枢神经系统感染性疾病患者的临床信息、常规实验室检测结果及mNGS结果等相关资料，评价mNGS技术在中枢神经系统感染性疾病诊断中的价值。 结果 在39例临床诊断为中枢神经系统感染性疾病的患者中，29例(74.4%)检出疑似致病病原体特异性序列，其中11例(37.9%)检出细菌，13例(44.8%)检出病毒，3例(10.3%)检出真菌，1例(3.5%)检出细菌及病毒，1例(3.5%)检出真菌及病毒，真阳性率为74.4%。10例报告阴性结果，假阴性率为25.6%。mNGS技术的阳性率明显高于临床常规病原学检查(包括脑脊液涂片、培养、病原体抗原及核酸聚合酶链式反应)的阳性率(74.4% 比23.7%)。 结论 相较于现有的临床常规病原学检查手段，mNGS技术在中枢神经系统感染性疾病诊断中具有更高的真阳性率，可能有助于中枢神经系统感染性疾病的早期诊断。 Abstract:Objective To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) technology in the central nervous system (CNS) infection. Methods Utilizing the Infectious Disease Metagenomic Testing Platform at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, we conducted a retrospective analysis of clinical data, routine laboratory test results, and mNGS results of patients diagnosed with infectious CNS diseases from April to December 2022. The aim was to assess the diagnostic significance of mNGS technology in CNS infection. Results Among 39 patients clinically with CNS infection, suspected pathogenic microorganism-specific sequences were detected in 29 cases (74.4%). Among them, 11 cases (37.9%) were positive for bacteria, 13 cases (44.8%) for viruses, 3 cases (10.3%) for fungi, 1 case (3.5%) for both bacteria and viruses, and 1 case (3.5%) for both fungi and viruses, yielding a positivity rate of 74.4%. Ten cases reported negative results, resulting in a false-negative rate of 25.6%. The positivity rate of mNGS was significantly higher than that of conventional clinical pathogen detection methods (including cerebrospinal fluid smears, cultures, pathogen antigens, and nucleic acid polymerase chain reactions), with rates of 74.4% compared to 23.7%, respectively. Conclusions Compared to available conventional clinical pathogen detection methods, mNGS technology demonstrates a higher positivity rate in the diagnosis of infectious CNS diseases. This advancement could potentially contribute to the early diagnosis of CNS infection. 作者贡献：陆旻雅、郭佳钰负责研究方案设计、数据分析及论文撰写；陆旻雅、郭佳钰、张栋、苏慧婷、高弈负责试验操作、报告发布和数据采集；赵颖、杨启文和徐英春负责数据审核及论文审校。利益冲突：所有作者均声明不存在利益冲突 -
表 1 39例中枢神经系统感染者的临床表现[n(%)]
临床表现 数值 发热 27(69.2) 头痛 19(48.7) 呕吐 4(10.3) 意识障碍 17(43.6) 癫痫发作 5(12.8) 肢体麻木/无力 4(10.3) 精神行为异常 2(5.1) 认知功能下降 2(5.1) 大小便障碍 2(5.1) 视物模糊 1(2.6) 听力下降 1(2.6) 语言障碍 1(2.6) 吞咽障碍 1(2.6) 行走不稳 1(2.6) 颅内占位 2(5.1) 皮疹 5(12.8) 
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表 2 29例阳性病例脑脊液mNGS病原体检测结果与临床验证情况
mNGS检测结果 临床验证方法 细菌感染(12例) 结核分枝杆菌(6例) 临床诊断结核性脑膜炎/脑膜脑炎并接受抗结核治疗(5例) 涂片阳性肺结核(1例) 脑脊液X-pert® MTB/XDR检测阳性(1例) 金黄色葡萄球菌(2例) 血培养阳性(1例) 脑脊液白细胞明显升高且以多个核细胞为主(2例) 肺炎克雷伯菌(1例) 血培养阳性(1例) 屎肠球菌及肺炎克雷伯菌混合感染(1例) 硬膜外脓肿脓液培养阳性(1例) 链球菌属(1例) 脑脊液培养阳性(1例) 表皮葡萄球菌(1例) 脑脊液培养阳性(1例) 病毒感染(13例，除外2例混合感染) 水痘‐带状疱疹病毒(9例) 临床诊断病毒性脑膜炎/脑膜脑炎/脑脊髓炎并接受抗病毒治疗(9例) 疱疹(5例) EB病毒(2例) 脑脊液EB病毒核酸PCR检测阳性(1例) 临床诊断病毒性脑膜炎/脑炎并接受抗病毒治疗(2例) 巨细胞病毒(1例) 脑脊液巨细胞病毒核酸PCR检测阳性(1例) 临床诊断病毒性脑膜炎/脑炎并接受抗病毒治疗(1例) 肠道病毒71型(1例) 临床诊断病毒性脑膜炎并接受抗病毒治疗(1例) 真菌感染(4例) 新型隐球菌(2例) 脑脊液隐球菌抗原阳性(2例) 脑脊液培养阳性(1例) 烟曲霉(1例) 血曲霉半乳甘露聚糖试验阳性(1例) 白色念珠菌(1例) 临床诊断念珠菌性中枢神经系统感染(1例) mNGS：宏基因组高通量测序；PCR：聚合酶链式反应
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