脑脊液二代测序在中枢神经系统感染中的病原学诊断价值  

Etiological diagnostic value of cerebrospinal fluid metagenomic next-generation sequencing in central nervous system infection

作　　者：孟翠翠 袁丁[1] 余言午 王金柱 郭建军[1] 朱桂英[1] 韦毅萌 陈继红[1] 张蕾蕾[1] 高艳霞[1] Meng Cuicui;Yuan Ding;Yu Yanwu;Wang Jinzhu;Guo Jianjun;Zhu Guiying;Wei Yimeng;Chen Jihong;Zhang Leilei;Gao Yanxia(Emergency Department,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Critical Care Medicine,Zhengzhou Central Hospital,Zhengzhou 450001,China;General Practice Department,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院郑东院区急救中心,郑州450000 [2]郑州市中心医院重症医学科,郑州450001 [3]郑州大学第一附属医院全科医学科,郑州450000

出　　处：《中华急诊医学杂志》2022年第4期471-476,共6页Chinese Journal of Emergency Medicine

基　　金：国家科技重大专项子课题(2017ZX10103005-009);河南省高等学校重点科研项目(20A320046);中国初级卫生保健基金会项目(YLGX-JZ-2020001);郑州市科技惠民计划项目(2020KJHM0001);睿E(睿意)急诊医学科研专项基金(R2020014)。

摘　　要：目的探讨宏基因组二代测序技术(metagenomic next-generation sequencing,mNGS)在中枢神经系统(central nervous system,CNS)感染性疾病中的病原学诊断价值。方法以2018年1月至2020年6月郑州大学第一附属医院收治的中枢神经系统感染患者为研究对象,根据纳入和排除标准最终确定170例患者。收集患者的一般临床资料以及病原体检测结果。纳入患者均送检常规以及mNGS检测,将检测结果分为常规方法检测组及mNGS检测组。符合正态分布的计量资料用均数±标准差(x±s)表示;不符合正态分布的计量资料用中位数及四分位数表示;分类资料采用例数及百分比[n(%)]表示;比较采用χ2检验或Fisher's精确检验;一致性检验以Kappa值表示;对比分析两种方法对病原微生物的检出情况及检出病原谱的规律。结果在CNS感染性疾病中mNGS检测的总体阳性率高于常规方法(58.23%vs.18.82%),且差异有统计学意义(P<0.01)。两种检测方法均阳性的20例样本中,所检出病原体种类完全一致者10例,完全不一致者和部分一致者各5例。在结核性神经系统感染病例检测中,检测阳性率从高到低依次为血T-SPOT、脑脊液mNGS、结核杆菌DNA、腺苷脱氨酶(ADA)以及结核特异性抗原抗体检测,分别为66.7%、53.8%、40.0%、24.0%、4.0%,抗酸染色阳性率为0%;mNGS与常规方法结合的检测阳性率为80.8%。结论脑脊液mNGS在CNS感染中病原菌检出率总体优于常规方法;但对结核杆菌的检测阳性率较T-SPOT未显示出明显优势;mNGS检测的病原菌更为广泛,有助于深入全面地了解中枢神经系统感染的菌种特点,两者结合在一定程度上弥补了临床常规检测的不足,可最大化提升检出率。Objective To investigate the etiological diagnostic value of metagenomic sequencing in central nervous system(CNS)infectious diseases.Methods A total of 170 patients with central nervous system infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2020 were selected as the study subjects according to inclusion and exclusion criteria.General clinical data and pathogen test results were collected.All included patients underwent routine examination and mNGS test,and were divided into the conventional method test group and mNGS test group according to the test results.The measurement data conforming to normal distribution were represented by±s;The measurement data that did not conform to normal distribution were represented by median and interquartile range.The classification data were expressed by the number of cases and percentage(n,%),and were compared byχ2 test or Fisher's exact test.Consistency test was represented by Kappa value.The detection of pathogenic microorganisms by the two methods and the rule of pathogen spectrum were compared and analyzed.Results The overall positive rate of mNGS in CNS infectious diseases was higher than that of conventional methods(58.23%vs.18.82%),and the difference was statistically significant(P<0.01).Among the 20 samples which were both positive by the two methods,10 cases were completely pathogenic,5 cases were partially consistent and 5 cases were completely inconsistent.In the detection of tuberculous nervous system infection,the positive rates were 66.7%,53.8%,44.0%,40.0%,4.0%in blood T-SPOT,cerebrospinal fluid mNGS,ADA,Mycobacterium tuberculosis DNA and tuberculous specific antibody,respectively.The positive rate of acid-fast staining was 0.The positive rate of mNGS combined with conventional method was 80.8%.Conclusions The detection rate of mNGS in CNS infection is better than that of conventional methods.However,it does not show obvious superiority in the detection rate of Mycobacterium tuberculosis associated nervous sy

关 键 词：中枢神经系统感染 宏基因组二代测序 常规方法 病原微生物 

分 类 号：R741[医药卫生—神经病学与精神病学] R446.5[医药卫生—临床医学]