摘要
目的评价脑脊液宏基因组二代测序(mNGS)在获得性免疫缺陷综合征(AIDS)患者合并中枢神经系统(CNS)感染诊断中的临床应用价值,了解AIDS患者合并CNS感染的病原谱。方法收集2021年1月至2022年8月于武汉大学中南医院收治并诊断为AIDS合并CNS感染者的临床资料、mNGS与常规病原检测法检出的病原体信息。比较常规病原学检测与mNGS检出病原体情况,与临床诊断进行一致性评价。结果61例诊断为AIDS合并CNS感染者中,经mNGS联合常规病原学检测后60例(98.4%、60/61)患者明确病原学诊断,与单独常规病原学检测阳性率(49.2%、30/61)以及单独mNGS阳性率(83.6%、51/61)差异均具有统计学意义(χ^(2)=38.125、P<0.001,χ^(2)=8.093、P=0.004)。mNGS阳性患者51例(83.6%),高于常规病原体检测阳性30例(49.2%),差异具有统计学意义(χ^(2)=16.201、P<0.001)。其中mNGS方法结果中两种及以上的病原体同时检出率为41.0%(25/61),高于常规病原检测法[9.8%(6/61)],差异具有统计学意义(χ^(2)=15.612、P<0.001)。在隐球菌脑膜炎检出率中,常规检测方法[14.8%(9/61)]与mNGS检测方法[13.1%(8/61)]具有良好一致性,其中前者与临床诊断的一致性为90%(9/10),后者为80%(8/10);43例(70.5%)患者至少检出1种病毒,其中24例(39.3%)患者检出人疱疹病毒4型(EB病毒),15例(24.6%)患者检出人疱疹病毒5型(CMV),8例(13.1%)患者检出JC多瘤病毒。14例(23.0%)患者中共检出18株真菌,包括新型隐球菌8株、似平滑念珠菌3株、曲霉菌4株、马尔尼菲篮状菌、耶氏肺胞子菌及尖端赛多孢子菌各1株;非典型病原体8例(13.1%),包括刚地弓形虫3例、苍白密螺旋体3例、军团菌、猫立克次体各1例;结核及非结核分支杆菌各2例(6.6%)。61例患者中,3例死亡,病死率为4.9%(3/61)。结论AIDS晚期患者合并CNS感染中混合感染常见,病原谱依次包括病毒、真菌、细菌和非典型病原体等。mNGS联合常规病原学检测可显著提高颅内感染的病原检出率,有助于及时精准诊疗,提高患者生存率。
Objective To evaluate the clinical value of metagenomic next-generation sequencing(mNGS)of cerebrospinal fluid in acquired immune deficiency syndrome(AIDS)complicated with central nervous system(CNS)infection,and to investigate the pathogetic spectrum.Methods AIDS patients complicated with CNS infection in Zhongnan Hospital of Wuhan University from January 2021 to August 2022 were analyzed,including the clinical characteristics and pathogen information detected by mNGS and routine etiological examination.The pathogens detected by routine etiological examination and mNGS were compared,and the consistency with clinical diagnosis was evaluated.Results Among the 61 patients with CNS infection,60 patients(98.4%,60/61)were identified by mNGS combined with routine etiological examination,which was significantly higher than that of routine etiological examination alone(49.2%,30/61)and that of mNGS alone(83.6%,51/61),with significant differences(χ^(2)=38.125,P<0.001;χ^(2)=8.093,P=0.004).The positive rate of mNGS 83.6%(51/61)was significantly higher than that of routine etiological examination[49.2%(30/61)],with significant difference(χ^(2)=16.201,P<0.001).The detection rate of two or more pathogens by mNGS was 41.0%(25/61),which was significantly higher than that by routine etiological examination(9.8%,6/61),with significant difference(χ^(2)=15.612,P<0.001).For the detection rate of cryptococcal meningitis,conventional detection method[14.8%(9/61)]was in good agreement with mNGS[13.1%(8/61)],and the consistency with clinical diagnosis were 90%(9/10)and 80%(8/10),respectively.At least one virus was detected in 43(70.5%)patients,of which 24(39.3%)cases detected human herpesvirus 4(EBV),15(24.6%)cases detected human herpesvirus 5(CMV),and 8(13.1%)cases detected JC polyomavirus.Total of 18 strains of fungi were detected in 14(23.0%)patients,including 8 strains of Cryptococcus neoformans,4 strains of Aspergillus,3 strains of Candida parapsilosis,1 strain of Talaromyces marneffei,1 strain of Pneumocystosis jirovecii and 1 strain of Dosporium apiospermum.There were 8(13.1%)atypical pathogens detected,including 3 strains of Toxoplasma gondii,3 strain of Treponema pallidum,1 strain of Legionella and 1 strain of Rickettsia felis.Tuberculosis and non-tuberculous mycobacterium were detected in 2(6.6%)cases respectively.Total of 3 cases died,the mortality rate was 4.9%(3/61).Conclusions Mixed infections are common in advanced AIDS patients complicated with CNS infection,and the pathogetic spectrum includes virus,fungi,bacterial and atypical pathogens.mNGS combined with routine etiological examination could significantly improve the rapid pathogen detection rate of intracranial infections and the survival rate of patients.
作者
李倩
邓莉平
陈果
张忠威
莫平征
胡文佳
陈良君
张捷
张永喜
杨蓉蓉
熊勇
LI Qian;Deng Liping;Chen Guo;Zhang Zhongwei;Mo Pingzheng;Hu Wenjia;Chen Liangjun;ZhangJie;Zhang Yongxi;Yang Rongrong;Xiong Yong(Department of Infectious Diseases,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Clinicallaboratory,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Neurosurgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)
出处
《中华实验和临床感染病杂志（电子版）》
CAS
2023年第1期24-31,共8页
Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)
基金
2020年湖北省重点研发计划项目(No.2020BCB025)
武汉大学中南医院学科培育项目(No.ZNXKPY2021021)
关键词
宏基因组二代测序
获得性免疫缺陷综合征
人类免疫缺陷病毒
病原学检测
中枢神经系统感染
病原谱
Metagenomic next-generation sequencing
Acquired immune deficiency syndrome
Human immunodeficiency virus
Etiological examination
Central nervous systerm infection
Pathogetic spectrum
作者简介
通信作者:熊勇,Email:yongxiong64@163.com
