脑脊液宏基因组第二代测序在艾滋病疑似中枢神经系统 感染性疾病中的应用

doi:10.19871/j.cnki.xfcrbzz.2022.01.005

摘要/Abstract

摘要： 目的评估宏基因组第二代测序（mNGS）在艾滋病疑似中枢神经系统（CNS）感染中的应用价值,为艾滋病合并CNS感染诊断提供参考。方法对重庆市公共卫生医疗救治中心2019年7月至2020年7月收治的73例艾滋病疑似CNS感染并行脑脊液mNGS患者的资料进行回顾性分析,收集患者临床表现、影像学资料、脑脊液检查结果,计算感染人数,分析感染类型、病原学阳性情况。对比常规病原学检查与mNGS检出病原体情况,与临床诊断进行一致性评价,评估mNGS在此类疾病诊断中的应用价值。结果 73例患者以头痛、运动障碍、发热为主要临床表现,发生率分别为69.9%（51/73）、54.8%（40/73）、49.3%（36/73）。67例（91.8%）患者CD4⁺T淋巴细胞计数<200个/μl。最终46例（63.0%）患者临床诊断为CNS感染,46例患者共予以57例次的病原学诊断,mNGS联合常规病原学检查的总体阳性率为82.5%（47/57）,mNGS检测阳性率为64.9%（37/57）,高于常规病原学检查阳性率42.1%（24/57）,差异有统计学意义（P=0.015）。23例次病毒感染诊断中,mNGS诊断阳性率87.0%（20/23）,高于常规病原学检查阳性率34.8%（8/23）,差异有统计学意义（P=0.007）。结论艾滋病患者免疫功能受损,合并CNS感染率高,常规病原学检查阳性率低,mNGS具有较好的诊断价值,与常规检查方法联合使用,优势互补,可明显提高病原学诊断阳性率。

关键词: 艾滋病, 中枢神经系统感染, 脑脊液, 常规病原学检查, 宏基因组第二代测序

Abstract: Objective To evaluate the application value of metagenomic next generation sequencing (mNGS) in AIDS suspected central nervous system (CNS) infection, provide reference for diagnosis of AIDS complicated with CNS infection. Method In our hospital between July 2019 and July 2020, 73 cases of suspected AIDS CNS infections in patients with cerebrospinal fluid mNGS parallel data were retrospectively analyzed, collect clinical manifestations, imaging data, cerebrospinal fluid examination Result,calculate infections, a positive analysis of infection type, etiology.The pathogens detected by routine etiology examination and mNGS were compared, which was consistent with the clinical diagnosis Finally, the application value of mNGS in these patients was evaluated. Result Among 73 patients, Headache, dyskinesia and fever were the main clinical manifestations, and the incidence rates were 69.9% (51/73), 54.8%（40/73）and 49.3% (36/73), respectively. Immune function was severely impaired, and CD4⁺T lymphocyte count was <200 cells/μl in 67 patients (91.8%). Finally, 46 (63.0%)patients were clinically diagnosed as CNS infection, and 46 patients received a total of 57 times of etiological diagnosis. The overall positive rate of mNGS combined with conventional examination was 82.5% (47/57), and the positive rate of mNGS was 64.9% (37/57) higher than that of conventional examination 42.1%(24/57), the difference was statistically significant (P=0.015). In 23 cases of virus infection, the positive rate of mNGS diagnosis was 87.0% (20/23), which was higher than that of conventional examination 34.8%(8/23), and the difference was statistically significant (P=0.007). Conclusion AIDS patients have impaired immune function,high rate of central nervous system infection and low positive rate of routine etiological examination,mNGS has better diagnostic value,combined with conventional examination method, mNGS has complementary advantages and can significantly improve the positive rate of etiological diagnosis, which is worthy of clinical promotion.

Key words: Acquired immune deficiency syndrome, Central nervous system infection, Cerebrospinal fluid, Routine etiological examination, Metagenomic next generation sequencing

曾琴, 何坤, 杨红红, 吴玉珊, 李明俊, 石峰, 刘倩, 刘敏. 脑脊液宏基因组第二代测序在艾滋病疑似中枢神经系统感染性疾病中的应用[J]. 新发传染病电子杂志, 2022, 7(1): 21-25.

Zeng Qin, He Kun, Yang Honghong, Wu Yushan, Li Mingjun, Shi Feng, Liu Qian, Liu Min. Application of metagenomic next generation sequencing of cerebrospinal fluid in central nervous system infectious diseases suspected of AIDS[J]. Electronic Journal of Emerging Infectious Diseases, 2022, 7(1): 21-25.

参考文献

[1] 袁虹. 艾滋病合并脑内寄生虫感染的临床及影像表现[J/CD].新发传染病电子杂志,2018,3(3):239-243.
[2] MCGILL F, GRIFFITHS MJ, SOLOMON T.Viral meningitis: current issues in diagnosis and treatment[J]. Curr Opin Infect Dis, 2017,30(2):248-256.
[3] 鲁雁秋, 卢洪洲, 陈耀, 等. 重庆地区499例艾滋病合并中枢神经系统感染患者的疾病谱及预后影响因素分析[J]. 中华传染病杂志, 2018, 36(2):65-68.
[4] ONKARAPPA SA, PANPALIA NG, NAIK KR.Retrospective Hospital-based Study of Opportunistic Neuroinfections in HIV/AIDS[J]. Neurol India, 2020,68(4):875-879.
[5] 刘春礼, 赵清霞, 何云, 等. 艾滋病合并中枢神经系统病变128例临床分析[J]. 中国实用神经疾病杂志, 2012, 15(17):25-27.
[6] THAKUR KT.Application of Pathogen Discovery/Metagenomic Sequencing in CNS HIV[J]. Curr HIV/AIDS Rep, 2020, 17(5):507-513.
[7] WILSON MR, SAMPLE HA, ZORN KC, et al.Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis[J]. N Engl J Med, 2019, 380(24):2327-2340.
[8] XING XW, ZHANG JT, MA YB, et al.Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study[J]. Eur Neurol, 2018,80(5-6):283-288.
[9] ZHANG Y, CUI P, ZHANG HC, et al.Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection[J]. J Transl Med, 2020,18(1):199.
[10] 中华医学会感染病学分会艾滋病丙型肝炎学组,中国疾病预防与控制中心. 中国艾滋病诊疗指南(2018版)[J/CD]. 新发传染病电子杂志,2019,4(2):65-84.
[11] 《中华传染病杂志》编辑委员会. 中国宏基因组学第二代测序技术检测感染病原体的临床应用专家共识[J].中华传染病杂志, 2020, 38(11):681-689.
[12] THAKUR KT.CNS infections in HIV[J]. Curr Opin Infect Dis, 2020,33(3):267-272.
[13] KHATIB U, VAN DE BEEK D, BROUWER MC,et al. Adults with suspected central nervous system infection: A prospective study of diagnostic accuracy[J]. J Infect, 2017,74(1):1-9.
[14] XING XW, ZHANG JT, MA YB, et al.Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients[J]. Front Cell Infect Microbiol, 2020,10:88.
[15] STAHL JP, AZOUVI P, BRUNEEL F, et al.Guidelines on the management of infectious encephalitis in adults[J]. Med Mal Infect, 2017,47(3):179-194.
[16] BROWN JR, BHARUCHA T, BREUER J.Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases[J]. J Infect, 2018, 76(3):225-240.
[17] 冯绵烨, 娄燕. 病毒性脑炎的诊治研究进展[J/CD]. 中华诊断学电子杂志, 2019, 7(1):66-70.
[18] 吴婷娜, 王旻晋, 钟方财, 等. 疑似中枢神经系统感染患者脑脊液病原体多重PCR检测结果的研究[J]. 国际检验医学杂志, 2021, 42(1):8-11.
[19] 唐欷柯,彭智鹏,梁联哨,等.艾滋病合并神经梅毒感染的最新研究进展[J/CD].新发传染病电子杂志,2020,5(3):203-206.