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通过脑脊液宏基因组下一代测序技术在疑似中枢神经系统感染的 HIV 患者和非 HIV 患者中检测到的微生物组。

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

机构信息

Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.

Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China.

出版信息

HIV Med. 2024 Jul;25(7):794-804. doi: 10.1111/hiv.13634. Epub 2024 Mar 21.

Abstract

BACKGROUND

Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated.

METHODS

We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups.

RESULTS

Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001).

CONCLUSION

CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

摘要

背景

中枢神经系统(CNS)中的机会性感染可能对 HIV 感染者构成严重威胁。早期病因诊断和靶向治疗至关重要,但却很困难。宏基因组下一代测序(mNGS)比传统检测方法具有显著优势。然而,使用 mNGS 和常规检测方法检测 HIV 感染者和非 HIV 感染者疑似 CNS 感染患者的脑脊液(CSF)微生物组谱的差异尚未得到充分评估。

方法

我们在 2019 年 1 月至 2022 年 6 月期间在长沙市第一医院进行了一项回顾性队列研究,以调查使用 mNGS 检测的疑似 CNS 感染的 HIV 感染者和非 HIV 感染者的 CSF 微生物组。同时使用 mNGS 和传统检测方法确定引起 CNS 感染的病原体。比较两组之间确定的病原体谱。

结果

总体而言,我们的研究纳入了 173 名疑似 CNS 感染的患者(140 名 HIV 感染者和 33 名非 HIV 感染者)。共有 106 名(75.7%)HIV 感染者和 16 名(48.5%)非 HIV 感染者的 mNGS 检测结果为阳性(p=0.002)。在纳入的患者中,71 名 HIV 感染者和 5 名非 HIV 感染者(15.2%)检测出两种或两种以上病原体呈阳性(p<0.001)。HIV 感染者的真菌(20.7% vs. 3.0%,p=0.016)和 DNA 病毒(59.3% vs. 21.2%,p<0.001)比例显著高于非 HIV 感染者。与非 HIV 感染者相比,使用 mNGS 检测到 EBV(33.6%)是 HIV 感染者 CSF 中最常见的潜在病原体,其次是 CMV(20.7%)和 TT virus(13.8%)。非 HIV 感染者中鉴定出的前三种病原体是链球菌(18.2%)、EBV(12.1%)和结核分枝杆菌(9.1%)。共有 113 名 HIV 感染者被诊断为 CNS 感染。mNGS 检测 HIV 感染者 CNS 感染的病原体的检出率明显高于常规方法(93.8% vs. 15.0%,p<0.001)。

结论

疑似 CNS 感染的 HIV 感染者和非 HIV 感染者的 CSF 微生物组谱不同。mNGS 是 HIV 感染者 CNS 感染诊断的有力工具,特别是在混合感染中。

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