BackgroundOpportunistic 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.MethodsWe 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.ResultsOverall, 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).ConclusionCSF 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.

中文翻译：

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通过脑脊液宏基因组下一代测序检测疑似中枢神经系统感染的 HIV 感染者和非 HIV 患者中的微生物组

背景中枢神经系统（CNS）的机会性感染可能对艾滋病毒感染者构成严重威胁。早期病因诊断和针对性治疗至关重要但困难重重。宏基因组下一代测序（mNGS）比传统检测方法具有显着优势。然而，使用 mNGS 和常规检测方法，尚未充分评估感染和未感染 HIV 且疑似 CNS 感染的患者脑脊液 (CSF) 微生物组特征的差异。 2019 年和 2022 年 6 月，调查使用 mNGS 对感染和未感染 HIV 并疑似中枢神经系统感染的患者脑脊液检测到的微生物组。使用 mNGS 和传统检测方法同时鉴定引起 CNS 感染的病原体。比较两组之间鉴定出的病原体谱。结果总体而言，173 名疑似中枢神经系统感染的患者（140 名感染 HIV 的患者和 33 名未感染 HIV 的患者）纳入了我们的研究。总共有 106 名 (75.7%) 感染 HIV 的患者和 16 名 (48.5%) 未感染 HIV 的患者 mNGS 检测呈阳性（p= 0.002）。在纳入的患者中，71 名 (50.7%) 感染艾滋病毒的患者和 5 名未感染艾滋病毒的患者 (15.2%) 的两种或多种病原体检测呈阳性（p< 0.001）。 HIV 感染者的真菌比例明显更高（20.7% vs. 3.0%，p= 0.016）和 DNA 病毒（59.3% vs. 21.2%，p< 0.001) 与没有 HIV 的人相比。 EB 病毒 (33.6%) 是使用 mNGS 检测的 HIV 感染者脑脊液中最常见的潜在病原体，其次是巨细胞病毒 (20.7%) 和扭特诺病毒 (13.8%)。在未感染艾滋病毒的患者中发现的前三种致病病原体是链球菌属(18.2%)、爱泼斯坦-巴尔病毒 (12.1%) 和结核分枝杆菌（9.1%）。总共有 113 名艾滋病毒感染者被诊断为中枢神经系统感染。在患有中枢神经系统感染的艾滋病毒感染者中，mNGS 的病原体检出率显着高于传统方法（93.8% 与 15.0%，p < 0.001）。感染。 mNGS 是诊断 HIV 感染者（尤其是混合感染者）中枢神经系统感染的有力工具。