Clinical application of metagenomic next-generation sequencing in patients with acquired immune deficiency syndrome complicated with central nervous system infection

doi:10.3877/cma.j.issn.1674-1358.2023.01.005

Abstract

Abstract:

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 (χ² = 38.125, P < 0.001; χ² = 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 (χ² = 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 (χ² = 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.

Key words: Metagenomic next-generation sequencing, Acquired immune deficiency syndrome, Human immunodeficiency virus, Etiological examination, Central nervous systerm infection, Pathogetic spectrum

Qian LI, Liping Deng, Guo Chen, Zhongwei Zhang, Pingzheng Mo, Wenjia Hu, Liangjun Chen, Jie Zhang, Yongxi Zhang, Rongrong Yang, Yong Xiong. Clinical application of metagenomic next-generation sequencing in patients with acquired immune deficiency syndrome complicated with central nervous system infection[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(01): 24-31.

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References 27

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症状	例（%）
头晕头痛	33（54.1）
发热	31（50.8）
恶心呕吐	20（32.8）
四肢乏力伴行动障碍	17（27.9）
视力模糊	9（14.8）
意识障碍	7（11.5）
言语障碍	4（6.6）
呼吸困难	3（4.9）
癫痫发作	3（4.9）

症状	例（%）
头晕头痛	33（54.1）
发热	31（50.8）
恶心呕吐	20（32.8）
四肢乏力伴行动障碍	17（27.9）
视力模糊	9（14.8）
意识障碍	7（11.5）
言语障碍	4（6.6）
呼吸困难	3（4.9）
癫痫发作	3（4.9）

指标	数值
外周血CD4⁺ T淋巴计数[M（P25，P75），个/μl]	29（10，166）
CD4⁺ T细胞< 200.0个/μl [例（%）]	51（83.6）
外周血Lg HIV-VL	4.6（4.0，5.3）
外周血病原学指标[例（%）]
CMV DNA（+）	19（31.1）
EB DNA（+）	29（47.5）
1，3-真菌D葡聚糖（+）	14（23.0）
CSF有核细胞数[M（P25，P75），个/μl]	6（2，30）
CSF有核细胞> 8.0个/μl [例（%）]	28（45.9）
CSF生化
葡萄糖[M（P25，P75），mmol/L]	2.8（2.3，3.3）
葡萄糖< 2.5 mmol/L [例（%）]	19（31.1）
蛋白[M（P25，P75），g/L]	0.7（0.5，1.1）
蛋白> 0.4 g/L [例（%）]	48（78.7）
氯化物（ ± s，mmol/L）	122.5 ± 5.5
氯化物< 120.0 mmol/L [例（%）]	14（23.0）
CSF常规病原学检测[例（%）]
CMV DNA（+）	7（11.5）
EB DNA（+）	18（29.5）
HSV DNA（+）	0（0.0）
墨汁染色异常	4（6.6）
革兰染色异常	1（1.6）
抗酸染色异常	0（0.0）
CSF培养（+）[例（%）]	3（4.9）
结核DNA/X-pert（+）[例（%）]	2（3.3）
隐球菌抗原（+）[例（%）]	8（13.1）

指标	数值
外周血CD4⁺ T淋巴计数[M（P25，P75），个/μl]	29（10，166）
CD4⁺ T细胞< 200.0个/μl [例（%）]	51（83.6）
外周血Lg HIV-VL	4.6（4.0，5.3）
外周血病原学指标[例（%）]
CMV DNA（+）	19（31.1）
EB DNA（+）	29（47.5）
1，3-真菌D葡聚糖（+）	14（23.0）
CSF有核细胞数[M（P25，P75），个/μl]	6（2，30）
CSF有核细胞> 8.0个/μl [例（%）]	28（45.9）
CSF生化
葡萄糖[M（P25，P75），mmol/L]	2.8（2.3，3.3）
葡萄糖< 2.5 mmol/L [例（%）]	19（31.1）
蛋白[M（P25，P75），g/L]	0.7（0.5，1.1）
蛋白> 0.4 g/L [例（%）]	48（78.7）
氯化物（ ± s，mmol/L）	122.5 ± 5.5
氯化物< 120.0 mmol/L [例（%）]	14（23.0）
CSF常规病原学检测[例（%）]
CMV DNA（+）	7（11.5）
EB DNA（+）	18（29.5）
HSV DNA（+）	0（0.0）
墨汁染色异常	4（6.6）
革兰染色异常	1（1.6）
抗酸染色异常	0（0.0）
CSF培养（+）[例（%）]	3（4.9）
结核DNA/X-pert（+）[例（%）]	2（3.3）
隐球菌抗原（+）[例（%）]	8（13.1）

种类数	mNGS	常规检测方法	联合检测
0	10（16.4）	31（50.8）	8（13.1）
1	26（42.6）	24（3.9）	24（39.3）
2	12（19.7）	6（9.8）	15（24.6）
3	10（16.4）	0（0.0）	11（18.0）
4	0（0.0）	0（0.0）	0（0.0）
5	1（1.6）	0（0.0）	1（1.6）
6	0（0.0）	0（0.0）	0（0.0）
7	2（3.3）	0（0.0）	2（3.3）

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