The diagnostic value of metagenomic next⁃generation sequencing in infectious diseases.
The diagnostic value of metagenomic next⁃generation sequencing in infectious diseases.
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宏基因组新一代测序在传染病中的诊断价值
DOI：
10.1186/s12879-020-05746-5
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发表时间：
2021-01-13
影响因子：
3.7
通讯作者：
Xie S
中科院分区：
文献类型：
--
作者：
Duan H;Li X;Mei A;Li P;Liu Y;Li X;Li W;Wang C;Xie S
目前，传统的感染诊断技术虽然成熟且价格低廉，但大多耗时长、阳性率低。宏基因组下一代测序技术（mNGS）因其不依赖于细菌培养而能对所有病原体进行鉴定和分型，且能无偏倚地提取所有DNA而得到广泛研究。基于此背景，本研究旨在检测mNGS与传统培养方法的差异，并探讨mNGS结果与感染患者病情严重程度、预后的关系。本研究于2018年10月至2019年12月在上海市第十人民医院入组了109例成人患者。比较两种方法的诊断结果、阴性预测值、阳性预测值、假阳性率、假阴性率、病原体及标本类型。然后，收集感染组（ID）93例患者的样本和临床信息。根据mNGS是否检出病原体，将ID组患者分为阳性组67例和阴性组26例。检测外周血白细胞、C反应蛋白（CRP）、降钙素原（PCT）、中性粒细胞计数，ELISA法检测血清IL-2、IL-4、IL-6、TNF-α、IL-17 A、IL-10、INF-γ浓度。分析mNGS检测病原体阳性率与患者病情严重程度、住院天数及病死率的相关性。109份样本分为感染组（ID，92/109，84.4%）、非感染组（NID，16/109，14.7%）和未知组（1/109，0.9%）。血液标本最丰富（37例），其次为支气管肺泡灌洗液（36例）、组织、痰、胸腔积液、脑脊液（CSF）、脓液、骨髓和鼻拭子。在ID组中，大多数患者被诊断为下呼吸系统感染（73/109，67%），其次是血流感染、胸腔积液和中枢神经系统感染。mNGS法的敏感性明显高于培养法（67.4%vs23.6%，P < 0.001），尤其是支气管肺泡灌洗液标本类型（P = 0.002），血液mNGS与痰液培养法的特异性分别为68.8%和81.3%（P = 0.41），差异无显著性（P> 0.05）。mNGS阳性组的住院天数和28 d病死率均显著高于阴性组，差异有统计学意义（P < 0.05）。在mNGS阳性结果的多变量逻辑分析中，年龄具有显着性。研究发现，mNGS的敏感性高于传统方法，尤其是在血液、支气管肺泡灌洗液和痰液样本中。且mNGS阳性组住院时间、28 d病死率较高，提示病原体核酸序列检测阳性可能是成人患者预后不良的潜在高危因素，具有重要的临床价值。MNGS在病原体的早期诊断中应得到更多的应用。
Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients. 109 adult patients were enrolled in our study in Shanghai Tenth People’s Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed. 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS. The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.
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DOI：
10.1093/cid/cix596
发表时间：
2017-10-16
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Somasekar S;Lee D;Rule J;Naccache SN;Stone M;Busch MP;Sanders C;Lee WM;Chiu CY
通讯作者：
Chiu CY
缺乏可识别的病因的肺炎儿童中宏基因组学和泛病毒组聚合酶链反应的病毒病原体检测。
DOI：
10.1093/infdis/jix148
发表时间：
2017-05-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Schlaberg R;Queen K;Simmon K;Tardif K;Stockmann C;Flygare S;Kennedy B;Voelkerding K;Bramley A;Zhang J;Eilbeck K;Yandell M;Jain S;Pavia AT;Tong S;Ampofo K
通讯作者：
Ampofo K
影响因子：
5.7
作者：
Lecuit M;Eloit M
通讯作者：
Eloit M
DOI：
10.4269/ajtmh.2010.09-0584
发表时间：
2010-08
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Rhodes J;Hyder JA;Peruski LF;Fisher C;Jorakate P;Kaewpan A;Dejsirilert S;Thamthitiwat S;Olsen SJ;Dowell SF;Chantra S;Tanwisaid K;Maloney SA;Baggett HC
通讯作者：
Baggett HC
影响因子：
12.3
作者：
Grumaz S;Stevens P;Grumaz C;Decker SO;Weigand MA;Hofer S;Brenner T;von Haeseler A;Sohn K
通讯作者：
Sohn K