Value of metagenomic next-generation sequencing in children with severe infectious diseases

ZHENG Yi-Hui; LIN Wei; ZHANG Tian-Lei; FANG Yu; CHEN Bin-Wen; PAN Guo-Quan; LIN Zhen-Lang

doi:10.7499/j.issn.1008-8830.2110003

PDF(560 KB)

Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (3) : 273-278. DOI: 10.7499/j.issn.1008-8830.2110003

CLINICAL RESEARCH

Value of metagenomic next-generation sequencing in children with severe infectious diseases

ZHENG Yi-Hui, LIN Wei, ZHANG Tian-Lei, FANG Yu, CHEN Bin-Wen, PAN Guo-Quan, LIN Zhen-Lang

Author information +

History +

Abstract

Objective To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases. Methods An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time. Results Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture (P<0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi. The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS (P>0.05). Conclusions Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.

Key words

Infectious disease / Metagenomic next-generation sequencing / Severe illness / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

ZHENG Yi-Hui, LIN Wei, ZHANG Tian-Lei, FANG Yu, CHEN Bin-Wen, PAN Guo-Quan, LIN Zhen-Lang. Value of metagenomic next-generation sequencing in children with severe infectious diseases[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(3): 273-278 https://doi.org/10.7499/j.issn.1008-8830.2110003

References

1 Liu L, Johnson HL, Cousens S, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000[J]. Lancet, 2012, 379(9832): 2151-2161. PMID: 22579125. DOI: 10.1016/S0140-6736(12)60560-1.
2 Fauci AS, Morens DM. The perpetual challenge of infectious diseases[J]. N Engl J Med, 2012, 366(5): 454-461. PMID: 22296079. DOI: 10.1056/NEJMra1108296.
3 宏基因组分析和诊断技术在急危重症感染应用专家共识组. 宏基因组分析和诊断技术在急危重症感染应用的专家共识[J]. 中华急诊医学杂志, 2019, 28(2): 151-155. DOI: 10.3760/cma.j.issn.1671-0282.2019.02.005.
4 何波, 李渊龙, 陈秀灵, 等. 宏基因二代测序在儿童血流感染中的应用[J]. 中国热带医学, 2021, 21(5): 440-444. DOI: 10.13604/j.cnki.46-1064/r.2021.05.10.
5 黄珮琪, 陆小霞, 陈和斌. mNGS技术在儿童重症肺炎病原学诊断中的价值[J]. 分子诊断与治疗杂志, 2021, 13(3): 356-359. DOI: 10.3969/j.issn.1674-6929.2021.03.006.
6 许普, 王来栓. 病原微生物宏基因组检测在新生儿感染性疾病中的应用[J]. 中华实用儿科临床杂志, 2020, 35(11): 820-823. DOI: 10.3760/cma.j.cn101070-20200224-00237.
7 贾建超, 贾建敏, 刘姿, 等. 宏基因组学二代测序技术对重症肺炎真菌感染诊断价值[J]. 中华实用诊断与治疗杂志, 2020, 34(10): 1023-1025. DOI: 10.13507/j.issn.1674-3474.2020.10.014.
8 中国医师协会急诊医师分会, 中国研究型医院学会休克与脓毒症专业委员会. 中国脓毒症/脓毒性休克急诊治疗指南(2018)[J]. 临床急诊杂志, 2018, 19(9): 567-588. DOI: 10.13201/j.issn.1009-5918.2018.09.001.
9 Long Y, Zhang YX, Gong YP, et al. Diagnosis of sepsis with cell-free DNA by next-generation sequencing technology in ICU patients[J]. Arch Med Res, 2016, 47(5): 365-371. PMID: 27751370. DOI: 10.1016/j.arcmed.2016.08.004.
10 Jeon YJ, Zhou YL, Li YH, et al. The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform[J]. PLoS One, 2014, 9(10): e110240. PMID: 25329639. PMCID: PMC4203771. DOI: 10.1371/journal.pone.0110240.
11 Li H, Durbin R. Fast and accurate short read alignment with burrows-wheeler transform[J]. Bioinformatics, 2009, 25(14): 1754-1760. PMID: 19451168. PMCID: PMC2705234. DOI: 10.1093/bioinformatics/btp324.
12 崔廷玲, 俊梅. 小儿肺炎支原体肺炎76例临床分析[J]. 辽宁中医杂志, 2009, 36(11): 1921-1922. DOI: 10.13192/j.ljtcm.2009.11.102.cuitl.086.
13 张红敏, 胡静, 刘慧芳. 儿童败血症预后因素及生存分析[J]. 青岛医药卫生, 2011, 43(4): 272-276. DOI: 10.3969/j.issn.1006-5571.2011.04.017.
14 钟义宝. C反应蛋白及降钙素原对儿科细菌感染性疾病早期诊断的价值研究[J]. 儿科药学杂志, 2015, 21(7): 10-12. DOI: 10.13407/j.cnki.jpp.1672-108X.2015.07.004.
15 郑苗苗, 邵启民, 严伟玲, 等. 血清C-反应蛋白、降钙素原和免疫功能检测在儿童肺炎中的应用[J]. 中国妇幼保健, 2017, 32(22): 5625-5629. DOI: 10.7620/zgfybj.j.issn.1001-4411.2017.22.46.
16 李筱蟠, 刘有才, 余响霖, 等. 儿童过敏性紫癜不同时期血清D-二聚体、尿β2微球蛋白水平观察[J]. 中国现代医生, 2020, 58(8): 9-11.
17 中华医学会神经病学分会感染性疾病与脑脊液细胞学学组. 中枢神经系统感染性疾病的脑脊液宏基因组学第二代测序应用专家共识[J]. 中华神经科杂志, 2021, 54(12): 1234-1240. DOI: 10.3760/cma.j.cn113694-20210730-00532.
18 刘韦萍, 夏惠, 陶志勇. 宏基因组测序技术在感染性疾病诊断中的应用[J]. 中国病原生物学杂志, 2021, 16(05): 614-618. DOI: 10.13350/j.cjpb.210523.
19 谢栓栓, 李譞, 李萍, 等. 宏基因二代测序技术对感染性疾病患者的诊断价值及其临床应用[J]. 国际呼吸杂志, 2020, 40(9): 641-646. DOI: 10.3760/cma.j.cn131368-20191003-01366.
20 Zhang CJ, Fang XY, Huang ZD, et al. Value of mNGS in sonication fluid for the diagnosis of periprosthetic joint infection[J]. Arthroplasty, 2019, 1(1): 9. DOI: 10.1186/s42836-019-0006-4.
21 Wang Q, Wu B, Yang DL, et al. Optimal specimen type for accurate diagnosis of infectious peripheral pulmonary lesions by mNGS[J]. BMC Pulm Med, 2020, 20(1): 268. PMID: 33059646. PMCID: PMC7566056. DOI: 10.1186/s12890-020-01298-1.
22 Greninger AL. The challenge of diagnostic metagenomics[J]. Expert Rev Mol Diagn, 2018, 18(7): 605-615. PMID: 29898605. DOI: 10.1080/14737159.2018.1487292.
23 龚健仁. 我国恙虫病的分布状况与研究概况[J]. 中华疾病控制杂志, 2016, 20(11): 1176-1181. DOI: 10.16462/j.cnki.zhjbkz.2016.11.025.
24 Basu P, Williams A, O'Brien MT, et al. A case of Finegoldia magna (formerly Peptostreptococcus magnus) infection mimicking disseminated malignancy[J]. Int J Infect Dis, 2016, 53: 12-14. PMID: 27771471. DOI: 10.1016/j.ijid.2016.10.006.
25 刘丹, 王晓红, 张小彬, 等. 脓毒症患者肠道菌群紊乱的临床研究[J]. 中华急诊医学杂志, 2019, 28(6): 736-742. DOI: 10.3760/cma.j.issn.1671-0282.2019.06.015.
26 栾亮, 王璐, 褚美玲, 等. 左足软组织感染伴嗜胨菌和大芬戈尔德菌菌血症一例[J]. 中华临床感染病杂志, 2019, 12(3): 214-216. DOI: 10.3760/cma.j.issn.1674-2397.2019.03.011.
27 Kooi EJ, de Vries PJ, van Geloven AW, et al. Actinomycosis of the abdominal wall after cholecystectomy: transferral theory[J]. Neth J Med, 2016, 74(10): 451-454. PMID: 27966440.
28 Huang J, Jiang EL, Yang DL, et al. Metagenomic next-generation sequencing versus traditional pathogen detection in the diagnosis of peripheral pulmonary infectious lesions[J]. Infect Drug Resist, 2020, 13: 567-576. PMID: 32110067. PMCID: PMC7036976. DOI: 10.2147/IDR.S235182.
29 冯美琴. 宏基因组学的研究进展[J]. 安徽农业科学, 2008, 36(2): 415-416. DOI: 10.3969/j.issn.0517-6611.2008.02.013.
30 Chiu CY, Miller SA. Clinical metagenomics[J]. Nat Rev Genet, 2019, 20(6): 341-355. PMID: 30918369. PMCID: PMC6858796. DOI: 10.1038/s41576-019-0113-7.
31 孙雯雯, 顾瑾, 范琳. 宏基因组二代测序对不同类型结核病的诊断价值[J]. 中华结核和呼吸杂志, 2021, 44(2): 96-100. PMID: 33535323. DOI: 10.3760/cma.j.cn112147-20200316-00343.
32 钮月英, 吴晓虹, 应可净. 肺泡灌洗液宏基因二代测序技术对下呼吸道感染病原体检测的优势[J]. 中国实用内科杂志, 2020, 40(9): 754-758. DOI: 10.19538/j.nk2020090111.
33 顾嘉程, 吴洪, 陈星兆, 等. 宏基因组二代测序在诊断颅脑创伤相关中枢神经系统感染中的价值[J]. 中华神经外科杂志, 2020, 36(10): 993-997. DOI: 10.3760/cma.j.cn112050-20200401-00194.