病原体宏基因组二代测序在儿童粒细胞缺乏伴发热中的应用价值

Application value of metagenomic next-generation sequencing for pathogen detection in childhood agranulocytosis with fever

摘要:

目的 探讨病原体宏基因组二代测序（metagenomic next-generation sequencing，mNGS）在儿童粒细胞缺乏伴发热中的应用价值，以期为儿童粒细胞缺乏伴发热的诊疗提供新的方法和策略。 方法 回顾性收集2020年1月至2021年12月粒细胞缺乏伴发热116例患儿的病原体mNGS结果。mNGS结果阴性患儿为阴性组（n=38），78例阳性患儿根据主要病原体分为细菌组（n=22）、真菌组（n=23）及病毒组（n=31）。比较各组临床资料的差异。 结果 116例粒细胞缺乏伴发热患儿中位诊断年龄8岁，中位mNGS结果回报时间为2 d，mNGS检测阳性率为67.2%（78/116）。细菌组患儿降钙素原水平高于阴性组（P<0.05），真菌组患儿C-反应蛋白水平、(1,3)-β-D葡聚糖/半乳甘露聚糖试验阳性率高于阴性组（P<0.05），真菌组患儿热程长于阴性组（P<0.05）。培养阳性病例中mNGS结果符合率为41%（9/22），其中血培养阳性病例中mNGS结果符合率为47%（8/17）。28例（36%）患儿根据mNGS阳性结果调整用药，其中26例治愈好转出院。 结论 病原体mNGS技术具有很好的时效性和阳性率，能为粒细胞缺乏伴发热患儿病原学诊断提供有力证据。

Abstract:

Objective To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever. Methods A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups. Results For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-β-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged. Conclusions The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.