期刊
CLINICAL CHEMISTRY
卷 68, 期 8, 页码 1031-1041出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/clinchem/hvac067
关键词
metagenomic next-generation sequencing; infectious diseases; children; antimicrobial usage; fungal
资金
- Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics [20dz2260900]
- Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases [20dz2261100]
- Scientific and Technology Commission of Shanghai Municipality [20Y11903600]
- Shanghai Municipal Health Commission [2019SY049]
This study evaluated the clinical application of metagenomic next-generation sequencing (mNGS) in a large population of children with various types of infectious diseases. The results showed that mNGS had higher sensitivity in pathogen detection compared to standard tests, and it provided more diagnostic information. For critically ill pediatric patients with suspected infection, mNGS tests can provide valuable diagnostic information to guide clinical decision-making.
Background Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. Methods From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. Results According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). Conclusions For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.
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