Metagenomics next-generation sequencing for the diagnosis of central nervous system infection: A systematic review and meta-analysis

Abstract

ObjectiveIt is widely acknowledged that central nervous system (CNS) infection is a serious infectious disease accompanied by various complications. However, the accuracy of current detection methods is limited, leading to delayed diagnosis and treatment. In recent years, metagenomic next-generation sequencing (mNGS) has been increasingly adopted to improve the diagnostic yield. The present study sought to evaluate the value of mNGS in CNS infection diagnosis.MethodsFollowing the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2022 guidelines, we searched relevant articles published in seven databases, including PubMed, Web of Science, and Cochrane Library, published from January 2014 to January 2022. High-quality articles related to mNGS applications in the CNS infection diagnosis were included. The comparison between mNGS and the gold standard of CNS infection, such as culture, PCR or serology, and microscopy, was conducted to obtain true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values, which were extracted for sensitivity and specificity calculation.ResultsA total of 272 related studies were retrieved and strictly selected according to the inclusion and exclusion criteria. Finally, 12 studies were included for meta-analysis and the pooled sensitivity was 77% (95% CI: 70–82%, I2 = 39.69%) and specificity was 96% (95% CI: 93–98%, I2 = 72.07%). Although no significant heterogeneity in sensitivity was observed, a sub-group analysis was conducted based on the pathogen, region, age, and sample pretreatment method to ascertain potential confounders. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for CNS infection was 0.91 (95% CI: 0.88–0.93). Besides, Deek's Funnel Plot Asymmetry Test indicated no publication bias in the included studies (Figure 3, p > 0.05).ConclusionOverall, mNGS exhibits good sensitivity and specificity for diagnosing CNS infection and diagnostic performance during clinical application by assisting in identifying the pathogen. However, the efficacy remains inconsistent, warranting subsequent studies for further performance improvement during its clinical application.Study registration numberINPLASY202120002

Literature Review of Pathogen Agnostic Molecular Testing of Clinical Specimens From Difficult-to-Diagnose Patients: Implications for Public Health

“…However, the efficacy remains inconsistent, which warrants subsequent studies to further improve performance during clinical application. 49 , 52 In some cases, diagnostic sensitivity was increased by more than 18% to 20%, 49 , 51 without false positives, 51 independent of specimen type, 53 and without the need for viable or culturable pathogens. 35 However, mNGS can be less sensitive than polymerase chain reaction for detecting very low-level infections, 48 and as with other genomic methods, mNGS output still requires careful interpretation and substantial bioinformatics support.…”

The Utility of Metagenomic Next-Generation Sequencing (mNGS) in the Management of Patients With Bronchiectasis: A Single-Center Retrospective Study of 93 Cases

“…For instance, a study on lung infection by Chen et al indicated a bacteria and fungi detection rate as high as 95% using mNGS, contrasting a mere 60% detection rate with traditional methods [ 15 ]. In addition, for central nervous system infections, mNGS diagnostic sensitivity and specificity reached 77% (95% CI, 70%–82%; I 2 = 39.69%) and 96% (95% CI, 93%–98%; I 2 = 72.07%), respectively [ 16 ]. Given its higher sensitivity and efficiency compared with standard tests, mNGS offers universal diagnosis of complex or severe pathogen infections.…”