Abstract
ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.ConclusionsFor patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.
Highlights
Central nervous system infections (CNS infections), including meningitis, encephalitis, and abscesses, refer to inflammation of the brain and spinal cord caused by various pathogenic microbes
Among the 88 patients, 15 patients were etiologically diagnosed by metagenomic next-generation sequencing (mNGS) alone, five patients were etiologically identified by whole exome sequencing (WES) alone, and one patient was diagnosed by both mNGS and WES
For patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies
Summary
Central nervous system infections (CNS infections), including meningitis, encephalitis, and abscesses, refer to inflammation of the brain and spinal cord caused by various pathogenic microbes. For neonates with a CNS infection, early identification of the pathogen is the key to accurate treatment. Because of their immature immune function, newborns are at high risk of all types of infections. 60% - 85% of the bacteria detected by using the metagenomics method do not grow on standard bacterial culture media. (Simner et al, 2018) Polymerase chain reaction (PCR)-based and antigen or antibody methods only detect a limited number of pathogens in a single experiment. (Marcilla-Vazquez et al, 2018; WhiteduckLéveillée et al, 2016) The diagnostic workup for many patients requires extensive and serial testing that utilizes a combination of culture, antigen, serologic, and molecular methods, resulting in delayed or missed diagnoses and increased costs A presumption of pathogens is needed to select the appropriate primers and probes. (Marcilla-Vazquez et al, 2018; WhiteduckLéveillée et al, 2016) The diagnostic workup for many patients requires extensive and serial testing that utilizes a combination of culture, antigen, serologic, and molecular methods, resulting in delayed or missed diagnoses and increased costs
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