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Metagenomic Next-Generation Sequencing vs. Traditional Microbiological Tests for Diagnosing Varicella-Zoster Virus Central Nervous System Infection

BACKGROUND: Unbiased metagenomic next-generation sequencing (mNGS) detects pathogens in a target-independent manner. It is not well-understood whether mNGS has comparable sensitivity to target-dependent nucleic acid test for pathogen identification. METHODS: This study included 31 patients with chic...

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Detalles Bibliográficos
Autores principales: Zhu, Yunqi, Xu, Miaomiao, Ding, Chengyuan, Peng, Zhihang, Wang, Weixiao, Sun, Binghu, Cheng, Jian, Chen, Chen, Chen, Wei, Wei, Hongxia, Hu, Zhiliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814106/
https://www.ncbi.nlm.nih.gov/pubmed/35127608
http://dx.doi.org/10.3389/fpubh.2021.738412
Descripción
Sumario:BACKGROUND: Unbiased metagenomic next-generation sequencing (mNGS) detects pathogens in a target-independent manner. It is not well-understood whether mNGS has comparable sensitivity to target-dependent nucleic acid test for pathogen identification. METHODS: This study included 31 patients with chickenpox and neurological symptoms for screening of possible varicella-zoster virus (VZV) central nervous system (CNS) infection. Microbiological diagnosing of VZV cerebrospinal fluid (CSF) infection was performed on stored CSF samples using mNGS, quantitative and qualitative VZV-specific PCR assays, and VZV IgM antibodies test. RESULTS: The median age was 30.0 [interquartile range (IQR), 24.3–33.3] years. 51.6% of the patients were men. About 80.6% of the patients had normal CSF white blood cell counts (≤ 5 × 10(6)/L). VZV IgM antibodies presented in 16.1% of the CSF samples, and nucleic acids were detectable in 16.1 and 9.7% using two different VZV-specific real-time PCR protocols. Intriguingly, maximal identification of VZV elements was achieved by CSF mNGS (p = 0.001 and p = 007; compared with qualitative PCR and VZV IgM antibody test, respectively), with sequence reads of VZV being reported in 51.6% (16/31) of the CSF samples. All VZV PCR positive samples were positive when analyzed by mNGS. Of note, human betaherpesvirus 6A with clinical significance was unexpectedly detected in one CSF sample. CONCLUSIONS: Our study suggests that CSF mNGS may have higher sensitivity for VZV detection than CSF VZV PCR and antibody tests, and has the advantage of identifying unexpected pathogens.