Metagenomic next-generation sequencing for the etiological diagnosis of rabies virus in cerebrospinal fluid

Abstract

Background: Rabies is a highly fatal disease. Once symptoms develop, death usually occurs within days. Survivors were occasionally reported in the literatures. Ante-mortem diagnosis remains a challenge in most rabies endemic countries. A novel, accurate diagnostic assay is highly desirable. Methods: We used metagenomic next-generation sequencing (mNGS) to examine the cerebrospinal fluid (CSF) samples of a 49-year-old patient with rabies and validated the results by TaqMan PCR and RT-PCR/Sanger sequencing. Results: Metagenomic next-generation sequencing identified sequence reads uniquely aligned to the rabies virus (RABV). PCR confirmed the presence of the partial RABV N gene in the CSF. Phylogenetic analysis showed that the RABV grouped as an Asian clade, which is the most broadly distributed clade in China. Conclusion: Metagenomic next-generation sequencing may be a useful screening tool for the etiological diagnosis of rabies, especially in the absence of timely rabies laboratory testing or in patients with no exposure history.