Detection of Japanese Encephalitis by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid: A Case Report and Literature Review

Abstract

Japanese encephalitis (JE) is an acute viral central nervous system disease, although less than 1% of patients infected with Japanese encephalitis virus (JEV) result in JE, which has an extremely poor prognosis. The Routine detection methods for JEV are time-consuming or limited by hospital conditions, therefore, need the quicker and sensitive techniques to detect JEV. Here, we reported a 14-year-old female who was admitted to our hospital with a severe fever, progressively headache and unconsciousness. Based on the clinical presentation, Preliminary diagnosis on admission indicated central nervous system infection of suspected viral meningoencephalitis or autoimmune encephalitis. The patient's symptoms were unrelieved after being treated with empiric antiviral therapy. Magnetic resonance imaging (MRI) showed that the lesions were located in the bilateral thalamus, head of caudate nucleus, and right lenticular nucleus, so we had to consider the possibility of Flaviviruses infection. We sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately, subsequent result suggested the infection caused by JEV. Two days later the results of the serum agglutination test confirmed that virus immunoglobulin M antibody positive. After a week treatment with intravenous immunoglobulin (IVIG), meanwhile, the lumbar puncture was used to check the pressure and various indicators of the CSF again to evaluate the treatment effect, An decrease in the number of WBC indicates, protein and unique RNA reads that the previous experimental treatment was effective, accompany by temperature and consciousness of the patient was normalized. Two weeks after admission, the patient was transferred to the rehabilitation hospital, MR showed the lesions had disappeared completely after 2 months of follow-up. We believed that mNGS may be an effective method for rapid identification of JE.

Emergence of Japanese encephalitis in Australia: a diagnostic perspective

“…74,75 The agnostic nature of this approach enables unexpected pathogens to be revealed including emerging viruses or divergent genotypes of known pathogens that evade directed assays. 76,77 Appropriate sample types include brain tissue or CSF (or blood or urine in particular circumstances) in the context of a suggestive clinical history. While expense and technical constraints dictate that metagenomics still largely functions as a research tool, future advances in the field including dedicated funding streams should see this approach adopted into mainstream diagnostics for cases of unexplained encephalitis.…”

Viral Metagenomics for the Identification of Emerging Infections in Clinical Samples with Inconclusive Dengue, Zika, and Chikungunya Viral Amplification

“…Viral metagenomics has been of great value for confirmation of emerging or unknown viral agents in clinical samples with undetermined diagnosis and for viral discovery [9,10]. The major advantages of metagenomics include high specificity of viral identification and the unbiased nature of viral detection, which enables full annotation of all viruses present in the tested sample [11,12].…”

The Diagnostic Value of Oligoclonal Band Detection in Viral Encephalitis

“…However, clinical diagnosis of viral encephalitis in some patients is challenging due to the widespread use of antibiotics [2]. Numerous studies conducted globally and domestically [3] [4] have found that patients with viral encephalitis exhibit elevated levels of immunoglobulin (mainly IgG) in the cerebrospinal fluid (CSF) early in the disease course. Therefore, intrathecal synthesis of IgG serves as a valuable clinical indicator for the early diagnosis and differential diagnosis of viral encephalitis.…”