Adult Japanese encephalitis in a non-endemic area: A case highlighting diagnostic limitations of targeted next-generation sequencing.

Japanese encephalitis (JE) is a mosquito-borne viral disease that is rarely reported in non-endemic regions. We describe an adult patient presenting with acute meningoencephalitis in northern China, a non-endemic area. Targeted next-generation sequencing (tNGS) performed twice on cerebrospinal fluid was negative because JE virus was not included in the detection panel. The diagnosis was confirmed by a strongly positive JE IgM antibody. This case highlights that tNGS has inherent diagnostic limitations depending on pathogen coverage. In non-endemic areas near endemic regions, JE should be considered in the differential diagnosis, and serologic testing remains essential for accurate diagnosis. ONE-SENTENCE SUMMARY: We report an adult case of Japanese encephalitis from a non-endemic region that was initially missed by targeted next-generation sequencing, emphasizing the need for the combined use of molecular and serological testing in suspected central nervous system infections.