Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features

Dengue virus is the most common mosquito-borne virus on Earth, with an estimated 390 million infections every year. Most are asymptomatic; severe disease is acute and self-limiting; chronic infection had never been documented. This case challenges that picture. A 45-year-old man with a five-year history of severe progressive dementia, involuntary movements, postural instability, and chronic CNS inflammation was referred to the NIH Undiagnosed Diseases Program after every standard diagnostic workup came back inconclusive.

Researchers screened the patient’s serum and cerebrospinal fluid against the entire human virome using VirScan, a phage-display library encoding peptides from every virus known to infect humans. Antibodies against dengue virus were strikingly enriched in CSF relative to serum — a pattern that did not appear for closely related flaviviruses such as Japanese encephalitis virus despite elevated serum titers. The compartment-specific signal pointed the team back to the brain itself.

Postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative PCR, and sequencing. Dengue was also recoverable by PCR and sequencing from a brain biopsy collected 33 months antemortem, demonstrating a chronic infection sustained for years despite a robust antiviral antibody response. The work reframes how clinicians should approach undiagnosed encephalitis in dengue-endemic regions and in patients with travel histories — and it shows how unbiased virome-wide antibody profiling can identify pathogens that targeted assays were never built to detect.