Powassan Virus in the United States: An AI-Integrative One Health Scoping Review of Ecological Drivers, Zoonotic Interactions, Symptom Profiles, and Public Health Implications.

BACKGROUND: Powassan virus (POWV) is the only tick-borne encephalitis-group flavivirus endemic to the United States (U.S.) and is an increasingly serious public health threat. Reported U.S. cases remain relatively few but have grown steadily-from fewer than two annually before 2005 to a record 60 in 2024-and neuroinvasive disease carries a 10-15% case fatality with lasting neurological sequelae in roughly half of the survivors. Examining POWV through a One Health lens, we conducted a scoping review of its ecological and zoonotic drivers, its interactions with co-circulating tick-borne pathogens, its full clinical spectrum, and its distinction from other tick-borne diseases. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidance, we searched PubMed/MEDLINE, U.S. Centers for Disease Control and Prevention (CDC) surveillance databases, state health-department publications, and vetted public-health news through early 2026. The review was conducted as an AI-integrative partnership among the authors, the Global Infectious Diseases and Epidemiology Online Network (GIDEON) database, and Claude (Anthropic), enabling a synthesis of human-curated archival records collected over six years alongside the published literature; this yielded over 200 sources, almost half unavailable through an AI search alone. RESULTS: POWV is maintained in a sylvatic cycle involving I. scapularis ticks, small-mammal reservoirs, and incidental human spillover. Its clinical spectrum spans asymptomatic seroconversion to fatal meningoencephalitis; prodromal fever, headache, vomiting, and fatigue may progress to encephalitis, seizures, aphasia, cranial-nerve palsies, paralysis, and ataxia-the most severe neurological syndrome among U.S. tick-borne diseases. Cases cluster in the northeastern and Great Lakes states, with older males disproportionately affected, while viral evidence extends to the mid-Atlantic, southern, and western regions. POWV is distinguished by its flaviviral etiology, short (as little as 15 min) transmission window, absence of a characteristic rash, and complete antibiotic resistance. Of the 48 states surveyed, only 7 published POWV data. CONCLUSIONS: POWV is an escalating One Health threat driven by expanding vector tick ranges, land-use and climate change, and wildlife-human interface dynamics. Enhanced cross-sector surveillance integrating human, animal, and environmental monitoring, alongside improved public-health data reporting, is urgently needed.