Abstract
Tick-borne viral infections, including severe fever with thrombocytopenia syndrome virus (SFTSV), are increasingly recognized as a significant threat to global public health owing to their rapid dissemination and high mortality rates. While isolated outbreaks within single species have been documented, reports of multi-host cluster cases remain scarce. This study describes a consecutive, cross-species outbreak of severe fever with thrombocytopenia syndrome disease between April and May 2024 on a remote island in Nagasaki Prefecture that involved four cats and four humans. An interdisciplinary investigation integrating molecular phylogenetic analysis of viral genomes-including previously identified Nagasaki strains of SFTSV-and haplotype network analysis provided insights into the infection dynamics. Despite the absence of confirmed direct contact between cats and humans, four animals and one patient succumbed to the infection. Genomic analyses demonstrated high similarity to circulating Nagasaki strains, whereas haplotype analysis indicated multiple viral introduction events and complex transmission pathways, reflecting diverse sources. These findings underscore the critical need for a One Health approach-integrating human, animal, and vector surveillance-to effectively monitor, understand, and control tick-borne viruses globally, in both endemic and emerging regions.