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.

All four dengue virus serotypes (DENV-1 to DENV-4) can cause severe and potentially fatal disease. Understanding the interplay between host immune responses and viral genetic diversity is particularly crucial in hyperendemic regions, where serotype shifts frequently occur during outbreaks. In this cross-sectional, surveillance-based study, we analyzed 350 patients with confirmed secondary dengue infection in Lao PDR, with samples collected between 2022 and 2023. Of these, 80 were successfully serotyped by RT-PCR and included in the serotype-specific analyses. Viral genotyping was performed using envelope (E) gene sequencing, and neutralizing antibody (nAb) titers and antibody-dependent enhancement (ADE) activities against all four DENV serotypes were assessed using single-round infectious particles in both FcγRIIA-negative and FcγRIIA-positive BHK-21 cells. The nAb titers were highest against DENV-2, followed by DENV-1, DENV-4, and DENV-3. Nevertheless, DENV-2 exhibited the highest ADE activity, suggesting that high nAb titers may not necessarily prevent ADE. We also documented the co-circulation of DENV-2 Cosmopolitan and Asian I genotypes. Our findings highlight the complex interplay between neutralizing and enhancing antibody responses during secondary infection, particularly in the context of DENV-2 infection. Our results emphasize the need to understand the dynamics of DENV transmission in hyperendemic settings and may inform future vaccine development and evaluation strategies.