Addressing the elephant in the room: Proceedings of the third annual Dengue Endgame Summit

Dengue is a disease caused by four serologically and genetically distinct orthoflaviviruses spread by mosquitoes. It is the largest arthropod-borne viral disease in the world with millions of human cases each year. The third annual Dengue Endgame Summit was convened in Syracuse, New York, over August 12-14, 2025, to discuss the current state of dengue, global dengue control efforts, and paths towards achieving sustained and effective dengue control. The event brought together 181 participants from 48 institutions across 11 countries to address current dengue outbreaks, next-generation mosquito vector interventions, vaccine and antiviral development, immune correlates of protection, and human challenge models. Four key themes emerged from the in-depth and nuanced discussions at the summit: (1) dengue control will require globally coordinated but locally tailored approaches that account for regional transmission differences and diverse circulating viral serotypes and genotypes; (2) the evolving dengue burden necessitates the strategic deployment of countermeasures, including vaccines, antivirals, and vector control, matched to local epidemiology; (3) longstanding dogma surrounding dengue immunopathogenesis and immune correlates of protection should be systematically reevaluated in light of advances in our understanding of cellular immunity, trained innate immunity, and the interplay of multiple components of the immune response; and (4) sustained progress depends on multisectoral collaboration, adequate financial resources, political commitment, and integration with broader vector-borne disease control efforts. These discussions highlighted both the complexity of dengue control and the diverse opportunities for accelerating progress toward a dengue endgame.