On the verge of zoonosis: Mechanisms and risks of parasite spillover.

Zoonotic parasite spillover is a multi-host process shaped by interactions among wildlife, domestic animals, vector or intermediate hosts, humans, and the environment. Transmission is governed by complex parasite life cycles involving intermediate and bridge hosts and environmental stages, all of which regulate development, persistence, and exposure. Spillover occurs when host-parasite compatibility, ecological overlap, and human behaviors converge to enable cross-species transmission. Anthropogenic changes, including deforestation, urbanization, agricultural intensification, pollution, and climate change, are increasing ecosystem permeability, altering host immunity, and intensifying contact among species, thereby elevating spillover risk. Establishment in humans depends on the ability of parasites to overcome molecular and physiological barriers and, in some cases, sustain onward transmission. Although many zoonotic parasites establish dead-end infections, they may still impose significant morbidity. This Chapter revisits key concepts, including reservoirs, intermediate and bridge hosts, and the processes of shedding, spillover, and spread, integrating ecological and evolutionary mechanisms such as host-switching and parasite adaptation. We further examine how environmental change reshapes transmission pathways and host interactions and discuss key examples of parasite zoonotic spillover. Finally, we propose a One Health framework that incorporates life cycles, environmental processes, and multi-host networks, offering a more realistic foundation to understand, anticipate, and prevent zoonotic parasite emergence in a rapidly changing world.