Introduction: Mpox is a rare but potentially serious viral disease with a fatality rate of about 11% and is endemic to the Central and West African countries. Vaccination plays a crucial role in controlling and preventing the spread of the disease. However, due to limited resources and challenges in vaccine distribution, designing effective vaccination strategies becomes essential to optimize cost-effectiveness. In this study, we propose a game-theoretic model to evaluate different vaccination strategies for managing Mpox outbreaks via voluntary vaccination.

Methods: The game-theoretic model is designed to simulate interactions between different stakeholders involved in controlling the spread of Mpox. We created an epidemiological compartmental model that incorporates various parameters based on literature data to simulate the spread of monkeypox in three equilibria scenarios- disease free, fully endemic and semi-endemic (with disease existing only among humans)

Results: Our simulation model demonstrated that the effectiveness of vaccination strategies depends on the collaboration and decision-making strategies of the involved parties. The existence of semi-endemic equilibrium has severe implications should the MPX virus mutate to increase viral fitness in humans. We find that MPX is controllable and can be eradicated in a semi-endemic equilibrium by vaccination. However, in a fully endemic equilibrium, MPX cannot be eradicated by vaccination alone.

Discussion: Using the game-theoretical approach in conjunction with our mathematical model yielded insight into the complex dynamics in disease spread and prevention. Our model quantified the costs and benefits of getting the smallpox vaccine (85% effective in preventing MPX) and presented a sensitivity analysis to identify parameters that created the greatest change in controlling Mpox outbreaks. As cases of MPX become increasingly reported among humans, we hope that the models may serve as a predictive tool to better study the spread of MPX. We also showed a potential existence of the semi-endemic equilibrium, in which there is no infection in the squirrel population and the disease still persists in the human population. As evidenced in recent outbreaks in countries without a disease reservoir, a careful understanding of the semi-endemic equilibrium is needed when making decisions on optimal vaccination and preventative measures.