Epizootic dynamics of yellow fever in forest fragments: An agent-based model to explore the influence of vector and host parameters

Yellow fever (YF) is an acute infectious hemorrhagic disease caused by the yellow fever virus (YFV) and transmitted to humans by infected mosquitoes. In Brazil and other South American countries, the disease has been restricted to the sylvatic cycle, in which the virus circulates among mosquitoes and non-human primates in forested areas. Frequent outbreaks in the Amazon basin that spread to other Brazilian ecoregions have been observed in recent years. The most recent started in 2014 and spread to forests in densely populated areas on the Brazilian Atlantic Coast, resulting in the death of hundreds of humans and thousands of monkeys. However, the underlying ecological mechanisms that support YFV amplification and the severity of an epizootic and persis-tence of the virus on a microgeographic scale in these forest patches are still poorly understood. Here, we developed an agent-based model that simulates the dynamics of YFV transmission in a hypothetical forest fragment. The proposed model contains individual agents representing mosquitoes, breeding sites, howler monkeys (Alouatta) and other vertebrate species living and interacting in an environment where the YFV has emerged. The model simulations aimed to investigate the isolated and interaction effects of important input parameters linked to mosquitoes, monkeys, the environment and hypothetical alternative hosts on the following outcomes: (1) maximum proportion of infected mosquitoes, (2) proportion of dead monkeys and (3) YFV persistence in the environment. Local and global sensitivity analyses were used to assess the influence of different sets of input parameter values on the outputs. The model simulations indicated that mosquito abundance had the greatest influence on the outputs and made a major contribution to monkey mortality. Additionally, most of the variation in the outputs was due to complex and indirect effects of the different input parameters. These results suggest that mosquito density is one of the main factors responsible for YFV amplification during epizootics and reinforce the hypothesis that the severity and persistence of an outbreak depend on a complex web of in-teractions between different factors associated with vectors, hosts and the environment.