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Leishmaniasis is a vector-borne disease of worldwide distribution, currently present in 98 countries. Since late 2010, an unusual increase of human visceral and cutaneous leishmaniasis cases has been observed in the south-western Madrid region, totaling more than 600 cases until 2015. Some hosts, such as human, domestic dog and cat, rabbit (Oryctolagus cuniculus), and hare (Lepus granatensis), were found infected by the parasite of this disease in the area. Hares were described as the most important reservoir due to their higher prevalence, capacity to infect the vector, and presence of the same strains as in humans. Various measures were adopted to prevent and control the disease, and since 2013 there was a slight decline in the human sickness. We used a mathematical model to evaluate the efficacy of each measure in reducing the number of infected hosts. We identified in the present model that culling both hares and rabbits, without immediate reposition of the animals, was the best measure adopted, decreasing the proportion of all infected hosts. Particularly, culling hares was more efficacious than culling rabbits to reduce the proportion of infected individuals of all hosts. Likewise, lowering vector contact with hares highly influenced the reduction of the proportion of infected hosts. The reduction of the vector density per host in the park decreased the leishmaniasis incidence of hosts in the park and the urban areas. On the other hand, the reduction of the vector density per host of the urban area (humans, dogs and cats) decreased only their affected population, albeit at a higher proportion. The use of insecticide-impregnated collar and vaccination in dogs affected only the infected dogs’ population. The parameters related to the vector contact with dog, cat or human do not present a high impact on the other hosts infected by Leishmania. In conclusion, the efficacy of each control strategy was determined, in order to direct future actions in this and in other similar outbreaks. The present mathematical model was able to reproduce the leishmaniasis dynamics in the Madrid outbreak, providing theoretical support based on successful experiences, such as the reduction of human cases in Southwest Madrid, Spain. [ABSTRACT FROM AUTHOR]

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