Trade movements represent a major route for the spread of pathogens such as Mycobacterium avium subsp. paratuberculosis (Map) that causes paratuberculosis, in metapopulations of cattle herds. Our objective was to assess scenarios combining measures of Map spread control based either on test at purchase or internal biosecurity (including hygiene improvement, culling, or calf management). A metapopulation model was developed accounting for population and infection dynamics in each dairy herd. Within herd infection dynamics were connected through observed animal trade movements. When considered separately, simulated interventions slowed down the disease spread, but did not induce a decrease in the number of infected herds. Interestingly, in simulations combining several measures, both effects were achieved. In addition to introducing a model of Map spread at a regional scale, our study highlights the key challenges of controlling Map spread in a region endemically infected