P75

The level of transmission has been usually correlated with the TB burden, assuming it has a negligible impact in low incidence settings where imported latent TB cases are major contributors. Public health guidelines to control the disease has been designed based on that generalization. With whole genome sequencing we can now quantify and profile transmission in a setting with a precision not available before.  But whole genome sequencing population-based studies, required to compare transmission dynamics across settings, are still lacking. Here, we generate a population-based dataset from Valencia Region and compare it with available datasets from different TB-burden settings. Our main goal is to evaluate transmission dynamics and its correlation with disease burden. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamics methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in local transmission between low-burden TB settings, i.e clustering in the Valencia Region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission events, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal an important role of past epidemics in the on-going TB incidence, and highlight the need for in-depth characterization of local transmission dynamics, in order to design specifically-tailored TB control strategies.