Population structure and spatial distribution of Mycobacterium tuberculosis complex in Catalonia

Background Despite being a low-incidence area, Catalonia experiences substantial migration flows from countries with high tuberculosis (TB) burden, potentially making it a focal point for various Mycobacterium tuberculosis complex (MTBC) lineages. Aim We aimed to characterize the spatial structure of MTBC (sub)lineages in Catalonia, assess their associations with clinical and epidemiological factors, and identify spatiotemporal hotspots of cases belonging to the same sublineage. Methods Whole-genome sequencing (WGS) was performed on 783 MTBC isolates collected across Catalonia from December 2021 to June 2023. Lineages and sublineages were assigned using SNP-based typing. Associations with clinical presentation, country of origin, and migration timing were evaluated using logistic regression and Fisher’s exact test. SaTScan was used to identify space–time clusters of selected (sub)lineages. Results Lineage 4/Euro-American predominated (83%), with L4.1.2/Haarlem, L4.3/LAM, and L4.10/PGG3 widely distributed, particularly among Spanish-born individuals and long-term migrants. L1/EAI, L2/Beijing, L3/CAS, and L4.1.1/X showed geographically restricted patterns, predominantly linked to migrants from India, Pakistan, China, and Peru. L1/EAI, L3/CAS, and L4.10/PGG3 were significantly associated with extrapulmonary TB. Sublineage diversity increased from sparsely to densely populated areas. Spatiotemporal analysis identified four significant clusters involving L1/EAI, L3/CAS, and L4.10/PGG3 across seven counties, mainly within the Barcelona Metropolitan Area, with L4.10/PGG3 showing the strongest clustering. Conclusion L4 sublineages predominate in Catalonia, whereas L1/EAI, L2/Beijing, and L3/CAS are more geographically restricted and predominantly associated with migrants. The presence of sublineage-specific hotspots in dense urban areas highlights the role of migration dynamics and urbanization in shaping TB transmission.