Population structure and spatial distribution of mycobacterium tuberculosis in Catalonia

Abstract

Abstract Motivation: Even though Catalonia is a low-incidence area for tuberculosis (TB) transmission, high migration flow can make it a focal point for various Mycobacterium tuberculosis complex (MTBC) lineages. This study analyzed the population structure, geographical distribution, and hotspot locations of MTBC lineages/sublineages in Catalo-nia. Methods: Whole-genome sequencing (WGS) of 791 clinical MTBC strains enabled the construction of a Maximum Likelihood phylogenetic tree based on employing the General Time Reversible evolutionary model with gamma distribution for nucleotide substitution, and strains were typed into lineages and sublineages according to specific SNPs profiles. A logistic regression model was employed to analyze clinical phenotype associated with dominant MTBC lineages. The global Fisher’s exact test evaluated the distribution of lineages, including the assessment of migration factors. Post hoc Fisher’s exact test assessed the linkage between the country of origin and MTBC line-age. SatScan analysis identified hotspot areas for MTBC lineages across the study region. Results: WGS analysis revealed seven MTBC lineages in Catalonia: L4 (82.9%), L3 (6.8%), L2 (3.4%), L1 (2.6%), L6 (1.4%), M. bovis (1.9%), and L5 (0.3%). Within predominant Lineage 4, L4.1.2/Haarlem, L4.3/LAM, and L4.10/PGG3 sublineages were most prevalent. The L1/EAI, L2/Beijing, and L3/CAS exhibited localized distributions and adhered to the migrant community, while the L4.1.2/Haarlem, L4.3/LAM, and L4.10/PGG3 are almost ubiquitous in Catalonia. The L3/CAS and L4.10/PGG3 were significantly associated with extrapulmonary TB, while L4.1.2/Haarlem was linked with sputum smear-positive TB cases. Recent migrants from India and Pakistan showed a significantly higher risk of L3/CAS. Overall, the L4/Euro-American predominantly spreads among Spanish-born patients and long-term migrants with Senegalese and Moroccan migrants having 1.1- and 1.2-fold higher risks for L4.1.2/Haarlem and L4.10/PGG3 respectively. Migrants from Argentina, Venezuela, Senegal, Morocco, and Roma-nia demonstrated significant associations with L4.3/LAM, with aORs of 2.4, 2.4, 2.0, 1.6, and 1.1, respectively. Hotspots with multiple MTBC lineages involvement were identified in 9 counties Vallès Occidental, Barcelonès, Baix Llobregat, Garraf. Alt Penedès, Maresme, Moianès, Vallès Oriental, and Baix Camp, underscoring the need for targeted public health interventions. The L4.10/PGG3 exhibits a high propensity to form clusters compared to other lineages in Catalonia. Conclusion: In Catalonia, the L4/Euro-American dominates, particularly L4.1.2/Haarlem, L4.3/LAM, and L4.10/PGG3, each with distinct epidemiological profiles. Spatial analysis pinpointed transmission hotspots, high-lighting regional variability in MTBC lineage distribution. Targeted public health interventions are crucial in these high-risk areas and among certain migrant populations to mitigate TB transmission dynamics.