Deciphering the tangible spatio-temporal spread of a 25 years tuberculosis outbreak boosted by social determinants

Background. Outbreak strains are good candidates to look for intrinsic transmissibility as they are responsible for a large number of cases with sustained transmission. However, assessment of the success of long-lived outbreak strains has been flawed by the use of low-resolution typing methods and restricted geographical investigations. We now have the potential to address the nature of outbreak strains by combining large genomic datasets and phylodynamic approaches. Methods. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (GC) since 1993; accounting for ~20% of local TB cases. We selected a panel of specific SNP markers to in-silico search for additional outbreak related sequences within publicly-available TB genomic data. Using this information we inferred the origin, spread and epidemiological parameters of the GC-outbreak. Findings. Our approach allowed us to accurately trace both the historical and recent dispersion of the strain. We evidenced its high success within the Canarian archipelago but found a limited expansion abroad. Estimation of epidemiological parameters from genomic data contradicts a distinct biology of the GC-strain. Interpretation. With the increasing availability of genomic data allowing for an accurate inference of strain spread and key epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as routinely done for SARS-CoV-2 variants of concern. We show that the success of the GC-strain is better explained by social determinants rather than intrinsically higher bacterial transmissibility. Our approach can be used to trace and characterize strains of interest worldwide.This study was founded by Instituto de Salud Carlos III (FIS18/0336), Gobierno de Aragon/Fondo Social Europeo Construyendo Europa desde Aragon to SS. European Research Council (101001038-TB-RECONNECT), the Ministerio de Economía, Industria y Competividad (PID2019-104477RB-I00) to IC.N