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Outbreak strains of Mycobacterium tuberculosis are promising candidates as targets in the search for intrinsic determinants of transmissibility, as they are responsible for many cases with sustained transmission; however, the use of low-resolution typing methods and restricted geographical investigations represent flaws in assessing the success of long-lived outbreak strains. We can now address the nature of outbreak strains by combining large genomic data sets and phylodynamic approaches. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (the GC strain) since 1993, which accounts for ~20% of local tuberculosis cases. We selected a panel of specific single nucleotide polymorphism (SNP) markers for an in-silico search for additional outbreak-related sequences within publicly available tuberculosis genomic data. Using this information, we inferred the origin, spread, and epidemiological parameters of the GC strain. Our approach allowed us to accurately trace the historical and more recent dispersion of the GC strain. We provide evidence of a highly successful nature within the Canarian archipelago but limited expansion abroad. Estimation of epidemiological parameters from genomic data disagree with a distinctive biology of the GC strain. With the increasing availability of genomic data allowing for the accurate inference of strain spread and critical epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as is routinely carried out for SARS-CoV-2 variants of concern. We demonstrate that social determinants rather than intrinsically higher bacterial transmissibility better explain the success of the GC strain. Importantly, our approach can be used to trace and characterize strains of interest worldwide. IMPORTANCE Infectious disease outbreaks represent a significant problem for public health. Tracing outbreak expansion and unde

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.

Pág. 26-27 del libro de abstracts que se adjunta. Tuberculosis is an air spreading infectious disease and is still one of the ten top causes of death worldwide. Halting TB transmission is central to control and reduce disease incidence. Thus special attention should be paid to massive and uncontrolled transmission as occurs in outbreaks. In 1993 a Liberian refugee introduced a Beijing strain to Gran Canaria, it spread quickly and was reported as outbreak in 2001. In the following years the same strain were registered in other islands from the archipelago and also in the peninsula (2002). We applied whole genome sequencing and phylodynamic bayesian analysis to characterize the historical roots and the epidemiological patterns of this outbreak. We selected a total of 66 cases between 1993-2018 including one case from Switzerland obtained from public databases. In addition, we compared the strain against a database of 36000 genomes from global sources. The outbreak strain belongs to L2.2.3; as expected it has a phylogeographic relationship to West Africa but also to Vietnam. Our analysis revealed that the index case remained infectious over several months causing a secondary outbreak. The phylodynamics results revealed periods of expansion meaning that the outbreak is still uncontrolled. As conclusion, poor treatment adherence of the index case caused an outbreak that spread rapidly in The Canary Islands subsequently reached the continent to later become an ongoing international outbreak.