Genomic analysis of Mycobacterium tuberculosis reveals complex etiology of tuberculosis in Vietnam including frequent introduction and transmission of Beijing lineage and positive selection for EsxW Beijing variant

Tuberculosis (TB) is a leading cause of death from infectious disease and the global burden is now higher than at any point in history. Despite coordinated efforts to control TB transmission, the factors contributing to its successful spread remain poorly understood. Vietnam is identified as one of 30 high burden countries for TB and MDR-TB with an incidence of 137 TB cases per 100,000 individuals in 2015. Recent phylogenomic analyses of the causative agent Mycobacterium tuberculosis (Mtb) in other high-prevalence regions have provided insights into the complex processes underlying TB transmission. Here we examine the transmission dynamics of Mtb isolated from TB patients in Ho Chi Minh City (HCMC), Vietnam via whole genome analysis of 1,635 isolates and comparison with 3,085 isolates from other locations. The genomic data reveal an underlying burden of disease caused by endemic Mtb Lineage 1 associated with activation of long-term latent infection, on top of which is overlaid a three-fold higher burden associated with introduction of exotic Lineage 2 and 4 Mtb strains. We identify frequent transfer of Beijing lineage Mtb into the country, which are associated with higher levels of transmission in this host population than endemic Lineage 1 Mtb. We identify a mutation in the secreted protein EsxW in Beijing strains that also appears to be under positive selection in other Mtb lineages, which could potentially contribute to the enhanced transmission of the Beijing lineage in Vietnamese and other host populations.

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