Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis (Mtb) and one of the top 10 causes of death worldwide. To reduce 95% of TB deaths by 2035, and meet the WHO END-TB strategy goal, requires critical introduction of new and effective tools such as improved drugs, vaccines and diagnostic tests. Innovation for new tools for TB control is reliant on new knowledge of TB, which can be gained through applying host and pathogen genomics.
We are using a genomics approach to characterize the independent roles of host and pathogen genome variation, as well as their interaction, in active TB. We have a large cohort of sputum smear positive pulmonary TB patients from Vietnam (N=3000) and have conducted a human genome-wide association study (GWAS) of TB cases and controls and performed whole genome sequencing of Mtb isolates.
Our results demonstrate how pathogen genomics can define the population diversity and spread of Mtb and investigate drug resistance emergence. This has led to a current project to understand TB transmission in urban and rural areas of Nepal. Further, by combining human and pathogen genomic data using a targeted and genome-to-genome approach, we have the potential to uncover novel aspects of host and pathogen TB disease biology and gain insights into the mechanisms of protective immunity.