Comparative genomic analyses of Multi-Drug Resistant Genomic Analyses of Mycobacterium tuberculosis isolates from Nepal and other geographical locationsfromMulti-Drug Resistant Cases of TB in Nepal

Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. Here, we collected MDR-TB isolates in Nepal for next-generation sequencing. The objective of this study was to perform Wholewhole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n=19) to identified identify the specific mutations underlying their phenotypic resistance, and furthermore, detected resistance to fluoroquinolones among a high proportion of isolates. In addition, we compared examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to with a large panel of 1,274 genomes of international strains available from public databases. These analyses provided evidence that the XDR-TB isolates in our collection were not derived from importation of primary XDR-TB to Nepal but were more likely the result of acquisition of second-line drug resistance in Nepal. Resistance to fluoroquinolones was detected among a high proportion of the Nepal isolates. This has implications for the management of TB, including appropriate antimicrobial stewardship and susceptibility testing for fluoroquinolones and other second-line TB drugs, to minimise the development of XDR-TB among Nepal TB cases.