Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations |
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| Affiliation: | 1. Department of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Victoria, Australia;2. Department of Microbiology and Immunology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia;3. Department of Microbiology, College of Medicine, Nepalese Army Institute of Health Sciences, Kathmandu, Nepal;4. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia;5. National Tuberculosis Control Center, Bhaktapur, Nepal;6. HIV Reference Unit, National Public Health Laboratory, Kathmandu, Nepal |
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| Abstract: | 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. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n = 19) to identify the specific mutations underlying their phenotypic resistance. In addition, we examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to a panel of 1274 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. |
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