LAUSR

OBJECTIVES It is established that resistance to rifampicin (RIF) in 90% of the RIF resistantM. tuberculosis strains is attributable to point mutations in the rpoB gene while 50-95% of M. tuberculosis resistance to isoniazid (INH) is caused by mutations in katG gene. However, the patterns and frequencies of mutations vary with geographical differences. In Zambia, the genetic resistance of M. tuberculosis to RIF and INH were unreported before this study. METHODS Using sequencing, we analyzed rpoB, katG and inhA genes for 99 multidrug-resistant (MDR) and 49 pan-susceptible M. tuberculosis isolates stored at a tuberculosis reference laboratory from 2013 to 2016 and compared with published profiles from other African countries. RESULTS Ninety six percent (95/99) of the MDR-TB isolates carried mutations in bothrpoB and katG genes. No mutations were detected among the pan-susceptible isolates. rpoB gene codon 531 and katG gene codon 315 at 55.6 % (55/99) and 94.9 % (94/99) were the most altered among the RIF and INH resistant isolates, respectively. Distinctly, katG mutations were predominantly high among Zambian isolates (96%) compared to other countries in the region. CONCLUSION The drug resistant associated mutations to RIF and INH circulating in Zambia are similar to what have been reported globally, therefore our data validates the applicability of molecular diagnostic tools in Zambia. However,katG mutations were predominantly high among M. tuberculosis isolates in this study compared to other regional countries and might disassociate cross-boundary transmission of MDR-TB from other African nations.