The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi

  • Geoffrey Kumwenda The University of Malawi, College of Medicine, Blantyre, Malawi
  • Geoffrey Chipungu The University of Malawi, College of Medicine, Blantyre, Malawi
  • Derek Sloan University of St Andrews, Scotland
  • Yankho Kaimila The University of Malawi, College of Medicine, Blantyre, Malawi
  • Kondwani Chiumya The University of Malawi, College of Medicine – Wellcome Trust TB Research Laboratory, Blantyre, Malawi
  • Harry Pangani The University of Malawi, College of Medicine – Wellcome Trust TB Research Laboratory, Blantyre, Malawi

Abstract

Background The emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi. Methods A cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from ≥ 2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay. Results Out of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance. Conclusion The katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.

Published
2018-03-28
Section
Articles

Journal Identifiers


eISSN: 1995-7262
print ISSN: 1995-7262