ABSTRACT
Background: Multidrug resistant tuberculosis caused by Mycobacterium tuberculosis is an infection that is resistant to rifampicin and isoniazid. Management of Multidrug resistant tuberculosis is a serious challenge worldwide
Objectives: To investigate hotspot mutations in rpoB, katG and inhA genes and its possible co-relation with predominant genotypes in Khyber Pakhtunkhwa, Pakistan
Study design, settings and duration: This cross sectional study was conducted after approval from research and ethics committee of Provincial TB Control Program, Khyber Pakhtunkhwa in March 2015
Materials and Methods: A total of 166 clinical isolates were analysed which were collected from programmatic management of drug-resistant tuberculosis units. All samples were characterized by phonotypical drug susceptibility test, genotypic drug resistant test [line probe assay] and spoligotyping analysis using ''TB-SPRINT' micro bead assay
Results: Out of the total 166 samples, 97 strains were resistant to rifampicin [RIF] and 106 strains were resistant to isoniazid [INH]. Most common mutation in rpoB was S531L in 75 [77%] isolates followed by D516V in 10 [10%] and H526Y in 6 [6%] samples respectively. A rare mutation in rpoB gene at codon 522 and deletion of codon 518 was also reported. In 106 INH resistant strains, 97[91%] were associated with mutation in katG gene while resistance in 9 [8.4%] strain was due to mutation in the inhA promoter region. Spoligotyping analysis revealed 55 distinct types of different patterns. Spoligotyping patterns of 146 samples matched with 15 different linage of M.tuberculosis in which 101 [60%] were identified as the predominant CAS1-Delhi linage. The pattern of 20 strains [12%] did not matched to any other pattern in the SITVIT database and were named orphan KP
Conclusion: Molecular characterization of M.tuberculosis is very helpful in the early identification of MDR-TB. As CAS1-Delhi is the predominant type in this region, its association with drug resistance, treatment failure and patient demographic profiles should be investigated