Molecular and phenotypic drug resistance pattern of common Mycobacterium tuberculosis complex species and associated mutation: Evidence from selected TB treatment initiating centers in Ethiopia.

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Date

2020-06

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Addis Abeba University

Abstract

Background: Drug resistance in Mycobacterium tuberculosis complex remains major health burden in human history and still is a major leading cause of death in developing countries. Early detection of all forms of drug resistance tuberculosis is a key factor to reduce and contain the spread of these resistant strains. A better knowledge of the mechanisms of action of antituberculosis drugs and the development of drug resistance will allow identifying new drug targets and better ways to detect drug resistance. Drug Susceptibility test of certain drugs can also be technically challenging, in resource limited areas and cost prohibitive. Objective: The objective of this study was to asses molecular and phenotypic drug resistance Pattern of common Mycobacterium tuberculosis complex species and associated mutation. Methods: A cross sectional study design was followed, the data was collected using standard check list and sputum samples from a total 204 study individuals with bacteriologically confirmed tuberculosis cases. Sputum samples was analyzed using conventional Tuberculosis culture and Identification followed by molecular and then phenotypic drug susptability test for both first line and second line drugs was done as a gold standard to see the drug susptability pattern and associated mutations. Data was entered in to SPSS version 20 and export to STATA version 12 for analysis. Descriptive analysis and frequencies was used for analysis. Results: Out of 204 Clinical samples collected, Mycobacterium species were recovered from165 in which 160 were Mycobacterium tuberculosis complex and the remaining 5 isolates were nontuberculosis Mycobacterium species. Differentiation of Mycobacterium tuberculosis complex isolates was conducted by using genotype MTBC assay and the result revealed that all were found out to be M. tuberculosis. Out of 5 Non Tuberculosis Mycobacterium species: 2 M.fortuitum, 2 M.intracellulare and 1 M.gordonae were identified. Among 160 species of M. tuberculosis isolates 110(68.8%) and 50(31.2%) were susceptible and resistance to one of all drugs tested, respectively. Ninety-nine isolates were Multi drug resistance while 8(5%) isolate was Pre-Extensive drug resistance, whereas 1(0.6%) isolate identified as Extensive drug resistance. Out of genotypic resistance isolates highest frequency of mutation detected for katG 86(92.5%) followed by rpoB (93(58.15%), 4(4.3%) inhA and4 (4.3%) gyrase genes. A total of 30(18.7%) isolates found to be discordant from this 12(7.5%) for Rifampicin, 16 (16%) for Isoniazid, 3(1.8%) for Fluoroquinolone and 3(1.8%) for Second line injectable drugs. Conclusion: In conclusion, the present study findings in the phenotypic DST pattern showed that the magnitude of drug resistant TB in the previously treated TB cases was higher as compared to new cases. Highest proportion drug resistance detected for INH followed by RIF, resistance for EMB and STM all so higher. Determining the yield of drug resistance TB using both Phenotypic and Molecular DST methods were recommended for programmatic management of drug resistance Mycobacterium tuberculosis complex in Ethiopia.

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Keywords

Anti TB Drug Resistance, Gene mutation, Mycobacterium Tuberculosis Complex

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