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