Health Research Registry List

Research Registry No : HRID-00120_V3
 
University Departmental Research :
 
Registration Date : 2019-05-20
 
Title of Research : Molecular typing and detection of drug resistant mutations in multidrug resistant Mycobacterium tuberculosis strains from Myanmar
 
Principle Investigator : WAH WAH AUNG
 
Co-authors : Phyu Win Ei, Mi Mi Htwe, Jong Seok Lee, Chulhum L Chang, Wint Wint Nyunt, Thyn Lei Swe, Kay Thi Aye
 
Field of Research : Bacteriology
 
Publication Source : Antimicrob Agents Chemother. 2018;62(3):e01984-17.
 
 
Year of Publication : 2018
 
URL of Publication : http://aac.asm.org
 
Presentation Source : 48th World Conference on Tuberculosis and Lung Diseases
 
Placement of Presentation : Guadalajara, Mexico
 
Year of Presentation : 2017
 
Abstract : Background: Pyrazinamide (PZA) is a key component of short-course anti-tuberculosis treatment regimenand also of second-line regimen for multidrug-resistant TB (MDR-TB). There are limited data on PZA resistance because PZA susceptibility testing is rarely performed routinely due to technical difficulties.Mutations in pncA gene were responsible for PZA resistance by reduction or loss of pyrazinamidase activity in Mycobacterium tuberculosis (MTB).This study was carried out to detect prevalence of PZA resistance and pattern of pncA gene mutations responsible for PZA resistance in MDR-MTB strains in Myanmar. Method: MTB isolates were collected from patients enrolled for MDR-TB treatment in 2016 at Yangon and Mandalay TB Centers, Myanmar. Resistance to isoniazid and rifampicin was confirmed by solid culture based drug susceptibility testing. Phenotypic PZA resistance was detected byliquid culture based Mycobacterial Growth Indicator Tube (MGIT) method. Mutations in pncA gene and promoter region were detected by Sanger DNA sequencing method. Results: Among 45 MDR-MTB isolates, phenotypic PZA resistance was found in 26 (57.8%). And mutations were found in 27 (60%) of isolates. Thirty one different types of mutations were distributed on the pncA gene and 10 types of which were found to be novel mutations. Common mutations were found at the following regions of each of two strains: Lys96, Phe81, Thr135, Gly17 and Thr61 (4.4% each).Strong correlation between pncA mutations and phenotypic PZA resistance were detected (Kappa Index =0.94). Conclusion: The present findings showed high prevalence of PZA resistance amongMDR-TB patients in Myanmar and highlights the need for development of effective treatment regimens for PZA resistant MDR-TB. Pattern of pncA gene mutations conferring PZA resistance were scattered and diverse and this information can be used for further studies on the development of rapid PZA susceptibility assays. Our study also supported that routine PZA susceptibility testing is needed to be incorporated to treatment monitoring regimen and National drug resistance surveys.
 
 
IRB/PRC/ERC Approval Date : 2015-03-25
 
Placement of IRB/PRC/ERC : Department of Medical Research
 
IRB/PRC/ERC Approval Letter/Document : Dr WWA_Ethical Molecular typing TB _2015.pdf
 
Pre-existing Registration ID : -
 
Pre-existing Name of Organization : -
 
Pre-existing Website : -