Genotypic characterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia

Bwalya, Precious; Yamaguchi, Tomoyuki; Mulundu, Georgina; Nakajima, Chie; Mbulo, Grace; Solo, Eddie Samuneti; Fukushima, Yukari; Kasakwa, Kunda; Suzuki, Yasuhiko

Genotypic characterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia

Bwalya, Precious; Yamaguchi, Tomoyuki; Mulundu, Georgina et al.

Tuberculosis, 2018, 109, 117-122

Permalink : https://hdl.handle.net/2115/72910

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アクセス権	open access
URI	https://hdl.handle.net/2115/72910
タイトル	Genotypic characterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia
著者	Bwalya, Precious ; Yamaguchi, Tomoyuki ; Mulundu, Georgina ; Nakajima, Chie ; Mbulo, Grace ; Solo, Eddie Samuneti ; Fukushima, Yukari ; Kasakwa, Kunda ; Suzuki, Yasuhiko
著者名 Bwalya, Precious
著者名 Yamaguchi, Tomoyuki
著者名 Mulundu, Georgina
e-Rad_Researcher 60435964 著者名 Nakajima, Chie
著者名 Mbulo, Grace
著者名 Solo, Eddie Samuneti
著者名 Fukushima, Yukari
著者名 Kasakwa, Kunda
e-Rad_Researcher 90206540 著者名 Suzuki, Yasuhiko
言語	英語
キーワード	Pyrazinamide
	pncA
	Resistance
	Mutation
	BACTEC MGIT 960
発行日	2018-03
出版者	Elsevier
収録物名	Tuberculosis
巻(号)	109
ページ	117-122
抄録	Pyrazinamide forms a core part of treatment for all types of tuberculosis (TB) in Zambia. Due to challenges associated with pyrazinamide testing, little information is available to indicate the frequency of resistance to this drug in Zambia. To determine the frequency of pyrazinamide (PZA) resistance and its correlation with mutation in pncA in Mycobacterium tuberculosis isolated from patients in Lusaka, Zambia, BACTEC MGIT M960 was used for phenotypic PZA susceptibility testing while sequencing was used to determine resistance-conferring mutations in the pncA. Of the 131 isolates analyzed, 32 were phenotypically resistant to PZA. Among multidrug-resistant (MDR) M. tuberculosis isolates, the frequency of PZA resistance was 21 of 35 (58.3%). And 27 of 32 PZA resistant isolates had mutations in the pncA that seem to confer resistance. With BACTEC MGIT 960 as the reference standard, gene sequencing showed 84.4% sensitivity and 100% specificity. Nine new mutations were identified and the single nucleotide substitution T104G and C195T were the most frequent mutations. However, they were observed in both susceptible and resistant strains and indicating that they are non-resistance conferring mutations. This study has demonstrated that PZA susceptibility testing is necessary especially in patients suffering from MDR-TB as approximately half of the patients have PZA resistant TB. Similar studies will have to be carried out in other provinces to get an accurate estimate of PZA resistance in Zambia. Mutations in pncA were the major mechanism of PZA resistance with no involvement of rpsA and panD genes. However, the presence of mutations among phenotypically PZA susceptible M. tuberculosis isolates makes it challenging to independently use genotyping method for the determination of PZA resistance.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1472-9792
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.tube.2017.12.007