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028 _b Phone: +255 28 298 3384
028 _b Fax: +255 28 298 3386
028 _b Email: vc@bugando.ac.tz
028 _b Website: www.bugando.ac.tz
040 _cDLC
041 _aEnglish
100 _a Benson R Kidenya
_922909
245 _aGenotypic drug resistance using whole-genome sequencing of Mycobacterium tuberculosis clinical isolates from North-western Tanzania
260 _aMwanza, Tanzania:
_bChurchill Livingstone &
_bCatholic University of Health and Allied Sciences [CUHAS – Bugando]
_c2018/3/1
300 _aPages 97-101
490 _vTuberculosis Volume 109
520 _aAbstract Background: Drug resistant Tuberculosis (TB) is considered a global public health threat. Whole-genome sequencing (WGS) is a new technology for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles and genotypes for epidemiologic surveillance. Therefore, we used WGS to determine genotypic drug resistance profiles and genetic diversity of drug resistant Mycobacterium tuberculosis isolates from Mwanza, North-western Tanzania. Methods: A cross-sectional study was conducted at the Bugando Medical Center (BMC) from September 2014 to June 2015. Consecutively, smear-positive newly diagnosed TB patients aged ≥18 years were enrolled. Sputum samples were cultured on Löwenstein-Jensen (LJ) slants. Mycobacterial genomic DNA was extracted for WGS to determine drug resistant mutations for first and second line drugs as well as the spoligotypes. Results: A total of 78 newly diagnosed patients with pulmonary TB with a median age of 37 [IQR: 30–46] years were enrolled. Of these, 57.8% (45/74) were males and 34.6% (27/78) were HIV positive. Mycobacterium tuberculosis genomic DNA for WGS was obtained from isolates in 74 (94.9%) patients. Of the 74 isolates, six (8.1%) isolates harbored mutations for resistance to at least one drug. The resistance to the drugs was isoniazid 3/74 (4.1%), rifampicin mono-resistant 2/74 (2.7%), ethambutol 2/74 (2.7%) and streptomycin 1/74 (1.4%). None was isoniazid mono-resistant. Of the 74 only one (1.4%) patient had MDR-TB. The resistance to ethionamide, the second line drug, was detected in one patient (1.4%). None was resistant to pyrazinamide, fluoroquinolones, kanamycin, amikacin, or capreomycin. The mutations detected were mabA-inhA promoter region C(-15)T and katG Ser513Thr for isoniazid; rpoB His526Leu and rpoB Ser531Leu for rifampicin; embB Met306Val and embB Met306Ile for ethambutol; rpsL Lys43Arg for streptomycin; and mabA-inhA promoter region C(-15)T for ethionamide. The spoligotypes of the drug resistant Mycobacterium tuberculosis were distinct to all six isolates and belonged to T1, T2, T3-ETH, CAS1-DELHI, EAI5 and LAM11-ZWE lineages. Conclusion: The genetic drug resistance profile of Mycobacterium tuberculosis isolates from North-western Tanzania comprises of the common previously reported mutations. The prevalence of resistance to first and second line drugs including MDR-TB is low. Six drug resistant strains exhibited different spoligotypes, suggesting limited transmission of drug resistant strains in the region.
700 _aStephen E Mshana
_915820
700 _aDaniel W Fitzgerald
_923036
700 _a Oksana Ocheretina
_945480
856 _uhttps://doi.org/10.1016/j.tube.2018.02.004
942 _2ddc
_cVM
999 _c19476
_d19476