Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year's review.
Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year's review.
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乌干达耐药结核病患者二线耐药性的分子特征：一项为期两年半的回顾。
DOI：
10.1186/s12879-022-07339-w
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发表时间：
2022-04-11
影响因子：
3.7
通讯作者：
Ssengooba, Willy
中科院分区：
文献类型：
--
作者：
Mujuni, Dennis;Kasemire, Dianah Linda;Ibanda, Ivan;Kabugo, Joel;Nsawotebba, Andrew;Phelan, Jody E.;Majwala, Robert Kaos;Tugumisirize, Didas;Nyombi, Abdunoor;Orena, Beatrice;Turyahabwe, Irene;Byabajungu, Henry;Nadunga, Diana;Musisi, Kenneth;Joloba, Moses Lutakoome;Ssengooba, Willy
关键词：
结核病患者的二线耐药（SLD）是全球结核病控制面临的一个严重挑战。我们对2017年6月至2019年12月在乌干达国家结核病参考实验室（NTRL）检测的利福平和/或异烟肼（RIF和/或INH）耐药结核病患者的sld耐药突变进行了表征。这是对20,508株对RIF和/或INH耐药的新治疗和先前治疗的结核分枝杆菌分离株的描述性横断面二级数据分析。使用商业Line Probe Assay基因型MTBDRsl Version 2.0 Assay （Hain Life Science, Nehren, Germany）对具有有效结果的DNA条进行了回顾。使用STATAv15进行数据分析，采用交叉表法分析已知对注射药物（IA）和氟喹诺酮类药物（FQ）具有耐药性的突变的频率和比例。在符合条件的参与者中，12,993/20,508（63.4%）为男性，中位（IQR）年龄为32岁（24-43岁）。来自参与者的结核分枝杆菌分离株中，共有576/20,508（2.8%）对RIF和/或INH具有耐药性。这些包括;102/576株（17.7%）单一耐药，474/576株（82.3%）多重耐药。只有102例患者有FQ检测结果，其中70/102例（68.6%）和01/102例（0.98%）分别在gyrA和gyrB位点发生耐药突变。FQ耐药患者中以gyrAD94G（42.6%, 30.0 ~ 55.9%）和gyrA A90V（41.1%, 28.6 ~ 54.3）突变最多。在gyrB位点只检测到一个突变E540D。26例患者存在IA耐药突变，其中20/26 77.0%（56.4-91.0）患者存在rrs基因座A1401G突变。我们的研究表明，在利福平和/或异烟肼耐药的患者中，已知有很高比例的突变导致高水平的氟喹诺酮类药物耐药。利用现有分子诊断方法常规生成的实验室数据，可能有助于在资源有限的环境中实时监测新出现的结核病耐药性。
Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019. This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients’ resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ). Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24–43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0–55.9) and gyrA A90V 41.1% (28.6–54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4–91.0) had A1401G mutation in the rrs gene locus. Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings.
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影响因子：
1.2
作者：
Kambli P;Ajbani K;Nikam C;Sadani M;Shetty A;Udwadia Z;Georghiou SB;Rodwell TC;Catanzaro A;Rodrigues C
通讯作者：
Rodrigues C
影响因子：
3.7
作者：
Micheni LN;Kassaza K;Kinyi H;Ntulume I;Bazira J
通讯作者：
Bazira J
乌干达坎帕拉的结核病患者的结核病风险因素：对控制结核的影响。
影响因子：
4.5
作者：
Kirenga BJ;Ssengooba W;Muwonge C;Nakiyingi L;Kyaligonza S;Kasozi S;Mugabe F;Boeree M;Joloba M;Okwera A
通讯作者：
Okwera A
影响因子：
3.7
作者：
Raizada N;Sachdeva KS;Chauhan DS;Malhotra B;Reddy K;Dave PV;Mundade Y;Patel P;Ramachandran R;Das R;Solanki R;Wares DF;Sahu S;O'Brien R;Paramasivan CN;Dewan PK
通讯作者：
Dewan PK
影响因子：
14.2
作者：
Lipin, M. Y.;Stepanshina, V. N.;Shinnick, T. M.
通讯作者：
Shinnick, T. M.