National Tuberculosis Reference Laboratory/Supranational Reference Laboratory, Plot 106-1062 Butabika Road, Luzira, Uganda.
The Infectious Diseases Institute, College of Heath Sciences, Makerere University, P.O. Box 22418, Kampala, Uganda.
Antimicrob Resist Infect Control. 2022 May 12;11(1):68. doi: 10.1186/s13756-022-01101-2.
Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance.
Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda.
In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM).
This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient's clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up.
乌干达仍是结核病/艾滋病负担最重的国家之一。全球耐多药结核病仍然是一个重大挑战，需要采取新的战略有效控制方法。耐药性通常是由于对结核病患者的管理不当导致的，包括不适当的治疗方案和未能完成治疗疗程，这可能是由于供应不稳定或无法获得治疗，以及患者不遵守规定。
2020 年至 2021 年期间，在乌干达北部的利拉地区转诊医院，从 Xpert MTB/RIF® 检测诊断的耐多药结核病（MDR-TB）患者中采集了两份痰液样本，用于使用基于培养的方法进行全面常规分枝杆菌物种鉴定和药敏试验。随后，使用 Illumina MiSeq 平台在乌干达国家结核病参考实验室进行全基因组测序，检测耐药相关基因。
在这两个分离株中，均发现了广泛耐药结核病（XDR-TB），包括对异烟肼（katG p.Ser315Thr）、利福平（rpoB p.Ser450Leu）、莫西沙星（gyrA p.Asp94Gly）、贝达喹啉（Rv0678 Glu49fs）、氯法齐明（Rv0678 Glu49fs）、利奈唑胺（rplC Cys154Arg）和乙硫异烟胺（ethA c.477del）的耐药。对这两个高质量基因组的进一步分析表明，这位 32 岁的患者感染了拉丁美洲地中海结核株（LAM）。
这是首次在乌干达发现耐贝达喹啉、利奈唑胺和氯法齐明的广泛耐药结核分枝杆菌临床分离株。这些获得性耐药性是由于患者临床病史中观察到的不遵医嘱引起的。我们的研究还强烈强调了通过实施新一代测序来打击非洲耐多药结核病的重要性，该方法可以同时检测所有药物的耐药性，同时提供更快的周转时间。这可以促进对不遵医嘱或失访的耐多药结核病患者进行及时的临床决策。
