Kerubo Glennah, Ndungu Perpetua, Shuaib Yassir Adam, Amukoye Evans, Revathi Gunturu, Homolka Susanne, Kariuki Samuel, Merker Matthias, Niemann Stefan
Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany.
School of Medicine, Kenyatta University, Nairobi 43844-00100, Kenya.
Genes (Basel). 2022 Mar 8;13(3):475. doi: 10.3390/genes13030475.
Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients' demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1-L4). The two dominating lineages were L4 with 55.8% ( = 215) and L3 with 25.7% ( = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117/385) of the strains were clustered using a ≤5 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20/385) of the strains were multidrug-resistant (MDR), and 50.0% ( = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chains.
肯尼亚是一个结核病负担沉重的国家。然而，关于结核分枝杆菌复合群（MTBC）菌株的遗传多样性及其传播动态的知识却十分匮乏。因此，我们利用全基因组测序（WGS）来描述内罗毕城市和贫民窟环境中MTBC菌株的遗传多样性、耐药分子标志物以及可能的传播簇。我们结合患者的人口统计学数据，分析了2010年至2015年间收集的385株临床MTBC分离株。我们发现MTBC群体主要由四个谱系（L1 - L4）的菌株组成。两个主要谱系分别是L4，占所有菌株的55.8%（n = 215）和L3，占25.7%（n = 99）。基于基因组的聚类分析表明，使用≤5个单核苷酸多态性（SNP）阈值作为MTBC患者间直接传播的替代标志物时，30.4%（117/385）的菌株被聚类。此外，5.2%（20/385）的菌株为多重耐药（MDR），且50.0%（n = 10）属于基于基因组的聚类（即MDR MTBC的直接传播）。值得注意的是，30.0%（6/20）的MDR菌株对所有一线药物耐药，且属于一个分子聚类。此外，与来自贫民窟的患者相比，城市居住环境中的结核病患者感染耐药菌株的几率高出3.8倍（P值 = 0.002）。我们的结果表明，L4菌株是内罗毕结核病的主要病原体，MDR菌株传播是城市环境中一个新出现的问题。这强调了需要采取更有针对性的感染控制措施以及对MDR结核病患者进行接触者追踪，以打破传播链。
