Chatterjee Anirvan, Nilgiriwala Kayzad, Saranath Dhananjaya, Rodrigues Camilla, Mistry Nerges
The Foundation for Medical Research, 84-A, R. G. Thadani Marg, Worli, Mumbai 400 018, India.
The Foundation for Medical Research, 84-A, R. G. Thadani Marg, Worli, Mumbai 400 018, India; Sunandan Divatia School of Science, NMIMS (deemed-to-be) University, V. L. Mehta Road, Mumbai 400 056, India.
Tuberculosis (Edinb). 2017 Dec;107:63-72. doi: 10.1016/j.tube.2017.08.002. Epub 2017 Aug 9.
Amplification of drug resistance in Mycobacterium tuberculosis (M.tb) and its transmission are significant barriers in controlling tuberculosis (TB) globally. Diagnostic inaccuracies and delays impede appropriate drug administration, which exacerbates primary and secondary drug resistance. Increasing affordability of whole genome sequencing (WGS) and exhaustive cataloguing of drug resistance mutations is poised to revolutionise TB diagnostics and facilitate personalized drug therapy. However, application of WGS for diagnostics in high endemic areas is yet to be demonstrated. We report WGS of 74 clinical TB isolates from Mumbai, India, characterising genotypic drug resistance to first- and second-line anti-TB drugs. A concordance analysis between phenotypic and genotypic drug susceptibility of a subset of 29 isolates and the sensitivity of resistance prediction to the 4 drugs was calculated, viz. isoniazid-100%, rifampicin-100%, ethambutol-100% and streptomycin-85%. The whole genome based phylogeny showed almost equal proportion of East Asian (27/74) and Central Asian (25/74) strains. Interestingly we also found a clonal group of 9 isolates, of which 7 patients were found to be from the same geographical location and accessed the same health post. This provides the first evidence of epidemiological linkage for tracking TB transmission in India, an approach which has the potential to significantly improve chances of End-TB goals. Finally, the use of Mykrobe Predictor, as a standalone drug resistance and strain typing tool, requiring just few minutes to analyse raw WGS data into tabulated results, implies the rapid clinical applicability of WGS based TB diagnosis.
结核分枝杆菌（M.tb）耐药性的增强及其传播是全球控制结核病（TB）的重大障碍。诊断不准确和延误阻碍了适当的药物施用，这加剧了原发性和继发性耐药性。全基因组测序（WGS）可及性的提高以及耐药性突变的详尽编目有望彻底改变结核病诊断并促进个性化药物治疗。然而，WGS在高流行地区用于诊断的应用尚未得到证实。我们报告了来自印度孟买的74株临床结核分枝杆菌分离株的WGS，对一线和二线抗结核药物的基因型耐药性进行了表征。计算了29株分离株子集的表型和基因型药物敏感性之间的一致性分析以及对4种药物的耐药性预测敏感性，即异烟肼-100%、利福平-100%、乙胺丁醇-100%和链霉素-85%。基于全基因组的系统发育显示东亚菌株（27/74）和中亚菌株（25/74）的比例几乎相等。有趣的是，我们还发现了一个由9株分离株组成的克隆群，其中7名患者来自同一地理位置并就诊于同一卫生站。这为追踪印度结核病传播的流行病学联系提供了首个证据，这种方法有可能显著提高实现终结结核病目标的机会。最后，使用Mykrobe Predictor作为独立的耐药性和菌株分型工具，只需几分钟就能将原始WGS数据分析成表格结果，这意味着基于WGS的结核病诊断具有快速临床适用性。
