Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland; San Raffaele Scientific Institute, Milan, Italy.
Lancet Infect Dis. 2018 Jun;18(6):675-683. doi: 10.1016/S1473-3099(18)30073-2. Epub 2018 Mar 21.
In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis.
Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing.
Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing.
Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation.
Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.
在许多国家，由于表型药物敏感性测试的局限性，定期监测抗结核药物耐药性的出现受到阻碍。因此，我们评估了使用基因测序来监测结核病的耐药性。
在七个国家（阿塞拜疆、孟加拉国、白俄罗斯、巴基斯坦、菲律宾、南非和乌克兰）的医院和诊所进行了人群水平调查，以评估使用基因测序来估计结核分枝杆菌分离株对利福平、异烟肼、氧氟沙星、莫西沙星、吡嗪酰胺、卡那霉素、阿米卡星和卷曲霉素的耐药性。对于每种药物，我们通过比较基因测序测量的调整后耐药率与表型测试确定的真实耐药率来评估基因测序的准确性。
该研究于 2009 年 11 月至 2014 年 5 月期间纳入了 7094 名结核病患者，从这些患者中采集了分离株。在所有结核病病例中，基因测序预测耐药性的总体汇总敏感性值分别为 rpoB（利福平耐药）91%（95%CI 87-94）、katG、inhA 和 fabG 启动子联合（异烟肼耐药）86%（74-93）、pncA（吡嗪酰胺耐药）54%（39-68）、gyrA 和 gyrB 联合（氧氟沙星耐药）85%（77-91）以及 gyrA 和 gyrB 联合（莫西沙星耐药）88%（81-92）。对于几乎所有药物和大多数情况下，基因测序估计的耐药率与表型测试估计的耐药率之间存在很大重叠。
基因测序可以成为监测耐药性的有价值工具，为资源匮乏国家监测结核病耐药性提供了新的机会。在广泛应用于监测目的之前，需要标准化 DNA 提取方法、记录和报告命名法以及数据解释。
比尔及梅琳达·盖茨基金会、美国国际开发署、全球结核病药物开发联盟。
