Globally diverse Mycobacterium tuberculosis resistance acquisition: a retrospective geographical and temporal analysis of whole genome sequences.

Globally diverse Mycobacterium tuberculosis resistance acquisition: a retrospective geographical and temporal analysis of whole genome sequences.
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全球多样的结核分枝杆菌耐药性获取:整个基因组序列的回顾性地理和时间分析。

DOI:
10.1016/s2666-5247(20)30195-6
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发表时间:
2021-03
期刊:
The Lancet. Microbe
影响因子:
--
通讯作者:
Farhat MR
Farhat MR
中科院分区:
其他
文献类型:
--
作者:
Ektefaie Y;Dixit A;Freschi L;Farhat MR

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结核分枝杆菌全基因组测序(WGS)数据可以提供对耐药性获得的时间和地理趋势的见解,并为公共卫生干预提供信息。我们的目的是利用大量临床收集的结核分枝杆菌WGS和耐药表型数据来研究全球范围内如何、何时以及在何处获得耐药性。我们对WGS数据进行了回顾性分析。我们使用公共数据库和文献策展,策划了一组具有高质量测序和基于培养的药物敏感性数据(跨越非洲,亚洲,美洲和欧洲的四个谱系和52个国家)的临床结核分枝杆菌分离株。对于纳入,需要序列质量标准和原产国数据。我们构建了地理和谱系特异性结核分枝杆菌的遗传,并使用贝叶斯分子测年与BEAST,版本1.10.4,推断最近的共同易感祖先年龄的4869例耐药10种药物。在1987年1月1日至2014年9月12日期间,在10 299株结核分枝杆菌临床分离株中,共收集了8550株,其中来自15个国家的6099株(71%)符合分子测年标准。在所有国家中,独立耐药获得事件的数量低于耐药分离株的数量,表明耐药性正在传播。祖先的年龄分布支持存在的老阻力,20年或更长的时间之前,在大多数国家。在全球范围内观察到一致的耐药性获得顺序,从对异烟肼的耐药性开始,但耐药性祖先年龄因国家而异。我们发现人均国内生产总值与抵抗年龄之间存在直接相关性(r2= 0.47; p= 0.014)。据估计,多重耐药分离株中氟喹诺酮类和二线注射剂耐药性的扩增发生在最近(样本采集前的中位祖先年龄为4.7岁[IQR 1.9 - 9.8])。我们发现商业分子诊断对二线耐药的敏感性在不同国家有显著差异(p<0.0003)。我们的研究结果强调,耐药传播和扩增都对全球疾病负担有贡献,但因国家而异。较富裕国家更有可能具有旧的耐药性(最近的共同易感祖先在分离前>20年)的观察结果表明,计划性改进可以减少耐药性扩增,但合适的耐药菌株可以在随后的几十年内传播,这意味着需要继续监测。
Mycobacterium tuberculosis whole genome sequencing (WGS) data can provide insights into temporal and geographical trends in resistance acquisition and inform public health interventions. We aimed to use a large clinical collection of M tuberculosis WGS and resistance phenotype data to study how, when, and where resistance was acquired on a global scale. We did a retrospective analysis of WGS data. We curated a set of clinical M tuberculosis isolates with high-quality sequencing and culture-based drug susceptibility data (spanning four lineages and 52 countries in Africa, Asia, the Americas, and Europe) using public databases and literature curation. For inclusion, sequence quality criteria and country of origin data were required. We constructed geographical and lineage specific M tuberculosis phylogenies and used Bayesian molecular dating with BEAST, version 1.10.4, to infer the most recent common susceptible ancestor age for 4869 instances of resistance to ten drugs. Between Jan 1, 1987, and Sept 12, 2014, of 10 299 M tuberculosis clinical isolates, 8550 were curated, of which 6099 (71%) from 15 countries met criteria for molecular dating. The number of independent resistance acquisition events was lower than the number of resistant isolates across all countries, suggesting ongoing transmission of drug resistance. Ancestral age distributions supported the presence of old resistance, 20 years or more before, in most countries. A consistent order of resistance acquisition was observed globally starting with resistance to isoniazid, but resistance ancestral age varied by country. We found a direct correlation between gross domestic product per capita and resistance age (r2=0·47; p=0·014). Amplification of fluoroquinolone and second-line injectable resistance among multidrug-resistant isolates is estimated to have occurred very recently (median ancestral age 4·7 years [IQR 1·9–9·8] before sample collection). We found the sensitivity of commercial molecular diagnostics for second-line resistance to vary significantly by country (p<0·0003). Our results highlight that both resistance transmission and amplification are contributing to disease burden globally but vary by country. The observation that wealthier nations are more likely to have old resistance (most recent common susceptible ancestor >20 years before isolation) suggests that programmatic improvements can reduce resistance amplification, but that fit resistant strains can circulate for decades subsequently implies the need for continued surveillance.
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发表时间: 2015-03-01
期刊: NATURE GENETICS
影响因子: 30.8
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发表时间: 2017-11-03
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