Genetic Characterisation of Malawian Pneumococci Prior to the Roll-Out of the PCV13 Vaccine Using a High-Throughput Whole Genome Sequencing Approach
Genetic Characterisation of Malawian Pneumococci Prior to the Roll-Out of the PCV13 Vaccine Using a High-Throughput Whole Genome Sequencing Approach
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DOI：
10.1371/journal.pone.0044250
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发表时间：
2012-09-10
期刊：
影响因子：
3.7
通讯作者：
Bentley, Stephen D.
中科院分区：
文献类型：
--
作者：
Everett, Dean B.;Cornick, Jennifer;Bentley, Stephen D.
背景：马拉维于2011年11月开始将13价肺炎球菌结合疫苗（PCV13）纳入常规婴儿免疫接种计划。在这里，我们测试了高通量全基因组测序的效用，以提供疫苗前肺炎球菌流行病学和种群进化趋势的高分辨率视图，以预测引入后种群结构的潜在未来变化。方法：从随机选择的马拉维布兰太尔伊丽莎白女王中心医院的成人和儿童中提取的127例存档肺炎球菌分离株进行全基因组测序。结果：在引入疫苗之前，肺炎球菌种群以血清1型为主（20.5%的侵袭性分离株）。PCV13可能预防62.9%的循环侵袭性肺炎球菌（在5岁以下儿童中为78.3%）。几个肺炎球菌分子流行病学网络（PMEN）克隆目前在马拉维流通，这些克隆以前未被发现，但未发现大流行的多药耐药PMEN1谱系。基因组分析确定了一些新的序列类型和血清型转换。结论：高通量基因组测序是可行的，具有同时阐明血清型、序列型和详细遗传信息的能力。它能够在种群水平上进行表征，提供与疾病控制相关的种群结构和基因组进化的详细图像。由基因组测序支持的疫苗引入后监测对于全面了解PCV13对肺炎球菌种群结构的影响并为未来的公共卫生干预提供信息至关重要。
Background: Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.Methods: One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.Results: The pneumococcal population was dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine introduction. PCV13 is likely to protect against 62.9% of all circulating invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular Epidemiology Network (PMEN) clones are now in circulation in Malawi which were previously undetected but the pandemic multidrug resistant PMEN1 lineage was not identified. Genome analysis identified a number of novel sequence types and serotype switching.Conclusions: High throughput genome sequencing is now feasible and has the capacity to simultaneously elucidate serotype, sequence type and as well as detailed genetic information. It enables population level characterization, providing a detailed picture of population structure and genome evolution relevant to disease control. Post-vaccine introduction surveillance supported by genome sequencing is essential to providing a comprehensive picture of the impact of PCV13 on pneumococcal population structure and informing future public health interventions.