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Early Signals of Vaccine-driven Perturbation Seen in Pneumococcal Carriage Population Genomic Data.
Clinical Infectious Diseases ( IF 11.8 ) Pub Date : 2019-05-16 , DOI: 10.1093/cid/ciz404
Chrispin Chaguza 1, 2, 3, 4 , Ellen Heinsbroek 2, 5 , Rebecca A Gladstone 1 , Terence Tafatatha 6 , Maaike Alaerts 3, 7 , Chikondi Peno 3, 8 , Jennifer E Cornick 2, 3 , Patrick Musicha 2, 3, 9, 10 , Naor Bar-Zeev 2, 3, 11 , Arox Kamng'ona 2, 3, 12 , Aras Kadioglu 2 , Lesley McGee 13 , William P Hanage 14 , Robert F Breiman 15 , Robert S Heyderman 3, 16 , Neil French 2, 3 , Dean B Everett 3, 8 , Stephen D Bentley 1, 2, 17
Affiliation  

Background
Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden.
Methods
We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes.
Results
In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons ≥5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs)—namely 7C, 15B/C, and 23A—in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV.
Conclusions
We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV.


中文翻译:

在肺炎球菌运输人群基因组数据中看到了疫苗驱动的扰动的早期信号。

背景
肺炎球菌结合疫苗(PCV)已在全球范围内减少了肺炎球菌疾病。肺炎球菌基因组调查阐明了PCV对人群结构的影响,尽管疾病负担高,但在低收入人群中很少进行。
方法
我们对来自健康携带者的660株肺炎球菌分离株进行了全基因组测序(WGS),该调查是从引入13价PCV(PCV13)2年和在马拉维北部推广1年后的健康携带者进行的。我们调查了种群结构,谱系内血清型动力学,血清型多样性以及抗生素抗药性(ABR)和辅助基因的频率的变化。
结果
在<5岁的儿童中,PCV后疫苗血清型(VTs)的频率和多样性显着降低,但≥5岁的人没有发生明显变化。VT血清型的清除在不同的遗传背景(谱系)中是一致的。<5岁以下儿童的非疫苗血清型(NVT)有所增加,即7C,15B / C和23A,但两个年龄组的28F均增加。虽然最近的结果表明,由于替换血清型的影响,PCV携带率保持稳定,但NVT的多样性没有变化。另外,中抗青霉素的血统的频率在PCV后降低。尽管ABR基因的频率保持稳定,但其他辅助基因,特别是那些与移动遗传元件和细菌素相关的辅助基因,在PCV发生后的频率发生了变化。
结论
我们证明了主要由5岁以下儿童引起的疫苗血清型频率减少和少数NVT频率增加导致PCV发生重大人口重组的证据,持续进行WGS监测对于充分了解PCV术后残留的VT和替代NVT血清型的动态仍然至关重要。
更新日期:2020-03-19
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