Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi.
Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi.
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在马拉维共轭疫苗之前，种群遗传结构，抗生素抗性，胶囊切换和侵入性肺炎的演变。
DOI：
10.1016/j.vaccine.2017.07.009
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发表时间：
2017-08-16
期刊：
影响因子：
5.5
通讯作者：
Everett DB
中科院分区：
文献类型：
--
作者：
Chaguza C;Cornick JE;Andam CP;Gladstone RA;Alaerts M;Musicha P;Peno C;Bar-Zeev N;Kamng'ona AW;Kiran AM;Msefula CL;McGee L;Breiman RF;Kadioglu A;French N;Heyderman RS;Hanage WP;Bentley SD;Everett DB
在血清型和序列型（ST）方面，肺炎球菌种群多样性高。疫苗接种前IPD发病率的下降与特定血清型无关。血清1型分离株的高流行率和抗生素耐药率。高水平的胶囊（血清型）转换预接种。监测对于了解肺炎球菌流行病学仍然至关重要。肺炎球菌感染在撒哈拉以南非洲（SSA）造成很高的死亡人数，但最近推出的肺炎球菌结合疫苗（PCV）将减轻疾病负担。为了更好地了解这些疫苗对人群的影响，需要对疫苗接种前取样的大量肺炎球菌分离物进行全面分析。在这里，我们提出了在马拉维实施PCV13之前采样的侵袭性肺炎球菌分离株的群体基因组研究。我们从2004年至2010年对585株侵袭性分离株进行了回顾性取样和全基因组测序。我们确定了肺炎球菌群体遗传结构，并评估了血清型患病率、抗生素耐药率和血清型转换的发生。种群结构分析显示22个遗传差异序列簇（SCs），由亲缘关系较近的分离株组成。SC2分支中与疫苗相关的血清型1 （ST217）患病率最高（19.3%），耐多药率最高（81.9%），其次是SC10分支中与非疫苗相关的血清型12F，耐多药率为57.9%。在接种疫苗之前，血清型的流行率是稳定的，尽管2010年SC1支系中PMEN19克隆血清型5 ST289有所增加，表明可能发生未被发现的局部暴发。聚结分析揭示了sc最近的出现，并且有证据表明在没有疫苗诱导的选择压力的情况下存在天然胶囊切换。此外，大多数高度流行的胶囊转换分离株与获得疫苗靶向胶囊有关。这项研究提供了胶囊切换血清型和可能导致疫苗接种后血清型替代的血清型的描述，如12F。持续监测对于监测这些血清型和抗生素耐药性至关重要，以便设计更好的感染预防和控制措施，例如在未来的结合疫苗中纳入新出现的替代血清型。
High pneumococcal population diversity in terms of serotypes and sequence types (ST). Decline in IPD incidence pre-vaccination not associated with specific serotypes. High prevalence and antibiotic resistance rates in serotype 1 isolates. High levels of capsule (serotype) switching pre-vaccination. Surveillance remains crucial to understand pneumococcal epidemiology. Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines.
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影响因子：
3.6
作者：
Black, S;Shinefield, H;Edwards, K
通讯作者：
Edwards, K
影响因子：
6.7
作者：
Brueggemann, Angela B.;Pai, Rekha;Beall, Bernard
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Beall, Bernard
影响因子：
3.7
作者：
Donkor ES;Adegbola RA;Wren BW;Antonio M
通讯作者：
Antonio M
影响因子：
9.4
作者：
Brueggemann, AB;Spratt, BG
通讯作者：
Spratt, BG
影响因子：
9.4
作者：
Dicuonzo, G;Gherardi, G;Beall, B
通讯作者：
Beall, B