Post-PCV pneumococcal population genetics and resistance

描述（由申请人提供）：尽管使用肺炎球菌结合疫苗（PCV）成功地对7种血清型肺炎链球菌（SP）进行了儿童免疫接种，但关于SP血清型疫苗的长期效果和抗菌素耐药性的关键问题仍然存在。用非疫苗类型替代（通过扩大已经流行的菌株、输入新菌株或切换荚膜）和新出现的抗生素耐药性可能再次增加肺炎球菌感染的发病率。在2001年和2004年对来自16个社区的SP分离株进行分析的基础上，我们将在2007年和2009年对携带率和血清型特异性抗菌素耐药性的变化进行多社区评估。分离株将进行耐药性测试、血清分型、脉冲场凝胶电泳和多位点序列分型，以确定普遍免疫时代SP社区携带变化的生物学过程。具体而言，我们将：1)测量SP携带趋势，包括患病率，携带血清型和血清型特异性抗生素耐药性。2)检验PCV7引入后肺炎球菌种群结构变化的相互竞争的假设，包括非疫苗类型的抗生素耐药机制。3)确定先前记录的SP携带的危险因素（易感和非易感）是否继续预测pcv7后时代的携带。对SP社区宿主的流行病学和群体遗传学的持续评估将为未来对局部和侵袭性肺炎球菌疾病的预期提供信息。

DESCRIPTION (provided by applicant): Despite successful immunization of children against 7 serotypes of S. pneumoniae (SP) with pneumococcal conjugate vaccine (PCV), critical questions remain regarding long-term vaccine effects on SP serotypes and antimicrobial resistance. Replacement with non-vaccine types (through expansion of already circulating strains, importation of new strains, or capsular switching) and emerging antibiotic resistance could again increase morbidity from pneumococcal infection. Building on our analysis of SP isolates from 16 communities in 2001 and 2004, we will perform a multi-community assessment of changes in carriage prevalence and serotype-specific antimicrobial resistance in 2007 and 2009. Isolates will undergo resistance testing, serotyping, pulse field gel electrophoresis, and multi-locus sequence typing to determine the biological processes which underlie changes in community carriage of SP in the era of universal immunization. Specifically we will: 1)Measure trends in carriage of SP, including prevalence, serotypes carried, and serotype-specific antibiotic resistance. 2) Test competing hypotheses for shifts in pneumococcal population structure following PCV7 introduction, including the mechanism of antibiotic resistance among non-vaccine types. 3) Determine if previously documented risk factors for carriage of SP (susceptible and non-susceptible) continue to predict carriage in the post-PCV7 era. Continuing assessment of the epidemiology and population genetics of the community reservoir of SP will inform future expectations regarding localized and invasive pneumococcal disease.