目的:肺炎链球菌(Spn)是儿童死亡的主要原因。我们在儿科发烧诊所调查了肺炎链球菌的流行病学,并探索了全球血清型14菌株有限疫苗反应的基因组学基础。
方法:根据WHO的标准,于2019年底在三级儿童医院诊断出发热性疾病和肺炎。通过培养从鼻咽(NP)拭子中分离Spn。通过lytA-baseqPCR测定密度。分离物通过Quellung进行血清分型,并进行了抗菌药物敏感性测试。全基因组测序用于分子血清分型,MLST,抗生素基因测定,SNP呼叫,重组预测,和系统发育分析。
结果:鼻咽中存在肺炎球菌(87.5%,7/8,p=0.0227)和高托架(100%,7/7,p=0.0123)与肺炎发展显着相关。与兄弟姐妹生活在一起(73.7%,14/19,p=0.0125)和非疫苗接种(56.0%,28/50,p=0.0377)对Spn运输的贡献显着。血清型14是最普遍的菌株(16.67%,5/30)。对1497株14型菌株的基因组分析表明,S14/ST876菌株仅在中国流行,呈现有限的疫苗反应,在其cps基因座内具有较高的重组活性,和基因wzg和lrp的独特变异模式。
结论:随着独生子女政策的取消,对于有多个孩子的家庭来说,在中国接种PCV疫苗至关重要。由于cps位点的高度变异和胶囊脱落和结合蛋白基因的独特变异模式,流行的S14/ST876菌株对当前疫苗的反应较差.有必要继续监测该疫苗逃逸克隆的分子流行病学。
OBJECTIVE: Streptococcus pneumoniae (Spn) is a major cause of child death. We investigated the epidemiology of S. pneumoniae in a pediatric fever clinic and explored the genomics basis of the limited vaccine response of serotype 14 strains worldwide.
METHODS: Febrile disease and pneumonia were diagnosed following criteria from the WHO at the end of 2019 at a tertiary children\'s hospital. Spn was isolated by culture from nasopharyngeal (NP) swabs. The density was determined by lytA-base qPCR. Isolates were serotyped by Quellung and underwent antimicrobial susceptibility testing. Whole-genome sequencing was employed for molecular serotyping, MLST, antibiotic gene determination, SNP calling, recombination prediction, and phylogenetic analysis.
RESULTS: The presence of pneumococcus in the nasopharynx (87.5%, 7/8, p = 0.0227) and a high carriage (100%, 7/7, p = 0.0123) were significantly associated with pneumonia development. Living with siblings (73.7%, 14/19, p = 0.0125) and non-vaccination (56.0%, 28/50, p = 0.0377) contributed significantly to the Spn carriage. Serotype 14 was the most prevalent strain (16.67%, 5/30). The genome analysis of 1497 serotype 14 strains indicated S14/ST876 strains were only prevalent in China, presented limited vaccine responses with higher recombination activities within its cps locus, and unique variation patterns in the genes wzg and lrp.
CONCLUSIONS: With the lifting of the one-child policy, it will be crucial for families with multiple children to get PCV vaccinations in China. Due to the highly variant cps locus and distinctive variation patterns in capsule shedding and binding proteins genes, the prevalent S14/ST876 strains have shown poor response to current vaccines. It is necessary to continue monitoring the molecular epidemiology of this vaccine escape clone.