幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-反应关系

Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children

摘要:

目的 了解幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的潜在关系，为指导疫苗接种和开发新型蛋白疫苗提供依据。方法 采用分层整群随机抽样方法，抽取佛山市顺德区6所幼儿园中1 830名健康儿童，进行鼻咽拭子采样并分离鉴定肺炎链球菌。采用基于限制性立方样条的logistic回归模型分析儿童年龄与肺炎链球菌相关疫苗覆盖率间的剂量-反应关系。结果 幼儿园儿童鼻咽部肺炎链球菌携带率为22.46%（411/1 830），常见血清型为6B、19F、15A、23A、34与23F。对于肺炎链球菌结合疫苗（pneumococcal conjugate vaccine, PCV），PCV10与PCV13血清型覆盖率分别为53.0%、57.9%，且儿童年龄与PCV10和PCV13血清型覆盖率间存在明显的非线性剂量-反应关系（均P<0.05），2岁组儿童的PCV10（88.0%）和PCV13（91.1%）血清型覆盖率均较高。儿童年龄与菌毛基因岛（pilus islet, PI）相关基因PI-1、PI-2覆盖率间存在非线性剂量-反应关系（均P<0.05），PI-1（37.7%）和PI-2（16.1%）覆盖率较低，且各年龄组儿童的PI-1（13.0%~58.5%）和PI-2（6.0%~29.4%）覆盖率均较低。候选蛋白疫苗相关的毒力基因lytA（99.5%）、ply（99.0%）覆盖率高。结论 幼儿园儿童年龄与PCV10、PCV13血清型覆盖率存在明显的非线性剂量-反应关系，且2岁组幼儿园儿童具有较高的PCV血清型覆盖率；毒力基因lytA与ply的各年龄段高流行使其有望作为候选毒力因子开发新一代重组蛋白疫苗。

Abstract:

Objective To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines.Methods The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage.Results The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates.Conclusions There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.