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挪威 1996 年至 2019 年无细胞百日咳疫苗时代博德特氏菌的进化。

Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019.

机构信息

Norwegian Institute of Public Health, Oslo, Norway.

European Program for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.

出版信息

Eur J Clin Microbiol Infect Dis. 2022 Jun;41(6):913-924. doi: 10.1007/s10096-022-04453-0. Epub 2022 May 11.

Abstract

We described the population structure of Bordetella pertussis (B. pertussis) in Norway from 1996 to 2019 and determined if there were evolutionary shifts and whether these correlated with changes in the childhood immunization program. We selected 180 B. pertussis isolates, 22 from the whole cell vaccine (WCV) era (1996-1997) and 158 from the acellular vaccine (ACV) era (1998-2019). We conducted whole genome sequencing and determined the distribution and frequency of allelic variants and temporal changes of ACV genes. Norwegian B. pertussis isolates were evenly distributed across a phylogenetic tree that included global strains. We identified seven different allelic profiles of ACV genes (A-F), in which profiles A1, A2, and B dominated (89%), all having pertussis toxin (ptxA) allele 1, pertussis toxin promoter (ptxP) allele 3, and pertactin (prn) allele 2 present. Isolates with ptxP1 and prn1 were not detected after 2007, whereas the prn2 allele likely emerged prior to 1972, and ptxP3 before the early 1980s. Allele conversions of ACV genes all occurred prior to the introduction of ACV. Sixteen percent of our isolates showed mutations within the prn gene. ACV and its booster doses (implemented for children in 2007 and adolescents in 2013) might have contributed to evolvement of a more uniform B. pertussis population, with recent circulating strains having ptxA1, ptxP3, and prn2 present, and an increasing number of prn mutations. These strains clearly deviate from ACV strains (ptxA1, ptxP1, prn1), and this could have implications for vaccine efficiency and, therefore, prevention and control of pertussis.

摘要

我们描述了 1996 年至 2019 年期间挪威博德特氏菌(B. pertussis)的种群结构,并确定是否存在进化转变,以及这些转变是否与儿童免疫计划的变化相关。我们选择了 180 株博德特氏菌分离株,其中 22 株来自全细胞疫苗(WCV)时代(1996-1997 年),158 株来自无细胞疫苗(ACV)时代(1998-2019 年)。我们进行了全基因组测序,并确定了 ACV 基因的等位变体分布和频率以及时间变化。挪威博德特氏菌分离株在包括全球菌株的系统发育树中均匀分布。我们确定了 7 种不同的 ACV 基因的等位基因谱(A-F),其中谱 A1、A2 和 B 占主导地位(89%),所有这些都具有百日咳毒素(ptxA)等位基因 1、百日咳毒素启动子(ptxP)等位基因 3 和 pertactin(prn)等位基因 2。2007 年后未检测到 ptxP1 和 prn1,而 prn2 等位基因可能在 1972 年之前出现,ptxP3 则在 1980 年代初之前出现。ACV 基因的等位基因转换均发生在 ACV 引入之前。我们的 16%的分离株在 prn 基因中显示突变。ACV 及其加强剂量(2007 年为儿童接种,2013 年为青少年接种)可能促成了更均匀的博德特氏菌种群的进化,最近流行的菌株具有 ptxA1、ptxP3 和 prn2,并且 prn 突变的数量不断增加。这些菌株明显偏离了 ACV 菌株(ptxA1、ptxP1、prn1),这可能对疫苗效率产生影响,从而影响百日咳的预防和控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9865/9135841/af3292d3dffc/10096_2022_4453_Fig1_HTML.jpg

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