Molecular epidemiology of Bordetella pertussis and analysis of vaccine antigen genes from clinical isolates from Shenzhen, China.
Molecular epidemiology of Bordetella pertussis and analysis of vaccine antigen genes from clinical isolates from Shenzhen, China.
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深圳百日咳博德特氏菌分子流行病学及临床分离株疫苗抗原基因分析
DOI：
10.1186/s12941-021-00458-3
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发表时间：
2021-08-18
影响因子：
5.7
通讯作者：
Shi X
中科院分区：
文献类型：
--
作者：
Wu S;Hu Q;Yang C;Zhou H;Chen H;Zhang Y;Jiang M;He Y;Shi X
虽然全球百日咳病例已通过扩大免疫方案得到控制，但近年来百日咳发病率大幅上升，免疫覆盖率高的发达国家出现百日咳“死灰复燃”。随着经济的快速发展，深圳的人口已达到1400万，成为中国人口规模最大的五个城市之一。这里的百日咳发病率约为2.02/10万，远超全省和全国（均< 1/10万）。有越来越多的报告表明百日咳杆菌抗原和基因的变异，这可能与发病率增加有关。收集2018年深圳市从387例疑似病例中分离的50株百日咳杆菌，进行基因型和分子流行病学分析。2018年6月至8月，深圳监测点共入组百日咳疑似病例387例。收集疑似百日咳病例的鼻咽拭子进行细菌培养，并通过实时PCR确认推定的百日咳博德特氏菌分离株的身份。记录每例患者的免疫史。用第二代测序法分析了无细胞百日咳疫苗（APV）百日咳毒素（ptxA、ptxC）、百日咳毒素（prn）和菌毛（fim 2和fim 3）抗原基因以及百日咳毒素启动子区（ptxP）。使用可从GenBank，National Institutes of Health，Bethesda，MD，USA（https：//www.ncbi.nlm.nih.gov/genbank/）公开获得的序列进行遗传和系统发育分析。药敏试验采用纸片扩散法。从387例疑似病例鼻咽拭子中分离出50株百日咳杆菌，阳性率为16.79%，其中男28株，女22株，分别占56.0%和44.0%。发现50例患者中有38例（76%）为B阳性。百日咳菌群培养在有疫苗接种史的阳性病例中，30/42例（71.4%）有国家推荐的不完全百日咳疫苗接种史。三个系统发育组（PG 1-PG 3），每个包含一个占主导地位的基因型。两种疫苗株CS和Tohama I与这三个群体有较远的亲缘关系。50株分离株中有3 - 1株（62%）属于基因型PG 1，等位基因谱为prn 2/ptxC 2/ptxP 3/ptxA 1/fim 3 -1/fim 2 -1。50株分离株中有18株（36%）存在A2047 G突变，对红霉素高度耐药，均属于PG 3基因型（prn 1/ptxA 1/ptxP 1/ptxC 1/fim 3 -1/fim 2 -1），与近期北方流行株关系密切。1岁以下患儿阳性率明显高于其他年龄组，应加强监测。50株深圳分离株的优势抗原基因型与美国、澳大利亚及欧洲多个国家的流行株密切相关。尽管APV免疫接种率很高，但最近在这些国家发生了百日咳流行。因此，对B.应继续开展百日咳防治工作，因为这将有利于百日咳的控制和改进疫苗和治疗策略的开发。
Although pertussis cases globally have been controlled through the Expanded Programme on Immunization (EPI), the incidence of pertussis has increased significantly in recent years, with a “resurgence” of pertussis occurring in developed countries with high immunization coverage. Attracted by its fast-developing economy, the population of Shenzhen has reached 14 million and has become one of the top five largest cities by population size in China. The incidence of pertussis here was about 2.02/100,000, far exceeding that of the whole province and the whole country (both < 1/100,000). There are increasing numbers of reports demonstrating variation in Bordetella pertussis antigens and genes, which may be associated with the increased incidence. Fifty strains of Bordetella pertussis isolated from 387 suspected cases were collected in Shenzhen in 2018 for genotypic and molecular epidemiological analysis. There were 387 suspected cases of pertussis enrolled at surveillance sites in Shenzhen from June to August 2018. Nasopharyngeal swabs from suspected pertussis cases were collected for bacterial culture and the identity of putative Bordetella pertussis isolates was confirmed by real-time PCR. The immunization history of each patient was taken. The acellular pertussis vaccine (APV) antigen genes for pertussis toxin (ptxA, ptxC), pertactin (prn) and fimbriae (fim2 and fim3) together with the pertussis toxin promoter region (ptxP) were analyzed by second-generation sequencing. Genetic and phylogenetic analysis was performed using sequences publicly available from GenBank, National Institutes of Health, Bethesda, MD, USA (https://www.ncbi.nlm.nih.gov/genbank/). The antimicrobial susceptibility was test by Kirby-Bauer disk diffusion. Fifty strains of Bordetella pertussis were successfully isolated from nasopharyngeal swabs of 387 suspected cases, with a positivity rate of 16.79%, including 28 males and 22 females, accounting for 56.0% and 44.0% respectively. Thirty-eight of the 50 (76%) patients were found to be positive for B. pertussis by culture. Among the positive cases with a history of vaccination, 30 of 42 (71.4%) cases had an incomplete pertussis vaccination history according to the national recommendation. Three phylogenetic groups (PG1-PG3) were identified each containing a predominant genotype. The two vaccines strains, CS and Tohama I, were distantly related to these three groups. Thirty-one out of fifty (62%) isolates belonged to genotype PG1, with the allelic profile prn2/ptxC2/ptxP3/ptxA1/fim3-1/fim2-1. Eighteen out of fifty (36%) isolates contained the A2047G mutation and were highly resistant to erythromycin, and all belonged to genotype PG3 (prn1/ptxA1/ptxP1/ptxC1/fim3-1/fim2-1), which is closely related to the recent epidemic strains found in northern China. The positive rate of cases under one-year-old was significantly higher than that of other age groups and should be monitored. The dominant antigen genotypes of 50 Shenzhen isolates are closely related to the epidemic strains in the United States, Australia and many countries in Europe. Despite high rates of immunization with APV, epidemics of pertussis have recently occurred in these countries. Therefore, genomic analysis of circulating isolates of B. pertussis should be continued, for it will benefit the control of whooping cough and development of improved vaccines and therapeutic strategies.
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影响因子：
11.8
作者：
Mooi FR;van Loo IH;van Gent M;He Q;Bart MJ;Heuvelman KJ;de Greeff SC;Diavatopoulos D;Teunis P;Nagelkerke N;Mertsola J
通讯作者：
Mertsola J
DOI：
10.1097/01.inf.0000160909.24879.e6
发表时间：
2005-05-01
期刊：
The Pediatric infectious disease journal
影响因子：
--
作者：
Schellekens, Joop;von Konig, Carl-Heinz Wirsing;Gardner, Pierce
通讯作者：
Gardner, Pierce
影响因子：
8.4
作者：
Simmonds, Kimberley;Fathima, Sumana;Drews, Steven J.
通讯作者：
Drews, Steven J.
DOI：
10.1098/rspb.2015.2309
发表时间：
2016-01-13
影响因子：
4.7
作者：
de Celles, Matthieu Domenech;Magpantay, Felicia M. G.;Rohani, Pejman
通讯作者：
Rohani, Pejman
影响因子：
3.1
作者：
Mooi, FR;van Oirschot, H;Willems, RJL
通讯作者：
Willems, RJL