Laboratory of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Nosocomial Infection Control Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Pediatric Intensive Care Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Clin Microbiol Infect. 2024 Nov;30(11):1439-1446. doi: 10.1016/j.cmi.2024.08.016. Epub 2024 Aug 28.
China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events.
We performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains.
From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism.
We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.
在中国，新冠肺炎疫情后百日咳病例显著增加，发病年龄向大龄儿童转移，疫苗逃逸增加，以及大环内酯类耐药博德特氏菌（Bordetella pertussis）的流行率显著上升。在此，我们对这些事件进行了基因组流行病学调查。
我们对 2016 年至 2024 年期间从中国上海分离的培养阳性 B 型百日咳进行了回顾性观察性研究。我们通过整合 723 株全基因组测序、抗生素药敏性、转录组谱和临床数据，分析了菌株和百日咳流行病学动态。我们将上海株的基因组序列与 6450 株中国和全球株进行了比较。
从新冠肺炎疫情前（2019 年 12 月前）到疫情后，患者从以婴儿为主（90%，397/442）转为大龄儿童（婴儿：16%，132/844）的比例更高，接种人群的比例从 31%（107/340）飙升至 88%（664/756）。大环内酯类耐药博德特氏菌的流行率从 60%（267/447）上升至 98%（830/845）。一个独特的能够引起大龄儿童和接种人群大量感染的 ptxP3- 谱系大环内酯类耐药克隆，MR-MT28 的出现和扩张与百日咳的爆发和流行病学转变密切相关。尽管 MR-MT28 表现出更高表达编码百日咳毒素的基因，但与明显更轻微的临床症状和更低的住院率相关。MR-MT28 可能在 2016 年前后在中国起源，获得了包括一个新的 prn150 等位基因在内的几个关键突变，并在中国多个地区检测到。此外，26%（50/195）的 MR-MT28 已经进化为预测的无丝状血凝素（PRN）缺陷株，IS481 插入是主要机制。
我们报告称，中国新冠肺炎疫情后百日咳的爆发与 ptxP3-MR-MT28 有关，并提供了证据表明病原体进化可能是导致百日咳爆发、发病年龄转移和疫苗逃逸的主要因素。MR-MT28 存在很高的全球传播风险，需要全球监测。
