Leroux Pauline, Matczak Soraya, Bouchez Valérie, Volant Stevenn, Ouziel Antoine, Launay Elise, Faye Albert, Rabier Valérie, Sarlangue Jean, Jeziorski Eric, Maakaroun-Vermesse Zoha, Madhi Fouad, Pinquier Didier, Lorrot Mathie, Pouletty Marie, Cantais Aymeric, Javouhey Etienne, Aït Belghiti Fatima, Guillot Sophie, Rodrigues Carla, Brisse Sylvain, Cohen Jérémie F, Toubiana Julie
Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France; National Reference Center for Whooping Cough and Other Bordetella Infections, Institut Pasteur, Paris, France.
Clin Microbiol Infect. 2025 Feb;31(2):233-239. doi: 10.1016/j.cmi.2024.09.009. Epub 2024 Sep 19.
Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates.
Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 10/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph.
We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83).
PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.
致病原百日咳博德特氏菌的毒力因子可能与暴发性百日咳有关，暴发性百日咳是婴儿百日咳（pertussis）最严重的形式。我们旨在评估暴发性百日咳与百日咳博德特氏菌临床分离株的百日咳黏附素（PRN）产生状态之间的关联。
纳入2008年至2019年间百日咳博德特氏菌培养阳性的6个月以下有症状婴儿。通过国家百日咳监测网络从法国医院实验室收集百日咳博德特氏菌分离株和临床数据。暴发性百日咳定义为白细胞计数>40×10⁹/L且符合以下至少一项标准的病例：呼吸衰竭、肺动脉高压、休克或多器官功能衰竭。通过蛋白质印迹法评估PRN的产生。比较有和没有暴发性百日咳的患者之间婴儿的基线特征和微生物学发现。为了确定与暴发性百日咳相关的患者和微生物学特征，构建了一个多变量修正泊松回归模型，使用有向无环图选择混杂因素。
我们纳入了361例百日咳婴儿（中位年龄63天[四分位间距，39 - 86天]），其中32例（9%）进展为暴发性百日咳。没有一位母亲在孕期接种过疫苗。在361株相关的百日咳博德特氏菌分离株中，294株（81%）产生PRN。暴发性百日咳患者更常为新生儿（调整后相对风险[aRR]：3.62，95%置信区间[CI]：1.76 - 7.44）、有早产史的婴儿（aRR：7.08，95% CI：3.06 - 16.36）、未接种疫苗的婴儿（aRR：4.42，95% CI：1.02 - 19.24）以及感染产生PRN分离株的婴儿（aRR：3.76，95% CI：1.02 - 13.83）。
产生PRN的百日咳博德特氏菌与暴发性百日咳风险增加独立相关。在含PRN的无细胞百日咳疫苗促使PRN缺陷型分离株出现的背景下，我们的研究表明此类疫苗在推动百日咳博德特氏菌种群向毒力降低方向进化方面具有积极作用。
