Association between Fulminant Pertussis and Pertactin-Producing <i>Bordetella Pertussis</i> in Infants: A Multicenter Study in France, 2008-2019

Background: Fulminant pertussis (FP) is the most severe form of whooping cough (pertussis). Virulence factors of the causative agent, Bordetella pertussis, may be involved in disease severity. We aimed to assess the association between FP and pertactin production status of B. pertussis clinical isolates.Methods: Infants <6 months with whooping cough and a positive B. pertussis culture between 2008 and 2019 were included. B. pertussis isolates and clinical data were collected through the French pertussis surveillance network. FP was defined as an episode with a leukocyte count >40 G/L and at least one of the following criteria: respiratory failure requiring non-invasive or mechanical ventilation, pulmonary hypertension, multiple organ failure, shock requiring vasoactive or inotropic agents. Pertactin (PRN) production was assessed by Western blot. Multivariable logistic regression was performed to identify patient and microbiological features associated with FP.Findings: We included 361 infants (median age 63 days [range, 15-182]), of which 32 (9%) progressed to FP. Eighty-one percent of isolates produced PRN. All patients who died (n=10) had FP. Children with FP were significantly more often neonates (adjusted odds ratio [aOR] 4.3 95% confidence interval [CI] 1.7-11.1), infants with a history of prematurity under 34 weeks of gestation (aOR 13.7, 95%CI 2.9-64.0), non-vaccinated infants (aOR 5.9, 95%CI 1.2-28.6), and cases caused by B. pertussis isolates producing PRN (aOR 4.8, 95%CI 1.1-21.7).Interpretation: In this large multicenter study, pertactin production status was identified as a microbiological feature independently associated with FP.Funding: JT received funding from Ville-de-Paris as part of the EMERGENCE program. PL and SM received funding from the Fondation pour la Recherche Médicale (FRM), PL received funding from Fédération Hospitalo-Universitaire (FHU) CHILD (Janusz Korczak Award, 2020) and SM from Société de Pathologie Infectieuse de Langue Française (SPILF). The NRC for whooping cough receives financial support from Santé publique France, the national public health agency.Declaration of Interest: The authors did not declare any conflict of interest.Ethical Approval: This study was approved by the ‘Comité éthique et scientifique pour les recherches, les études et les évaluations dans le domaine de la santé’ (CESREES, registration number 2428977b, 11/02/2021). The study data management was also authorized by and the ‘Institut national des données de santé’ (INDS) and the ‘Commission nationale de l’informatique et des libertés’ (CNIL, registration number DR-2021-216, 20/07/2021). Written consent was not required for this retrospective study. Parents and/or legal guardians were informed of the research and were offered the opportunity to withdraw from the study. A waiver was obtained for data of patients deceased and/or prior to 2015.