Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019

Pauline Leroux; Soraya Matczak; Valérie Bouchez; Stevenn Volant; Antoine Ouziel; Elise Launay; Albert Faye; Valérie Rabier; Jean Sarlangue; Eric Jeziorski; Zoha Maakaroun-Vermesse; Fouad Madhi; Didier Pinquier; Mathie Lorrot; Marie Pouletty; Aymeric Cantais; Etienne Javouhey; Fatima Aït Belghiti; Sophie Guillot; Carla Rodrigues; Sylvain Brisse; Jérémie F Cohen; Julie Toubiana

doi:10.1016/j.cmi.2024.09.009

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019

Clin Microbiol Infect. 2024 Sep 19:S1198-743X(24)00440-3. doi: 10.1016/j.cmi.2024.09.009. Online ahead of print.

Authors

Pauline Leroux¹, Soraya Matczak¹, Valérie Bouchez², Stevenn Volant³, Antoine Ouziel⁴, Elise Launay⁵, Albert Faye⁶, Valérie Rabier⁷, Jean Sarlangue⁸, Eric Jeziorski⁹, Zoha Maakaroun-Vermesse¹⁰, Fouad Madhi¹¹, Didier Pinquier¹², Mathie Lorrot¹³, Marie Pouletty¹⁴, Aymeric Cantais¹⁵, Etienne Javouhey⁴, Fatima Aït Belghiti¹⁶, Sophie Guillot¹⁷, Carla Rodrigues¹⁷, Sylvain Brisse², Jérémie F Cohen¹⁸, Julie Toubiana¹⁹

Affiliations

¹ Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
² 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.
³ Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France.
⁴ Department of Pediatric Emergency and Intensive Care Unit, Hospices Civils de Lyon, Lyon, France.
⁵ University Hospital Center of Nantes, Department of General Pediatrics and Pediatric Infectious Diseases, Nantes, France.
⁶ Department of General Pediatrics, Hôpital Robert Debré, APHP, Université Paris Cité, Paris, France.
⁷ Department of Internal Medicine and Infectious Diseases, Center of Saint-Brieuc, France.
⁸ Department of General Pediatrics, University Hospital Center of Bordeaux, Bordeaux, France.
⁹ Department of General Pediatrics, University Hospital Center of Montpellier, Montpellier, France.
¹⁰ Department of General Pediatrics, University Hospital Center of Tours, Tours, France.
¹¹ Department of General Pediatrics, Centre Hospitalier Intercommunal Créteil, Université Paris Est, Créteil, France.
¹² Neonatal and Pediatric Intensive Care Department, University Hospital Center Charles Nicolle, Rouen University, Rouen, France.
¹³ Department of General Pediatrics, Hôpital Armand-Trousseau, APHP, Université Paris Sorbonne, Paris, France.
¹⁴ Department of Pediatric Intensive Care Unit, Necker-Enfants Malades Hospital, APHP, Université Paris Cité, Paris, France.
¹⁵ Department of Pediatric Emergency, University Hospital Center of Saint Etienne, Saint Etienne, France.
¹⁶ Unité des Infections Respiratoires et Vaccination, Santé publique France, Saint Maurice, France.
¹⁷ National Reference Center for Whooping Cough and Other Bordetella Infections, Institut Pasteur, Paris, France.
¹⁸ Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université Paris Cité, Paris, France; Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center of Research in Epidemiology and Statistics, INSERM UMR 1153, Université Paris Cité, Paris, France.
¹⁹ 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; Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université Paris Cité, Paris, France. Electronic address: julie.toubiana@pasteur.fr.

PMID: 39306091
DOI: 10.1016/j.cmi.2024.09.009

Abstract

Objectives: 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.

Methods: 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 × 10⁹/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.

Results: 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).

Discussion: 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.

Keywords: Bacterial variants; Disease severity; Fulminant pertussis; Infant; Malignant pertussis; Pertactin; Risk factors.