Following an analysis of bacterial samples from infants with whooping cough, scientists from the National Reference Center (CNR) for Whooping Cough and other Bordetellosis have revealed that the most severe forms of the disease are associated with specific strains expressing a key vaccine antigen. This discovery suggests that the bacteria may have evolved into less virulent and therefore less dangerous forms because of mass vaccination.
Sometimes referred to as the "100-day cough", whooping cough is a highly infectious respiratory infection that can cause serious illness in infants. Several factors may explain the fact that in 2024, France experienced its worst outbreak of whooping cough for at least 25 years. Although widespread vaccination has dramatically reduced the number of cases observed, this essential preventive measure remains an imperfect solution, as the protection conferred by vaccination weakens over time, and regular boosters are required. Over the past decade, scientists at the National Reference Center (CNR) for Whooping Cough and other Bordetella Infections monitoring the bacteria responsible for whooping cough, Bordetella pertussis (B. pertussis), have also observed a rise in strains lacking the expression of one of the vaccine antigens, pertactin. This reflects an adaptation of the pathogen to widespread vaccination with acellular vaccines: the strains that do not produce pertactin partly evade the immune response in vaccinated individuals and spread more effectively than the original strains which expressed the antigen.
Pertactin, a protein associated with severe forms of whooping cough
In a recent study coordinated by the Institut Pasteur, scientists from the CNR for Whooping Cough and other Bordetella Infections, in collaboration with pediatricians from several French hospitals, examined the extent to which B. pertussis strains that still express pertactin are associated with malignant pertussis, the most severe form of whooping cough in infants. Between 2008 and 2019, they analyzed the bacterial isolates found in 361 infants aged under six months with whooping cough.
"Our research confirms that age, preterm birth and an absence of whooping cough vaccination are independent risk factors for malignant pertussis. Moreover, and this is the major new finding of our study, we show that the strains that still produce pertactin are associated with the most severe forms of whooping cough in infants," explains Professor Julie Toubiana, Deputy Director of the CNR for Whooping Cough and other Bordetella Infections and a scientist in the Biodiversity and Epidemiology of Bacterial Pathogens Unit.
Less virulent bacteria as a result of vaccination?
The research suggests that vaccination also plays another key role. The link between the most severe forms of whooping cough and the presence of pertactin suggests that vaccination exerts selective pressure on B. pertussis, causing the bacteria to evolve towards less virulent strains lacking pertactin. In other words, widespread vaccination could reduce the severity of the disease and decrease the risk of severe whooping cough in infants.
By demonstrating an indirect yet significant advantage of vaccination, this research could influence the decisions of public health authorities and improve future whooping cough vaccine strategies.
Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019, Clinical Microbiology and Infection, September 19, 2024
Pauline Leroux1, y, Soraya Matczak1, y, Valerie Bouchez1, 2, Stevenn Volant3,Antoine Ouziel4, Elise Launay5, Albert Faye6, Valerie Rabier7, Jean Sarlangue8,Eric Jeziorski9, Zoha Maakaroun-Vermesse10, Fouad Madhi11, Didier Pinquier12,Mathie Lorrot13, Marie Pouletty14, Aymeric Cantais15, Etienne Javouhey 4, Fatima Aït Belghiti16, Sophie Guillot2, Carla Rodrigues2, Sylvain Brisse 1, 2, Jérémie F. Cohen 17, 18, Julie Toubiana 1, 2, 17,*
1Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France
2National Reference Center for Whooping Cough and Other Bordetella Infections, Institut Pasteur, Paris, France
3Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France
4Department of Pediatric Emergency and Intensive Care Unit, Hospices Civils de Lyon, Lyon, France
5University Hospital Center of Nantes, Department of General Pediatrics and Pediatric Infectious Diseases, Nantes, France
6Department of General Pediatrics, Hôpital Robert Debré, APHP, Université Paris Cité, Paris, France
7Department of Internal Medicine and Infectious Diseases, Center of Saint-Brieuc, France
8Department of General Pediatrics, University Hospital Center of Bordeaux, Bordeaux, France
9Department of General Pediatrics, University Hospital Center of Montpellier, Montpellier, France
10Department of General Pediatrics, University Hospital Center of Tours, Tours, France
11Department of General Pediatrics, Centre Hospitalier Intercommunal Créteil, Université Paris Est, Créteil, France
12Neonatal and Pediatric Intensive Care Department, University Hospital Center Charles Nicolle, Rouen University, Rouen, France
13Department of General Pediatrics, Hôpital Armand-Trousseau, APHP, Université Paris Sorbonne, Paris, France
14Department of Pediatric Intensive Care Unit, Necker-Enfants Malades Hospital, APHP, Université Paris Cité, Paris, France
15Department of Pediatric Emergency, University Hospital Center of Saint Etienne, Saint Etienne, France
16Unite des Infections Respiratoires et Vaccination, Santé publique France, Saint Maurice, France
17Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants Malades, APHP, Université Paris Cité, Paris, France
18Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center of Research in Epidemiology and Statistics, INSERM UMR 1153, Université Paris Cité, Paris, France
*Corresponding author
y These authors contributed equally to this work
