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Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study
Pauline Leroux1, Soraya Matczak1, Valérie Bouchez2
1Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
Insights
Pertactin (PRN)-producing Bordetella pertussis strains are linked to a higher risk of severe infant pertussis. This suggests that current vaccines, which contain PRN, may help reduce pertussis virulence over time.
Area of Science:
- Bacteriology
- Pediatric Infectious Diseases
- Vaccinology
Background:
- Fulminant pertussis, a severe infant illness, may be linked to Bordetella pertussis virulence factors.
- Pertactin (PRN) is a key virulence factor of B. pertussis.
- Understanding the role of PRN in pertussis severity is crucial for public health.
Purpose of the Study:
- To investigate the association between PRN production by B. pertussis clinical isolates and the development of fulminant pertussis in infants.
- To identify risk factors for fulminant pertussis.
Main Methods:
- Retrospective study of infants (<6 months) with B. pertussis culture (2008-2019).
- Fulminant pertussis defined by high leukocyte count and severe clinical criteria (respiratory failure, shock, etc.).
- PRN production assessed by western blotting; multivariable modified Poisson regression used for analysis.
Main Results:
- 361 infants included; 32 (9%) developed fulminant pertussis.
- PRN-producing B. pertussis isolates were associated with increased risk of fulminant pertussis (aRR: 3.76).
- Risk factors for fulminant pertussis included prematurity, lack of vaccination, and neonatal age.
Conclusions:
- PRN-producing B. pertussis strains are independently associated with a higher risk of fulminant pertussis.
- The study suggests a potential role for PRN-containing vaccines in reducing B. pertussis virulence.
- Vaccination strategies may influence the evolution of B. pertussis populations.
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.
