Noémie Lefrancq
28 April 2022

Led by Noémie Lefrancq and Valérie Bouchez, and a collaboration between the Department of Genetics, the Vet School, Institut Pasteur Paris, and the EuPertStrain consortium, a new paper entitled Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis is out now in Science Translational Medicine.

The study was supervised by Sylvain Brisse from Institut Pasteur Paris, and Henrik Salje from Department of Genetics at the University of Cambridge.

Bordetella pertussis (Bp), which causes whooping cough, infects >24 million individuals annually despite widespread vaccination. Asymptomatic carriage and multiple circulating lineages hide the underlying dynamics of Bp from surveillance systems. Therefore, the extent of spread across spatial scales remains a mystery, as does the role of vaccines in driving changes in strain fitness. In this study we use models informed by pathogen sequences to help answer these key questions.

We analysed 3,344 genomes from 23 countries, covering an 85-year period, thanks to the establishment of the EuPertStrain consortium of national reference laboratories and publicly available data GenBank. We found substantial diversity within communities, consistent with widespread subclinical transmission, and a strong association between the number of transmission chains circulating within subnational regions and the host population size. Bp strains are able to spread both nationally and internationally in just a few years, e.g. it takes only 5-10 years for individual lineages to be homogeneously distributed throughout Europe or the United States. Next, we developed an analytical model that estimates the relative fitness of different genotypes across countries. Heterogeneity in vaccine introductions provides a natural experiment to characterize fitness changes following switches in the local vaccine type being used. Our framework recovered the substantially different genotype dynamics that have been observed across countries, enabling us to estimate the relative fitness of the different genotypes, by vaccination era. We found that increased fitness of pertactin-deficient strains following implementation of acellular vaccines, but reduced fitness otherwise, can explain the long-term genotype dynamics.

This work provides a first detailed view of the strength of spatial structure and rate of geographic spread, highlighting how Bp spread is a globally interconnected issue. It further provides a quantitative description of strains fitness and highlights the key role of vaccine policy decision-making in driving ecological change.