Phylodynamics of pertussis in the vaccine era: transition to re-emergence

Abstract

AbstractBordetella pertussis causes whooping cough in humans. Despite high routine vaccination coverage, pertussis has become the most prevalent vaccine-preventable disease in many industrialized countries, since the 1990s. While a plethora of candidate explanations for the resurgence remain hotly debated, two prevailing ideas focus on vaccine driven pathogen adaptation and on the switch to the latest generation vaccines. We use a suite of genomic and epidemiological approaches to characterize pertussis transmission in the Netherlands, between 1949 and 2017, investigate drivers of B. pertussis population diversity, and the role of allele shifts in the resurgence. Reconciling the epidemiological data with sequence data has allowed us to characterize a resurgence that is not accompanied with increased transmission but has unique functional genomic signatures of decreased diversity. Here we show a positive association between genetic diversity and incidence which validates the hypothesis that the resurgence is associated with the expansion of more pathogenic strains. We see a direct effect of vaccination on the replicative fitness of pathogens. Our models suggest, large outbreaks are unlikely to be due to immune evasion and the vaccine switch cannot be contributing to increased pertussis incidence. Therefore, efforts aimed at mitigating the resurgence in the population at large, and particularly in vulnerable infants, are more likely to succeed by maintaining routine vaccine coverage high.