Bordetella pertussis and vaccination: the persistence of a genetically monomorphic pathogen

Before childhood vaccination was introduced in the 1950s, pertussis or whooping cough was a major cause of infant death worldwide. Widespread vaccination of children was successful in significantly reducing morbidity and mortality. However, despite vaccination, pertussis has persisted and, in the 1990s, resurged in a number of countries with highly vaccinated populations. Indeed, pertussis has become the most prevalent vaccine-preventable disease in developed countries with estimated infection frequencies of 1-6%. Recently vaccinated children are well protected against pertussis disease and its increase is mainly seen in adolescents and adults in which disease symptoms are often mild. The etiologic agent of pertussis, Bordetella pertussis, is extremely monomorphic and its ability to persist in the face of intensive vaccination is intriguing. Numerous studies have shown that B. pertussis populations changed after the introduction of vaccination suggesting adaptation. These adaptations did not involve the acquisition of novel genes but small genetic changes, mainly SNPs, and occurred in successive steps in a period of 40 years. The earliest adaptations resulted in antigenic divergence with vaccine strains. More recently, strains emerged with increased pertussis toxin (Ptx) production. Here I argue that the resurgence of pertussis is the compound effect of pathogen adaptation and waning immunity. I propose that the removal by vaccination of naïve infants as the major source for transmission was the crucial event which has driven the changes in B. pertussis populations. This has selected for strains which are more efficiently transmitted by primed hosts in which immunity has waned. The adaptation of B. pertussis to primed hosts involved delaying an effective immune response by antigenic divergence with vaccine strains and by increasing immune suppression through higher levels of Ptx production. Higher levels of Ptx may also benefit transmission by enhancing clinical symptoms. The study of B. pertussis populations has not only increased our understanding of pathogen evolution, but also suggests way to improve pertussis vaccines, underlining the public health significance of population-based studies of pathogens.