Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Abstract

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Genomic epidemiology and multilevel genome typing ofBordetella pertussis

“…MGT4 ST56 and ST106) and those that continued to cause infections in Australia (MGT4 ST88, ST10, ST113, and ST9). MGT also clearly demonstrates that the majority of isolates in STs after 2011 were Prn deficient, supporting previous work demonstrating the increased fitness of such strains [6,22,38].…”

“…The effective surveillance of ptxP3 strains (MGT2 ST2) and their subtypes is vital given its global dominance. Existing nomenclatures, such as fim3 alleles or SNP based approaches, have been used to describe the evolution of different groups within ptxP3 [4,6,[22][23][24], however each has limitations. fim3 alleles can only divide ptxP3 into 2 types therefore providing only a marginal improvement in resolution.…”

“…By contrast MGT typing can divide the ptxP3 strains into numerous subtypes from MGT3 to MGT5, which enabled detailed description of its epidemiology. For example, Prn deficient isolates have been shown to have a fitness advantage [6,38] and have increased in frequency in both Australia and the USA. However, the genetic cause of the loss of prn production varies between these countries indicating that these strains were of independent origin.…”

“…The rapid increase of Prn deficient isolates (Prn-) in the last 15 years has been associated with multiple independent mutational events across the B. pertussis population [6,36].…”

“…Studies have suggested that the selection pressure from vaccine-induced immunity has acted on B. pertussis evolution in recent years [4][5][6][7], and therefore the use of ACV may have been a significant contributor to the resurgence of pertussis [8]. Increased variation of ACVantigen genes, a mismatch of alleles between the vaccine strain and the current circulating B. pertussis strains and the recent increase in Prn-negative isolates all point to vaccine selection [4][5][6][7][9][10][11].…”