Bordetella pertussis population dynamics and phylogeny in Japan after adoption of acellular pertussis vaccines. Bordetella pertussis Japan

Bordetella pertussis, the causative agent of whooping cough, has experienced a resurgence in the past fifteen years, despite the existence of both whole cell- and acellular vaccines. We performed whole genome sequencing analysis of 149 strains that caused disease in Japan between 1982 and 2014, after Japan became the first country to adopt acellular vaccines against B. pertussis. In addition to these isolates obtained from the Japanese National Institute of Infectious Diseases (NIID), we also sequenced 39 strains procured from the Konan Kosei hospital in the Aichi prefecture, Honshu, Japan. The genome sequences afforded an insight into B. pertussis genome variability and population dynamics in Japan, and revealed that the current B. pertussis population in Japan is characterized by two major clades that divided more than 40 years ago. The pertactin gene was disrupted in about 20% of the 149 NIID isolates, by either a deletion within the signal sequence (ΔSS) or the insertion of the IS element IS481 (prn::IS481). Divergence dating traced the first appearance of pertactin-deficient mutants to around 1993 (ΔSS) and around 1995 (prn::IS481), and revealed that strains containing the alternative pertactin allele prn2 may have arrived in Japan around 1973. Japanese isolates displayed a higher rate of genetic variants in pertactin, compared to a previously published collection of worldwide strains where most isolates predated acellular vaccine usage. Molecular clock data revealed that observed fluctuations in B. pertussis population size may have coincided with changes in vaccine usage, suggesting that environmental changes may impact pathogen evolution. The failure to eradicate the disease in Japan and other parts of the world warrants an exploration of novel vaccine compositions, containing improved versions of currently used antigens and/or hitherto unexplored proteins.