title: Bordetella pertussis strains with increased toxin production associated with pertussis resurgence.
abstract: Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated populations, and pertussis has become the most prevalent vaccine-preventable disease in industrialized countries. We present evidence that in the Netherlands the dramatic increase in pertussis is temporally associated with the emergence of Bordetella pertussis strains carrying a novel allele for the pertussis toxin promoter, which confers increased pertussis toxin (Ptx) production. Epidemiologic data suggest that these strains are more virulent in humans. We discuss changes in the ecology of B. pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively.
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, the Netherlands. frits.mooi@rivm.nl
authors.forename: Frits R
authors.initials: FR
authors.lastname: Mooi
authors.forename: Inge H M
authors.initials: IH
authors.lastname: van Loo
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Gent
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
authors.forename: Marieke J
authors.initials: MJ
authors.lastname: Bart
authors.forename: Kees J
authors.initials: KJ
authors.lastname: Heuvelman
authors.forename: Sabine C
authors.initials: SC
authors.lastname: de Greeff
authors.forename: Dimitri
authors.initials: D
authors.lastname: Diavatopoulos
authors.forename: Peter
authors.initials: P
authors.lastname: Teunis
authors.forename: Nico
authors.initials: N
authors.lastname: Nagelkerke
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
mesh_terms: D000293:Adolescent; D000483:Alleles; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D001483:Base Sequence; D001886:Bordetella pertussis / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D002648:Child; D002675:Child, Preschool; D021821:Communicable Diseases, Emerging / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D007223:Infant; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009426:Netherlands / Q000453:epidemiology; D037342:Pertussis Toxin / Q000096:biosynthesis* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D014774:Virulence / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000096:biosynthesis; D014917:Whooping Cough / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D010566:Virulence Factors, Bordetella; C068929:pertactin; D037342:Pertussis Toxin