The Bordetella pertussis epidemic

The current Bordetella pertussis epidemic began in 2008. The peak of the outbreak was reached in 2009 with 35,000 cases (156 per 100,000 population) with the most affected age group being the 5-9 year old cohort.

Though immunisation is above 90% for the <12 month old and 24 month old populations, only ~ 81% of 5 year olds received their booster injections. These rates have remained relatively stable and changes in immunisation behaviour are not a factor.

The whole cell vaccine for B. pertussis was withdrawn in 1999 and replaced with the acellular 3 component formulation as the previously used vaccine was associated with some severe side effects. There are three antigenic targets in the vaccine: the pertussis toxin (Ptx), pertactin (prn) and filamentous haemagglutinin. B. pertussis produces several other virulence factors including a haemolysin and adenylate cyclase. This vaccine therefore provides protection against one toxin and two adhesion factors.

Selection pressures have favoured mutant organisms with antigens that are dissimilar to vaccine components. The new prn2-ptxP3 constitutes ~4% of clinical isolates. Mutations in two of these targets are thought to be clinically relevant. The prn2 variant have a selective advantage in ACV inoculated communities. Further, ptxP3 (Ptx gene promoter, not toxin mutant) strains produce greater amounts of pertussis toxin, they are more virulent. An increased level of hospitalisation and morbidity is observed in ptxP3 positive strains. These new strains has spread nationally and internationally.

Overall, vaccine susceptible strains are the major component of the epidemic. Waning immunity maintains a reservoir of pertussis in the community. Antibodies recognising P.69 Prn are required for phagocytosis of B. pertussis, whilst antibodies to Ptx attenuate disease.

Could antigenic changes to P.69 Prn but not PTX explain the phenomenon of colonisation and attenuated disease in some vaccinated cases?

References

• Differential protection of the Bordetella pertussis protein Pertactin studied in two mouse models [PDF]
• A placebo-controlled trial of a pertussis-toxoid vaccine. N Engl J Med. 1995 Oct 19;333(16):1045-50. [PMID 7675047]
• Newly Emerging Clones of Bordetella pertussis Carrying prn2 and ptxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008–2010 J Infect Dis. 2012 Apr 15;205(8):1220-4. Epub 2012 Mar 13. [PMID 22416243]
• Targeted mutations that ablate either the adenylate cyclase or hemolysin function of the bifunctional cyaA toxin of Bordetella pertussis abolish virulence. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4898-902. [PMID 1594590]