Number and Order of Whole Cell Pertussis Vaccines in Infancy and Disease Protection FREE

To the Editor: Due to their lower rate of adverse events, acellular pertussis vaccines (diphtheria-tetanus-acellular pertussis; DTaP) replaced whole cell vaccines (diphtheria-tetanus-whole cell pertussis; DTwP) in many developed countries during the 1990s. DTaP became available in Queensland, Australia, in 1996 and replaced DTwP for publicly funded primary course immunizations delivered at ages 2 months, 4 months, and 6 months in March 1999. This meant children born in 1998 could receive a primary course consisting of only DTwP, only DTaP, or a mixed schedule.

Similar to North America,¹ Australia is experiencing a sustained pertussis epidemic,² with the highest incidence rates in Queensland during 2011 in children aged 6 to 11 years. The recent changes in pertussis epidemiology may be related to the shift from DTwP to DTaP. To test this hypothesis, we compared pertussis reporting rates by primary course vaccination in the 1998 birth cohort.

Reporting pertussis cases to the health department is mandatory in Queensland. For children born in 1998, we calculated pertussis reporting rates in both the preepidemic (1998-2008) and outbreak periods (2009-2011), by number and order of DTwP doses given before their first birthday. We linked data from the Queensland vaccination register (QVR) with case reports of pertussis. The QVR is not a population-based register so we could not construct a group of wholly unvaccinated children for comparison. Children were censored following initial reporting. We calculated average annual incidence rates, incidence rate differences, incidence rate ratios, and 95% confidence intervals using Stata version 12 (StataCorp). The Queensland Children's Health Services ethics committee approved the study.

Of 58 233 children born in 1998 identified in the QVR, 40 694 (69.9%) received at least 3 doses of any pertussis-containing vaccine during the first year from a Queensland vaccine service provider and were included in the analysis. Overall, 267 first pertussis cases were reported from this cohort between 1999 and 2011; 2 second reports were excluded.

Children who received a 3-dose DTaP primary course had higher rates of pertussis than those who received a 3-dose DTwP primary course in the preepidemic and outbreak periods (Table and Figure). Among those who received mixed courses, rates in the current epidemic were highest for children receiving DTaP as their first dose. This pattern remained when looking at subgroups with 1 or 2 DTwP doses in the first year of life, although it did not reach statistical significance (Table). Children who received a mixed course with DTwP as the initial dose had incidence rates that were between rates for the pure course DTwP and DTaP cohorts (Table).

Infant priming with DTwP was associated with a lower risk of subsequent pertussis than DTaP only primed children in this cohort. This difference persisted for more than a decade, being evident in preepidemic and outbreak periods. A primary course using even a moderately effective DTwP vaccine may be more protective than DTaP.³ In the preacellular era, Australia used a locally produced DTwP vaccine with very good to excellent effectiveness.⁴ Our findings suggest the most important factor, in this cohort, may be the initial vaccine received.

It is unlikely our findings during the current outbreak are the result of detection bias because this would require health care–seeking behavior, or the likelihood of laboratory testing or reporting, to be associated with the primary course received by children over a decade previously.

Possible explanations for our findings could include antigenic shifts in circulating Bordetella pertussis strains² or the different immune responses from acellular and whole-cell priming.⁵ The lesser protection provided by DTaP, both as the initial vaccine or full primary course, may be due to linked epitope suppression, when the initial exposure locks in the immune response to certain epitopes and inhibits response to other linked epitopes on subsequent exposures.⁶

The challenge for future pertussis vaccine development is to address the benefit-risk trade-off highlighted by our study, and to develop vaccines that induce long-lasting protection from the first dose, without the adverse events associated with DTwP use.