July 31, 2012
The protection provided by acellular pertussis vaccines (DTaP) as a first dose may fall short of that provided by first-dose whole-cell pertussis vaccines (DTwP), which were phased out in the 1990s because of higher rates of adverse events, an Australian study showed.
Among children born in 1998, rates of pertussis were higher among those who received an acellular vaccine instead of a whole-cell vaccine for the first three doses in the primary series, according to Sarah Sheridan, BMed, of Queensland Children’s Medical Research Institute in Brisbane, Australia, and colleagues.
The difference was evident during a pre-epidemic period from 1999 to 2008 and during a period of elevated pertussis rates from 2009 to 2011, they reported in a research letter in the Aug. 1 issue of the Journal of the American Medical Association.
“The challenge for future pertussis vaccine development is to address the benefit-risk trade-off highlighted by our study,” they wrote, “and to develop vaccines that induce long-lasting protection from the first dose, without the adverse events associated with DTwP use.”
In many developed countries, including the U.S. and Australia, DTaP (diphtheria, tetanus, and acellular pertussis) replaced DTwP (diphtheria, tetanus, and whole-cell pertussis) in the 1990s because it carried a lower risk of such adverse events as injection-site reactions and fever.
DTaP became available in Queensland in 1996 but did not fully displace DTwP for publicly funded immunizations until March 1999. Thus, children born in 1998 received primary courses with DTaP only, DTwP only, or a combination of the two.
Similar to what has been occurring in the U.S., Australia has seen increasing rates of pertussis in the last few years. Sheridan and colleagues explored whether the rise could be related to the switch from one vaccine type to the other.
The researchers analyzed data on pertussis cases reported to the health department in Queensland from 1999 to 2008, considered the pre-epidemic period, and from 2009 to 2011 or the outbreak period. That information was linked to data from the Queensland vaccination registry.
Of 58,233 children born in 1998, 69.5% received at least three doses of any pertussis vaccine during the first 6 months of life. Among the vaccinated children, there were 267 first pertussis cases reported through 2011.
Children who received the three-dose primary series with DTaP only had higher rates of pertussis compared with those who received the primary series with DTwP only, both during the pre-epidemic period (13.2 versus 5.2 per 100,000 per year) and the outbreak period (373.1 versus 113.3 per 100,000 per year).
For children who received a mix of both types of vaccine, rates of pertussis were higher during the outbreak period for those who received DTaP as the first dose (409.0 versus 113.3 per 100,000 per year).
“It is unlikely our findings during the current outbreak are the result of detection bias because this would require healthcare-seeking behavior, or the likelihood of laboratory testing or reporting, to be associated with the primary course received by children over a decade previously,” the authors wrote.
It is possible, they noted, that the higher rates of disease with the acellular vaccine could be related to changes in the circulating Bordetella pertussis strains or differences in the immune responses induced by the two types of vaccine.
“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,” the researchers wrote.
Sheridan is supported by an Australian postgraduate award from the Australian government and a clinical scholarship from Queensland Children’s Medical Research Institute. One of her co-authors is supported by an early career fellowship from the National Health and Medical Research Council and is a Queensland Children’s Medical Research Institute senior research fellow.
Sheridan reported that she had no conflicts of interest. Her co-authors reported relationships with GlaxoSmithKline and Sanofi Pasteur.
Primary source: Journal of the American Medical Association