The 138 children who tested positive for pertussis were compared with two control groups. One included the 54,339 children matched by gender, race/ethnicity and medical clinic to the children with pertussis. The other control group included the 899 children who had tested negative for pertussis with the PCR test. PCR, for polymerase chain reaction, is one of three ways to test for pertussis and is most effective within the first four weeks of infection.
Among the children with confirmed pertussis, those whose first four shots had all been acellular were at 5.6 times higher risk for pertussis than those who had four whole cell shots. Those who had received a mixture of acellular and whole-cell shots were at almost fourfold (3.77 times) higher risk for pertussis. The researchers calculated that for each DTaP shot the children received instead of the whole-cell DTP, their risk of pertussis increased by 40 percent. Although such an observational study cannot prove that the waning of the acellular vaccine and discontinuation of the whole vaccine caused the recent pertussis outbreaks, the findings adds more to the theory.
“The bright side is that this vaccine is much safer, but the price you pay is that you traded efficacy for safety,” Offit says. “The surprise is how big that trade was, which I don’t think anyone anticipated.” Because the older vaccine was made from the entire bacterial organism, it contained between 2,000 and 3,000 antigens—the components that an immune response can potentially target and remember in the event of a later infection. The acellular vaccines contain three to five antigens.
Managing pertussis outbreaks
Aside from the difference in antigens, though, scientists remain unsure what made the whole-cell vaccine so effective. “Even with the new immunological studies, we can’t tell what’s special about the whole-cell vaccine that makes it better,” says Kathryn Edwards, the director of the Vanderbilt University School of Medicine Vaccine Research Center. “That’s unfortunate, because if we knew what the differences were, we might be able to add that to the acellular vaccine.”
Bringing back the whole-cell vaccine is unlikely, Edwards and Offit say, because of the safety concerns, but Edwards suggests it might be possible to modify a new whole-cell vaccine that’s less reactive or to add antigens to the acellular vaccine. Another possibility, Offit says, is adding an enhancing compound (known as an adjuvant) to the acellular vaccine to strengthen the body’s immune response to the formula.
The study authors conclude that boosting teens with the Tdap is the best option. Offit, Edwards and Saad Omer, an associate professor at Emory University’s Vaccine Center, concur. “On a policy level, this adds to the cumulative evidence that may lead to exploration of other strategies for controlling pertussis, and it may be necessary to tweak the timing of the childhood schedule to be sure there are no gaps in protection,” Omer says.
The CDC’s Advisory Committee on Immunization Practices has already taken some steps to address the nationwide increase in pertussis cases by recommending in October 2012 that pregnant women receive the Tdap booster between 27 and 36 weeks of pregnancy, even if they have already received a previous Tdap. “The thinking was this: it looks like more children are dying, so as a first step, let’s prevent the deaths,” Offit says. Of the 18 pertussis fatalities in 2012 (pdf), 13 were under three months old. The hope is that pregnant women will pass along some of their immunity to their newborns for added protection until the infants’ first DTaP shots at two months. Another way to protect the youngest babies is cocooning—immunizing everyone around the baby with Tdap boosters.