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Shooting the Wheeze: Whooping Cough Vaccine Falls Short of Previous Shot’s Protection

Long considered a conquered childhood disease, pertussis has made a comeback in the U.S., in part because the combination vaccine, DTap, appears less effective than its predecessor, DTP
Coughing sick child



Flickr/anjanettew

Protection against the disease pertussis, or whooping cough, doesn’t appear to be as strong with the currently administered vaccine when compared with the older version administered up until the 1990s, according to a new study in Pediatrics. During a pertussis outbreak in 2010–11 in California teens who had received four doses of the current vaccine were at almost six times more likely to get pertussis as those who had received four doses of the older preparation.

The study offers more precise evidence that the earlier pertussis vaccine was superior to the current one, building on previous research that had already shown that the newer vaccine’s effectiveness wanes sooner than expected. The new formula’s reduced effectiveness is most likely driving the recent epidemics of pertussis, says the study’s lead author, Nicola Klein, co-director of Kaiser Permanente Vaccine Study Center in Oakland, Calif. After more than three decades that never saw annual U.S. pertussis cases top 10,000 (they usually totaled fewer than 3,000), the number of cases began climbing rapidly in the late 1990s. The 27,550 cases in 2010 were the highest since 1959, and the preliminary 2012 numbers, at 41,880, were the highest since 1955.

The lower level of protection offered by the current vaccine, however, does not mean it isn’t effective, says Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “You’re still eightfold less likely to get pertussis if you’ve gotten the acellular vaccine than if you didn’t,” he says. “It’s an imperfect vaccine, but it’s the best that we have.”

Out with the old
Pertussis is a bacterial infection of the lungs that leads to uncontrollable, deep coughs. The condition can be fatal for very young children. The current vaccine is acellular, meaning it contains protein pieces of the Bordetella pertussis bacterium, given in combination with the tetanus and diphtheria vaccines in the DTaP formulation for infants and children up to six years old. The adolescent and adult booster is a similar compound called Tdap. The older vaccine, DTP, used whole cells of the pertussis bacterium but had more dramatic side effects, often causing high fevers and sometimes fever-induced seizures.

Although no evidence has shown that the seizures caused any long-term damage, they were frightening and led scientists to develop the acellular version. Phased in throughout the U.S. during the 1990s, the acellular vaccine was officially adopted in the U.S. Centers for Disease Control’s childhood immunization schedule in 1997. At Kaiser Permanente Northern California, which conducted the study, the first use of the new DTaP was in the vaccine’s fifth booster shot in 1991, followed by its use for the fourth booster the next year. The three-dose initial series of DTaP began in 1997; by 1999, all five shots for kids under age 10 used the DTaP.

This study focused on the children who got their five-shot series during that transitional period between vaccines. The researchers examined the medical records of all children born from 1994 to 1999 who received all five shots—the first four before age two and the fifth by age seven—and who were in the Kaiser Permanente system during the pertussis outbreak from January 2010 to December 2011.

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.

“The implications of the study are that it is really important to give the vaccine, including the Tdap booster, because these vaccines do work in the short-run,” Klein says. “The way forward is to come up with new vaccines that provide long-lasting immunity as well as a strong safety profile.”

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