James GAthany/CDC

Ouch. New pertussis vaccines are safer, but they may not be more effective.

Uptick in Whooping Cough Linked to Subpar Vaccines

Whooping cough, or pertussis, has exploded in the United States in recent years. A new study confirms what scientists have suspected for some time: The return of the disease is caused by the introduction of new, safer vaccines 2 decades ago. Although they have far fewer side effects, the new shots don't offer long-lived protection the way older vaccines do.

Pertussis bacteria colonize the upper airways, causing a severe cough and shortness of breath that can be fatal in babies. The disease seemed to have mostly disappeared from the United States by the late 1970s—in fact, scientists believe, it continued to spread, undiagnosed, among adults—but over the past 2 decades the disease has bounced back with a vengeance, with strong outbreaks among school-aged children in 2010 and last year, when the United States reported 40,000 cases. Many European countries have also seen increases.

Researchers have long suspected that new vaccines might have something to do with it. Until the 1990s, children routinely received a so-called whole-cell vaccine, made from pertussis bacteria, Bordetella pertussis, that were killed by exposure to formalin or other chemicals. These vaccines were known to contain a toxin that can provoke powerful side effects. Most vaccinated infants had fever and severe pain at the injection site, sometimes accompanied by febrile seizures or fainting fits in which the infant turned pale, unresponsive, and "floppy."

During the 1980s, U.S. parents successfully sued manufacturers, alleging that the whole-cell vaccine also caused long-term brain damage. A 1991 Institute of Medicine report concluded that this was unproven, but by then many pertussis vaccine manufacturers had withdrawn from the market, leading Congress to create a federal vaccine injury compensation program for families who could show a strong case for vaccine damage.

Since then, vaccinemakers have introduced newer, "acellular" vaccines that consist of refined pertussis proteins that provide immunity against disease without severe side effects.

Physicians at Kaiser Permanente of Northern California compared the protective effects of these vaccines with the old ones when included in a four-dose series of shots called DTP (for diphtheria-tetanus-pertussis), given to children before the age of 2. They studied children born between 1994 and 1999, years in which Kaiser Permanente gradually introduced the new vaccines. As a result, some children had received only the old-style shots, some only the new ones, and some a mixture of both. Of the 1037 children included in the main part of the study, 138 got pertussis during a massive epidemic in California in 2010 to 2011.

Children who had received only the acellular vaccine were more than 5.6 times more likely to get sick than those who received the old, whole-cell vaccine, the team will report next month in Pediatrics. Those receiving one or more of each type had an intermediate risk.

The results confirm other recent research. In August, a study published in The Journal of the American Medical Association found that acellular vaccine-vaccinated children in Australia were six times more likely to get sick than those receiving the old vaccine. And a study of another California population, published online in March by Clinical Infectious Diseases, showed an eightfold increased risk of illness associated with the new vaccine.

"We're now finding out that the acellular vaccine's doesn't offer protection for as long," says the first author of the new study, pediatrician Nicola Klein. "It does work well in the short term. But there was definitely a tradeoff in phasing out the whole-cell vaccine."

Whole-cell vaccines, still the standard of care in many lower-income countries, provide more lasting immunity in part because they consist of many more antigens—the proteins that trigger the immune system—than acellular vaccines, current versions of which contain three to five antigens, says James Cherry, a pediatrician at the University of California, Los Angeles. There is also some evidence, he adds, that pertussis strains have mutated in response to vaccination campaigns, rendering antibodies less effective.

Pertussis experts have held two international meetings in the past several months to consider what to do about the waning immunity issue. Cherry thinks that we'd be better off with the old vaccine, but he concedes that there's no going back. "It had to go," says pediatrician Scott Halperin of Dalhousie University in Halifax, Canada. "It's a vaccine that would not be accepted in the societies we have in North America and Europe."

"As much pertussis as we're seeing now, we're still seeing in most places pretty good control in the very young," who are at the highest risk of dying form pertussis, Halperin says. "We're seeing lapsed immunity in school-age kids and we have to solve that. But those kids aren't dying."

Instead, most pertussis experts say what's needed is a new generation of vaccines that provide longer-lasting immunity—but that may take at least a decade. "The scientific community back in the 1990s felt that it had pertussis solved," Halperin says. "We're now seeing that we don't have a solution yet."

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