By late summer 2010 an alarming number of children in California had developed pertussis, or whooping cough—five times as many as in the first half of 2009. David Witt, a physician and infectious disease specialist who works at Kaiser Permanente San Rafael Medical Center, cared for some of those sick children. His practice lies in the heart of Marin County, the famously counterculture spit of land north of San Francisco. At first, he assumed that the outbreak was a consequence of parents refusing vaccinations for their children. As the incidence continued to climb month after month, however—not just in northern California but all across the state—Witt began to wonder whether something else was going on.
Working with his college-age son Maxwell and his pediatrician colleague Paul Katz, Witt retrieved the records for 132 Kaiser Permanente patients younger than 18 who had tested positive for pertussis between March and October 2010.
“The bulk of the cases were in fully vaccinated children between eight and 12 years old,” Witt says. “That was a total surprise.”
As Witt's small study spotted, and larger ones have since confirmed, protection granted by the vaccine, which has been used for the past two decades, is wearing off much faster than public health planners anticipated. Rates of pertussis increased at least threefold between 2011 and 2012 in 21 states. Whereas some of these cases occurred among children who had never been vaccinated, most of the affected children had in fact received vaccines; those inoculations simply failed to safeguard them over the long term.
Now health authorities are scrambling to devise new strategies for protecting kids. There are no easy solutions. No one is developing a better vaccine to replace the current one. Attempting to recommend additional shots would trigger years of public health debate, and it is not clear whether extra doses of vaccine would make a difference. Even discussing the problem provokes uneasiness: with antivaccine sentiments and vaccine refusal at historic highs, nobody wants to impeach one of public health's crucial tools.
Before a vaccine became available in the 1940s, many parents learned firsthand that pertussis was a terrible disease. The bacterium that causes it, Bordetella pertussis, produces a toxin that damages the tiny sweeping hairs that coat the lining of the lungs, preventing them from clearing the airways of mucus and the microbial invaders. Following uncontrollable coughing fits—some of which are strong enough to cause seizures and brain damage—children wheeze and gasp for breath, giving the illness its name. In the pre-vaccine era, whooping cough afflicted as many as 200,000 children each year in the U.S. and killed about 8,000. The new vaccine shrank the incidence of pertussis from around 157 cases for every 100,000 members of the population to one in 100,000.
This success came at a cost, though. Researchers crafted the original pertussis vaccine from dead pertussis bacteria that could not reproduce but retained many microbial proteins by which immune cells could recognize and attack B. pertussis before it caused disease. Unfortunately, those whole-cell preparations also contained other molecular components that could cause unwanted immune system reactions, such as swelling near the injection site and, in rare cases, high fevers that could dangerously inflame the brain. “People didn't pay much attention to the reactions in the early days, because the death rate before the vaccine came along had been so staggering,” says James Cherry, a longtime professor of pediatrics and vaccine researcher at the David Geffen School of Medicine at U.C.L.A.
Over the next few decades, however, concern surrounding the vaccine's side effects intensified. In the 1970s Sweden and Japan ceased using the vaccine altogether. A government study published in England in 1981 concluded that the vaccine caused permanent brain damage once in every 310,000 doses (a result that was later disputed). And in 1982 an NBC broadcast aired criticisms of the vaccine, turning public opinion against it and jump-starting the U.S. antivaccine movement.
The U.S. and other countries began industry-wide efforts to find a better vaccine, focusing on “acellular” formulas that used a few purified bacterial proteins to establish immunity rather than the whole cell, reducing the risk of inflammatory reactions. Researchers combined the new pertussis vaccine with vaccines against tetanus and diphtheria. DTaP, as it was known, was ready for the doctor's office in 1992. In the U.S., children receive it at two, four and six months; once between 15 and 18 months; and once between the ages of four and six, before they enter school.
From the start, public health authorities understood that an acellular vaccine might confer more temporary immunity than the problematic whole-cell vaccine. So, in 2005, they added a booster to the regimen to guarantee that children would be protected throughout adolescence. Officials determined the booster would be most effective for 11- to 12-year-olds but authorized it for use in any adult, eventually including pregnant women.
A Failure to Protect
After California's 2010 pertussis outbreak, additional outbreaks hit Wisconsin, Vermont and Washington, among other states, in 2012. Analyses of who was getting sick revealed the same pattern every time. Tom Clark, a physician and pertussis expert at the Centers for Disease Control and Prevention, describes it as a “striking stair-step appearance, rising by year: six, seven, eight, nine, 10 years old. If you go back several years [to when whole-cell vaccines were used], that stair-step is not there.”
The stair-step indicated that the more time elapsed since a child's most recent pertussis shot, the more likely the child would develop whooping cough after exposure to the bacteria. Many of these children were too young to have received their booster, so researchers hoped that once children got their additional shots, the unpredicted vulnerability would cease. New data from the Washington State outbreak quashed that hope: 13- and 14-year-olds were catching pertussis even after they received their booster shot. Other studies demonstrated that the vaccine was behaving differently from the older, reactive one: children who had received even one dose of the older, whole-cell formula while it was still on the market were better protected against pertussis than those who received only the newer vaccine. (Of course, children who received the new vaccine were still better off than those who had never been vaccinated.)
Clark points out that the original research on acellular vaccine in the 1980s tested whether it would protect but not for how long it would protect. Some diseases for which acellular vaccines are typically used, such as Hib meningitis, are only dangerous to children for a short time early in life, so long-lasting immunity is not necessary. Today, however, immunologists have better laboratory tools and a much more nuanced understanding of how immunity is evoked and sustained. “A lot of what you would do to develop a vaccine today was never done for the pertussis vaccine,” Clark says.
“The big answer is that we need a better vaccine,” says Mark Sawyer, a professor of clinical pediatrics at the University of California, San Diego, and chair of a working group collaborating with the Advisory Committee on Immunization Practices (ACIP), which helps to set federal vaccine policy. “But the ACIP can't just make that happen. That is up to the scientists who would do a study of what would make a better vaccine, and it is up to the pharmaceutical companies.”
If a new vaccine were formulated, demonstrating its superiority would be challenging. Every developed country vaccinates its children against pertussis, so there is no large unprotected population that could help prove a new vaccine's worth. And before encouraging manufacturers to consider developing a new vaccine, federal planners would have to weigh the unintended consequences of the endeavor. Diverting too much of the manufacturers' limited resources to one new vaccine could cause shortages of others, for example. Another concern is whether parents would heed the advice to bring children in for yet more shots.
The ACIP has been researching the problem for more than a year. The committee is in uncharted territory because this type of failure has never occurred with any other vaccine. In June the working group concluded that because the booster's protection against pertussis is so short-lived, adding more shots to the typical regimen would do little to reduce the overall prevalence of pertussis. The group therefore advised the committee not to change policy to include a second booster in adulthood but rather to increase the number of pregnant women who get their booster in the first place. The CDC estimates that currently only 6 percent of pregnant women receive the shot. Yet newborns, who cannot be vaccinated, are the most vulnerable to the dangerous effects of pertussis; improving the immunity of their closest contacts could be the best way to prevent pertussis deaths.
Given the current vaccine's faults, Clark says bluntly that in the general population “there's going to be a lot of pertussis.” But he adds that although pertussis cases are increasing, deaths are not; when vaccinated children develop whooping cough, they have milder symptoms. So the newer pertussis vaccines are still valuable because they reduce not just the likelihood of death and severe illness but also the health care spending—not to mention emotional trauma—that accompany those dire results. On that basis, Sawyer says, public health officials should urge the 90 percent of American teens and adults who failed to get their booster shot to receive one and thereby protect both themselves and the most vulnerable among us. “We do need a new vaccine,” he says. “But we can do a lot better with the ones we have.”