A California whooping cough epidemic in 2010 was one of the worst U.S. outbreaks of the disease in the past several decades. Ten infant deaths occurred among the more than 9,000 cases—the most in that state since 1947. Now, a study reveals that parental refusals to vaccinate their children may have played a part in that epidemic and possibly in a concurrent nationwide resurgence of the disease. The research found significant overlaps of areas with high numbers of whooping cough cases and areas where more parents had sought legal exemptions to opt out vaccinating their children.

Whooping cough, or pertussis, is a highly contagious bacterial infection in the lungs that causes violent coughing and sometimes lasts for months. A combination vaccine called the DTaP (for diphtheria, tetanus, and acellular pertussis) protects children up to six years old from pertussis, and a similar formulation called Tdap is used to protect older children and adults. Previous research has found, however, that neither vaccine, made from the pertussis toxin and other genetic pieces of the bacterium, is as effective as DTP vaccine, a preparation that contained the whole bacterial cell; it was discontinued in the 1990s. Accordingly, pertussis cases remained low when DTP was the standard of care—typically fewer than 5,000 U.S. cases annually—but made a comeback in the past decade.

Parents in many states may opt out of vaccinating their children by seeking legal exemptions to public school immunization requirements. All but two states—Mississippi and West Virginia—allow religious exemptions, and 19 states, including California, offer some variation of a philosophical or “personal belief” exemption, depending on the law’s language. California’s rates of nonmedical exemptions tripled from 0.77 percent in 2000 to 2.33 percent in 2010, and some schools had 2010 nonmedical exemption rates as high as 84 percent.

In the new study, published September 30 in Pediatrics, lead author Jessica Atwell and her colleagues mapped “clusters”—statistically unusual aggregations—of nonmedical exemptions for kindergartners between 2005 and 2010. The researchers identified 39 clusters of such opt outs, including one that covered nearly all of northern California. In each of these clusters the area covered contained a statistically higher concentration of kindergartners with exemptions than the areas outside the clusters. Atwell’s team then used a similar modeling method to identify two pertussis outbreak clusters—areas where the cases reached statistically higher numbers than the rest of California. One such cluster included most of central California between May and October 2010. The other included San Diego County between July and November 2010. Then the researchers analyzed the clusters’ overlap.

“The strength of our approach was not just to find out the clustering of cases but also the statistical significance of the clustering overlap,” says senior author Saad Omer, an associate professor at Emory University School of Medicine’s Vaccine Center. “This tells us whether the clustering is by chance or not.” Neither the clusters nor their overlapping was by chance. Census tracts within a nonmedical exemption cluster were 2.5 times more likely to be within a pertussis cluster, even after accounting for population characteristics including racial demographics, population density, household income, average family size, percentage of residents with a college degree and location within a metropolitan area. Residents living in a census tract within a nonmedical exemption cluster were 20 percent more likely to catch pertussis than those outside a cluster, the analysis revealed.

Past research has already revealed that the weaker vaccine is driving whooping cough outbreaks and epidemics in the past decade. The new findings reveal there is more to the story. “What this study tells us is that if more and more people choose not to get a vaccine,” says Paul Offit, director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, “then you’ll have bigger and bigger outbreaks.” This study also backs up the results in a 2008 study led by Omer that similarly found overlaps in pertussis outbreaks and nonmedical exemptions in Michigan during an 11-year period.

Atwell, a PhD candidate in Global Disease Epidemiology and Control at the Johns Hopkins Bloomberg School of Public Health, says it is difficult to quantify the contributions of different factors to the resurgence of pertussis and that it is a multifaceted issue. “There are a lot of factors, including waning immunity from the vaccine, increased case detection and possible changes in circulating strains,” she says, “but our study shows that nonmedical exemptions and clustering of unvaccinated individuals may have also played a role.”

Public health efforts to prevent epidemics of infectious diseases typically rely on herd immunity: The more people in a community are vaccinated or otherwise protected from a disease, the less likely it is to be transmitted throughout the population. This approach is particularly crucial with pertussis, which is almost as contagious as measles and requires about 95 percent vaccination coverage to maintain herd immunity. Increasing numbers of parents opting out of vaccinating their children can erode this immunity. “When you look at statewide or countywide data, the increases in nonmedical exemptions don’t look that significant,” Atwell says, “but when you look at community-wide coverage, it is much lower than the threshold needed to maintain herd immunity in some areas.”

Unvaccinated individuals in the 2010 epidemic were eight times more likely to contract pertussis than vaccinated ones. But unvaccinated individuals pose risks to the community as well. “It’s a choice you make for yourself and a choice you make for those around you,” Offit says. “Infants need those around them to be protected in order not to get sick. We have a moral and ethical responsibility to our neighbors as well as to ourselves and our children.”

Data has shown exemptions are more prevalent where they are easier to obtain. In California parents currently can obtain exemptions simply by signing a form. A law takes effect there next year requiring parents to meet with a health care provider before obtaining an exemption. “I hope the legislation will help address the increased risk for pertussis and raise immunization rates in those areas,” says Richard Pan, a pediatrician and member of the California State Assembly who sponsored the bill. He says the law may not effect much change in areas with strong pockets of vaccine-refusing parents, but he hopes more of the parents feeling uncertain about immunization will realize the benefits after getting accurate information from a health care professional.

Parents who turn down vaccinations for their children are often misinformed about the safety and effectiveness of vaccines. “I don’t think people understand that our control of vaccine-preventable diseases such as pertussis and measles is fragile,” Atwell says. “We need to continue to educate people about the implications of not vaccinating their children.”