Waning potency of pertussis vaccine a significant contributor to recent whooping cough outbreaks

New Kaiser Permanente study suggests under-vaccination is only one factor contributing to whooping cough outbreaks

Oakland, Calif. — In a large new Kaiser Permanente study, children who were up to date on their pertussis vaccine schedule were far less likely to develop the disease than unvaccinated children. However, most pertussis cases were in fully vaccinated children. The risk of vaccinated children becoming ill increased with the time since vaccination, suggesting that waning effectiveness between doses was a significant contributor to recent outbreaks.

The study, “Acellular Pertussis Vaccine Effectiveness Over Time,” was published on June 10 in the journal Pediatrics.

Pertussis, widely known as whooping cough, is a highly contagious and potentially life-threatening respiratory infection caused by the bacterium Bordetella pertussis. To help prevent it, the Centers for Disease Control and Prevention (CDC) recommends five doses of DTaP vaccine–a combination vaccine that protects against pertussis, diphtheria, and tetanus–between the ages of two months and six years.

“Most DTaP research has explored either vaccination status or waning effectiveness, but we looked at both at once,” said Ousseny Zerbo, PhD, lead author of the new study and a staff scientist with the Vaccine Study Center at Kaiser Permanente Northern California’s Division of Research.

Dr. Zerbo and his colleagues retrospectively analyzed the electronic health records of 469,982 children under the age of 11 who were members of Kaiser Permanente Northern California. Focusing on data from January 2006 through June 2017, they performed a series of statistical analyses to determine risk of pertussis according to vaccination status and time since a child’s last dose.

The researchers found that risk of pertussis was 13 times higher for children who had never received DTaP than for children who were fully vaccinated with all recommended doses for their age. Under-vaccinated children–those who had received at least one dose but were behind schedule–were almost twice as likely to develop pertussis than were fully vaccinated children.

“However, for fully vaccinated children, we found that risk of pertussis increased as more time passed since their last dose,” Dr. Zerbo said. Among age-appropriately vaccinated children between the ages of 19 months and 7 years the risk of pertussis was 5 times higher when they were more than 3 years from their last vaccine dose. Notably, most children diagnosed with pertussis in the study were up to date on DTaP. Of 738 pertussis cases, 603 were fully vaccinated, 99 completely unvaccinated, and 36 were partially vaccinated but behind schedule.

These findings suggest that in a US population where vaccine coverage is high, waning DTaP effectiveness is a significant driver of outbreaks, including the 2010 and 2014 outbreaks in California that each resulted in more than 9,000 pertussis cases.

“The big question has been whether pertussis outbreaks are due to under-vaccination, as in other diseases like measles, or to waning immunity,” said Nicola P. Klein, MD, PhD, senior study author and director of the Vaccine Study Center. “The answer is that both factors matter.”

More research is needed to quantify the relative roles of vaccine waning and under-vaccination in pertussis outbreaks. Still, the new findings point to the need for a better vaccine that lasts longer between doses. Meanwhile, the authors emphasize that families and clinicians should continue vaccinating children according to the CDC’s recommended schedule.

The researchers emphasize that those vaccinated had lower rates of pertussis than those not vaccinated at all.

“Despite increased media attention on parents choosing not to vaccinate, children in our study had high coverage, which was not completely surprising,” Dr. Zerbo said. One percent of the children with pertussis were unvaccinated, and 3 percent were under vaccinated. “We need to continue to encourage vaccination, no doubt about it,” he said.

This study builds on a growing body of research from the Vaccine Study Center beginning with a 2012 study in New England Journal of Medicine which found that protection against pertussis after 5 DTaP doses wanes rapidly among school age children who had only ever received DTaP vaccines. This was followed by 2016 and 2017 studies in Pediatrics, one which showed that the routine adolescent Tdap booster also wanes rapidly, and one which showed that Tdap given to pregnant women was highly effective in preventing pertussis in newborns.

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Funded by the National Institute of Allergy and Infectious Diseases, the new study adds to the Vaccine Study Center’s pioneering and influential body of work on pertussis vaccines. Additional authors on the study include Joan Bartlett, MPH, MPP; Kristin Goddard, MPH; Bruce Fireman, MA; and Edwin Lewis, MPH, of the Kaiser Permanente Vaccine Study Center in Oakland, California.

About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 400 epidemiological and health services research projects. For more information, visit http://www.dor.kaiser.org or follow us @KPDOR.

About Kaiser Permanente

Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, Kaiser Permanente has a mission is to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve more than 12 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal Permanente Medical Group physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to share.kaiserpermanente.org.

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