Study Suggests Bringing Back Whole-Cell Pertussis Vaccine

Marcia Frellick

March 29, 2016

Switching to a whole-cell pertussis priming strategy could reduce incidence of whooping cough by up to 95%, new research indicates.

Studies have widely agreed that pertussis protection from the current vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), is limited, and a new vaccine is not imminent. Meanwhile, cases are climbing. In 2012, there were 48,277 whooping cough diagnoses in the United States, a record high since 1955, and that number included 16 infant deaths.

Haedi DeAngelis, MA, from New Mexico State University at Las Cruces, and colleagues propose that a new strategy of priming with the whole-cell pertussis vaccine (wP) and completing the schedule with acellular pertussis vaccine (aP) would work and would be cost-effective in the meantime. Results from their modeling study were published online March 28 in JAMA Pediatrics.

The 95% fewer incidences includes 96% (95% confidence interval [CI], 92% - 98%) fewer infections in infants.

"Although there may be an increase in the number of vaccine adverse effects, we nonetheless estimate a 95% reduction in quality-adjusted life-years lost with a switch to the combined strategy and a cost reduction of 94% (95% CI, 91-97), saving more than $142 million annually," the authors write.

The combined vaccine strategy would lead to significantly more adverse events compared with an aP-only approach, including a 2917% increase in fever (95% CI, 1642% - 4180%), and a 240% increase in seizure (95% CI, 152% - 333%). However, the absolute increases are estimated to be low with the combined strategy (10.3 per 100,000 for fever and 0.07 per 100,000 for seizures).

"Additionally, the combined strategy is predicted to cause a rate of encephalopathy of 5.78 × 10−4 (95% CI, 5.59 × 10−4 to 5.87 × 10−4) per 100 000 total population," the authors write.

Current Strategy Started Failing in 2010

A second study published in the same issue by Tami H. Skoff, MS, and Stacey W. Martin, MSc, from the Meningitis and Vaccine Preventable Diseases Branch of the Centers for Disease Control and Prevention, Atlanta, Georgia, pinpoints when the Tdap vaccine started to lose effectiveness.

They looked at pertussis cases in the United States between 1990 and 2014 and found that Tdap was successful from its introduction in 2005 until 2010, when reported pertussis incidence among adolescents began to increase at a faster rate than disease among all other age groups.

"We observed an abrupt shift in the direction of rate ratios in 2010, the very year that children aged 11 years would have been the first cohort born after the 1997 transition from wP to acellular vaccines to have received acellular vaccines for all doses of the childhood series," the authors write.

The study demonstrates the bad news of the Tdap vaccine, Mark H. Sawyer, MD, from the University of California, San Diego, School of Medicine and Rady Children's Hospital, writes in an accompanying editorial. He explains that the benefits occurred mostly in adolescents who had at least some of the wP vaccine as infants. Now that younger people who had only the aPs are getting the Tdap, the problem has come to light.

"It turns out we did not know enough about the differences in immune responses between whole-cell and the new acellular vaccines," Dr Sawyer writes. "Several studies have now shown us that the immune responses to the 2 types of vaccine are quite different and unfortunately the response to acellular vaccines is inferior. We are going to continue to see a lot of pertussis until new vaccines are developed."

Editorial: Results Must Be Considered Preliminary

Dr Sawyer says that what DeAngelis' team is proposing may be effective in the interim, but warns that the results must be considered preliminary because of some assumptions they make.

"For example," he writes, "much of the effect on the number of cases of pertussis predicted by the model is based on the observation that acellular vaccines may allow asymptomatic infection, while whole-cell vaccines do not. To date, this phenomenon has been demonstrated in nonhuman primates but not yet convincingly in humans. Nevertheless, we do know that [wPs] induce an immune response that is more effective in preventing clinical disease."

Whole-cell vaccines are widely used elsewhere in the world and could be reintroduced in the United States relatively easily, he notes.

But would parents accept it, especially given the adverse effects, which were the reason the vaccines were changed in the first place? The current generation of parents has demonstrated intolerance to vaccines with adverse effects being given to healthy children, he notes.

What is beyond dispute is that pertussis is back. While we await new vaccines or alternative strategies, Dr Sawyer says, "we can at least do a better job of preventing pertussis-related deaths in infants by immunizing pregnant women during each pregnancy. We know that is safe and effective and is being increasingly accepted by pregnant women."

The DeAngelis study was supported by the National Science Foundation Research Experience for Undergraduates, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. The authors and editorialist have disclosed no relevant financial relationships.

JAMA Pediatrics. Published online March 28, 2016. DeAngelis abstract, Skoff and Martin abstract, Editorial extract


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