Replacing the first dose of acellular pertussis vaccine with its whole-cell predecessor could cut the rate of whooping cough by about 95% – including in neonates at greatest risk of severe outcomes, researchers reported March 28 in JAMA Pediatrics.
Their model also predicted 95% fewer lost quality-adjusted life-years under the combined (whole-cell and acellular) vaccination strategy – even after accounting for vaccine-related adverse events, said Dr. Benjamin Althouse of the Santa Fe Institute and New Mexico State University, Las Cruces, and his associates. “Although new pertussis vaccines combining the safety of acellular pertussis and the efficacy of whole-cell pertussis are in early development, [they are] still a number of years away from regulatory approval,” they wrote. “In the interim, switching to the combined strategy is an effective option for reducing the disease and mortality burdens of Bordetella pertussis.”
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The Centers for Disease Control and Prevention currently recommends five doses of acellular pertussis vaccine between 2 months and 4 to 6 years old. Infants born in the 1990s during the switch from the whole-cell vaccine to the safer acellular vaccine often received an initial whole-cell dose, followed by acellular doses. These “primed” children had less than half the rate of whooping cough than children who received only the acellular vaccine, multiple studies later showed. Since then, U.S. pertussis rates have surged, with more than 48,000 cases reported in 2012. Waning immunity is one factor, but the acellular vaccine also failed to prevent secondary B. pertussis transmission in a study of nonhuman primates, Dr. Althouse and his associates noted (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2016.0047).
They compared the efficacy and cost-effectiveness of the acellular vaccination schedule with a schedule in which the first dose was whole-cell vaccine and the next four doses were acellular vaccine. In a model fitted to pertussis data from 2012, incidence was about 95% lower (95% confidence interval, 91%-98%) with the combined strategy, and infection rates in neonates fell by 96% (95% CI, 92%-98%). Even after accounting for adverse events, loss of quality-adjusted life-years also fell by about 95%, and healthcare costs dropped by 94%, saving more than $142 million per year.
The acellular pertussis vaccine was licensed as a booster for adolescents and adults in 2005. Over the next several years, pertussis rates dropped faster among 11- to 18-year-olds than among other age groups (Arch Pediatr Adolesc Med. 2012;166:344-9). But that encouraging trend “abruptly reversed” in 2010, “corresponding directly to the aging of acellular pertussis-vaccinated cohorts” who were primed with the acellular vaccine, said the authors of a follow-up study also published March 28 in JAMA Pediatrics (JAMA Pediatr. 2016 Mar 28. doi: 10.1001/jamapediatrics.2015.4875).
For this study, Tami Skoff and Stacey Martin of the CDC analyzed all pertussis cases reported in the United States between 1990 and 2014. Between 1990 and 2003, rates rose from 1.7 to 4.0 cases per 100,000 individuals, and pertussis epidemics dominated later years, the researchers said. The acellular vaccine helped reverse infection rates among adolescents immediately after its introduction, but after 2010, infection rates rose faster among 11- to 18-year-olds than among all other age groups combined (slope, 0.5727; P less than .001). By 2014, adolescents had the highest infection rates of any group except infants under 1 year old, who had the highest pertussis incidence throughout the study period.
The findings “support the accumulating literature on waning acellular vaccine-induced immunity,” said the researchers. Because immunity with the acellular vaccine wanes after about 2 years, additional vaccinations are unlikely to have much impact, they noted. They also emphasized the importance of timely vaccination and vaccinating pregnant women to protect infants.
Dr. Althouse and his associates were funded by the National Science Foundation, the National Institutes of Health, the Omidyar Group, and the Santa Fe Institute. Skoff and Martin reported no external funding sources. None of the investigators had disclosures.