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Acellular Pertussis Vaccine's Waning Immunity Caused California Epidemic

Major Finding: By the sixth year after children received their fifth childhood vaccination with the acellular pertussis vaccine, the rate of children susceptible to pertussis infection was fourfold to 15-fold higher compared with the first year following vaccination.

Data Source: Two analyses from the Centers for Disease Control and Prevention: a case-control study with 682 children aged 4-10 years infected with pertussis in any of 15 California counties during 2010 and 2,016 uninfected children from the same counties and age range; and an analysis of immunization registry and surveillance data including 224,378 immunized children and 521 pertussis cases in Minnesota, and 179,011 immunized children and 99 cases in Oregon.

Disclosures: Dr. Tartof, Dr. Edwards, Dr. Long, and Dr. Misegades all said that they had no relevant financial disclosures.

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Waning Pertussis Immunity Comes as No Surprise

I’m not surprised to hear that the CDC studies found pertussis immunity waned after the fifth childhood acellular vaccine dose in some 7- to 10-year-olds. The half-life of antibody-mediated immunity against pertussis toxin is fairly short-lived, about 36 days. By the time children receive the fifth dose they also produce cellular immunity, but this response is not as robust as after other vaccines, such as the measles vaccine.


Dr. Carol J. Baker

Most children now receive their fifth pertussis dose at age 4 years because that’s when they start school, and many states have laws that mandate the fifth dose at that time. That starts the child’s vaccination clock early, but it would be hard to switch to routinely giving the fifth dose at an older age. And we will never go back to the cellular vaccine. It’s time to start thinking about trying to produce a better pertussis vaccine, but vaccines are developed by companies and they need to believe they will recoup their development costs.

Children born in 1998 were the first cohort to exclusively receive the acellular vaccine. Following that, the first big U.S. pertussis outbreak occurred in 2005. Pertussis outbreaks occur in 5-year cycles, so the next big outbreak was in 2010. The California epidemic was caused by underimmunization of some children, and by waning immunity in fully vaccinated children. It showed that we are not where we need to be to have herd immunity. The 2010 California outbreak caught everyone’s attention. It demonstrated that we need a better vaccine, and perhaps we also need to change the vaccination schedule.

Dr. Carol J. Baker is professor of pediatrics and microbiology at Baylor College of Medicine in Houston. Dr. Baker said that she had no relevant financial disclosures. She made these remarks in an interview.


 

FROM THE ANNUAL MEETING OF THE INFECTIOUS DISEASES SOCIETY OF AMERICA

BOSTON – The acellular pertussis vaccine’s failure to deliver durable infection protection to children aged 7-10 years led to the 2010 California pertussis epidemic, and prompted infectious diseases experts to question the current schedule of childhood pertussis vaccination.

"An increase in the risk of pertussis is occurring in the time since completion of the five-dose DTaP [diphtheria, tetanus, acellular pertussis] series, with similar trends seen in California, Minnesota, and Oregon," Sara Tartof, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

Dr. Sara Tartof

"Continued evaluation of DTaP duration of protection is needed to determine the appropriateness of timing of pertussis vaccinations," said Dr. Tartof, an epidemic intelligence officer in the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases in Atlanta.

Dr. Tartof and a second CDC researcher presented results from two independent studies that both showed children faced a substantially increased rate of pertussis infection 4 or more years out from their fifth and final childhood vaccination, which these days usually occurs when U.S. children are 4 years old. Recent surges in U.S. pertussis cases, which began in 2005, and then spiked even higher in 2010, implicated the acellular vaccine as the cause.

"It certainly caused the 2010 California epidemic, and it happened in Minnesota and Oregon, too. Waning immunity with acellular pertussis led to greater vulnerability in 7- to 10-year-olds," commented Dr. Kathryn M. Edwards, Sarah H. Sell professor of pediatrics and director of the Vaccine Research Program at Vanderbilt University in Nashville, Tenn.

"The durability of protection with the acellular vaccine is not as good as with the whole cell vaccine, but the problem with the whole-cell vaccine was that it was quite reactive," causing local reactions and fevers, she said in an interview.

"At this point, people would not accept the whole-cell vaccine," which means something needs to be done with the acellular vaccine, she said. Possible options include additional boosted vaccinations, or moving administration of the fifth childhood dose of DTaP from 4-year-olds to 6-year-olds.

The CDC’s recommended vaccination schedule already calls for delivery of the fifth dose at ages 4-6 years, but in reality most U.S. children receive it at age 4 when they enter preschool.

Pertussis "is a difficult disease. Even after five doses, susceptibility increases after 1 year. It’s really a toughie," said Dr. Sarah Long, professor of pediatrics at Drexel University and chief of infectious diseases at St. Christopher’s Hospital for Children, both in Philadelphia.

One of the CDC studies focused on pertussis cases that appeared in any of 15 California counties during the state’s 2010 epidemic. Chart reviews by CDC researchers identified 682 pertussis cases among children aged 4-10 years, and 2,016 unmatched controls from the same age group and counties. Roughly 70% of the children who had received all five scheduled doses had received their fifth dose at 4 years, and about 30% received their fifth dose at 5 years, with less than 1% of the children receiving their last dose at 6 years. One percent of the control children and 8% of the cases had received no doses of DTaP.

Dr. Lara K. Misegades

An analysis of the time elapsed following the fifth dose relative to when pertussis infection occurred showed that after 2 years the vaccine’s efficacy was 92% of what it had been during the first year following the fifth dose, after 3 years the efficacy fell to 87%, after 4 years it dropped to 83%, and after 5 years the vaccine efficacy was 71% below where it stood immediately after the fifth dose, reported Lara K. Misegades, Ph.D., an epidemic intelligence officer also with the CDC’s National Center for Immunization and Respiratory Diseases.

This translated into a 15-fold higher relative risk for infection in children during the sixth year following their final dose, compared with children during the first 12 months following their fifth vaccine dose, Dr. Tartof said.

The second CDC study, presented by Dr. Tartof, used data collected by the immunization registries of Minnesota and Oregon for children immunized against pertussis during 1998-2003, and data on pertussis cases in these two states from reports to the CDC through the National Notifiable Disease Surveillance System. This analysis included 224,378 fully immunized children and 521 pertussis cases in Minnesota, and 179,011 fully immunized children and 99 reported cases in Oregon.

Dr. Tartof and her associates used these data to calculate a pertussis incidence rate during each year following delivery of the fifth childhood dose, and reported the relative risk for infection during each follow-up year relative to the first 12 months after the fifth dose. By the sixth year, the risk was seven-fold higher in Minnesota, and four-fold higher in Oregon, she reported. The risk for infection rose steadily during each year following the fifth dose.

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