In the Journals

Waning immunity from DTaP vaccines fueling ongoing outbreaks

Photo of Ousseny Zerbo
Ousseny Zerbo

Pertussis cases appear most frequently among age-appropriately vaccinated children, which suggests that suboptimal DTaP vaccine effectiveness plays a major role in epidemics, according to a retrospective cohort study published in Pediatrics.

“The finding that most pertussis cases occurred among highly vaccinated children suggests that waning of vaccine immunity played a strong role in recent pertussis cases,” Ousseny Zerbo, PhD, staff scientist at the Vaccine Study Center at Kaiser Permanente Northern California Division of Research, told Infectious Diseases in Children. “Although pertussis vaccine immunity wanes, it is important that children continue to be vaccinated according to CDC’s vaccination recommendation. The pertussis vaccine is effective at preventing pertussis but for a short period of time. If a child is not vaccinated or is undervaccinated, his or her risk is much higher than a child who is fully vaccinated.”

The researchers followed children born at Kaiser Permanente Northern California between 1999 and 2016 — restricting their analysis to children who received only acellular pertussis vaccines, which were introduced in the 1990s. They classified children as fully vaccinated “if they received the expected number of DTaP doses by 1 month after the [Advisory Committee on Immunization Practices]-recommended age,” they wrote. Children were defined as undervaccinated if they had fewer doses than expected for their age, whereas children with one more dose than expected at that age were classified as fully vaccinated plus one dose.

Among 469,982 children aged 3 months to 11 years, the researchers identified 738 pertussis cases, of which 99 were unvaccinated, 515 were fully vaccinated and 88 were fully vaccinated plus one dose, according to the study.

Pertussis risk was 13 times higher for unvaccinated children (adjusted HR = 13.53; 95% CI, 10.64-17.21) vs. fully vaccinated children and 1.9 times higher (aHR = 1.86; 95% CI, 1.32-2.63) among undervaccinated children, the researchers wrote. These finding are “broadly consistent” with two previous case-control studies, one from 2013 and another from 2017, the researchers said.

Among vaccinated children aged 19 to younger than 84 months, the risk was five times higher (aHR = 5.04; 95% CI, 1.84-13.8) in 3 years or more vs. less than 1 year after vaccination. Children aged 84 to 132 months had a two times higher risk (aHR = 2.32; 95% CI, 0.97-5.59) at 6 years or more vs. less than 3 years after vaccination.

“Our results reveal that waning of DTaP immunity was an important cause of pertussis in children [older than] 18 months of age who have a longer interval between recommended doses,” Zerbo and colleagues wrote. “By age 19 months, nearly all children had received at least one DTaP dose, and children who were age-appropriately vaccinated accounted for [more than] 95% of follow-up.”

Kathryn Edwards
Kathryn M. Edwards

In a related editorial, Infectious Diseases in Children Editorial Board Member Kathryn M. Edwards, MD, professor of pediatrics at Vanderbilt University School of Medicine, wrote that “given the markedly increased risk of pertussis in unvaccinated and undervaccinated children, universal DTaP vaccination should be strongly recommended.”

Secondly, she said “the addition of maternal Tdap vaccination administered during pregnancy has been shown to significantly reduce infant disease before primary immunization and should remain the standard.”

However, Edwards added that addressing the waning immunity of DTaP vaccination proves more problematic, suggesting extensive safety studies in younger children would be needed before potential options — including a live-attenuated pertussis vaccine administered intranasally or the addition of other antigens to current vaccines — can be implemented. – by Joe Gramigna

References:

Edwards KM, et al. Pediatr. 2019;doi:10.1542/peds.2018-3466.

Glanz JM. JAMA Pediatr. 2013;doi:10.1001/jamapediatrics.2013.2353 .

Huang WT, et al. Hum Vaccin Immunother. 2017;doi:10.1080/21645515.2016.1249552.

Zerbo O, et al. Pediatrics. 2019;doi:10.1542/peds.2018-3466.

Disclosures: Zerbo reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Photo of Ousseny Zerbo
Ousseny Zerbo

Pertussis cases appear most frequently among age-appropriately vaccinated children, which suggests that suboptimal DTaP vaccine effectiveness plays a major role in epidemics, according to a retrospective cohort study published in Pediatrics.

“The finding that most pertussis cases occurred among highly vaccinated children suggests that waning of vaccine immunity played a strong role in recent pertussis cases,” Ousseny Zerbo, PhD, staff scientist at the Vaccine Study Center at Kaiser Permanente Northern California Division of Research, told Infectious Diseases in Children. “Although pertussis vaccine immunity wanes, it is important that children continue to be vaccinated according to CDC’s vaccination recommendation. The pertussis vaccine is effective at preventing pertussis but for a short period of time. If a child is not vaccinated or is undervaccinated, his or her risk is much higher than a child who is fully vaccinated.”

The researchers followed children born at Kaiser Permanente Northern California between 1999 and 2016 — restricting their analysis to children who received only acellular pertussis vaccines, which were introduced in the 1990s. They classified children as fully vaccinated “if they received the expected number of DTaP doses by 1 month after the [Advisory Committee on Immunization Practices]-recommended age,” they wrote. Children were defined as undervaccinated if they had fewer doses than expected for their age, whereas children with one more dose than expected at that age were classified as fully vaccinated plus one dose.

Among 469,982 children aged 3 months to 11 years, the researchers identified 738 pertussis cases, of which 99 were unvaccinated, 515 were fully vaccinated and 88 were fully vaccinated plus one dose, according to the study.

Pertussis risk was 13 times higher for unvaccinated children (adjusted HR = 13.53; 95% CI, 10.64-17.21) vs. fully vaccinated children and 1.9 times higher (aHR = 1.86; 95% CI, 1.32-2.63) among undervaccinated children, the researchers wrote. These finding are “broadly consistent” with two previous case-control studies, one from 2013 and another from 2017, the researchers said.

Among vaccinated children aged 19 to younger than 84 months, the risk was five times higher (aHR = 5.04; 95% CI, 1.84-13.8) in 3 years or more vs. less than 1 year after vaccination. Children aged 84 to 132 months had a two times higher risk (aHR = 2.32; 95% CI, 0.97-5.59) at 6 years or more vs. less than 3 years after vaccination.

“Our results reveal that waning of DTaP immunity was an important cause of pertussis in children [older than] 18 months of age who have a longer interval between recommended doses,” Zerbo and colleagues wrote. “By age 19 months, nearly all children had received at least one DTaP dose, and children who were age-appropriately vaccinated accounted for [more than] 95% of follow-up.”

PAGE BREAK
Kathryn Edwards
Kathryn M. Edwards

In a related editorial, Infectious Diseases in Children Editorial Board Member Kathryn M. Edwards, MD, professor of pediatrics at Vanderbilt University School of Medicine, wrote that “given the markedly increased risk of pertussis in unvaccinated and undervaccinated children, universal DTaP vaccination should be strongly recommended.”

Secondly, she said “the addition of maternal Tdap vaccination administered during pregnancy has been shown to significantly reduce infant disease before primary immunization and should remain the standard.”

However, Edwards added that addressing the waning immunity of DTaP vaccination proves more problematic, suggesting extensive safety studies in younger children would be needed before potential options — including a live-attenuated pertussis vaccine administered intranasally or the addition of other antigens to current vaccines — can be implemented. – by Joe Gramigna

References:

Edwards KM, et al. Pediatr. 2019;doi:10.1542/peds.2018-3466.

Glanz JM. JAMA Pediatr. 2013;doi:10.1001/jamapediatrics.2013.2353 .

Huang WT, et al. Hum Vaccin Immunother. 2017;doi:10.1080/21645515.2016.1249552.

Zerbo O, et al. Pediatrics. 2019;doi:10.1542/peds.2018-3466.

Disclosures: Zerbo reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.