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Tdap effectiveness wanes rapidly in teens

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A cough, not a whoop, in teens with pertussis

When adolescents contract whooping cough, a.k.a. pertussis, they usually don’t whoop but they cough, sometimes for 3 months. The illness is impactful for them and they are contagious to others, so the infection spreads to classmates and within families. Waning immunity after experiencing pertussis infection, after receiving the old DTwP vaccine that was discontinued in the United States years ago due to safety issues, and after receiving the newer DTaP and Tdap vaccines, has been known to occur for many years. What is new in this article is the rapidity of waning immunity in the study population.

Dr. Michael E. Pichichero

First, it is important to note that the study population is from California, a state where pertussis has been circulating much more than in most other states. The exact reasons for a higher prevalence of pertussis in California are not fully understood, but a high rate of vaccine refusers may be a significant factor. Secondly, the study uses a mathematical model, so it is an estimate of waning immunity. Nevertheless, the observations alert health care providers and the community that pertussis can occur even in vaccinated persons, especially as time passes after vaccination.

The solutions are few at this time. Public health care officials are unlikely to recommend boosters more frequently than already advocated, although that is an option. Alternative formulations of Tdap to include other or additional ingredients could be a path forward, but the vaccine industry is tackling so many new diseases with vaccine development programs that a push for a better DTaP or Tdap is unlikely in the near term.

Dr. Michael E. Pichichero, specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no relevant financial disclosures.


 

FROM PEDIATRICS

References

The Tdap vaccine’s effectiveness against pertussis wanes so rapidly in the year after administration in teens that it provides too little protection to prevent outbreaks, according to results of a new study.

The Tdap is the booster vaccine against tetanus, diphtheria, and pertussis that adults and children ages 10 and older can receive. The corresponding acellular pertussis vaccine for children ages 6 and younger is the DTaP.

“Widespread Tdap vaccination, although associated with a transient decrease in pertussis incidence, did not prevent outbreaks among this population of teenagers who have only ever received acellular pertussis vaccines,” reported Dr. Nicola P. Klein and her associates at the Kaiser Permanente Vaccine Study Center in Oakland, Calif. “This study demonstrates that despite high rates of Tdap vaccination, the growing cohort of adolescents who have only received acellular pertussis vaccines continue to be at high risk of contracting pertussis and sustaining epidemics,” they wrote online (Pediatrics. 2016 Feb 5. [doi: 10.1542/peds.2015-3326]).

©CDC

The researchers tracked 279,493 members of Kaiser Permanente Northern California who had received only DTaP vaccines, as opposed to the whole-cell DTwP formulation previously used, from age 10 onward. These included all members who were born from 1999 onward or were born from 1996-1998 and received three infant doses of DTaP, excluding children who had previously received Tdap or had pertussis. Among these, 175,094 children received the Tdap.

For the purposes of tracking pertussis cases in unvaccinated versus vaccinated adolescents, individuals were considered unvaccinated in the analysis until they received their first Tdap, after which they were vaccinated and time since vaccination was a continuous variable. Overall, 96.5% of the children were vaccinated by their 14th birthday.

Across 792,418 person-years between January 2006 and March 2015, including 418,595 vaccinated person-years for the children who received the Tdap, 1,207 cases of pertussis occurred. The vast majority of these – 85% – occurred among those ages 10-13 years. Teens aged 14-16 years comprised 15% of the cases, and only 0.5% of cases occurred among older teens. During each year of outbreaks, incidence dropped off precipitously among the age groups composed of children who would have received the whole-cell pertussis vaccine.

For example, “pertussis incidence in the 2010 outbreak sharply declined after this peak [of 10- to 11-year-olds] and stayed low at older ages, a decline that we have previously demonstrated to be associated with the receipt of whole cell instead of acellular pertussis vaccines in infancy and childhood as well as with Tdap receipt,” the authors wrote.

The researchers estimated the Tdap’s effectiveness at 69% throughout the first year after vaccination. This dropped to 57% in the second year after vaccination and then to 25% in the third year. By 4 years or later after Tdap receipt, the vaccine’s effectiveness sat at just 9%.

For each year after Tdap vaccination, children’s risk of pertussis increased 35% (hazard ratio, 1.35), and cases were mild or moderate regardless of vaccination status. Nearly all (98%) of the children with pertussis had visited the doctor within 5 days on either side of their positive polymerase chain reaction test, 86% received a diagnosis of pertussis, and 96% received a prescription for azithromycin, except for 1 for erythromycin. In addition, 4% (50) of the cases visited the emergency department. No differences in rate of ED visits or prescriptions existed between vaccinated and unvaccinated children.

“The strategy of routinely vaccinating adolescents to prevent future disease did not prevent the 2014 epidemic, arguably because the protection afforded by a dose of Tdap was too short-lived,” the authors noted. They also pointed out that Tdap waning estimates likely also include ongoing DTaP waning.“This study was unable to disentangle the waning of Tdap effectiveness from the ongoing waning of previous doses of DTaP because the years since vaccination for Tdap and the fifth DTaP dose are closely correlated,” they wrote.

Most of the Tdap vaccines administered were Adacel (Sanofi Pasteur), but Boostrix (GlaxoSmithKline) was used as well. Waning occurred in both brands, and although not directly compared, no major differences in waning seemed to exist.

“We expect future pertussis epidemics to be larger as the cohort that has only received acellular pertussis vaccines ages,” the authors concluded. “The results in this study raise serious questions regarding the benefits of routinely administering a single dose of Tdap to every adolescent aged 11 or 12 years.”

The research was funded by Kaiser Permanente. Dr. Klein has received research funding from GlaxoSmithKline for a separate pertussis vaccine effectiveness study, and Dr. Klein and one coauthor also have received research funding from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Novartis, Protein Science, Nuron Biotech, and MedImmune. The remaining coauthors said they had no relevant financial disclosures. GlaxoSmithKline and Sanofi Pasteur manufacture the pertussis vaccines purchased by Kaiser Permanente for this study.

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