The Journal of Pediatrics
Volume 149, Issue 5 , Pages 589-591, November 2006

Recommendation for an adolescent dose of tetanus and diphtheria toxoids and acellular pertussis vaccine: Reassurance for the future

  • Scott A. Halperin, MD

      Affiliations

    • Halperin has received grant and contract funding from both manufacturers of adult formulation Tdap vaccines and has on occasion participated in consultancy meetings with both manufacturers on the subject of vaccines.
    • Corresponding Author InformationReprint requests: Scott A. Halperin, MD, Canadian Center for Vaccinology, Halifax, Dalhousie University, IWK Health Centre, 5850/5980 University Ave, Halifax, Nova Scotia B3K 6R8 Canada.

Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada

Article Outline

Abbreviations: ACIP, Advisory Committee on Immunization Practices, Td, Diphtheria and tetanus toxoid vaccine, Tdap, Tetanus and diphtheria toxoids and acellular pertussis vaccine

 

In response to the resurgence of pertussis in adolescents and adults,1, 2 the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention and the Committee on Infectious Diseases of the American Academy of Pediatrics recently recommended3 that all adolescents be given a dose of 1 of 2 approved4, 5 adult-formulation tetanus and diphtheria toxoids and acellular pertussis vaccines (Tdap) at the 11- and 12-year-old preadolescent visit. ACIP also has recommended that all adults, and particularly health care and childcare workers scheduled for their decennial diphtheria and tetanus toxoid (Td) booster be immunized with Tdap instead.6 These recommendations follow similar recommendations in Canada, Australia, Germany, and France.7, 8

See related article, p 603

Injection-site reactions tend to increase with increasing number of doses of acellular pertussis vaccine, with rates after the fourth dose exceeding those of the first 3 doses; rates of injection-site erythema and swelling over 2 cm can exceed 50% after the fifth consecutive dose at 4 to 6 years of age.9 The generally nonpainful injection-site erythema and swelling after the preschool acellular pertussis vaccine dose differ from the painful erythema and swelling that previously were reported commonly after the fifth dose of whole-cell pertussis vaccine10 and are substantially less concerning to the children and parents.11 The cause of these injection-site reactions has not been determined but may be, in part, related to preexisting antibody levels against 1 or more of the antigens, as well as to cell-mediated immunity12; hypersensitivity phenomena do not appear to be involved.13

Although the fifth consecutive dose of an acellular pertussis-containing vaccine generally was tolerated well despite the erythema and swelling, there are concerns that a sixth consecutive dose might not be tolerated by preadolescents and adolescents. In a number of prelicensure studies, Tdap was tolerated well by adolescents and adults, with the nature and rate of adverse events associated with immunization not substantially different from those associated with the licensed and widely used Td vaccine.14, 15, 16 However, these studies were completed in adolescents and adults who had received whole-cell pertussis vaccine for most or all of their previous doses of pertussis-containing vaccine. With the preschool booster, the lowest rates of injection-site reactions were reported by children who received a dose of acellular pertussis vaccine after 4 previous doses of whole-cell pertussis vaccine.10 In a postlicensure study assessing the safety of giving Tdap after a prior pertussis-containing vaccine, the rates of adverse events tended to be higher in Tdap recipients whose prior dose had been an acellular pertussis-containing vaccine compared with a whole-cell pertussis-containing vaccine.17 Thus there is concern that the rates of adverse events in the prelicensure studies of Tdap underestimate the rates that would be seen in adolescents who received acellular pertussis vaccine for all of their previous doses. Indeed, there is some suggestion that changing from an acellular pertussis vaccine from one manufacturer to one produced by another manufacturer for a booster dose might be associated with fewer injection-site reactions.18 Use of Tdap as the fifth dose rather than the higher antigen content pediatric formulation does decrease the rates of injection-site reactions.19

Although it will be several years before the general adolescent population routinely will be given their sixth consecutive dose of acellular pertussis vaccine, the study by Zepp at al20 provides reassurance that this dose will be well tolerated and will not adversely affect the pertussis immunization strategy. In their study, 321 adolescents between 10 and 12 years of age who had participated previously in clinical trials of 5 consecutive doses of an acellular pertussis vaccine were randomized to receive either a sixth dose of Tdap or hepatitis A vaccine. Most of the participants (195/321) had received 5 doses of the pediatric formulation of the acellular pertussis vaccine manufactured by GlaxoSmithKline Biologicals. The other participants had received 4 doses of the pediatric formulation and the fifth dose as either Tdap (n = 83) or an acellular pertussis vaccine without diphtheria or tetanus toxoids (n = 42). The mean time since the previous dose was 5.8 years. Redness (51.7%), swelling (41.4%), and pain (63.6%) were reported more frequently after Tdap than hepatitis A vaccine; most reactions were reported as mild. In comparing adverse reactions after the fifth and sixth dose reported by the same children, injection-site pain was more frequent, and erythema and swelling were less frequent after the sixth compared with the fifth dose. No whole limb erythema or swelling21, 22 was reported after the sixth dose; 3 adolescents reported large injection-site swelling that resolved spontaneously. Of note, none of the 22 adolescents with large local reactions after the fifth dose had a large local reaction after the sixth dose.

These first reassuring safety data on 6 consecutive doses of acellular pertussis vaccine are timely, given the recent recommendations for universal adolescent pertussis immunization and early indications on the effectiveness of this strategy in decreasing rates of pertussis in adolescents. Although acellular pertussis vaccine was shown to be efficacious in a large clinical trial,23 data from areas of Canada in which there was early implementation of universal adolescent pertussis immunization suggest that the strategy also is effective under conditions of routine use. Early data from Newfoundland and Labrador24 and the Northwest Territories25 show a dramatic decline in pertussis in the immunized adolescent cohorts.

Although these preliminary results are promising, gaps in the data remain that must be addressed through additional research. As Zepp et al26 suggest, the safety of the sixth consecutive dose of Tdap given concurrently with the routinely recommended tetravalent meningococcal conjugate vaccine (with its relatively high diphtheria toxoid content) need to be undertaken. The effectiveness of the targeted adult immunization strategy compared with feasibility and effectiveness of a universal adult pertussis immunization strategy also needs further exploration. Finally, the effect of the adolescent and adult immunization programs on the incidence of disease among vulnerable neonates needs to be assessed along with the safety and immunogenicity of Tdap during pregnancy and its effect on the newborn infant. The results reported in this issue by Zepp et al20 are a reassuring first step.

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References 

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PII: S0022-3476(06)00795-5

doi:10.1016/j.jpeds.2006.08.032

Refers to article:

  • Safety of reduced-antigen-content tetanus–diphtheria–acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis–containing vaccine

    Fred Zepp, Markus Knuf, Pirmin Habermehl, Wilma Mannhardt-Laakmann, Barbara Howe, Leonard R. Friedland
    The Journal of Pediatrics November 2006 (Vol. 149, Issue 5, Pages 603-610.e1)

The Journal of Pediatrics
Volume 149, Issue 5 , Pages 589-591, November 2006

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