ATLANTAThe Advisory Committee on Immunization Practices (ACIP) is drafting recommendations for the use of acellular pertussis vaccines, pending Food and Drug Administration approval.
Several license applications for diphtheria-tetanus-acellular pertussis (DTaP) vaccines have been filed; one vaccine (Tripedia, Connaught) is awaiting final approval.
The ACIP is preparing draft recommendations in anticipation of licensure. A number of issues must still be decided, and at its recent meeting, the committee discussed ifand howa preference for either type of vaccine should be stated.
The wording of the ACIP's recommendation is a critical consideration. The committee uses the phrases "highly preferred," "preferred," "may be preferred," and "is equivalent to" to convey subtle shades of difference in the strength of its recommendations.
The criteria that will determine the strength of the statement for acellular pertussis vaccines appear straightforward: adverse reactions, both mild and severe; vaccine efficacy; immunogenicity; number of injections; and availability, including not only the supply of the vaccine but also cost.
The information to address those criteria, however, is incomplete. For example, availability and cost information is unknown until acellular pertussis vaccines begin to be used for the infant series.
The average prices of the DTaP vaccines currently available for the fourth and fifth doses are about $5 higher than for whole-cell vaccines, said Walter Orenstein, MD, Director, National Immunization Program, Centers for Disease Control and Prevention (CDC). This cost may change as acellular vaccines are more widely used.
Until that price is reduced, using DTaP for the entire series will add $1.5 million for every 100,000 children immunized, said ACIP member Ed Thompson, MD, State Health Officer, Mississippi State Department of Health.
The importance of immunogenicity is another unknown, said Hamid Jafari, MD, a Medical Epidemiologist for the CDC's National Immunization Program.
"A correlate of immunologic protection against pertussis has not been identified in any of the studies," Jafari said. "Thus, immunogenicity cannot be used to predict efficacy of a vaccine."
All of the DTaP vaccines included in the recently completed European trials were equally or more efficacious than at least one of the diphtheria-tetanus-whole cell pertussis (DTP) vaccines currently used in the United States, Jafari said.
The only criteria that separate the two types of vaccines, therefore, are adverse reactions and number of injections.
"DTaP vaccines are associated with a significantly lower frequency of mild adverse reactions than whole-cell vaccines," Jafari said. "Fever equal to or more than 40°C, hyporesponsive/hypotonic episodes, and persistent crying are less firmly associated with DTaP than with whole-cell vaccine...Convulsions are also significantly fewer among the recipients of acellular vaccine. We do not have enough experience with acellular vaccines to evaluate the risk of more severe adverse reactions, such as anaphylactic shock and acute encephalopathy."
The advantage of whole-cell vaccines is that they require fewer injections. DTP vaccines are available in combination with Haemophilus influenzae type b vaccines, whereas the initial acellular pertussis vaccines will only be combined with diphtheria and tetanus toxoids.
The ACIP is also considering a switch from oral to injected polio vaccine for the first two doses. Therefore, in a worst-case scenario, the number of injections could climb to four at 2 months of age, three each at 4 months and 6 months, and four during the second year of life. A best-case scenario following the current schedule requires two injections at 2 months of age followed by one at 4 months, two at 6 months, and three or four during the second year.
The additional injections may mean more visits if pediatricians are reluctant to administer more than three injections at once.
Safety, however, is the paramount issue, Orenstein said. "The reason we are [talking] about acellular vaccines is vaccine safety...There is roughly a 25% difference in use of antipyretics with any DTaP [vaccine] vs. whole-cell vaccine. That translates, at any dose, to at least 1 million children not using antipyretics if they got DTaP vs DTP. At every dose, it could be 5 million children...There are very important safety considerations, and if there is not a major difference in efficacy, why not consider that this would be preferred?...We need to remember what brought us to this point, and that is vaccine safety," Orenstein said.
Georges Peter, MD, a liaison representative from the American Academy of Pediatrics, noted that public confidence in vaccines, which was shaken by highly publicized reports of rare adverse events associated with whole-cell pertussis vaccines, needs to be restored.
"The safety issue is more than just safety for that vaccine," Peter said. "It relates to public credibility and what [the public] thinks of the vaccine program....This is a broad issue that goes well beyond sore arms; it goes to public confidence. Safety should be our overriding concern, assuming at least equivalent efficacy."
Issues still remain for the ACIP to consider, including the future role of whole-cell vaccines, whether acellular and whole-cell vaccines can be used interchangeably, and if acellular vaccine may be used to complete the primary immunization series in a child who experienced a reaction after vaccination with the whole-cell vaccine.
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