March 6, 2006

Reactions to last DTaP vaccine not prevented

Group Health research finds no help from ibuprofen, acetaminophen

Seattle—A red splotch forms where most preschoolers get their fifth, and last, shot of the acellular diphtheria-tetanus-pertussis (DTaP) vaccine, and it can last a few days. Neither of two common over-the-counter drugs—ibuprofen (Advil) and acetaminophen (Tylenol)—help prevent this side effect, according to a Group Health Cooperative study appearing in the March issue of Pediatrics.

In about 1 in 5 children, this "local reaction" measures at least 4 inches, spreading over the whole upper arm (or thigh) in about 1 in 100. But it is seldom serious and usually does not hurt.

"Often children don't notice they have it," said Lisa A. Jackson, MD, MPH, a senior investigator at Group Health's Center for Health Studies and the study's lead investigator. "But it can concern parents, leading to medical visits or even needless antibiotic treatment, so we'd like to make it rarer."

Jackson and Group Health colleagues observed 372 children from 4 to 6 years old who were due for their fifth DTaP dose after getting 4 doses of this vaccine since age 2 months. Four in 10 children were randomly assigned to receive ibuprofen; 4 in 10, acetaminophen; and 2 in 10, placebo (providers and families were "blind" to who got what).

The medication was given preventively 3 times: at 2 hours before, and 6 and 12 hours after, the vaccination. About a third of each group had local reactions at least 2 inches wide. The placebo and treatment groups did not differ significantly in their proportions of children whose reactions lasted at least 3 days or whose vaccinated limb swelled by about 1 inch or more.

Acetaminophen is commonly given to help prevent post-vaccine fever in babies, who are more likely than toddlers or preschoolers to have fever after vaccination.

"Acetaminophen is an effective anti-pyretic (fever reducer)," Jackson explained. "But it isn't an anti-inflammatory (inflammation reducer)." So even though acetaminophen is commonly given to older children for their later immunizations, Jackson was not surprised that her study showed it failed to prevent preschoolers' local reactions, which are likely caused by inflammation.

What Jackson did not expect is that the anti-inflammatory drug ibuprofen would prove similarly ineffective at preventing these local reactions. "We certainly thought that ibuprofen, through its anti-inflammatory effect, might make the local reactions less common or severe," she said. "We all want to decrease discomfort in children, so we were disappointed not to show a prevention effect for ibuprofen; but on the other hand we got a fairly definitive answer, and that's why we do research."

Possible explanations? Maybe a different kind of inflammation, which ibuprofen doesn't interrupt, causes the local reaction, Jackson said. Or perhaps taking any anti-inflammatory drug by mouth doesn't get enough active ingredients to the site of the vaccination—and reaction. Future approaches include evaluating more dilute DTaP vaccines. "These vaccines with a lower antigen content may be just as effective, but may be associated with fewer reactions, in 4 to 6 year olds," she said.

The acellular vaccine, licensed in 1997, contains only those parts of the diphtheria (whooping cough) bacteria that are critical to providing immunity. The previous version—whole cellular diphtheria-tetanus-pertussis (DTP) vaccine—contained whole bacteria. The older whole-cell pertussis vaccines also caused local reactions, but they happened less often with the later (fourth and fifth) doses than with the earlier ones; by contrast, the reaction risk from the newer acellular vaccine rises with the fourth dose and is highest with the fifth. The newer acellular shot results in less fever in 2- and 4-month-old babies than did the older whole-cell shot. This is significant because fever can lead to seizures—rare, but serious, adverse events associated with the DTP shot.

Sanofi-Aventis Group, which manufactures the Tripedia DTaP vaccine, funded the study. Other researchers contributing to the study were Maya Dunstan, RN; Patty Starkovich, RN; Onchee Yu, MS; Jennifer C. Nelson, PhD; Thom Rees, MHA; and Ann Zavitkovsky, MPH; and Group Health pediatrician John Dunn, MD, MPH. Nelson, like Jackson, has a joint appointment at the University of Washington.

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Onchee Yu, MS

Principal Collaborative Biostatistician
Kaiser Permanente Washington Health Research Institute

Jennifer C. Nelson, PhD

Director, Biostatistics; Senior Investigator
Kaiser Permanente Washington Health Research Institute

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