November 1999
ATLANTA - The Advisory Committee on Immunization Practices (ACIP) recently voted to no longer recommend rotavirus vaccine (RotaShield, Wyeth Lederle Vaccines) for routine use in children.
The unanimous vote was based on an overwhelming amount of data presented to the Centers for Disease Control and Prevention (CDC) advisory committee - all indicating a strong association between rotavirus vaccine and bowel obstruction among some infants during the first one to two weeks following vaccination.
Wyeth Lederle Vaccines pulled the vaccine from the market and has requested immediate return of all doses of the vaccine.
As of Oct. 15, a total of 102 confirmed and presumptive cases of intussusception following receipt of rotavirus vaccine were reported to the Vaccine Adverse Events Reporting System (VAERS). Fifty-seven had onset within seven days of receipt of the vaccine and 29 underwent surgery; seven required bowel resection. One fatal case was reported in a 5-month-old, according to John Livengood, MD, director of the Epidemiology and Surveillance Division, National Immunization Program, CDC.
Livengood also presented data from a population-based cohort study of intussusception and rotavirus vaccination. The data were collected from the Vaccine Safety Datalink (VSD), including four HMOs consisting of 2% of the U.S. population, which was also linked with computerized vaccination, medical visits and covariates records. Additional results are still pending.
The preliminary results of the population-based cohort study suggested that rotavirus vaccine is associated with elevated risk of intussusception, with the greatest risk between three and seven days after vaccination.
The case definition of intussusception was defined as intussusception that occurred in a child age 1-11 months (born between Dec. 2, 1997-June 15, 1999). The cases had to have occurred between Dec. 1, 1998, and July 16, 1999, and were diagnosed by radiological procedure (barium or air contrast with barium enema, or directly at the time of surgery or at autopsy.
Case-series and case-control analyses based on a multistate investigation of intussusception in recipients of rotavirus vaccine was also conducted in conjunction with the NIP and local and state health departments from 19 states.
The case series data indicated an overall risk of intussusception was increased by 60% after rotavirus vaccination among cases ever vaccinated, compared with cases who were never vaccinated (P<0.0003). For dose one, the risk of intussusception was increased 19-fold in the first three to seven days after vaccination and almost fourfold (3.6) in the eight to 14 days after vaccination (P<0.0002).
Similar results occurred with the interim results of the case-control analysis. These data indicate that the risk of intussusception is increased by 80% after rotavirus vaccination in an ever vs. never comparison. For dose one, the risk of intussusception increased 25-fold in the first three to seven days following vaccination and 7.1-fold in eight to 14 days after vaccination. For dose two, the risk of intussusception increase 13.4-fold in three to seven days after rotavirus vaccination.
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While the ACIP recommendation stated that RotaShield no longer be routinely given to children, the statement also stressed the clinical impact of rotavirus disease and encouraged future research toward the development of new rotavirus vaccines, said ACIP member Paul Offit, MD, chief of the section of infectious diseases, Children's Hospital of Philadelphia. "There remains a need for a safe and effective rotavirus vaccine," he said.
According to Larry K. Pickering, MD, editor of the American Academy of Pediatrics' 2000 Red Book and director of the Center for Pediatric Research, Norfolk, Va., studies must now be conducted to monitor the continuing effect of rotavirus as a cause of disease in infants and children, since the wild-type strains will continue to infect children.
"We must also continue to evaluate methods to prevent infection and disease," said Pickering, a member of the Infectious Diseases in Children editorial board.
Offit suggested that the events surrounding rotavirus vaccine will have an impact on the industry in general.
He said it is arguable whether intussusception is a consequence of natural infection. Normally when vaccines are associated with an adverse event, biological plausibility - was it something that could have predicted - is mentioned. Offit said intussusception associated with rotavirus vaccine was not predictable and occurs fairly rarely, 1:4,500 children.
"That sets a new bar for the future for how the Food and Drug Administration and pharmaceutical companies deal with this, and I think it has an impact on not only rotavirus vaccine, but for all vaccines," he said.
For more information:
- CDC. Intussusception among recipients of rotavirus vaccine - United States, 1998-1999. MMWR.1999;48(27):577-581.
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