Increased risk of intussusception following rotavirus vaccination in infants

Rotavirus infection causes diarrheal disease, mostly in infants, and was associated with more than 600,000 deaths each year globally prior to the availability of vaccine.  Rotashield, an infant rotavirus vaccine licensed in 1998, was voluntarily withdrawn from the market within a year when an increased risk of intussusception, a rare kind of intestinal blockage, after vaccination was discovered.  Two newer rotavirus vaccines, RotaTeq and Rotarix, were licensed in the U.S. in 2006 and 2008, respectively, after large clinical trials designed to be able to detect an excess risk of intussusception similar to that of Rotashield (approximately 1-1.5 excess cases per 10,000 vaccine recipients).  Although no such risk was observed in the clinical trials, several postlicensure studies conducted in other countries subsequently suggested an increased risk of intussusception after both Rotarix and RotaTeq. 
 
In 2010, the FDA, through Mini-Sentinel’s Post-licensure Rapid Immunization Safety Monitoring (PRISM) project, launched a large population-based study to quantify the risk of intussusception after rotavirus vaccination among U.S. infants. The study, led by Katherine Yih, PhD, MPH, found evidence of an association between one of the rotavirus vaccines, RotaTeq, and intussusception, with the highest risk occurring in the 3-7 days after the first dose.  The risk was estimated at approximately 1.1-1.5 excess cases per 100,000 first-dose recipients, or about 1/10 the risk associated with the original, discontinued vaccine, Rotashield.  Based on published data, the benefit of the vaccine in preventing hospitalizations and deaths from diarrheal disease continues to outweigh the risk of intussusception.  
 
As a result of this study, the FDA approved a change to the RotaTeq product label.  Dr. Yih presented the findings to the Advisory Committee on Immunization Practices (ACIP) in June, which is evaluating them together with results of other recent studies but does not foresee major changes in rotavirus vaccination policy.
 
The full report is posted to the Mini-Sentinel Website.