Rotavirus Vaccine and Intussusception: Rarely, at Least in Some Places

Abstract & Commentary

By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine, and Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.

Dr. Jenson reports no financial relationships relevant to this field of study.

Synopsis: Recent post-marketing surveillance from Mexico and Australia has identified a very low but increased risk of intussusception following rotavirus vaccination with Rotarix, especially following the first dose.

Source: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases: Statement regarding Rotarix and RotaTeq rotavirus vaccine that intussusception. Issued November 3, 2010 at http://www.cdc.gov/vaccines/vpd-vac/rotavirus/intussusception-studies-acip.html, accessed November 12, 2010.

Post-marketing surveillance outside the United States of the two FDA-licensed rotavirus vaccines, RotaTeq (Merck, licensed in 2006) and Rotarix (GSK Biologicals, licensed in 2008), have identified a very low but increased risk (1 case/100,000 vaccinated infants) of intussusception following Rotarix vaccination. On Sept. 22, 2010, the FDA approved a label change for Rotarix based on data from Mexico. Analysis of one population in Mexico revealed clustering of 18 hospitalizations for intussusception in the 1-7 days following the first dose of Rotarix. This rate is 4-5 times higher than in later periods after vaccination, after adjusting for age. A second analysis of a different population in Mexico revealed a possible 1.8-fold increased risk of intussusception in the 30 days following the first dose of Rotarix, with the clustering of cases in the first week after vaccination. No increased risk was identified in the post-marketing surveillance studies of Rotarix in Brazil. Other post-marketing surveillance studies in Australia identified a few cases of intussusception that suggest the possibility of an increased risk of intussusception in the first week after vaccination with either Rotarix or RotaTeq vaccines.

Pre-licensure trials for Rotarix and RotaTeq vaccines each involved more than 60,000 participants and showed no increased risk for intussusception. More than 27 million doses of RotaTeq and more than 2.7 million doses of Rotarix have been distributed in United States. Postmarketing surveillance and studies have not identified an increased risk of intussusception in the United States, including a new study of 800,000 total doses of RotaTeq vaccine conducted in response to this new information, though a risk as low as that reported with Rotarix in Mexico cannot be excluded by these analyses.

Commentary

A previous rotavirus vaccine, RotaShield, was withdrawn from the market because post-marketing surveillance revealed an association with intussusception (1 case/10,000 vaccinated infants). From that experience, the risk for this adverse event was specifically included in the design and evaluation of pre-licensure trials for each of the two current vaccines; an association with intussusception was not observed. The risk continues to be monitored by post-marketing surveillance in the United States and many other countries.

The impact of rotavirus vaccine in the United States has been significant. Hospitalization and emergency department care of infants and children with rotavirus disease have decreased by about 85%, with an estimated 40,000-60,000 fewer gastroenteritis-related hospitalizations annually among children less than 5 years of age. The proven benefit of rotavirus vaccination is significantly greater than the very small risk of intussusception that may result from rotavirus vaccine. The role of wild-type rotavirus causing intussusception remains unsettled. The CDC continues to recommend both Rotarix and RotaTeq vaccines to prevent severe rotavirus disease in United States.