Rotavirus Vaccine Tied to Short-Term Risk for Intussusception

From Medscape Medical News Megan Brooks June 17, 2011 — The monovalent rotavirus vaccine (RV1; Rotarix, GlaxoSmithKline) carries a short-term risk for bowel intussusception in roughly 1 of every 51,000 to 68,000 vaccinated infants, a new study indicates. However, the benefits of the vaccine far outweigh the risks, the study team emphasizes. The study appears in the June 16 issue of the New England Journal of Medicine. In 1999, a rotavirus vaccine (RotaShield, Wyeth Laboratories) was withdrawn from the US market after postlicensure surveillance showed it caused intussusception in 1 of every 10,000 infant recipients. This prompted Manish M. Patel, MD, from the Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues to assess the association of the new monovalent RV1 vaccine with intussusception in Brazil and Mexico. Brazil added RV1 to their national childhood immunization programs in March 2006, and Mexico followed in May 2007. A total of 615 infants with intussusception (285 in Mexico and 330 in Brazil) and 2050 control infants (739 in Mexico and 1311 in Brazil) were enrolled in the study. Of these, 594 patients with intussusception (97%) and 2033 control patients (99%) had a history of vaccination. Among infants from Mexico, there was roughly a 5-fold increased risk for intussusception 1 to 7 days after the first dose of RV1. Using a case-series method, the incidence ratio was 5.2 (95% confidence interval [CI], 3.0 - 9.3). Using a case-control method, the odds ratio was 5.8 (95% CI, 2.6 - 13.0). Among infants in Brazil, no significant risk for intussusception was found after the first dose. However, a small but significantly increased risk was seen 1 to 7 days after the second dose in both the case-series analysis (incidence ratio, 2.6; 95% CI, 1.3 - 5.2) and the case-control series (odds ratio, 1.9; 95% CI, 1.1 - 3.4). Benefits Clearly Outweigh Risks The authors point out that the first week after dosing corresponds to the period of peak intestinal virus replication, during which a local inflammatory response in the lymphatic tissue or intestines may occur, "a response that has been implicated in the pathogenesis of intussusception." They emphasize, however, that the increased risks uncovered from their analysis translated into an annual excess of 96 hospitalizations for intussusception, and 5 deaths in the 2 countries combined. These figures, they say, "are outweighed by the real-world benefits of RV1 vaccination, which has annually prevented more than 80,000 hospitalizations and 1300 deaths in Mexico and Brazil." They further point out that these "emerging" data on RV1 have been reviewed by the World Health Organization, as well as by regulatory agencies and immunization advisory committees in Brazil, Mexico, and the United States. All of these organizations have unanimously favored continuing the recommendation that rotavirus vaccination be administered to infants to prevent severe and potentially fatal rotavirus disease. The study was supported in part by the Global Alliance for Vaccines and Immunization and the US Department of Health and Human Services. The authors have disclosed no relevant financial relationships. N Engl J Med. 2011;364:2283-2292. Full text