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Rotavirus vaccine linked to slightly increased risk for intussusception

One of the currently licensed rotavirus vaccines was associated with a short-term risk for intussusception, according to results of a study published online this week

The risk for intussusception was seen in approximately one of every 51,000 to 68,000 vaccinated infants, but the incidence of morbidity and mortality associated with rotavirus was greatly reduced, and the benefits of the vaccine far exceeded the risks.

Harry B. Greenberg, MD, senior associate dean for research at the Stanford University School of Medicine, wrote a commentary to accompany the study and said this is the second study to suggest an intussusception risk in the two commercially available rotavirus vaccines.

“The vaccines’ pluses so outnumber the minuses that it’s almost immaterial to talk about the minuses,” Greenberg said. “In places like the United States or Western Europe, the new vaccines substantially reduce hospitalizations and morbidity. They save hospital costs, plus the cost of work lost to parents who have to bring their child to the doctor or have the child hospitalized.”

In the current study, researchers identified 615 case patients — 285 in Mexico and 330 in Brazil — and 2,050 controls. They noted an “increased risk of intussusception 1 to 7 days after the first dose among infants in Mexico with the use of both the case-series method (incidence ratio=5.3; 95% CI, 3.0-9.3) and the case–control method (OR=5.8; 95% CI, 2.6-13.0),” after the children were administered Rotarix (RV1, GlaxoSmithKline). There was no significant risk after the first dose in children in Brazil, but some increased risk 1 to 7 days after vaccination.

“However, RV1 prevented approximately 80,000 hospitalizations and 1,300 deaths from diarrhea each year in these two countries,” the researchers wrote.

Greenberg said in his editorial that these two studies, taken with previous data from the older rotavirus vaccine, RotaShield (Wyeth), which was pulled from shelves, suggest that natural rotavirus infection itself probably causes intussusception at some low frequency.

“Several lines of evidence support that idea. In a large safety study of one of the vaccines, the children who got vaccinated had statistically fewer intussusceptions over the following 1-year period than the children who didn’t get vaccinations,” he said in a press release about the commentary. “Data just coming out of Australia now shows an increased rate of intussusception in that first week or two after vaccination among those vaccinated as compared with those who weren’t, but that increase evaporated over time. And a very large epidemiology study of the first-generation rotavirus vaccine detected no overall increase in intussusception rates.”

Disclosure: The study was funded in part by the GAVI Alliance and the HHS.

The study by Patel and coworkers sheds new light on a question raised more than 10 years ago. In 1998, RotaShield, a simian-human reassortant rotavirus vaccine, was licensed and recommended for US children. About 1 year after licensure, a CDC study showed that the vaccine was a rare cause of intussusception with an attributable risk of about 1 per 10,000 vaccinees. Given that natural rotavirus infection was not a known cause of intussusception, this post-licensure finding was surprising. Seven years passed before the next rotavirus vaccines were licensed. In 2006, RotaTeq, a bovine-human reassortant rotavirus vaccine, and RotaRix, an attenuated human rotavirus vaccine, were licensed in many countries throughout the world. Patel's data shows that both of these vaccines are probably also rare causes of intussusceptions, albeit much rarer than that found with RotaShield.

Because RotaRix is an attenuated human virus, it raises the question of whether natural rotavirus infections are also a rare cause of intussusception. So which is rarer: intussusception caused by vaccine or intussusception caused by natural virus? The question can be answered rather easily by determining the incidence of intussusception before and after vaccine introduction. To date, as suggested by Harry Greenberg in an accompanying editorial, the incidence of intussusception has not changed appreciably. These data further support the use of rotavirus vaccines in both the developed and developing world.

Paul A. Offit, MD
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Offit reports no financial disclosures.

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