Author Insights: More Reassuring Data on Rotavirus Vaccine Safety

Rotavirus vaccination with one of the new rotavirus vaccines is not associated with an increased risk of intussusception in US infants, according to a study by Irene M. Shui, ScD, of the department of population medicine at Harvard University, and her colleagues. (Image: Irene M. Shui)

A new study of the safety of the rotavirus vaccine should reassure parents that the risk of a rare but serious adverse event linked with a previous generation of the vaccine does not appear to be associated with the vaccine currently used in the United States. The study was published today in JAMA.

In 1999, the RotaShield vaccine was pulled from the US market after studies found that in the first week after vaccination, it was associated with a 30-fold increased risk in infants of intussusception, a rare but potentially life-threatening adverse event. Intussusception is a condition in which part of the intestine telescopes into itself, which can lead to a blockage in the intestine or impeded blood flow to the affected area of the intestine. Infants with this condition may experience severe pain and require timely intervention to prevent damage to the intestine.

Although US studies had not observed this adverse event associated with a new generation of rotavirus vaccines, a study in Mexico and one in Australia found a 5-fold increased risk of intussusception in the week after the first dose of the Rotarix vaccine. To further probe the safety profile of 1 of the 2 new rotavirus vaccines, RotaTeq, Irene M. Shui, ScD, of the department of population medicine at Harvard University, and her colleagues conducted a prospective safety-monitoring study of 800 000 doses of the vaccine given to US children. Shui discussed her team’s findings with news@JAMA.

news@JAMA: Why was it important to do this study?

Dr Shui: The rotavirus vaccine has made a huge impact on the incidence of rotavirus-related diarrhea in the United States and around the world. But with all vaccines that are given to almost all the child population, we have to closely monitor safety.

news@JAMA: What did you find?

Dr Shui: Our study didn’t find a statistically significant increased risk of intussusception. We could rule out a risk as high as 1.5 per 100 000, but a lower-level risk we might not be able to rule out.

news@JAMA: Why were your results different from the international studies?

Dr Shui: It’s really important in this situation to note that even though they found a potential low-level risk of intussusception, the main finding of the international studies was that the benefits of rotavirus vaccination far outweighed the very-low-level risks. Because intussusception was so rare in the international studies, a 5-fold increased risk if it occurred in the US would translate into 40 to 50 excess cases a year. This would be a very small risk compared to the 50 000 diarrhea-related hospitalizations that are prevented in the US each year by vaccination against rotavirus. In countries like Mexico, the benefits of vaccination are even greater. Our study provides further evidence supporting the conclusion that the benefits far outweigh the risk.

news@JAMA: Are there reasons why vaccination might be associated with an increased risk of intussusception in one country and not another?

Dr Shui: They studied the Rotarix vaccine and we studied RotaTeq. There could be genetic differences in the populations they studied. Or individuals in those countries could have different environmental exposures.

news@JAMA: Is there a plausible biological mechanism that might explain how a rotavirus vaccine might increase the risk of intussusception?

Dr Shui: Intussusception is very rare, and often the cause is unknown. One reason it might be possible is that it’s an oral vaccine that replicates in intestine, so it could cause an immune response that might increase the risk of intussusception. However, no clear biological mechanism has been firmly established. Other groups are studying whether rotavirus infection itself is associated with intussusception. It’s possible that while the transient risk of intussusception may increase with a rotavirus vaccination, it may provide protection in the longer term. But it needs to be studied.

news@JAMA: What message would you like parents and pediatricians to take away from your study?

Dr Shui: It’s extremely important for us to conduct vaccine safety studies to make sure parents and pediatricians have the information they need to make decisions about vaccinations. Every intervention has risks, but we need to put those risks into context. In the case of rotavirus vaccination, the benefits far outweigh the risk.

Categories: Evidence-Based Medicine, Immunization, Pediatrics