In 1999, the simian-human reassortant rotavirus vaccine, RotaShield®, was removed from the United States market because it was found to be a rare cause of intussusception. At the time, the attributable risk of intussusception following vaccination was estimated to be 1 per 10,000 recipients; however, there was not clear evidence that RotaShield increased the overall rate of intussusception in the United States. After 10 months of using RotaShield, high-use states, like New York, had the same incidence of intussusception as low-use states, like Texas. The rates of intussusception in these states remained the same before and after the introduction of the vaccine. This phenomenon remained unexplained.
Seven years passed.
In 2006, the bovine-human reassortant rotavirus vaccine, RotaTeq®, was recommended for routine use in infants. Two years later, in 2008, the attenuated human rotavirus, RotaRix®, was also recommended for routine use. With widespread use of these two vaccines, the incidence of rotavirus-induced disease, dehydration, and subsequent hospitalization has been dramatically reduced. Essentially, rotavirus vaccine virus has replaced wild-type rotavirus. So, what’s happened to the rate of intussusception in the United States? Has it gone up, down, or stayed the same?
Jacqueline Tate and coworkers at the Centers for Disease Control and Prevention (CDC) recently published a study that answered this question (Tate J, Yen C, Steiner CA, Cortese MM, Parahar UD. Intussusception Rates Before and After the Introduction of Rotavirus Vaccine, Pediatrics. 2016 Sep;138(3). pii: e20161082). Tate and her coworkers found that at 8 to 11 weeks of age, a time when children were most likely to receive their first dose of rotavirus vaccine, the incidence of intussusception increased by 46 percent to 101 percent (range: 16.7 to 22.9 per 100,000). However, they also found something else that was rather surprising and that helps to explain the unusual observation made following administration of RotaShield in high- and low-use states. The CDC group found that when examining all children less than 12 months of age, the incidence of intussusception before and after the introduction of RotaTeq and RotaRix was the same.
In an accompanying editorial, Emmanuel Walter and Mary Allen Staat, researchers at Duke University School of Medicine and the University of Cincinnati College of Medicine, respectively, provide an explanation for these unusual findings (Walter EB, Staat MA. Rotavirus Vaccine and Intussusception Hospitalizations, Pediatrics. 2016 Sep;138(3):12-13). “By increasing our knowledge about intussusception,” they wrote, “we may be able to better understand the intriguing age-related findings in this study where there were no differences in the overall rate of intussusception hospitalizations for children < 12 months of age pre- and post-licensure. A possible explanation could be due to a shift of intussusception events for certain susceptible children that is induced by rotavirus vaccine and a lower rate of intussusception in older children due to the prevention of wild-type, rotavirus-associated intussusception.”
Another possible explanation is that certain children are at higher risk of intussusception than others. And although a rotavirus vaccine might trigger that first intussusception event, it is going to happen eventually, presumably by the end of the first year of life. This situation would be analogous to the relationship between receipt of the whole-cell pertussis vaccine and infantile spasms. While the pertussis vaccine could clearly trigger the first seizure, the vaccine didn’t increase the overall rate of infantile spasms because another infection-induced fever by the end of the first year of life would eventually trigger it.