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Rotavirus: No Increased Intussusception Risk in Infants Given RV5


 

FROM JAMA

After nearly 800,000 doses of the pentavalent rotavirus vaccine have been given in the United States, infants who received them showed no increase in the risk of developing intussusception during the week or month following immunization, according to a report in the Feb. 8 issue of JAMA.

Moreover, no rise in the overall rate of intussusception occurred after introduction of the RV5 (RotaTeq, Merck) vaccine in 2006, compared with the rate in prevaccine years.

However, severe rotavirus disease has shown large declines, with an estimated decrease of 55,000 rotavirus hospitalizations in 1 year alone. "Thus, the known benefits of rotavirus vaccination in the U.S. outweigh any potential low-level risk for intussusception that might exist," said Irene M. Shui, Sc.D., of the department of epidemiology, Harvard School of Public Health, Boston, and her associates.

Two recent reports from overseas have raised concerns about intussusception risk associated with the rotavirus vaccine. An Australian study found a nearly fivefold rise in risk during the week after the first dose of RV5. And another study found a fivefold increase in risk during that week in Mexico but no such increase in Brazil. Previous studies have identified the 30-day period following vaccination as another "window of risk."

"The known benefits of rotavirus vaccination in the U.S. outweigh any potential low-level risk for intussusception that might exist."

In what they described as "the largest prospective study to date to assess the association of RV5 and intussusception," Dr. Shui and her colleagues assessed postlicensure safety of the immunization using data from the Vaccine Safety Datalink population. The VSD is a collaborative project between the Centers for Disease Control and Prevention (CDC) and several managed care organizations containing detailed medical data on member-patients.

For this study, rates of intussusception were analyzed among infants aged 4-34 weeks who received the vaccine in 2006-2010, an interval in which 786,725 doses of RV5 were given. These were compared with rates of intussusception among infants who received other recommended vaccines but not RV5 during the same period (389,026 office visits) and with an estimate of the expected number of intussusception visits based on background rates in 2001-2005.

A total of 56 cases of intussusception were identified among the vaccinated infants – 30 after receiving RV5 and 26 after receiving other immunizations, a difference that was not significant. Cases of intussusception showed no increase during either the 7-day "risk window" after vaccination or the 30-day "risk window."

These results remained robust in several sensitivity analyses of the data, the researchers said (JAMA 2012;307:598-604).

In the historical comparison, 589 cases of intussusception were identified, for an overall incidence of 47 per 100,000 person-years. "No clear trend in intussusception rates was noted after the implementation of rotavirus vaccination in 2006," said Dr. Shui, who is also in the department of population medicine at Harvard University, and her associates.

Again, cases of intussusception showed no increase during either the 7-day "risk window" or the 30-day "risk window" after vaccination.

The study findings "are especially important given that rotavirus vaccine coverage in the U.S. has steadily increased since its introduction and averaged 72% in June 2009 among 5-month-olds selected from 8 different sentinel sites across the country," the investigators noted.

It remains unclear why this U.S. experience and the experience reported from Brazil differ so markedly from those reported in Australia and Mexico. "Because intussusception is a rare event, we cannot rule out a chance finding of risk in Australia and Mexico as well as the possibility of not detecting a low-level risk in the United States and Brazil," they said.

It’s also possible that some environmental or genetic factor that differs among these populations could be a contributor, such as differences in infant diet, breast-feeding practices, or maternal antibodies.

This study was supported in part by the Vaccine Safety Datalink contract with America’s Health Insurance Plan (AHIP), funded by the CDC. Dr. Shui reported ties to AHIP, and her associates reported ties to MedImmune, Merck, GlaxoSmithKline, Pfizer, Sanofi Pasteur, and Novartis.

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