Monitoring of Intussusception after RotaTeq Vaccination

Rotavirus is the leading cause of severe acute gastroenteritis (vomiting and severe diarrhea) among children worldwide. Before vaccines were used in the United States, rotavirus was responsible for 55,000 to 70,000 hospitalizations and 20 to 60 deaths each year in children younger than 5 years of age.

Intussusception is a form of bowel blockage where the bowel folds back into itself like a telescope causing an obstruction. It is most common in infants in the first year of life and occurs in approximately 1 in 2,000 young children every year. A previous rotavirus vaccine, RotaShield®, was associated with intussusception, primarily in the first week after the first dose, and was taken off the market in 1999.

Newer Rotavirus vaccines

• Two different rotavirus vaccines, both given orally, are currently licensed for use in infants in the United States. The vaccines are RotaTeq® (RV5), licensed for use in 2006 and Rotarix® (RV1), licensed for use in 2008. Before being licensed, both vaccines were tested in clinical trials and shown to be safe and effective.
• CDC's Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of infants with either three doses of RotaTeq given orally at ages 2, 4, and 6 months, or two doses of Rotarix given orally at 2 and 4 months.
• CDC and the Food and Drug Administration (FDA) conduct routine safety monitoring for new vaccines through the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD).
• Some, but not all, studies suggest that the newer rotavirus vaccines (RotaTeq and Rotarix) may possibly be associated with a small increase in the risk of intussusception. However, the benefits of these vaccines outweigh this possible risk and CDC continues to recommend routine rotavirus vaccination of U.S. infants.

Monitoring with the Vaccine Adverse Events Reporting System (VAERS). 

• VAERS receives reports of possible adverse events after immunization from health care providers, vaccine manufacturers, patients, and family members.
• From 2006 through August 2011, VAERS received 518 reports of confirmed intussusception following RotaTeq. Researchers noted a possible cluster of intussusception reports during the first week after the first dose of RotaTeq. This could mean a small increase in risk, but because of the limitations of VAERS, researchers did not draw any firm conclusions from this.
• From 2008 through August 2011, VAERS received 37 reports of confirmed intussusception following Rotarix. Because of the small number of reports, researchers were unable to determine if there are any clusters of intussusception following Rotarix.
• As of August 2010, the total number of vaccine doses that had been distributed in the U.S. since licensure was approximately 38 million for RotaTeq and approximately4.7 million for Rotarix.
• VAERS has received fewer reports of intussusception following Rotarix than RotaTeq because Rotarix has not been on the market as long and is not as commonly used in the U.S.
• VAERS serves as an early warning system for possible adverse events following immunizations, but is not used for formal studies of vaccine risk. CDC encourages healthcare providers and others to report cases of adverse events following vaccination to VAERS.

Monitoring with the Vaccine Safety Datalink (VSD)

• The VSD receives information from 10 managed care organizations across the country. After vaccines have been licensed, the VSD is the primary system that CDC uses to assess vaccine risk.
• The VSD completed the largest study to date, published in the Journal of the American Medical Association (JAMA), to assess the association of RotaTeq and intussusception. The study was conducted from May 2006 to February 2010 to look at intussusception risk among infants 4 to 34-weeks-old at participating VSD study sites. The VSD examined over 800,000 doses of RotaTeq vaccine, including more than 300,000 first doses given. The study looked for an association between the use of RotaTeq and intussusception using two comparison groups—infants who received other vaccines without RotaTeq during the same healthcare visit and the expected number of intussusception healthcare visits based on RotaTeq pre-licensure background rates (from 2001 to 2005). This study found no observed increased risk of intussusception following RotaTeq.
• A previous VSD study which included information on about 200,000 doses of RotaTeq during May 2006-May 2008 also found no increased risk of intussusception following RotaTeq. However, VSD cannot rule out a risk as low as that reported in some other studies (see below).
• Rotarix has not been used commonly by managed care organizations in the VSD, and therefore VSD has not been able to study the risk of intussusception after Rotarix.

Other studies of the newer rotavirus vaccines and intussusception

• Before being licensed, both RotaTeq and Rotarix were tested in more than 30,000 infants each and no increased risk of intussusception was found.
• After RotaTeq was licensed, an evaluation in the United States sponsored by Merck & Co., Inc., the manufacturer of RotaTeq, did not show evidence of an increased risk of intussusception. This study also could not rule out a low—level increased risk.
• A safety monitoring study of infants who received Rotarix rotavirus vaccine conducted in Mexico by the vaccine’s manufacturer, GlaxoSmithKline, suggests that Rotarix vaccine may cause intussusception in infants during the first week after they receive the first dose of the vaccine.
• During 2008-2010, CDC collaborated on a study of Rotarix in Mexico and Brazil. In Mexico, there was an increase in the risk of intussusception in the first week after the first dose of Rotarix. However, in Brazil, there was an increased risk in the first week after the second dose of Rotarix.
• In Australia, post-marketing surveillance studies found an increase in intussusception cases in the first week after vaccination with both Rotarix and RotaTeq vaccines, although these findings are based on a relatively small number of cases.
• Although some of these studies of newer rotavirus vaccines found an increased risk of intussusception, this risk was much lower than the risk found for the vaccine that was taken off the market in 1999 (Rotashield).

Risk Benefit Analysis

• Even if the newer rotavirus vaccines cause a small increase in the risk of intussusception (about 0-4 excess cases per 100,000 infants vaccinated), calculations show that the number of deaths and hospitalizations prevented by the vaccines is much higher than the number that might be caused by the vaccines.
• For example, if the newer rotavirus vaccines did cause a small increase in intussusception, each year in the U.S. they might cause 50-60 cases of intussusception but prevent more than 50,000 hospitalizations due to rotavirus disease.

Conclusions

• Some, but not all, studies suggest that the newer rotavirus vaccines (RotaTeq and Rotarix) may possibly cause a small increase in the risk of intussusception.  However, the benefits of these vaccines far outweigh this possible risk and CDC continues to recommend routine rotavirus vaccination of U.S. infants.

More Information

• Rotavirus Disease
• Rotavirus Vaccination
• Vaccine Information Statement (VIS) for Rotavirus Vaccine [PDF - 166 KB]
• Questions and Answers about Intussusception
• For Healthcare Professionals: Updated vaccine label for Rotarix
• Statement regarding Rotarix® and RotaTeq® Rotavirus vaccines and intussusception
• For Parents and Caregivers: Statement on Rotarix® vaccine: rare side effect possible

Related Scientific Articles

CDC Publications

• Centers for Disease Control and Prevention (CDC).  Prevention of Rotavirus Gastroenteritis Among Infants and Children Recommendations of the Advisory Committee on Immunization Practices (ACIP).  Cortese M M, Parashar UD.  MMWR. 2009; 58(RR02):1-25
• Centers for Disease Control and Prevention (CDC). Intussusception among recipients of rotavirus vaccine--United States, 1998-1999. MMWR 1999;48(27):577–581.
• Centers for Disease Control and Prevention (CDC).Withdrawal of rotavirus vaccine recommendation. MMWR 1999;48(43):1007.

Journal Articles

• Shui I, Baggs J, Patel M, Parashar U, Rett M, Belongia E, Hambidge S, Glanz J, Klein N, Weintraub E. Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants. JAMA 2012;307(6):598-604.
• Patel M, Vesta RichardsonLópez-Collada, Marília Mattos Bulhões, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil.  N Engl J Med 2011;364.
• Intussusception following rotavirus vaccine administration: Post-marketing surveillance in the National Immunization Program in Australia.  Buttery JP, Danchin MH, Lee KJ, et al. Vaccine. 2011;29:3061-3066.
• Belongia EA, Irving SA, Shui IM, Kulldorf M, Lewis E, Yiu R, Lieu TA, Weintraub E, Yih WK, Li R, Baggs J, Vaccine Safety Datalink Investigation Group. Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent bovine-derived rotavirus vaccine. Pediatr Inf Dis J. 2010 Jan;29(1):1-5.
• Haber P, Patel M, Inzurieta HS, Baggs J, Gagiullo P, Weintraub E, Cortese M, Braun MM, Belongia EA, Miller E, Ball R, Iskander J, Parashar UD. Postlicensure monitoring of intussusception after RotaTeq vaccination in the United States, February 1, 2006, to September 25, 2007. Pediatrics 2008 Jun;121(6):1206-12.

CDC encourages health care providers and others to report cases of adverse events following vaccination to VAERS.