Rotavirus is the leading cause of severe diarrhea and dehydration in young infants worldwide. Each year, rotavirus illness is responsible an estimated 453,000 deaths among infants around the world. Before the introduction of a rotavirus vaccine, rotavirus illness caused in an estimated 55,000 to 70,000 hospitalizations and 20-60 deaths in children under 5 years of age in the United States each year. To learn more visit Rotavirus and Rotavirus Vaccination.
Currently, there are 2 licensed vaccines that protect infants from rotavirus illness:
- Rotarix. The Food and Drug Administration (FDA) licensed this vaccine for use in the U.S. in 2008.
- RotaTeq. FDA licensed this vaccine for use in 2006.
Many studies were done before the vaccines were licensed and found that they are safe.
Vaccines continue to be monitored for safety after they are licensed. This is because pre-licensure trials are often too small to detect rare events and special populations may not be adequately represented. One of these rare events is intussusception (a bowel blockage that occurs when one portion of the bowel slides into the next, much like the pieces of a telescope; it is treated in a hospital and may require surgery). In the first year of life, the background rate of intussusception hospitalizations in the US has been estimated to be approximately 34 per 100,000 infants. Regardless of vaccination, approximately 34 per 100,000 infants will be hospitalized for intussusception in the first year of life in the US.
Since licensure, CDC and FDA have been closely checking the safety of rotavirus vaccines through 3 monitoring systems. These systems can monitor adverse events (health problems) already known to be caused by vaccines, as well as detect rare adverse events that were not identified during pre-licensure clinical trials. The 3 systems are:
- The Vaccine Adverse Event Reporting System (VAERS)–an early warning public health system that helps CDC and FDA detect possible side effects or adverse events following vaccination.
- The Vaccine Safety Datalink (VSD) –a collaboration between CDC and several health care organizations which monitors and evaluates adverse events following vaccination.
- The Clinical Immunization Safety Assessment (CISA) Network– a collaboration between CDC and medical research centers in the U.S. which conduct research on adverse events that might be caused by vaccines.
- The January 31, 2014, issue of CDC’s MMWR, “Rotavirus Vaccine Administration Errors” looked closely at reports submitted to the Vaccine Adverse Events Reporting System (VAERS) of administration of rotavirus vaccines by injection. VAERS found 39 reports of incorrect administration of rotavirus vaccines by injection and 27 reports of eye splashes. The report serves to remind clinicians that rotavirus vaccines should not be injected into a child. Vaccine providers should follow instructions in package inserts (Rotateq [PDF-459 KB] and Rotarix [PDF - 184 KB]) on proper administration using the manufacturers’ oral applicator devices (squirted gently and slowly into the child’s cheek).
- From 2006 through April 2012, VAERS received 584 reports of confirmed intussusception following RotaTeq; during this time 47 million doses of Rotateq had been distributed. The study,Intussusception After Rotavirus Vaccine Reported to US VAERS, 2006-2012, more reports of intussusception were observed during 3-6 days after the first dose of RotaTeq than at other times. This could mean a small increase in risk of intussusception, but because of the limitations of VAERS, researchers are not able to draw any firm conclusions from the reports.
- From 2008 through April 2012, VAERS received 58 reports of confirmed intussusception following Rotarix; during this time 6.1 million doses of Rotarix had been distributed. More reports of intussusception were observed in the first week after Rotarix administration than at other times. As with RotaTeq, because of the limitations of VAERS, researchers are not able to draw firm conclusions from the reports.
- 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.
- A 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. In the study, Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants , 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.
- However, VSD cannot rule out a risk as low as that reported in some other studies (see below).
- VSD data also indicate an increased risk of intussusception following dose 1 and dose 2 of Rotarix®. Over 200,000 doses of Rotarix have been given to children monitored in VSD. Based on these findings, one case of intussusception would be expected for approximately each 20,000 children, who are fully vaccinated.
- Both rotavirus vaccines continue to be monitored.
A recent study sponsored by the FDA found cases of intussusception were observed within the first 21 days of following the first dose of RotaTeq. Based upon the results, approximately 1 to 1.5 excess cases of intussusception occur per 100,000 vaccinated US infants within 21 days following the first dose of RotaTeq.
This information is now included in the Postmarketing Experience subsection [PDF - 182 KB] of the Adverse Reactions section of the prescribing information and in the information for the patient. For more information, see Update: Information on Rotateq - Labeling Revision Pertaining to Intussusception.
Further Safety Studies
Before being licensed, RotaTeq and Rotarix were each tested in about 60,000 to 70,000 infants, half of whom got the vaccine and half got a placebo. No increased risk of intussusception was found. Since then, millions of infants in the United States have gotten Rotarix and RotaTeq safely.
- After RotaTeq was licensed, an evaluation in the U.S. sponsored by Merck & Co., Inc., its manufacturer, did not show evidence of an increased risk of intussusception. This study also could not rule out a low—level increased risk.
Update: Information on RotaTeq- Labeling Revision Pertaining to Intussusception [PDF - 333 KB]
- During 2008-2010, CDC collaborated on a study (Intussusception and Rotavirus Vaccines)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.
- A safety monitoring study of infants who received Rotarix rotavirus vaccine was conducted in Mexico by the vaccine’s manufacturer, GlaxoSmithKline.
- Final results from this study showed an increased risk of intussusception in infants within 31 days, but particularly within 7 days of getting the first dose of Rotarix.
- Based on this study, it is estimated that approximately 1 to 3 out of 100,000 U.S. infants might develop intussusception within 7 days after receiving the first dose of Rotarix. So far, a risk of intussusception from Rotarix has not been documented in the U.S. However, the current data available do not allow us to exclude a possible low risk like in Mexico.
- This information is now included in the Postmarketing Experience subsection [PDF - 182 KB] of the Adverse Reactions section of the prescribing information and in the information for the patient. For more information, see Update: Information on Rotarix - Labeling Revision Pertaining to Intussusception.
- 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.
- Based on studies from these geographic areas, the level of risk of intussusception showed 1-3 excess cases per 100,000 infants.
Some, but not all, studies suggest that RotaTeq and Rotarix vaccines may possibly cause a small increase in the risk of intussusception. It is possible that an estimated 1 to 3 U.S. infants out of 100,000 might develop intussusception within 7 days of getting their first dose of rotavirus vaccine. That means 40 to 120 vaccinated U.S. infants might develop intussusception each year.
The benefits of rotavirus vaccines in preventing hospitalizations and deaths from rotavirus illness far outweigh the small possible risk of intussusception. Rotavirus vaccines prevent more than 65,000 hospitalizations from rotavirus illness. CDC continues to recommend routine rotavirus vaccination of U.S. infants.
- 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
- Updated FDA Qs&As on RotaTeq
- Mini-Sentinal study “Intussusception Risk After Rotavirus Vaccination in U.S. Infants”
- Update: Information on Rotarix - Labeling Revision Pertaining to Intussusception
- Rotarix Package Insert and Patient Information [PDF - 182 KB]
- Statement regarding Rotarix® and RotaTeq® Rotavirus vaccines and intussusception
- For Parents and Caregivers: Statement on Rotarix® vaccine: rare side effect possible
- 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, Parashar U. MMWR. 2009; 58(RR02):1-25
- Centers for Disease Control and Prevention (CDC). 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.
- 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.