Vaccine Information

Entry last updated: May 28, 2004

- Understanding the Disease
- Available Vaccines
- History of the Vaccine
- Who Should and Should Not Receive the Vaccine
- Dose Schedule
- Effectiveness of the Vaccine
- Known Side Effects
- Related Issues
- Key References and Sources of Additional Information

Understanding the Disease

Rotavirus is an intestinal virus that infects virtually all children by three years of age. It is the most common cause of diarrhea in children, including hospital-acquired diarrhea, and childcare center outbreaks are common. The disease usually lasts a week or longer and can cause persistent infection in immunocompromised people. Most rotavirus infections are mild, but about 1 in 50 cases develop severe dehydration. Each year in the U.S., rotavirus results in the hospitalization of 50,000 infants younger than two years of age. In developing countries, rotavirus leads to an estimated 480,000 to 640,000 deaths each year.

Available Vaccines

N/A

History of the Vaccine

RotaShield®, a reassortant rhesus-human rotavirus vaccine tetravalent (RRV-TV), was licensed by the Food and Drug Administration (FDA) in August 1998. However, in July 1999, after approximately 1 million children had been immunized with the vaccine, the CDC recommended that use of the rotavirus vaccine be temporarily suspended. The CDC was concerned that the vaccine might be causing a serious bowel disease called "intussusception," since 15 cases of this condition had been reported in children who had received the vaccine. The vaccine was voluntarily withdrawn from the market by the manufacturer in October 1999.

Subsequent studies reported that an infant's risk of developing intussusception indeed increased after receiving RotaShield®, especially within one or two weeks after immunization. In one study, the records of 463,277 infants, 56,253 of whom had received one or more doses of RRV-TV, were reviewed. Investigators calculated that the risk of intussusception attributable to the vaccine was 1 per 11,073 infants vaccinated, three times higher than for the unvaccinated children in this study. The risk of intussusception was greatest three to seven days after the first dose (Kramarz et al. 2001). Another study of infant medical records examined 429 infants with intussusception and 1,763 healthy children matched by age. While only 12.8% of the healthy children had been vaccinated, 17.2% of children with intussusception had received RotaShield®. This study estimated that if a national rotavirus vaccine program were re-implemented, 1 case of intussusception out of 4,670 to 9,474 cases could be attributed to the vaccine (Murphy et al. 2001). However, in another study that reviewed the medial records of children hospitalized for intussusception in New York, researchers found that only a few more cases of intussusception were documented during the year the vaccine was administered, than in the years before RotaShield® was introduced (Chang et al. 2001).

Those who received the rotavirus vaccine in 1998 and 1999 are not at continuing risk of developing intussusception.

Who Should and Should Not Receive this Vaccine

No rotavirus vaccine is recommended for use at this time, though vaccine trials are in progress.

Dose Schedule

N/A

Effectiveness of the Vaccine

N/A

Known Side Effects

Before the vaccine was voluntarily withdrawn from the market, the relative risk of RRV-TV associated intussusception was calculated to be almost three times higher than in unvaccinated infants. No deaths have been attributed to side effects of the vaccine, although some infants required surgical intervention to alleviate the intussusception.

Related Issues

There are several mechanisms in place to assure that licensed vaccines are safe. Prelicensure clinical studies are the first step, but are limited by a relatively small number of individuals in the study groups. After licensure, vaccines are monitored for safety by the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink. The reports to VAERS served to alert the CDC to the probability that there is an increased risk for intussusception among infants receiving the rotavirus vaccine.

Although a recent study reported that RRV-TV caused few additional cases of intussusception (see History of the Vaccine), it still seems that the vaccine has some connection to intussusception, especially since the intussusception cases observed during the year RotaShield® was on the market more often occurred in the early weeks following vaccination, instead of throughout the year. Further studies need to be done in states with large populations of children who received the rotavirus vaccine. If the vaccine is found to have only a weak link to intussusception, scientists may conclude that the vaccine's benefits outweigh its risks, especially in developing countries where many children die from rotavirus diarrhea.

Trials examining several other rotavirus vaccines are in progress.

Key References and Sources of Additional Information

• American Academy of Pediatrics (AAP), Committee on Infectious Diseases. (1999). Possible association of intussusception with rotavirus vaccination. Pediatrics, 104(3), 575.
• AAP, Committee on Infectious Diseases. (2003). Rotavirus. In LK Pickering (Ed.), Red Book: Report of the Committee on Infectious Diseases (26th ed., pp. 534-536). Elk Grove Village, IL: Author.
• Centers for Disease Control and Prevention. (1999). Intussusception among recipients of rotavirus vaccine--United States, 1998-1999. Morbidity and Mortality Weekly Report, 48 (27), 577-581.
• Chang HG, Smith PF, Ackelsberg J, Morse DL, and Glass RI. (2001). Intussusception, rotavirus diarrhea, and rotavirus vaccine use among children in New York state. Pediatrics, 108(1), 54-60.
• Offit PA, Glass RI, Clark HF, and Ward RL (2004). Rotavirus vaccines. In Plotkin and Orenstein (Eds.), Vaccines (4th ed.) (pp. 1327-1345). Philadelphia: W.B. Saunders Company.
• Cohen J. (2001). Rethinking a vaccine's risk. Science, 293(5535), 1576-1577.
• Hall AJ. (2001). Ecological studies and debate on rotavirus vaccine and intussusception. Lancet, 358(9289), 1197-1198.
• Kombo LA, Gerber MA, Pickering LA, Atreya CD, and Breiman RF. (2001). Intussusception, infection, and immunization: Summary of a workshop on rotavirus. Pediatrics, 108(2), e37.
• Kramarz P, France EK, Destefano F, Black SB, Shinefield H, Ward JI, Chang EJ, Chen RT, Shatin D, Hill J, Lieu T, and Ogren JM. (2001). Population-based study of rotavirus vaccination and intussusception. Pediatric Infectious Disease Journal, 20(4), 410-416.
• McPhillips HA, Davis RL, Marcuse RL, and Taylor JA. (2001). The rotavirus vaccine's withdrawal and physician's trust in vaccine safety mechanisms. Archives of Pediatrics and Adolescent Medicine, 155, 1051-1056.
• Murphy TV, Gargiullo PM, Massoudi MS, et al. (2001). Intussusception among infants given an oral rotavirus vaccine. New England Journal of Medicine, 344(8), 564-572.
• Rennels MB. (2000). The rotavirus vaccine story: A clinical investigator's view. Pediatrics, 106(1), 123-125.
• Simonsen I, Morens DM, Elixhauser A, Gerber M, Van Raden M, Blackwelder WC. (2001). Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception. Lancet, 358(9289), 1224-1229.

Also see our image gallery of diseases.