On July 16, 1999, CDC recommended that health-care providers suspend use of the licensed rhesus-human rotavirus reassortant-tetravalent vaccine (RRV-TV) (RotaShield®, Wyeth Laboratories, Inc., Marietta, Pennsylvania) in response to 15 cases of intussusception (i.e., a bowel obstruction in which one segment of bowel becomes enfolded within another segment) among infants who received RRV-TV. The Vaccine Adverse Event Reporting System (VAERS) monitored for adverse events following licensure of RRV-TV on August 31, 1999. After the recommendation to suspend use of the vaccine, no additional cases were reported. This report describes the surveillance activities used to identify this vaccine adverse event, the emergency response, and follow-up investigations. Suspension of RRV-TV after the initial cases of intussusception parallels the removal of the Broad Street pump handle in response to John Snow's epidemiologic studies; both were decisive, life-saving public health actions.
VAERS, operated by CDC and the Food and Drug Administration (FDA), is a national passive surveillance system that monitors the safety of vaccines. Health-care providers, consumers, and vaccine manufacturers are encouraged to report adverse events involving all U.S.-licensed vaccines. During 1998-1999, CDC and FDA monitored VAERS for reports of intussusception and other severe gastrointestinal events among RRV-TV recipients. As a requirement for FDA licensure, the vaccine manufacturer funded a postlicensure phase IV trial of RRV-TV at Northern California Kaiser Permanente (NCKP) to monitor possible adverse events. Intussusception had been observed at low rates in prelicensure clinical trials, but a causal association with the vaccine was not proven; this information and a request for reporting to VAERS were included in the vaccine product label and recommendations of the Advisory Committee on Immunization Practices (ACIP).
During December 18, 1998-June 2, 1999, a total of 10 cases of intussusception were reported to VAERS (Figure 1). Four cases of intussusception involving other vaccines had been reported to VAERS during the preceding 8 years.[2,5] The cases appeared to be nonrandom in distribution; among the majority of infants, intussusception occurred after receiving the first dose of RRV-TV and within 1 week after receiving any dose. The temporal clustering after receipt of RRV-TV suggested a causal relationship. These early findings prompted CDC to request data from NCKP and initiate two validation studies, a 19-state case-control study and case-series analysis, and a cohort study in 10 managed care organizations. CDC alerted ACIP on June 17, 1999.
By July 6, 1999, the number of cases reported to VAERS had increased to 15, a higher number than expected, accounting for likely underreporting, available baseline estimates of intussusception, and the estimated number of doses of RRV-TV distributed; ( Table ). Preliminary data from both NCKP and from Minnesota, a state participating in one of the CDC studies, suggested a similar elevated risk for intussusception within the first week after RRV-TV vaccination. On July 16, 1999, in an MMWR report, CDC recommended temporarily suspending use of RRV-TV, pending the results of CDC studies that subsequently confirmed the initial observation that the greatest risk for intussusception was within 3-7 days after the first dose of RRV-TV.[4,6]
By December 31, 1999, a total of 112 cases of intussusception with illness onset before August 15, 1999, had been reported to VAERS (Figure 2) 1 month after the suspension of the rotavirus vaccination program. Ninety-five cases among infants were confirmed by review of medical records, and three were confirmed by primary-care providers. No cases of RRV-TV-associated intussusception occurred in infants and children vaccinated after July 16, 1999. When the VAERS findings were confirmed by more definitive studies,[4,6] the manufacturer voluntarily recalled the vaccine, and the ACIP recommendations were withdrawn in October 1999.
Reported by: Food and Drug Administration. J Iskander, MD, P Haber, MPH, TV Murphy, RT Chen, MD, Epidemiology and Surveillance Div, National Immunization Program; M Sabin, PhD, EIS Officer, CDC.
Morbidity & Mortality Weekly Report. 2004;53(34) © 2004 Centers for Disease Control and Prevention (CDC)
Cite this: Suspension of Rotavirus Vaccine After Reports of Intussusception ---United States, 1999 - Medscape - Sep 01, 2004.