To improve comparability of vaccine safety data, The Brighton Collaboration Intussusception Working Group has developed a case definition and guidelines for intussusception, applicable in study settings with different availability of resources, in health care settings that differ by availability of and access to health care, and in different geographic regions.
This definition was developed on the basis of a report prepared for the Steering Committee on Diarrhoeal Disease Vaccines, Vaccine Development, World Health Organization (WHO), Geneva [1] and through group consensus of The Brighton Collaboration Intussusception Working Group. The WHO report is a comprehensive description of the incidence, clinical presentation, and management of acute intussusception in infants and children; it is based on a review of the published literature from 70 developing and developed countries [1]. The phase 1 search of Medline and PubMed resulted in the identification of >3200 references published from 1966 through February 2001. The search was then limited to reflect the epidemiology and clinical presentation of intussusception in children ages 0–18 years. This search strategy resulted in the identification of 330 publications for review, of which 269 publications were selected and summarized in the WHO report.
1.1. Background on intussusception and rotavirus disease
Intussusception is the most common cause of acute intestinal obstruction in infants and young children. Intussusception occurs when one segment of intestine invaginates in a segment of distal intestine. As the intussusceptum is propagated distally along the intestine it draws with it the blood vessels. Initially, compression of the blood vessels causes venous congestion and bowel-wall edema. As the obstruction progresses, the arterial supply may be compromised, resulting in intestinal ischemia. If the intussusception is not recognized and reduced, intestinal infarction and perforation may occur. Untreated, intussusception is a potentially life-threatening condition; however, diagnosis and non-surgical reduction has resulted in a significant reduction in the morbidity and mortality previously associated with this condition. In many developing countries where access to pediatric radiological and surgical expertise is limited, mortality remains high (>20%) [1].
Recent attention to this vaccine adverse event that can occur postimmunization stems from US experience with a rotavirus vaccine. In 1999, use of the rhesus tetravalent rotavirus vaccine (RRV-TV, Rotashield®, Wyeth Lederle Laboratories, Philadelphia) was discontinued because of the reported temporal association between the development of intussusception and receipt of the vaccine. The attributable risk of developing intussusception was later estimated to be between 1 in 4670 and 1 in 9474 infants vaccinated [2], [3], [4], [5]. The study design of subsequent clinical trials of other oral vaccines has been based on those estimates.
