By the beginning of October 1999, 101 confirmed and presumed cases of intussusception had been reported to VAERS. The rate of reporting increased greatly after the July 1999 announcement of the temporary postponement of rotavirus vaccination. Fifty-two patients required surgery, nine required bowel resection and one patient died. Fifty-seven of these children developed intussusception within seven days of vaccine dose, and 70% developed their intussusception after the first dose. There was a clear clustering of cases from day 3 to day 8 after the dose of vaccine. In case-control studies, risk ratios of developing postvaccine intussusception varied from seven to 30, depending on the study and type of analysis. It was estimated that these data would have translated into around 1200 potential additional cases of intussusception annually in the United States if rotavirus vaccine policy had been fully implemented. Based on these data, the ACIP concluded that intussusception frequency was significantly increased in the first one to two weeks after vaccination, particularly after the first dose, and decided to withdraw its rotavirus vaccine recommendations. The American Academy of Pediatrics also withdrew its recommendations. On October 15, 1999, Wyeth- Lederle Vaccines announced that it was withdrawing the Rotashield vaccine from the market and requested the immediate return of all distributed doses.
These events demonstrate very clearly that postmarketing surveillance is an essential component of vaccine program implementation. Data obtained before licensure did not reveal an excess risk of intussusception following vaccination with rota- virus vaccine. However, postlicensure surveillance showed quite convincingly that rotavirus vaccine administration was associated with an increased risk of intussusception, particularly in the week following administration of the first dose. These events also demonstrate the power of active surveillance systems: Preliminary data from active systems in Minnesota and the Northern California Kaiser Permanente Health Maintenance Organization suggested an increased risk of intussusception following RRV-TV. Further accumulation and analysis of the data both from the VAERS and from the various postmarketing surveillance systems led the expert committees to withdraw their recommendations concerning the use of this vaccine.
In Canada, the vaccine had not yet been approved for use by the Therapeutic Products Program when data suggesting that the vaccine might be associated with an increased risk of intussusception became known. This vaccine is not expected to be approved in Canada, at least in the foreseeable future. However, other vaccines have recently been approved for use, for example, varicella, and others should soon be approved for use (conjugate pneumococcal and meningococcal). The events surrounding the introduction of the rotavirus vaccine show clearly that Canada needs to have a strong postmarketing surveillance system in place, particularly for newly introduced vaccines.
What systems exist in Canada? The Immunization Monitoring Program ACTive (IMPACT), an active surveillance system for severe side effects following immunization, is a central component of the postmarketing surveillance system in Canada. This program is operated under contract by the Canadian Paediatric Society, with funds provided by Health Canada, for the primary purpose of postmarketing surveillance of vaccine safety. The surveillance system is based upon 11 pediatric referral centres (soon to be 12) extending from St John’s, Newfoundland to Vancouver, British Columbia. These centres comprise over 2000 paediatric beds and admit over 90,000 children annually, encompassing about 80% of paediatric admissions to Canadian academic centres. The investigators are infectious diseases specialists who act as volunteers. Each centre employs a nurse monitor who carries out the routine active surveillance activities in each centre. In addition to IMPACT, Health Canada operates a passive surveillance system similar to VAERS in the United States, which collects data on adverse reactions following immunizations reported by physicians and public health units. Finally, Health Canada has set up the Advisory Committee on Causality Assessment, whose task is to evaluate the role of immunization as the cause of reactions reported either by IMPACT or through other sources. These systems are complimentary to one another and form a network of surveillance activities that ensure adequate safety monitoring of licensed vaccines in Canada. The recent rotavirus vaccine story illustrates the usefulness of these activities, and should convince Health Canada that continued funding of IMPACT and of the other components of the vaccine safety monitoring program is of great importance to the health of Canadians.
Efficient treatment has got less costly: find at best online pharmacy