Safety of meningococcal B vaccines
GACVS was presented with data relating to the safety of outer membrane-vesicle based meningococcal B vaccines based on their usage in Cuba, France, New Zealand and Norway. It noted in particular the very carefully designed safety monitoring programme that had been set up in New Zealand to ascertain possible serious AEFI following the vaccination of around 1 million people aged <20 years from July 2004 onwards, including 200 000 vaccinees monitored through linkages to hospital admission records. The various surveillance methods used to detect potentially serious AEFI consistently found no evidence of such effects attributable to vaccination.
The committee also appraised the evidence of vaccine safety derived from studies in Norway, where the vaccine formulation originated. Although the vaccine had never been introduced into routine use in Norway, because of waning of the meningococcal disease epidemic, there had been extensive use of the vaccine in trials among teenagers and young adults. In some age cohorts, up to 40% of the population had been vaccinated. Despite media reports on possible increased risk of myalgic encephalomyelitis (ME), also called chronic fatigue syndrome, the results from these trials provided no specific causes for concern with respect to serious AEFI. The committee noted that a case–control study had been conducted of ME in Norway, involving all 273 cases in whom ME had been diagnosed at the 2 major referral hospitals in Norway, in the 1972–1977 birth cohorts, of whom 201 participated in the case-control study. This study had been prompted by media reports of a possible increased risk of ME associated with the use of meningococcal B vaccine. A random sample of 889 controls was drawn from the general population, of whom 389 participated in the study. About 45% of both case and control groups had received meningococcal vaccine, and the study thus provided no evidence of an increased risk of ME associated with vaccination (relative risk = 1.06, 95% confidence interval, 0.67–1.66).
The Norwegian-type vaccine had also been used in France in a 3-dose schedule to vaccinate around 2700 children aged 12 months to 5 years in 1 administrative region (Department of Seine-Maritime), following an increased incidence of meningococcal disease in that department. It was noted that there had been little prior experience of use of the vaccine in young children in the Norwegian trials. Parents of vaccinees were sent a questionnaire to ascertain possible adverse events. A high proportion of these were returned and 9 serious adverse events were identified, 8 of which were purpura (1 idiopathic thrombocytopenic purpura (ITP), 3 Henoch-Schönlein purpura, 4 febrile purpura) and 7 of which occurred after the second vaccine dose. All of these 7 had received a third dose of vaccine with no reported ill effect. The case of ITP, considered unlikely to be causally related to vaccination, was the only one not to have recovered. The significance of the cases of purpura following vaccination was difficult to evaluate because of the absence of data on background rates of purpura in the general population.
The most widely used meningococcal B vaccine has been that produced in Cuba. Over 55 million doses have been used in Cuba and other Latin American countries over the past 20 years. The committee was presented with data from the original Phase 3 study involving over 100 000 people, in which no evidence of an excess of serious AEFI had been identified in the vaccinated group. Also, no evidence of an excess of serious AEFI had been reported from the extensive use of the vaccine in vaccination programmes in Cuba and other Latin American countries, but the sensitivity of monitoring of serious AEFI with these uses of the vaccine was unclear.
GACVS noted that several new meningococcal vaccines were being developed, at least one of which was closely related to the vaccine used in New Zealand. While it would be important to set up careful safety studies of these new vaccines, the committee was reassured by the absence of evidence of serious AEFI of existing meningococcal B vaccination, which had been assessed particularly carefully in studies in New Zealand and Norway.