Analysis of mortality following a mass immunization campaign with serogroup C meningococcal conjugate vaccine: Methodological difficulties and imperfect solutions

BackgroundIn 2001, a mass immunization campaign was implemented in the province of Quebec, Canada, using a new serogroup C meningococcal conjugate vaccine (C-MCV).ObjectiveTo describe methodological difficulties in the investigation of the mortality risk associated with administration of C-MCV using large administrative databases, and to present possible solutions.Materials and methodsThe study population included approximately 1.9 million residents in Quebec aged 2 months to 20 years. Death certificates in 2001 and 2002 were linked with vaccination registry data. Age-specific and age-adjusted mortality rates were compared between 1.4 million persons who had been vaccinated with C-MCV, and a mixed control group including 0.5 million individuals. In the C-MCV group, deaths within the 6-month period after vaccination were analyzed to identify any clustering, using the exponentially weighted moving average technique.ResultsAll cause mortality was more than three times higher in the control group than in the C-MCV group, and the excess was seen for all major categories of causes. Two time-clusters were detected in the C-MCV group, but none of them appeared to be plausibly related to the administration of C-MCV. In the C-MCV group, there was no death caused by meningococcal disease, Guillain–Barré syndrome, anaphylactic shock, or a complication of vaccination.ConclusionData concerning the safety of C-MCV are reassuring. However, the very strong “healthy vaccinee” effect limits our ability to detect any excess mortality risk in the vaccinated cohort and there is no perfect method to overcome this problem.