Sudden and unexpected deaths after the administration of hexavalent vaccines (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b): is there a signal?
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Deaths in temporal association with vaccination of hexavalent vaccines have been recently reported. The objective of this paper is to assess whether these temporal associations can be attributed to chance. Standardised mortality ratios (SMR) for deaths within 1 to 28 days after administration of either of the two hexavalent vaccines in the 1st and 2nd year of life were determined using the respective annual rates for sudden unexpected deaths (SUDs) from the national vital statistics. The distribution of SUD cases and the vaccination uptake by month were estimated from surveys and sales figures for the individual vaccines. Sensitivity analyses were performed to account for limitations in the data sources. For one of the vaccines, Vaccine B, all SMRs were well below one. For the other, Vaccine A, SMRs exceeded one insignificantly on the 1st day after vaccination in the 1st year of life. In the 2nd year of life, however, the SMRs for SUD cases within 1 day of vaccination with vaccine A were 31.3 (95% CI 3.8–113.1; two cases observed; 0.06 cases expected) and 23.5 (95% CI 4.8–68,6) for within 2 days after vaccination (three cases observed; 0.13 cases expected). Extensive sensitivity analyses could not attribute these findings to limitations of the data sources. Conclusion: These findings based on spontaneous reporting do not prove a causal relationship between vaccination and sudden unexpected deaths. However, they constitute a signal for one of the two hexavalent vaccines which should prompt intensified surveillance for unexpected deaths after vaccination.
KeywordsSafety Standardised mortality ratios Sudden unexpected death Vaccines
diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b
Paul Ehrlich Institute
standardised mortality ratio
sudden unexplained death
The reports for the SUD cases in temporal association with the administration of hexavalent vaccines were made available to us by Dr. Brigitte Keller-Stanislawski from the PEI, Langen, Germany. This work was supported by a grant from the PEI.
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