Safety of hexavalent vaccines - June 2005
Extract from report of GACVS meeting of 9-10 June 2005, published in the WHO Weekly Epidemiological Record on 15 July 2005
In December 2004, GACVS reviewed the available data concerning a purported association between sudden unexplained death (SUD) and hexavalent diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, poliovirus and hepatitis B (DTaP-Hib-IPV-HepB) combination vaccines. The Committee concluded at that time that the evidence did not support a causal association between hexavalent vaccines and SUD, but recommended that additional studies be conducted to extend the observation period to the first 2 years of life.5
There have been no additional signals from Germany, where the first reports originated. The results from a population-based Italian study on sudden infant death (SID) and SUD cases in 5 birth cohorts (between 1999 and 2003) have produced no evidence of an increased risk of SID or SUD in the 48 hours following any immunization in the first year of life. Neither has any increased risk been observed related to the number of vaccine doses administered.
In Italy, between 1990 and 2001, infant mortality from any cause fell from 8.1 to 4.8 per 1000 births. Between 1991 and 2002, infant mortality from SID decreased in Germany, from 1.5 to 0.6 per 1000 births. This happened notwithstanding the introduction in the 2 countries of several new vaccines in the infant schedule, and increased immunization coverage in both countries.
GACVS concluded that these data are inconsistent with any association between hexavalent vaccines and SID or SUD.
5 See No. 1, 2005, p.6.
Safety of hexavalent vaccines - December 2004
Extract from report of GACVS meeting of 2-3 December 2004, published in the WHO Weekly Epidemiological Record on 7 January 2005
Two hexavalent diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type B, poliovirus and hepatitis B (DTaP-Hib-IPV-HepB) combination vaccines were licensed and introduced in Europe in 2000. They have contributed to a significant increase in the infant vaccine coverage against hepatitis B in Austria, Germany, Italy and Switzerland. In late 2000, the description of a cluster of 3 cases of sudden unexplained death (SUD) in close temporal association with the administration of a hexavalent vaccine in southern Germany raised concern. The German and European licensing authorities convened several expert meetings to review available data on all identified cases of SUD following immunization with each of the two available hexavalent vaccines.
A retrospective analysis was performed, using available data from various sources, to compare the calculated number of expected cases with that of observed cases of SUD following hexavalent immunization within a 3-year period. This analysis concluded that there was no association between SUD and hexavalent vaccination in the first year of life. However, the observed number of 3 cases of SUD within 48 hours of administration of a booster dose of one particular brand of hexavalent vaccine exceeded the number of cases expected (0-1) in 700 000 children given a booster dose during the 3-year period analysed. Consequently, the European Medicines Agency's scientific committee, the Committee for Proprietary Medicinal Products (CPMP), concluded in December 2003 that this temporal relationship constituted a possible signal for this hexavalent vaccine, despite the limitations of the data sources and the methods used to calculate the expected numbers. The CPMP could find no plausible biological cause for such an association and recommended further studies to establish whether or not there is a risk.
The retrospective analysis was presented to GACVS, together with additional information. On the basis of all the available data, GACVS concluded that there is no evidence to support a causal association between the administration of hexavalent vaccines and SUD. In response to the potential signal observed in the second year of life, the Committee encouraged studies to be conducted that are designed to provide more powerful evidence on the presence or absence of an association. GACVS was informed that a retrospective analysis of the possible association of any deaths within the first 2 years of life with vaccination is currently being conducted in Italy. The Committee will review the results of the study at its next meeting in mid-2005.