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Wkly Epidemiol Rec. 1992 Nov 27;67(48):357-61.

Expanded programme on immunization (EPI). Safety of high titre measles vaccines.

[Article in English, French]
[No authors listed]


Unexpected results suggesting decreased survival when compared with standard titre vaccine administered at 9 months of age have been found in some field studies evaluating the performance of high titre measles vaccine. Analytical difficulties have arisen because the studies were not specifically designed to measure survival. Nonetheless, careful analysis of the results from all of the high titre vaccine trials showed decreased survival of high titre vaccine recipients, in areas with high background mortality rates, compared with recipients of standard measles vaccines at 9 months. No systematic biases could be found in the studies to explain these differences. Statistical analysis of these data suggested that the findings were unlikely to be attributable to chance alone. The panel recommended that high titre measles vaccine derived from the original Edmonston measles vaccine isolate should no longer be recommended for use in immunization programmes. Further post-licensure field studies of new measles vaccines should take into account the results of these studies. Additional detailed epidemiological studies in populations that have received high titre vaccines and their controls were encouraged.


A WHO group recommended in October 1989 that health workers in countries where measles is a significant cause of death for infants under 9 months old use the high titer Edmonston-Zagreb (EZ) measles vaccine for 6-month old infants, or as soon as possible thereafter, instead of the standard titer vaccine at 9 months. In 1990, reports from Senegal and Guinea Bissau showed that infants receiving the high titer measles vaccine before 9 months old were dying at a faster rate than those who received the standard titer vaccine at 9 months of age. These reports precipitated a WHO consultative meeting in February 1991 where participants reviewed the data in question. They considered the data to be inconclusive and recommended that countries continue to use the 1989 guidelines. Other issues later emerged causing WHO to reconvene the working group to reexamine all the safety immunogenicity, and efficacy data of the high titer measles vaccines in infants under 9 months old. Participants at the October 1991 meeting found that a link between the high titer measles vaccine and decreased survival was consistent in the 4 studies with high background infant mortality (relative risk = 1.25; p = .05), but such an association did not exist in the countries with low background infant mortality, suggesting that the vaccine had a multiplicative effect. In 3 of the 4 studies, girls were more likely to experience greater reduced survival than boys (p .02). In all 4 studies, the dose of the vaccine was a leading factor linked to reduced survival. The EZ vaccine was more immunogenic than the Schwartz vaccine at 4-6 months, particularly when maternal antibodies were present. The participants examined a mathematical model based on the submitted data and it indicated that the high titer vaccine would provide only a marginal benefit. They concluded that immunization programs should no longer use the EZ vaccine and that no more field trials of this vaccine should occur.

[Indexed for MEDLINE]

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