Background: The World Health Organization (WHO) recommended the use of high titre measles vaccine in 1989. Subsequent long term follow-up of several trials yielded results suggesting higher mortality among children inoculated with medium and high titre vaccines compared to standard titre vaccines, although none of the individual trials found significant differences in mortality.
Methods: Long term survival after standard, medium and high titre measles vaccines has been investigated in a combined analysis of all West African trials with mortality data. In trials from Guinea-Bissau, The Gambia and Senegal, children received medium or high titre vaccines from 4 months of age and were compared to control groups recruited at the same time later receiving standard titre vaccine from 9 months of age. All children were followed up to at least 3 years old.
Results: Combining trials of high titre vaccines showed higher mortality among the high titre group compared to the standard group: mortality ratio (MR) = 1.33 (95% CI : 1.02-1. 73). Mortality among recipients of medium titre vaccines was not different from that in the standard vaccine group, MR = 1.11 (95% CI: 0.54-2.27). In a combined analysis by sex, the adjusted mortality ratios comparing high titre vaccine with standard vaccine were 1.86 (95% CI : 1.28-2.70) for females and 0.91 (95% CI : 0.61-1.35) for males. The trials were not designed to study long term mortality. Adjustments for several possible sources of bias did not alter the results.
Conclusions: The combined analysis showed a decreased survival related to high titre measles vaccine compared with standard titre vaccines, though solely among females. As a result of these studies from West Africa and a study from Haiti, WHO has recommended that high titre measles vaccine no longer be used.
PIP: A prospective survey of the use of high and medium-titre measles vaccine in Guinea-Bissau, the Gambia, and Senegal indicated that this regimen is associated with higher long-term child mortality than the standard titre vaccine. Children enrolled in trials in these three countries received medium or high-titre vaccines at three months of age and survival data were compared to findings from controls who received the standard titre at nine months of age. There were 339 deaths among the 3073 children (11,129 child-years) followed for up to three years of age. Combination of all West African data for medium and high-titre vaccines yielded a mortality rate of 1.21 (95% confidence interval, 0.89-1.63). The excess mortality was statistically significant at the p 0.05 level only when high-titre vaccine was compared to the standard regimen (1.33; 95% confidence interval, 1.02-1.73). No difference in mortality was found between medium or high-titre recipients and control children who had not yet received any vaccine. The excess mortality in the high-titre groups was restricted to females. There was no interaction between age and vaccine type. As a result of these findings, the World Health Organization reversed its 1989 recommendation for use of high-titre measles vaccine. Urged are community studies of measles-related morbidity and mortality that investigate the gender differential identified in this survey.