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Child mortality following standard, medium or high titre measles immunization in West Africa
K M Knudsen1, P Aaby, H Whittle
1Epidemiology Research Unit, Danish Epidemiology Science Centre, Staten Seruminstitut, Copenhagen, Denmark.
Insights
High titre measles vaccines showed increased mortality in children, particularly females, compared to standard vaccines. This finding led the World Health Organization to recommend against the use of high titre measles vaccines.
Area of Science:
- Pediatrics
- Vaccinology
- Epidemiology
Background:
- The World Health Organization (WHO) recommended high titre measles vaccines in 1989.
- Follow-up studies indicated higher mortality with medium and high titre vaccines versus standard titre vaccines, though individual trials lacked statistical significance.
Purpose of the Study:
- To investigate long-term survival rates associated with standard, medium, and high titre measles vaccines.
- To analyze combined mortality data from West African trials.
Main Methods:
- A combined analysis of West African trials (Guinea-Bissau, The Gambia, Senegal) with mortality data was conducted.
- Children received medium or high titre vaccines from 4 months, compared to controls receiving standard titre vaccine from 9 months.
- All participants were followed up to at least 3 years of age.
Main Results:
- High titre measles vaccines were associated with increased mortality (Mortality Ratio = 1.33) compared to standard titre vaccines.
- No significant difference in mortality was observed for medium titre vaccines (MR = 1.11).
- Sex-specific analysis revealed higher mortality in females (adjusted MR = 1.86) receiving high titre vaccines, but not in males (adjusted MR = 0.91).
Conclusions:
- A combined analysis indicated decreased survival linked to high titre measles vaccine use, specifically in females.
- Based on these findings and a study from Haiti, the WHO recommended discontinuing the use of high titre measles vaccine.
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.
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