title: The optimal age of measles immunisation in low-income countries: a secondary analysis of the assumptions underlying the current policy.
abstract: OBJECTIVE
  The current policy of measles vaccination at 9 months of age was decided in the mid-1970s. The policy was not tested for impact on child survival but was based on studies of seroconversion after measles vaccination at different ages. The authors examined the empirical evidence for the six underlying assumptions.
  
  
  METHODS
  Secondary analysis.
  
  
  METHODS
  These assumptions have not been research issues. Hence, the authors examined case reports to assess the empirical evidence for the original assumptions. The authors used existing reviews, and in December 2011, the authors made a PubMed search for relevant papers. The title and abstract of papers in English, French, Portuguese, Spanish, German and Scandinavian languages were assessed to ascertain whether the paper was potentially relevant. Based on cumulative measles incidence figures, the authors calculated how many measles cases had been prevented assuming everybody was vaccinated at a specific age, how many 'vaccine failures' would occur after the age of vaccination and how many cases would occur before the specific age of vaccination. In the combined analyses of several studies, the authors used the Mantel-Haenszel weighted RR stratifying for study or age groups to estimate common trends.
  
  
  METHODS
  African community studies of measles infection.
  
  
  METHODS
  Consistency between assumptions and empirical evidence and the predicted effect on mortality.
  
  
  RESULTS
  In retrospect, the major assumptions were based on false premises. First, in the single study examining this point, seronegative vaccinated children had considerable protection against measles infection. Second, in 18 community studies, vaccinated measles cases ('vaccine failures') had threefold lower case death than unvaccinated cases. Third, in 24 community studies, infants had twofold higher case death than older measles cases. Fourth, the only study examining the assumption that 'vaccine failures' lead to lack of confidence found the opposite because vaccinated children had milder measles infection. Fifth, a one-dose policy was recommended. However, the two randomised trials of early two-dose measles vaccination compared with one-dose vaccination found significantly reduced mortality until 3 years of age. Thus, current evidence suggests that the optimal age for a single dose of measles vaccine should have been 6 or 7 months resulting in fewer severe unvaccinated cases among infants but more mild 'vaccine failures' among older children. Furthermore, the two-dose trials indicate that measles vaccine reduces mortality from other causes than measles infection.
  
  
  CONCLUSIONS
  Many lives may have been lost by not determining the optimal age of measles vaccination. Since seroconversion continues to be the basis for policy, the current recommendation is to increase the age of measles vaccination to 12 months in countries with limited measles transmission. This policy may lead to an increase in child mortality.
authors: Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
authors: Peter
authors: P
authors: Aaby
authors: Cesário L
authors: CL
authors: Martins
authors: May-Lill
authors: ML
authors: Garly
authors: Amabelia
authors: A
authors: Rodrigues
authors: Christine S
authors: CS
authors: Benn
authors: Hilton
authors: H
authors: Whittle