Article Text

The optimal age of measles immunisation in low-income countries: a secondary analysis of the assumptions underlying the current policy
  1. Peter Aaby1,2,
  2. Cesário L Martins1,
  3. May-Lill Garly1,
  4. Amabelia Rodrigues1,
  5. Christine S Benn1,2,
  6. Hilton Whittle3
  1. 1Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau
  2. 2Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen S, Denmark
  3. 3London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr Peter Aaby; p.aaby{at}bandim.org

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.

Design Secondary analysis.

Data sources and 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.

Setting and participants African community studies of measles infection.

Primary and secondary outcomes 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.

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Footnotes

  • Independence The funders had no role in the study design, data collection, data analysis, data interpretation, decision to publish or preparation of the manuscript.

  • To cite: Aaby P, Martins CL, Garly M-L, et al. The optimal age of measles immunisation in low-income countries: a secondary analysis of the assumptions underlying the current policy. BMJ Open 2012;2:e000761. doi:10.1136/bmjopen-2011-000761

  • Contributors PA, CB and HW planned the present study. The first of many drafts was written by PA and all authors contributed critically to the refinement of the arguments and the final version of the paper. All authors approved the final version of the paper. PA will act as guarantor of the study.

  • Funding The Bandim Health Project received support from the DANIDA and the Danish National Research Foundation. PA holds a research professorship grant from the Novo Nordisk Foundation. CSB holds an ERC Starting Grant (ERC-StG-243149). We received no funding specifically for the present study.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.

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