The mortality effects of disregarding the strategy to save doses of measles vaccine: a cluster-randomised trial in Guinea-Bissau.

introductionMeasles vaccine (MV) may improve health beyond measles protection. To avoid wastage from multi-dose vials, children in Guinea-Bissau are only measles vaccinated when aged 9-11 months and when six or more children are present. We assessed health impacts of providing MV to all measles-unvaccinated children 9-35 months.

methodsWe cluster-randomised 182 village clusters under demographic surveillance in rural Guinea-Bissau to an 'MV-for-all-policy' arm where we offered MV regardless of age and number of children present at our bi-annual village visits, or a 'Restrictive-MV-policy' arm where we followed national policy. Measles-unvaccinated children aged 9-35 months were eligible for enrolment and followed to 5 years of age. In intention-to-treat analyses, we compared mortality using Cox regression analyses with age as underlying timescale. The primary analysis was for children aged 12-35 months at eligibility assessment. Interactions with several background factors were explored.

resultsBetween 2011 and 2016, we followed 2778 children in the primary analysis. MV coverage by 3 years was 97% among children eligible for enrolment under the MV-for-all-policy, and 48% under the Restrictive-MV-policy. Mortality was 59% lower than anticipated and did not differ by trial arm (MV-for-all-policy: 45/1405: Restrictive-MV-policy: 44/1373; HR: 0.95 (95% CI 0.64 to 1.43)). The effect of MV-for-all changed over time: The HR was 0.53 (95% CI 0.27 to 1.07) during the first 1½ years of enrolment but 1.47 (95% CI 0.87 to 2.50) later (p=0.02, test of interaction). Explorative analyses indicated that the temporal change may be related to interactions with other childhood interventions.

conclusionThe MV-for-all-policy increased MV coverage but had no overall effect on overall mortality. TRIAL REGISTRATION NUMBER: NCT01306006.