Effect of early two-dose measles vaccination on childhood mortality and modification by maternal measles antibody in Guinea-Bissau, West Africa: A single-centre open-label randomised controlled trial
Sebastian Nielsen, Ane Bærent Fisker, Isaquel da Silva, Stine Byberg, Sofie Biering‐Sørensen, Carlitos Balé, Amarildo Barbosa, Morten Bjerregaard-Andersen, Nadja Skadkær Hansen, Vu An, Ole Bæk, Stine Møller Rasmussen, Lone Damkjær, Sophus Hvidt, Olga Baltzersen, Amabélia Rodrigues, Cesário Martins, Kristoffer Jarlov Jensen, Hilton Whittle, Gaby Smits, Fiona van der Klis, Peter Aaby, Christine Stabell Benn
Abstract
Background: Early 2-dose measles vaccine (MV) at 4 and 9 months of age vs. the WHO strategy of MV at 9 months of age reduced all-cause child mortality in a previous trial. We aimed to test two hypotheses: 1) a 2-dose strategy reduces child mortality between 4 and 60 months of age by 30%; 2) receiving early MV at 4 months in the presence versus absence of maternal measles antibodies (MatAb) reduces child mortality by 35%. Methods: Single-centre open-label community-based randomised controlled trial in Guinea-Bissau, with 2:1 block-randomisation by sex to a 2-dose (4 + 9 months) vs. 1-dose (9 months) MV strategy. Healthy children were eligible 4 weeks after the 3rd diphtheria-tetanus-pertussis-containing vaccine. Before randomisation a blood sample was collected to determine MatAb level. The primary outcome was all-cause mortality. Hazard ratios (HR) were derived from Cox regression in the per protocol population. We tested for interactions with national campaigns with oral polio vaccine (C-OPV). Trial registration: NCT01486355. Findings: =31/1,028]. Interpretation: The main result contrasts with previous findings but may, though based on a small number of events, be explained by frequent OPV campaigns that reduced the mortality rate, but apparently interacted negatively with early MV. The beneficial non-specific effects of MV in the presence of MatAb should be investigated further. Funding: ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.