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.

Heterologous effecs Maternal antibody Maternal priming Measles Mortality Non-specific effects Vaccines

Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Jul 2022
Historique:
received: 22 02 2022
revised: 26 04 2022
accepted: 05 05 2022
entrez: 24 6 2022
pubmed: 25 6 2022
medline: 25 6 2022
Statut: epublish

Résumé

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%. 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. Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n 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. ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.

Sections du résumé

Background UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n
Interpretation UNASSIGNED
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 UNASSIGNED
ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.

Identifiants

pubmed: 35747181
doi: 10.1016/j.eclinm.2022.101467
pii: S2589-5370(22)00197-3
pmc: PMC9156892
doi:

Banques de données

ClinicalTrials.gov
['NCT01486355']

Types de publication

Journal Article

Langues

eng

Pagination

101467

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

OB received a scholarship from the Lundbeck Foundation. All other authors declare no competing interests.

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Auteurs

Sebastian Nielsen (S)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
Bandim Health Project, OPEN, Odense Patient data Explorative Network, Institute of Clinical Research, and Danish Institute of Advanced Science, Odense University Hospital/ University of Southern Denmark, Denmark.

Ane B Fisker (AB)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
Bandim Health Project, OPEN, Odense Patient data Explorative Network, Institute of Clinical Research, and Danish Institute of Advanced Science, Odense University Hospital/ University of Southern Denmark, Denmark.

Isaquel da Silva (I)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Stine Byberg (S)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Sofie Biering-Sørensen (S)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Carlitos Balé (C)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Amarildo Barbosa (A)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Morten Bjerregaard-Andersen (M)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Nadja Skadkær Hansen (NS)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Vu An Do (VA)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Ole Bæk (O)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Stine Møller Rasmussen (SM)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Lone Damkjær (L)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Sophus Hvidt (S)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Olga Baltzersen (O)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Amabelia Rodrigues (A)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Cesario Martins (C)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.

Kristoffer J Jensen (KJ)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
Bandim Health Project, OPEN, Odense Patient data Explorative Network, Institute of Clinical Research, and Danish Institute of Advanced Science, Odense University Hospital/ University of Southern Denmark, Denmark.

Hilton C Whittle (HC)

London School of Hygiene and Topical Medicine, Keppel Street, London, UK.

Gaby Smits (G)

National Institute of Public Health and the Environment, Bilthoven, The Netherlands.

Fiona van der Klis (F)

National Institute of Public Health and the Environment, Bilthoven, The Netherlands.

Peter Aaby (P)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
Bandim Health Project, OPEN, Odense Patient data Explorative Network, Institute of Clinical Research, and Danish Institute of Advanced Science, Odense University Hospital/ University of Southern Denmark, Denmark.

Christine S Benn (CS)

Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
Bandim Health Project, OPEN, Odense Patient data Explorative Network, Institute of Clinical Research, and Danish Institute of Advanced Science, Odense University Hospital/ University of Southern Denmark, Denmark.

Classifications MeSH