Mike L T Berendsen1, Christian Bjerregård Øland1,2, Pauli Bles1, Aksel Karl Georg Jensen2,3, Poul-Erik Kofoed4, Hilton Whittle5, L Charlotte J de Bree2,6, Mihai G Netea6, Cesario Martins1, Christine S Benn2,7, Peter Aaby1,2. 1. Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau. 2. Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej, Copenhagen, Denmark. 3. Section of Biostatistics, University of Copenhagen, Denmark. 4. Department of Paediatrics, Kolding Hospital, Sygehusvej, Kolding, Denmark. 5. London School of Hygiene and Tropical Medicine, United Kingdom. 6. Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands. 7. OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital.
Abstract
BACKGROUND AND HYPOTHESIS: Maternal priming might enhance the beneficial nonspecific effects (NSEs) of live measles vaccination (MV). Children with a bacillus Calmette-Guérin (BCG) vaccine scar have a lower mortality rate than those without a scar that is not explained by protection against tuberculosis. We examined the hypothesis that BCG scarring would have a stronger effect on a child if the mother also had a BCG scar. METHODS: In a randomized controlled trial (RCT) of early MV in children aged 4.5 months, the BCG-scar status of the children and their mother were registered at enrollment at 4.5 months of age. The children were followed up until they were 36 months of age. Using a Cox proportional hazards model, we compared mortality rate ratios according to maternal and child BCG-scar status after adjusting for where the BCG vaccine was given (the national hospital or elsewhere). We censored for other interventions that have immunomodulating effects on child survival, including neonatal vitamin A supplementation and early MV. RESULTS: A total of 2213 children had not received neonatal vitamin A supplementation and early MV; 83% of these children and 44% of the mothers had a BCG scar. Children whose mother had a BCG scar were not more likely to have a BCG scar than those whose mother did not have a BCG scar (risk ratio, 1.01 [95% confidence interval (CI), 0.98-1.05]). Among the children, having a BCG scar was associated with a 41% (95% CI, 5%-64%) lower mortality between the ages of 4.5 and 36 months. The reduction in mortality was 66% (95% CI, 33%-83%) if the mother also had a BCG scar but only 8% (95% CI, -83% to 53%) if the mother had no BCG scar (test of interaction, P = .04). CONCLUSIONS: Maternal BCG priming might be important for the effect of BCG vaccination on child survival. Ensuring better BCG vaccine scarring among mothers and children could have a considerable effect on child mortality levels.
RCT Entities:
BACKGROUND AND HYPOTHESIS: Maternal priming might enhance the beneficial nonspecific effects (NSEs) of live measles vaccination (MV). Children with a bacillus Calmette-Guérin (BCG) vaccine scar have a lower mortality rate than those without a scar that is not explained by protection against tuberculosis. We examined the hypothesis that BCG scarring would have a stronger effect on a child if the mother also had a BCG scar. METHODS: In a randomized controlled trial (RCT) of early MV in children aged 4.5 months, the BCG-scar status of the children and their mother were registered at enrollment at 4.5 months of age. The children were followed up until they were 36 months of age. Using a Cox proportional hazards model, we compared mortality rate ratios according to maternal and childBCG-scar status after adjusting for where the BCG vaccine was given (the national hospital or elsewhere). We censored for other interventions that have immunomodulating effects on child survival, including neonatal vitamin A supplementation and early MV. RESULTS: A total of 2213 children had not received neonatal vitamin A supplementation and early MV; 83% of these children and 44% of the mothers had a BCG scar. Children whose mother had a BCG scar were not more likely to have a BCG scar than those whose mother did not have a BCG scar (risk ratio, 1.01 [95% confidence interval (CI), 0.98-1.05]). Among the children, having a BCG scar was associated with a 41% (95% CI, 5%-64%) lower mortality between the ages of 4.5 and 36 months. The reduction in mortality was 66% (95% CI, 33%-83%) if the mother also had a BCG scar but only 8% (95% CI, -83% to 53%) if the mother had no BCG scar (test of interaction, P = .04). CONCLUSIONS: Maternal BCG priming might be important for the effect of BCG vaccination on child survival. Ensuring better BCG vaccine scarring among mothers and children could have a considerable effect on childmortality levels.
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