Ane B Fisker1,2,3, Eric Nebie4, Anja Schoeps5, Cesario Martins1, Amabelia Rodrigues1, Alphonse Zakane4, Moubassira Kagone4, Stine Byberg1,2, Sanne M Thysen1,2, Justin Tiendrebeogo4, Boubacar Coulibaly4, Osman Sankoh6,7,8, Heiko Becher5,9, Hilton C Whittle10, Fiona R M van der Klis11, Christine S Benn1,2,3, Ali Sie4, Olaf Müller5, Peter Aaby1,2. 1. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau. 2. Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, University of Southern Denmark, Denmark. 3. OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Denmark. 4. Centre de Recherche en Santé de Nouna, INDEPTH Network, Nouna, Burkina Faso. 5. Institute of Public Health, Ruprecht-Karls-University, Heidelberg, Germany. 6. INDEPTH Network, Accra, Ghana. 7. School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 8. College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone. 9. University Medical Center Hamburg-Eppendorf, Institute of Medical Biometry and Epidemiology, Germany. 10. London School of Hygiene and Tropical Medicine, United Kingdom. 11. National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Abstract
Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods:Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.
RCT Entities:
Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods:Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.
Authors: Ane B Fisker; Justiniano S D Martins; Andreas M Jensen; Cesario Martins; Peter Aaby; Sanne M Thysen Journal: Trials Date: 2022-04-23 Impact factor: 2.728
Authors: Laura M Nic Lochlainn; Brechje de Gier; Nicoline van der Maas; Rob van Binnendijk; Peter M Strebel; Tracey Goodman; Hester E de Melker; William J Moss; Susan J M Hahné Journal: Lancet Infect Dis Date: 2019-09-20 Impact factor: 25.071
Authors: Laura M Nic Lochlainn; Brechje de Gier; Nicoline van der Maas; Peter M Strebel; Tracey Goodman; Rob S van Binnendijk; Hester E de Melker; Susan J M Hahné Journal: Lancet Infect Dis Date: 2019-09-20 Impact factor: 25.071