Seasonal vaccination with RTS,S/AS01 E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.

Autor:	Dicko A; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Ouedraogo JB; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Zongo I; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Sagara I; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Cairns M; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK., Yerbanga RS; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Issiaka D; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Zoungrana C; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Sidibe Y; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Tapily A; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Nikièma F; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Sompougdou F; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Sanogo K; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Kaya M; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Yalcouye H; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Dicko OM; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Diarra M; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Diarra K; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Thera I; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Haro A; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Sienou AA; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Traore S; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Mahamar A; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Dolo A; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Kuepfer I; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK., Snell P; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK., Grant J; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK., Webster J; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK., Milligan P; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK., Lee C; PATH, Seattle, USA., Ockenhouse C; PATH, Seattle, USA., Ofori-Anyinam O; GSK, Wavre, Belgium., Tinto H; Institut des Sciences et Techniques-Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso., Djimde A; The Malaria Research and Training Center, University of Science, Technology and Techniques of Bamako, Bamako, Mali., Chandramohan D; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK., Greenwood B; Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: brian.greenwood@lshtm.ac.uk.
Jazyk:	angličtina
Zdroj:	The Lancet. Infectious diseases [Lancet Infect Dis] 2024 Jan; Vol. 24 (1), pp. 75-86. Date of Electronic Publication: 2023 Aug 22.
DOI:	10.1016/S1473-3099(23)00368-7
Abstrakt:	Background: Seasonal vaccination with the RTS,S/AS01 E vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years. Methods: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01 E plus placebo SMC, or SMC plus RTS,S/AS01 E . They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01 E -alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete. Findings: In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01 E -alone group, and 133 in the combined group. The combination of RTS,S/AS01 E and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01 E (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01 E was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01 E -alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected. Interpretation: Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission. Funding: UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation). Translation: For the French translation of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests OO-A is an employee of the GSK group of companies and has restricted shares in the GSK group of companies. All of the authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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