{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:01:27Z","timestamp":1793624487023,"version":"4.5.0"},"reference-count":17,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"UK Joint Global Health Clinical Trials","award":["MR\/P006876\/1"],"award-info":[{"award-number":["MR\/P006876\/1"]}]},{"name":"PATH MVI","award":["18269"],"award-info":[{"award-number":["18269"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,7,31]]},"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Seasonal malaria chemoprevention (SMC), with sulphadoxine\u2013pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S\/AS01\n                      <jats:sub>E<\/jats:sub>\n                      malaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC. This trial aims to determine whether seasonal vaccination with RTS,S\/AS01\n                      <jats:sub>E<\/jats:sub>\n                      vaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This is an individually randomised, double-blind, placebo-controlled trial. 5920 children aged 5\u201317 months were enrolled in April 2017 in Mali and Burkina Faso. Children in group 1 received three priming doses of RTS,S\/AS01\n                      <jats:sub>E<\/jats:sub>\n                      vaccine before the start of the 2017 malaria transmission season and a booster dose at the beginning of two subsequent transmission seasons. In addition, they received SMC SP+AQ placebo on four occasions each year. Children in group 2 received three doses of rabies vaccine in year 1 and hepatitis A vaccine in years 2 and 3 together with four cycles of SMC SP+AQ\u2009each year. Children in group 3 received RTS,S\/AS01\n                      <jats:sub>E<\/jats:sub>\n                      vaccine and four courses of SMC SP+AQ. Incidence of clinical malaria is determined by case detection at health facilities. Weekly active surveillance for malaria is undertaken in a randomly selected subset of children. The prevalence of malaria is measured in surveys at the end of each transmission season. The primary endpoint is the incidence of clinical malaria confirmed by a positive blood film with a minimum parasite density of 5000 \/\u00b5L. Primary analysis will be by modified intention to treat defined as children who have received the first dose of the malaria or control vaccine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The protocol was approved by the national ethics committees of Mali and Burkina Faso and the London School of Hygiene and Tropical Medicine. The results will be presented to all stakeholders and published in open access journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03143218\">NCT03143218<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-035433","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T13:39:31Z","timestamp":1680701971000},"page":"e035433","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S\/AS01\n                    <sub>E<\/sub>\n                    vaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03143218","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"given":"Daniel","family":"Chandramohan","sequence":"first","affiliation":[{"name":"Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alassane","family":"Dicko","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issaka","family":"Zongo","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Sciences de la Sant\u00e9, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issaka","family":"Sagara","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cairns","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Kuepfer","sequence":"additional","affiliation":[{"name":"Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modibo","family":"Diarra","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadou","family":"Tapily","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djibrilla","family":"Issiaka","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koualy","family":"Sanogo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almahamoudou","family":"Mahamar","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Sompougdou","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Sciences de la Sant\u00e9, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Yerbanga","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Sciences de la Sant\u00e9, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismaila","family":"Thera","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Center, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Milligan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halidou","family":"Tinto","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Sciences de la Sant\u00e9, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opokua","family":"Ofori-Anyinam","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Biologicals SA, Wavre, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Bosco","family":"Ouedraogo","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Sciences de la Sant\u00e9, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2026062608020633000_10.9.e035433.1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.6.1.9677"},{"key":"2026062608020633000_10.9.e035433.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60721-8"},{"key":"2026062608020633000_10.9.e035433.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06957-4"},{"key":"2026062608020633000_10.9.e035433.4","unstructured":"BACKGROUND PAPER ON THERTS,S\/AS01 MALARIA VACCINE, 2015. Available: https:\/\/www.who.int\/immunization\/sage\/meetings\/2015\/october\/1_Final_malaria_vaccine_background_paper_v2015_09_30.pdf"},{"key":"2026062608020633000_10.9.e035433.5","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00514-16"},{"key":"2026062608020633000_10.9.e035433.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016976"},{"key":"2026062608020633000_10.9.e035433.7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1000407","article-title":"Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial","volume":"8","author":"Dicko","year":"2011","journal-title":"PLoS Med"},{"key":"2026062608020633000_10.9.e035433.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000408"},{"key":"2026062608020633000_10.9.e035433.9","unstructured":"Ndiaye JL , Ciss\u00e9 B , EH B , et al . Safety of seasonal intermittent preventive treatment against malaria with sulfadoxine pyrimethamine + amodiaquine when delivered to children under 10 years of age by district health staff in Senegal. PLoS One. In Press."},{"key":"2026062608020633000_10.9.e035433.10","unstructured":"Malaria Consortium . Seasonal malaria chemoprevention, 2020. Available: http:\/\/www.malariaconsortium.org\/pages\/access-smc.htm"},{"key":"2026062608020633000_10.9.e035433.11","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1056\/NEJMoa1811400","article-title":"Effect of adding azithromycin to seasonal malaria chemoprevention","volume":"380","author":"Chandramohan","year":"2019","journal-title":"N Engl J Med"},{"key":"2026062608020633000_10.9.e035433.12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.10.1152"},{"key":"2026062608020633000_10.9.e035433.13","doi-asserted-by":"crossref","DOI":"10.3402\/gha.v6i0.21518","article-title":"Revising the who verbal autopsy instrument to facilitate routine cause-of-death monitoring","volume":"6","author":"Leitao","year":"2013","journal-title":"Glob Health Action"},{"key":"2026062608020633000_10.9.e035433.14","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-223"},{"key":"2026062608020633000_10.9.e035433.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505819"},{"key":"2026062608020633000_10.9.e035433.16","doi-asserted-by":"crossref","unstructured":"Xu Y , Lam KF , Cheung YB . Estimation of intervention effects using recurrent event time data in the presence of event dependence and a cured fraction. Stat Med 2014.","DOI":"10.1002\/sim.6093"},{"key":"2026062608020633000_10.9.e035433.17","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv010"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2019-035433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:23:43Z","timestamp":1782728623000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2019-035433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":17,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9,15]]},"published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1136\/bmjopen-2019-035433"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2019-035433","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]}}}