Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK
Malaria Research and Training Center, Bamako, Mali.
BMJ Open. 2020 Sep 15;10(9):e035433. doi: 10.1136/bmjopen-2019-035433.
Seasonal malaria chemoprevention (SMC), with sulphadoxine-pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01 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 vaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits.
This is an individually randomised, double-blind, placebo-controlled trial. 5920 children aged 5-17 months were enrolled in April 2017 in Mali and Burkina Faso. Children in group 1 received three priming doses of RTS,S/AS01 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 each year. Children in group 3 received RTS,S/AS01 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 /µL. Primary analysis will be by modified intention to treat defined as children who have received the first dose of the malaria or control vaccine.
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.
NCT03143218; Pre-results.
季节性疟疾化学预防（SMC）使用磺胺多辛-乙胺嘧啶加阿莫地喹（SP+AQ）是有效的，但不能提供对临床疟疾的完全保护。RTS,S/AS01 疟疾疫苗在接种后不久提供高水平的保护，但这种保护迅速减弱。这种疫苗可以替代或补充 SMC。本试验旨在确定季节性接种 RTS,S/AS01 疫苗是否可以替代 SMC，以及两种干预措施的联合使用是否会带来额外的益处。
这是一项个体随机、双盲、安慰剂对照试验。2017 年 4 月，在马里和布基纳法索共招募了 5920 名 5-17 个月大的儿童。第 1 组的儿童在 2017 年疟疾传播季节开始前接受了三剂 RTS,S/AS01 疫苗的基础免疫，并在随后两个传播季节开始时接受了一剂加强免疫。此外，他们每年接受四次 SMC SP+AQ 安慰剂。第 2 组的儿童在第 1 年接受 3 剂狂犬病疫苗，在第 2 年和第 3 年接受 3 剂甲型肝炎疫苗，同时每年接受 4 个周期的 SMC SP+AQ。第 3 组的儿童接受 RTS,S/AS01 疫苗和 4 个周期的 SMC SP+AQ。临床疟疾的发病率通过在医疗机构发现病例来确定。每周对随机选择的一部分儿童进行疟疾主动监测。在每个传播季节结束时进行疟疾患病率调查。主要终点是通过最小寄生虫密度为 5000/µL 的阳性血片确认的临床疟疾发病率。主要分析将根据修改后的意向治疗定义进行，即已接受疟疾或对照疫苗第一剂的儿童。
该方案已获得马里和布基纳法索的国家伦理委员会以及伦敦卫生与热带医学学院的批准。结果将提交给所有利益攸关方，并在开放获取期刊上发表。
NCT03143218；预结果。
