MICA: Seasonal vaccination with the RTS,S/AS01 malaria vaccine given with or without seasonal malaria chemoprevention (SMC): an extension study.

MICA：在有或没有季节性疟疾化学预防 (SMC) 的情况下使用 RTS,S/AS01 疟疾疫苗进行季节性疫苗接种：一项扩展研究。

• 批准号: MR/V005642/1
• 负责人: Brian Greenwood
• 金额: $ 250.09万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV005642%2F1
• 关键词: MICA; Seasonal; vaccination; RTS; AS01

There has been substantial progress in the control of malaria during the past decade, but it is estimated that in 2018 there were still 405 000 deaths from malaria, despite widespread deployment of insecticide treated bednets and an increase in access to diagnosis and effective treatment of malaria. In the African Sahel and sub-Sahel, the risk of malaria is concentrated in the few months of the rainy season, although some transmission continues during the rest of the year. The seasonality of malaria in this part of Africa has allowed the development of an effective control measure called Seasonal Malaria Chemoprevention (SMC), which involves treatment of young children, regardless of whether they have any symptoms, with the antimalarial drugs sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals on four occasions during the malaria transmission season. RTS,S/AS01E is the most advanced malaria vaccine. A trial conducted in seven countries in Africa in 2009-2014 in 15,439 children showed that when three doses of the RTS,S/AS01E vaccine were given to children aged 5-17 month, followed by a fourth dose a year later, the vaccine provided 37% protection against clinical attacks of malaria over a period of 4 years, and a similar level of protection against severe malaria. The vaccine caused febrile convulsions in about 1% of children and there was a small, unexplained, increase in the incidence of meningitis in vaccine recipients. Based on the balance of risks and benefits from these findings, the European Medicine Agency gave the vaccine a positive opinion in July 2015. However, WHO's SAGE committee recommended the conduct of three, large pilot studies prior to widespread introduction of the vaccine and these are now underway in approximately 750.000 children in Ghana, Kenya and Malawi. A characteristic feature of the RTS,S/AS01E vaccine is that it produces a high level of protection in the first few months after vaccination but that this subsequently wanes. This property of the vaccine suggest that it might be especially useful in areas where malaria transmission is concentrated in just a few months each year if given as an annual,seasonal vaccine in a manner comparable to seasonal influenza vaccination.To investigate the potential of RTS,S/AS01E as a seasonal vaccine, a trial was started in 2017 in Burkina Faso and Mali to compare the protective efficacy against clinical episodes of malaria of (a) administration of three doses of RTS,S/AS01 to young children followed by a second and third booser dose at the beginning of two subsequent malaria transmission seasons (b) administration of SMC with SP + AQ as recommended by WHO and (c) the combination of these two interventions. 5920 children were enrolled in the trial in 2017 and they have now been followed for nearly three years with recording of the incidence of episodes of uncomplicated and severe malaria throughout this period. This phase of the trial will finish in June 2020. Meanwhile, at the request of the Bill and Melinda Gates Foundation, an independent statistician has undertaken a preliminary analysis of the information collected until the end of November 2019. Based on the results of this review, the Foundation has recommended that the trial should continue, including all three groups, until the study children reach the age of five years, the age beyond which SMC is no longer recommended in most countries. This recommendation has been endorsed by the trial's Data Safety Monitoring Board. During the two years of the extension period, the same series of observations will be made in study children to those undertaken during the first phase of the trial including the incidence of uncomplicated and severe clinical malaria, anaemia and impaired nutrition. The costs of implementing seasonal vaccination and SMC will be measured and the preference of the local populations for each intervention will be determined.

过去十年来，疟疾控制取得了实质性进展，但尽管广泛使用经杀虫剂处理的蚊帐，并且获得疟疾诊断和有效治疗的机会有所增加，但估计 2018 年仍有 405 000 人死于疟疾。在非洲萨赫勒和萨赫勒以南地区，疟疾的风险集中在雨季的几个月，尽管在一年中的剩余时间里仍有一些传播。非洲这一地区疟疾的季节性使得能够开发出一种有效的控制措施，称为季节性疟疾化学预防（SMC），其中包括使用抗疟药物磺胺多辛-乙胺嘧啶（SP）对幼儿进行治疗，无论他们是否有任何症状。 ）和阿莫地喹（AQ），在疟疾传播季节期间每月四次。 RTS,S/AS01E 是最先进的疟疾疫苗。 2009-2014 年在非洲 7 个国家对 15,439 名儿童进行的一项试验表明，当给 5-17 个月大的儿童注射三剂 RTS,S/AS01E 疫苗，一年后注射第四剂时，该疫苗提供了4 年内针对疟疾临床发作的防护率为 37%，针对严重疟疾的防护水平也达到类似水平。该疫苗导致约 1% 的儿童出现热性惊厥，并且疫苗接种者脑膜炎的发病率出现小幅且无法解释的增加。基于这些研究结果的风险和益处的平衡，欧洲药品管理局于 2015 年 7 月对该疫苗给予了积极评价。然而，世卫组织的 SAGE 委员会建议在广泛引入该疫苗之前进行三项大型试点研究，这些研究是目前，加纳、肯尼亚和马拉维的约 750,000 名儿童正在接受这项治疗。 RTS,S/AS01E 疫苗的一个特征是，它在接种疫苗后的最初几个月内产生高水平的保护作用，但随后这种保护作用减弱。该疫苗的这一特性表明，如果以与季节性流感疫苗接种类似的方式作为年度季节性疫苗接种，它可能在疟疾传播集中于每年几个月的地区特别有用。为了研究 RTS 的潜力， S/AS01E 作为季节性疫苗，于 2017 年在布基纳法索和马里启动了一项试验，以比较 (a) 给幼儿注射三剂 RTS、S/AS01 对疟疾临床发作的保护效果在随后的两个疟疾传播季节开始时注射第二次和第三次加强剂量 (b) 按照世界卫生组织的建议使用 SMC 和 SP + AQ，以及 (c) 这两种干预措施的结合。 2017 年，有 5920 名儿童参加了该试验，现已对他们进行了近三年的跟踪，记录了在此期间单纯性和严重疟疾发作的发生率。此阶段的试验将于 2020 年 6 月结束。同时，应比尔及梅琳达·盖茨基金会的要求，独立统计学家已对 2019 年 11 月底之前收集的信息进行了初步分析。根据本次审查的结果，基金会建议继续进行试验，包括所有三组，直到研究儿童年满五岁，超过这个年龄，大多数国家就不再推荐使用 SMC。该建议已得到试验数据安全监测委员会的认可。在两年的延长期内，将对研究儿童进行与试验第一阶段相同的一系列观察，包括简单和严重的临床疟疾、贫血和营养不良的发生率。将衡量实施季节性疫苗接种和 SMC 的成本，并确定当地人群对每项干预措施的偏好。

项目成果

Seasonal vaccination with RTS,S/AS01E 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.

布基纳法索和马里 5 岁以下儿童季节性接种 RTS,S/AS01E 疫苗，并进行或不进行季节性疟疾化学预防：一项双盲、随机、对照 3 期试验。

• DOI: http://dx.10.1016/s1473-3099(23)00368-7
• 发表时间: 2024
• 期刊: The Lancet. Infectious diseases
• 作者: Dicko A

Delivery strategies for malaria vaccination in areas with seasonal malaria transmission

季节性疟疾传播地区的疟疾疫苗接种策略

• DOI: http://dx.10.1136/bmjgh-2023-011838
• 发表时间: 2023
• 期刊: BMJ Global Health
• 影响因子: 8.1
• 作者: Grant J