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.
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.
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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：
10.1016/s1473-3099(23)00368-7
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Dicko A
中科院分区：
文献类型：
--
作者：
Dicko A
RTS、S/AS 01 E疫苗季节性接种联合季节性疟疾化学预防（SMC）在3年内预防幼儿疟疾的效果比单独使用任何一种干预措施都要好。本研究的目的是建立是否增加保护提供的组合可以再持续2 years.MethodsThis是一个双盲，单独随机，对照，非劣效性和优越性，3期试验在两个网站：布古尼区和邻近地区在马里和洪代区，布基纳法索。在最初3年试验中入组的5-17个月的儿童最初被单独随机分配接受SMC+磺胺嘧啶-乙胺嘧啶和阿莫地喹+对照疫苗，RTS，S/AS 01 E+安慰剂SMC，或SMC + RTS，S/AS 01 E。他们继续接受同样的干预措施，直到5岁。主要试验终点是5年试验期间改良意向治疗人群和符合方案人群的临床疟疾发病率。在5年期间，非劣效性定义为RTS，S/AS 01 E单药治疗组的临床疟疾比SMC单药治疗组增加20%。优势被定义为联合干预组和单一干预组之间临床疟疾发病率的12%差异。该研究已在ClinicalTrials.gov注册，NCT 04319380，并已完成。结果在2020年4月，最初招募的6861名儿童中，5433名完成初始3年随访的儿童中有5098名（94%）重新入组扩展研究。5年内，SMC单独组每1000人-年的临床疟疾发病率为313，RTS、S/AS 01 E单独组为320，联合组为133。RTS、S/AS 0 1 E和SMC联合应用对临床疟疾的预防效果上级优于SMC（保护率57·7%，95% CI 53·3 ~ 61·7）和RTS、S/AS 0 1 E（保护率59·0%，95% CI 54·7 ~ 62·8）。RTS，S/AS 01 E非劣效于SMC（风险比1·03 [95% CI 0·95 - 1·12]）。在研究的5年期间，联合用药相对于SMC的保护有效性与前3年观察到的保护有效性非常相似，联合用药相对于SMC的保护有效性为57.7%（53.3至61.7），相对于RTS/AS 01 E单药的保护有效性为59.0%（54.7至62.8）。研究前3年的可比数字分别为62.8%（58.4至66.8）和59.6%（54.7至64.0%）。因世卫组织定义的严重疟疾而入院的人数减少了66.8%（95% CI 40.3至81.5），疟疾性贫血降低65.9%（34.1至82.4），输血减少68.1%（32.6至84.9），全因死亡减少44.5%（2.8至68.3），不包括外部原因或手术的死亡率为41.1%（-9.2至68.3），疟疾死亡率为66.8%（-2.7至89.3）。解释通过将季节性疟疾疫苗接种与季节性化学预防相结合，为季节性疟疾传播地区的疟疾控制提供了一种潜在的新方法。（通过比尔和梅林达盖茨基金会的赠款）。翻译关于摘要的法文翻译，见补充材料部分。
BackgroundSeasonal vaccination with the RTS,S/AS01Evaccine 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.MethodsThis 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/AS01Eplus placebo SMC, or SMC plus RTS,S/AS01E. 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/AS01E-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.FindingsIn 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/AS01E-alone group, and 133 in the combined group. The combination of RTS,S/AS01Eand SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01E(protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01Ewas 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/AS01E-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.InterpretationSubstantial 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.FundingUK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation).TranslationFor the French translation of the abstract see Supplementary Materials section.
影响因子：
3
作者：
Swysen C;Vekemans J;Bruls M;Oyakhirome S;Drakeley C;Kremsner P;Greenwood B;Ofori-Anyinam O;Okech B;Villafana T;Carter T;Savarese B;Duse A;Reijman A;Ingram C;Frean J;Ogutu B;Clinical Trials Partnership Committee
通讯作者：
Clinical Trials Partnership Committee
间歇性的预防性治疗疟疾可为已在布基纳Faso受杀虫剂治疗的床网受保护的儿童提供实质性的保护：一项随机，双盲，安慰剂对照试验。
影响因子：
15.8
作者：
Konaté AT;Yaro JB;Ouédraogo AZ;Diarra A;Gansané A;Soulama I;Kangoyé DT;Kaboré Y;Ouédraogo E;Ouédraogo A;Tiono AB;Ouédraogo IN;Chandramohan D;Cousens S;Milligan PJ;Sirima SB;Greenwood B;Diallo DA
通讯作者：
Diallo DA