Asante Kwaku Poku, Bozonnat Marie-Cécile, Savic Miloje, Owusu-Agyei Seth, Kaali Seyram, Otieno Walter, Boahen Owusu, Tivura Mathilda, Otieno Lucas, Agyapong Prince Darko, Ansah Patrick Odum, Sing'oei Valentine, Oyieko Janet, Adeniji Elisha, Ansah Nana Akosua, Harrison Samuel Bernard Ekow, Oguk Esther, Dosoo David, Schuerman Lode, Kaburise Michael Bandasua, Awuni Dennis Azabra, Kayan Kingsley, Cravcenco Cristina, Roman François, Haine Valérie
Kintampo Health Research Centre, Ghana Health Service, Kintampo, Ghana.
4Clinics c/o GSK, Wavre, Belgium.
Lancet Glob Health. 2025 May;13(5):e859-e869. doi: 10.1016/S2214-109X(25)00022-1.
The RTS,S/AS01 malaria vaccine was introduced in selected communities of Ghana, Kenya, and Malawi in 2019 under a WHO-coordinated pilot programme. The scarcity of background disease incidence rates might hamper the assessment of vaccine safety and effectiveness. We aimed to determine the incidence rates of malaria, meningitis, and death, and health outcomes leading to hospital admission in children younger than 5 years enrolled before RTS,S/AS01 implementation. Interim results from EPI-MAL-002 up to Oct 5, 2018, were reported previously. Here, we report results from the final analysis of the pre-vaccine introduction study.
This disease surveillance study combined two approaches: (1) prospective cohort event monitoring (home visits scheduled to mimic a future four-dose RTS,S/AS01 vaccination schedule [ie, a simulated vaccination schedule], with additional visits after the simulated schedule and continuous disease monitoring of outpatient visits and hospital admission) in children enrolled in two age groups (6-12 weeks [6-12W] and 5-17 months [5-17M]), and (2) hospital-based disease surveillance for children not enrolled in the prospective cohort, in three sites in Ghana and Kenya. Key outcomes were rates of meningitis, malaria, adverse events of special interest, other adverse events leading to hospital admission, all-cause mortality, and malaria-attributable mortality.
The final analysis included 23 427 children: 9032 in the 6-12W age group, 9694 in the 5-17M age group, and 4701 in hospital-based disease surveillance. In the 5-17M age group (corresponding to the WHO-recommended age for RTS,S/AS01 vaccination), the incidence rates of meningitis and cerebral malaria within an at-risk period of 1 year after the simulated vaccination schedule were both equal to 28 (95% CI 9-65) per 100 000 person-years. There were 11 (0·1%) children with an adverse event of special interest during hospital admission. In the 5-17M age group, the all-cause mortality rate was 643 (95% CI 531-771) per 100 000 person-years.
Observed incidence of meningitis and cerebral malaria were in the previously published range, whereas childhood mortality was lower, suggesting that the recent efforts to reduce mortality in children younger than 5 years have been impactful. Data from this study have public health use and will form the baseline evidence for ongoing evaluation of the benefit-risk of RTS,S/AS01.
GSK and PATH.
2019年，在世界卫生组织协调的一项试点计划下，RTS,S/AS01疟疾疫苗在加纳、肯尼亚和马拉维的部分社区推出。背景疾病发病率数据的匮乏可能会妨碍对疫苗安全性和有效性的评估。我们旨在确定在实施RTS,S/AS01疫苗之前入组的5岁以下儿童中疟疾、脑膜炎和死亡的发病率，以及导致住院的健康结局。先前已报告了截至2018年10月5日EPI-MAL-002的中期结果。在此，我们报告疫苗引入前研究的最终分析结果。
这项疾病监测研究结合了两种方法：（1）前瞻性队列事件监测（安排家访以模拟未来的四剂次RTS,S/AS01疫苗接种计划[即模拟接种计划]，在模拟计划之后进行额外家访，并对门诊就诊和住院情况进行持续疾病监测），对象为两个年龄组（6-12周龄[6-12W]和5-17月龄[5-17M]）的儿童，以及（2）在加纳和肯尼亚的三个地点，对未纳入前瞻性队列的儿童进行基于医院的疾病监测。主要结局为脑膜炎、疟疾、特殊关注的不良事件、导致住院的其他不良事件、全因死亡率和疟疾归因死亡率。
最终分析纳入了23427名儿童：6-12W年龄组9032名，5-17M年龄组9694名，基于医院的疾病监测组4701名。在5-17M年龄组（对应于世界卫生组织推荐的RTS,S/AS01疫苗接种年龄），模拟接种计划后1年的风险期内，脑膜炎和脑型疟疾的发病率均为每10万人年28例（95%CI 9-65）。住院期间有11名（0.1%）儿童出现特殊关注的不良事件。在5-17M年龄组，全因死亡率为每10万人年643例（95%CI 531-771）。
观察到的脑膜炎和脑型疟疾发病率在先前公布的范围内，而儿童死亡率较低，这表明最近为降低5岁以下儿童死亡率所做的努力是有成效的。本研究数据具有公共卫生用途，将为持续评估RTS,S/AS01的利弊提供基线证据。
葛兰素史克公司和PATH组织。
