本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(24)00004-7

摘要内容如下：

背景

RTS，S/AS01E疟疾疫苗（RTS，S）由加纳、肯尼亚和马拉维的国家免疫规划于2019年在大规模试点计划中引入。我们的目的是解决有关可行性和影响的问题，并评估在3期试验中观察到的安全性信号，包括RTS，S接受者中脑膜炎和脑型疟疾病例过多，以及接受RTS，S的女孩比对照组死亡人数过多的可能性，从而为更广泛使用的决策提供信息。

方法

在这项前瞻性评价中，158个地理集群（加纳的66个区；肯尼亚46个县；和马拉维的46组免疫接种诊所集水区）随机分配至早期或延迟引入RTS，S，在5个月至9个月之间施用三剂，在大约2岁时施用第四剂。计划在4年内进行的评估的主要结果是除伤害以外的所有原因的死亡率（IMPACT）、严重疟疾住院（IMPACT）、脑膜炎或脑型疟疾住院（安全性）、女孩与男孩相比的死亡率（安全性）和疫苗接种覆盖率（可行性）。监测了试点地区1-59个月儿童的死亡率。在加纳的8个哨点医院、肯尼亚的6个哨点医院和马拉维的4个哨点医院建立了脑膜炎和重症疟疾监测。疫苗接种后约18个月，在对12-23个月儿童的调查中测量了疫苗摄取情况。我们估计，24个月后将积累足够的数据，以在三个国家数据的汇总分析中评估每个安全性信号和对严重疟疾的影响。我们通过比较符合接种至少一剂疫苗（安全性结果）或符合接种三剂疫苗（影响结果）年龄的儿童的事件数量与实施地区不符合接种疫苗年龄的儿童的事件数量的比率，以及比较地区的相同比率，来估计发病率比率（IRR）。为了确定是否有证据表明女孩和男孩之间在疫苗对死亡率的影响方面存在差异，在实施地区和比较地区之间比较了有资格接种疫苗的年龄组中女性与男性的死亡率比率（相对于不符合条件的儿童的比率）。初步研究结果有助于世卫组织在2021年建议在中度至高度疟疾传播地区广泛使用RTS，S。

调查结果

截至2021年4月30日，652673名儿童接受了至少一剂RTS，S，494745名儿童接受了三剂。第一剂的覆盖率在加纳为76%，在肯尼亚为79%，在马拉维为73%，第三剂的覆盖率在加纳为66%，在肯尼亚为62%，在马拉维为62%。哨点医院收治1-59个月儿童26285人，通过死亡率监测报告死亡13198人。在有资格接受至少一剂RTS，S的儿童中，与对照地区相比，没有证据表明实施地区的脑膜炎或脑型疟疾病例过多（因脑膜炎入院：IRR 0.63[95%CI 0.22-1.79]；脑型疟疾住院：IRR 1.03[95%CI 0.61-1.74]）。RTS，S的引入对女孩和男孩死亡率的影响相似（相对死亡率比1.03[95%CI 0.88-1.21]）。在有资格接种三剂疫苗的儿童中，RTS，S的引入与严重疟疾住院减少32%（95%CI 5-51%）和全因死亡率（不包括伤害）减少9%（95%CI 0-18%）相关。

解释

在实施RTS，S的前两年，通过国家免疫规划有效地部署了三个主要剂量。没有证据表明在3期试验中观察到的安全信号，疫苗的引入与严重疟疾住院人数的大幅减少有关。评价工作继续评估四剂RTS，S的影响。

英文原文如下：

Abstracts

BACKGROUND  The RTS,S/AS01E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use.

METHODS  In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission.

FINDINGS  By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury).

INTERPRETATION  In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S.

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