Zoa Joseph Alexis, Njemguie Linjouom Rahi-Metou, Nyangono Ndongo Martin, Nkeck Jan Rene
Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmaceutical Sciences, The University of Ebolowa, Sangmelima, Cameroon.
Department of Galenics and Pharmaceutical Legislation, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
PLOS Glob Public Health. 2025 Jun 16;5(6):e0004387. doi: 10.1371/journal.pgph.0004387. eCollection 2025.
Numerous randomized controlled trials (RCTs) have demonstrated the safety of the RTS,S/AS01E vaccine in African children aged 5-17 months. However, conflicting evidence surrounding serious adverse events (SAEs) has prompted calls for further research to determine whether the benefits of the vaccine outweigh its risks, particularly in high-risk populations such as young children in malaria-endemic regions.
On February 12, 2025, a comprehensive literature search was performed across PubMed, Wiley Online Library, and Web of Science. The Patient/Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework was employed to screen and select relevant studies. Following initial screening, titles, abstracts, and full texts were filtered using EndNote software. Data were systematically extracted from each included study. SAEs were categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. The analysis focused on calculating proportions (%), risk ratios (RRs), and odds ratios (ORs) of SAEs. Pooled effect sizes and 95% confidence intervals (CIs) were derived using random-effects models from aggregated data meta-analysis. Publication bias was evaluated using the Begg's test, and Egger's test, with statistical significance assessed via Z tests.
This systematic review and meta-analysis included 11 studies involving 27949 children (16976 vaccinated with RTS,S/AS01E and 10973 vaccinated with rabies vaccine). The overall proportion of SAEs was 21.4% [95% CI: 17.5-25.5] in the RTS,S/AS01E group, compared to 26.2% [95% CI: 22.4-30.2] in the control group (rabies vaccine), yielding a pooled RR of 0.80 [95% CI: 0.72-0.88, P < 0.0001]. The pooled frequency of death was 1.37% [95% CI: 0.53-2.61] in the RTS,S/AS01E group and 1,31% [95% CI: 0.49-2.52] in the control group, with a non-significant odds ratio (OR) of 1.08% [95% CI: 0.83-1.41, P = 0.56]. Common SAEs included febrile convulsions, pneumonia, and severe malaria, with severe malaria being significantly more prevalent in children who received the rabies vaccine [OR = 0.61, 95% CI: 0.53-1.26, P < 0.00001]. The overall methodological quality of the included studies was high, with a low probability of bias.
The risk of SAEs is comparable between children who received the RTS,S/AS01E vaccine and those who received the rabies vaccine, except for severe malaria, which is significantly more frequent in the rabies vaccine group. This suggests that the RTS,S/AS01E vaccine may provide meaningful protection against severe forms of malaria, a critical outcome in high-burden regions. However, further long-term data are needed to confirm these findings and address several unresolved questions.
CRD42024321008.
众多随机对照试验（RCT）已证明RTS,S/AS01E疫苗在5至17个月大的非洲儿童中是安全的。然而，围绕严重不良事件（SAE）的相互矛盾的证据促使人们呼吁进行进一步研究，以确定该疫苗的益处是否大于风险，特别是在疟疾流行地区的幼儿等高风险人群中。
2025年2月12日，在PubMed、Wiley Online Library和Web of Science上进行了全面的文献检索。采用患者/人群、干预措施、对照、结局和研究设计（PICOS）框架筛选和选择相关研究。初步筛选后，使用EndNote软件对标题、摘要和全文进行筛选。从每项纳入研究中系统提取数据。SAE根据《药物监管活动医学词典》（MedDRA）术语进行分类。分析重点是计算SAE的比例（%）、风险比（RR）和比值比（OR）。使用随机效应模型从汇总数据的荟萃分析中得出合并效应量和95%置信区间（CI）。使用Begg检验和Egger检验评估发表偏倚，并通过Z检验评估统计学显著性。
这项系统评价和荟萃分析纳入了11项研究，涉及27949名儿童（16976名接种RTS,S/AS01E疫苗，10973名接种狂犬病疫苗）。RTS,S/AS01E组SAE的总体比例为21.4%[95%CI：17.5 - 25.5]，而对照组（狂犬病疫苗）为26.2%[95%CI：22.4 - 30.2]，合并RR为0.80[95%CI：0.72 - 0.88，P < 0.0001]。RTS,S/AS01E组的合并死亡频率为1.37%[95%CI：0.53 - 2.61]，对照组为1.31%[95%CI：0.49 - 2.52]，比值比（OR）为1.08%[95%CI：0.83 - 1.41，P = 0.56]，无统计学显著性。常见的SAE包括热性惊厥、肺炎和严重疟疾，接受狂犬病疫苗的儿童中严重疟疾更为普遍[OR = 0.61，95%CI：0.53 - 1.26，P < 0.00001]。纳入研究的总体方法学质量较高，偏倚可能性较低。
接受RTS,S/AS01E疫苗的儿童与接受狂犬病疫苗的儿童发生SAE的风险相当，但严重疟疾除外，狂犬病疫苗组中严重疟疾更为常见。这表明RTS,S/AS01E疫苗可能对严重形式的疟疾提供有意义的保护，这是高负担地区的一个关键结局。然而，需要进一步的长期数据来证实这些发现并解决几个未解决的问题。
PROSPERO注册号：CRD42024321008。
