Safety of RTS,S/AS01E vaccine for malaria in African children aged 5 to 17 months: A systematic review and meta-analysis of randomized controlled trials

Background: 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. Methods: 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. Results: 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