Peer-reviewed article
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.
Joseph Alexis Zoa, Rahi-Metou Njemguie Linjouom, Martin Nyangono Ndongo, Jan Rene Nkeck ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This systematic review and meta-analysis examined the safety of the RTS,S/AS01E malaria vaccine in African children aged 5 to 17 months by analysing 11 randomized controlled trials involving nearly 28,000 children. The vaccine showed a serious adverse event rate of 21.4%, which was actually lower than the 26.2% rate in children who received a rabies vaccine control. Death rates were similar between the two groups, and severe malaria was significantly less common in vaccinated children, suggesting the vaccine provides meaningful protection.
Key points
- Overall serious adverse event rate was 21.4% in RTS,S/AS01E group versus 26.2% in rabies vaccine control group (pooled RR 0.80)
- Death occurred in 1.37% of vaccinated children and 1.31% of control children, with no significant difference
- Severe malaria was significantly more prevalent in the rabies vaccine control group (OR = 0.61)
- Common serious adverse events included febrile convulsions, pneumonia, and severe malaria
- Included studies had high methodological quality with low probability of bias
Limitations
The document does not specify which African countries were included in the trials, limiting understanding of geographical generalizability. The document notes that further long-term data are needed to confirm findings and address unresolved questions about vaccine safety.
Abstract
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 < 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. CONCLUSIONS: 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. PROSPERO REGISTRATION NUMBER: CRD42024321008.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- RTS,S/AS01E malaria vaccine administered to children aged 5-17 months
- Population
- African children aged 5 to 17 months; 16,976 vaccinated, 10,973 controls
Key finding
RTS,S/AS01E group had lower serious adverse event rate (21.4%) compared to rabies vaccine control (26.2%), pooled RR 0.80 [95% CI: 0.72-0.88]
Zoa et al. · PubMed (US National Library of Medicine) · 16 Jun 2025