INTRODUCTION

The RTS,S vaccine has been approved for use in children under 5 living in moderate to high malaria transmission areas. However, clinically important adverse events have been reported in countries in sub-Saharan Africa. This systematic review aims to assess the frequency, severity and clinical importance of vaccine-related adverse events.

METHODS AND ANALYSIS

This systematic review protocol has been prepared following robust methods and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses for protocols guidelines. We will search PubMed, CINAHL, LILACS, Google Scholar, SCOPUS, WEB OF SCIENCE, Cochrane library, HINARI, , Trip Pro and TOXNET from 2000 to 30 September 2023, without language restrictions. We will also search conference proceedings, dissertations, World Bank Open Knowledge Repository, and WHO, PATH, UNICEF, Food and Drugs Authorities and European Medicines Agency databases, preprint repositories and reference lists of relevant studies for additional studies. Experts in the field will be contacted for unpublished or published studies missed by our searches. At least two reviewers will independently select studies and extract data using pretested tools and assess risk of bias in the included studies using the Cochrane risk of bias tool. Any disagreements will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (serious adverse events, cerebral malaria and febrile convulsion) as risk ratio (RR) with their 95% CI. We will perform subgroup analysis to assess the impact of heterogeneity and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation.

ETHICS AND DISSEMINATION

Ethical approval is not required for a systematic review. The findings of this study will be disseminated through stakeholder forums, conferences and peer-review publications.

PROSPERO REGISTRATION NUMBER

CRD42021275155.