RTS,S/AS01 malaria vaccine-proven safe and effective?

Area of Science:

• Global Health
• Vaccinology
• Pediatric Infectious Diseases

Background:

• The World Health Organization (WHO) recommended the RTS,S malaria vaccine in October 2021 for children aged 5 months and older in high-transmission areas.
• Recommendations were based on Phase 3 trials and an ongoing Malaria Vaccine Implementation Programme (MVIP).

Purpose of the Study:

• To critically evaluate the mortality data from the Malaria Vaccine Implementation Programme (MVIP).
• To assess the scientific evidence supporting the claimed impact of the RTS,S vaccine on child mortality.

Main Methods:

• Analysis of potential confounding factors in MVIP mortality data.
• Review of the statistical significance and duration of the MVIP assessment.
• Comparison of MVIP findings with Phase 3 trial results, particularly regarding sex-specific mortality.

Main Results:

• Identified significant issues with MVIP mortality data, including potential confounding and inappropriate use of surrogate markers.
• The observed effect on mortality was not statistically significant, and the assessment period was shorter than planned.
• Concerns remain regarding potential increased mortality in vaccinated girls compared to boys, as suggested by Phase 3 data.

Conclusions:

• The claimed mortality benefits of the RTS,S vaccine in the MVIP are not supported by robust scientific evidence.
• Further rigorous evaluation, including independent data assessment and adherence to planned analyses, is necessary.
• Future vaccine roll-outs must prioritize comprehensive safety evaluations, especially concerning sex-specific mortality differences.