RTS,S Malaria Vaccine Safety Profile
The RTS,S/AS01E malaria vaccine has demonstrated a favorable safety profile in large-scale implementation, with no evidence of the safety signals observed in earlier trials, including no excess risk of meningitis, cerebral malaria, or differential mortality between girls and boys. 1
Key Safety Findings from Real-World Implementation
The most robust safety data comes from the 2019-2021 pilot implementation across Ghana, Kenya, and Malawi, where over 652,000 children received at least one dose:
No excess meningitis risk: Hospital admissions for meningitis showed an incidence rate ratio of 0.63 (95% CI 0.22-1.79), indicating no increased risk and possibly a protective trend 1
No excess cerebral malaria risk: Hospital admissions for cerebral malaria showed an incidence rate ratio of 1.03 (95% CI 0.61-1.74), demonstrating no significant increase 1
No sex-differential mortality: The relative mortality ratio for girls versus boys was 1.03 (95% CI 0.88-1.21), refuting earlier concerns about excess deaths in vaccinated girls 1
Common Adverse Events
The vaccine is generally well-tolerated with typical vaccine-related reactions:
Local reactions and fever are the most common adverse events, consistent with other childhood vaccines 2, 3
Serious adverse events occur at rates comparable to control groups in clinical trials 3
Efficacy and Public Health Impact
Children 5-17 Months of Age
Clinical malaria protection: 46% vaccine efficacy (95% CI 42-50%) over 18 months post-vaccination 3
Severe malaria protection: 34% vaccine efficacy (95% CI 15-48%) 3
Real-world impact: 32% reduction (95% CI 5-51%) in hospital admissions for severe malaria in implementation areas 1
Mortality reduction: 9% reduction (95% CI 0-18%) in all-cause mortality excluding injury 1
Infants 6-12 Weeks of Age
Lower efficacy: 27% vaccine efficacy (95% CI 20-32%) against clinical malaria 3
No significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization in this younger age group 3
Recommendation: The vaccine is most effective when initiated at 5 months of age or older, not in young infants 2, 1
Special Populations: Immunocompromised Individuals
The provided evidence does not contain specific data on RTS,S vaccine safety in immunocompromised children. However, applying general vaccine principles:
RTS,S is a protein-based subunit vaccine with AS01 adjuvant, not a live vaccine 4, 5
As an inactivated vaccine, it does not pose the theoretical risks associated with live vaccines in immunocompromised hosts 6
Caution: Immunocompromised children may have reduced vaccine efficacy due to impaired immune responses, similar to other vaccines in this population 6
Clinical judgment required: While likely safe from a theoretical standpoint, efficacy data in immunocompromised children are lacking 2, 3
Important Clinical Caveats
Waning immunity: Vaccine efficacy decreases over time, necessitating the fourth dose at approximately 2 years of age 3, 1
Partial protection: RTS,S provides incomplete protection and must be used alongside other malaria control measures (bed nets, antimalarials, vector control) 2, 3
Geographic variation: Vaccine impact varies by transmission intensity, with greatest benefit in high-transmission areas 3
Coverage challenges: Achieving adequate coverage of all four doses requires strong immunization program infrastructure 1