Abstract

Malaria remains the leading cause of morbidity and mortality in sub-Saharan Africa, prompting the development 
and deployment of vaccination strategies. RTS, S/AS01 was the first malaria vaccine recommended by WHO for 
children in endemic regions, targeting Plasmodium falciparum. This review aimed to critically assess the efficacy, 
safety profile, and population-level impact of RTS, S/AS01 vaccine implementation in malaria-endemic settings. A 
systematic literature search was conducted across peer-reviewed journals and WHO reports focusing on Phase III 
trials, pilot implementation programs, and post-marketing surveillance studies published within the past decade. 
RTS, S/AS01 demonstrated moderate efficacy against clinical malaria (approximately 30-40%) and severe malaria 
(around 30%) following a four-dose schedule in children aged 5-17 months; efficacy wanes over time but is partially 
restored by a fourth booster dose. Safety data indicated a generally favorable profile, with febrile seizures being the 
most common vaccine-related adverse event; signals of increased meningitis and cerebral malaria incidence have 
been observed but are inconclusive and require further post-implementation surveillance. Population-level modeling 
and early pilot program data revealed reductions in malaria cases and hospitalizations, though challenges such as 
vaccine hesitancy, logistical implementation issues, and ensuring equitable coverage persist. RTS, S/AS01 offers a 
valuable addition to malaria control in endemic regions with proven benefits despite partial protection and some 
safety concerns. Continued monitoring and tailored implementation strategies are essential to maximize public 
health impact.