Timing of the fourth dose of RTS,S/AS01 malaria vaccine in perennial settings: a modelling study

BackgroundThe recommendation of the RTS,S/AS01 malaria vaccine for use in children in moderate to high transmission areas by the WHO in 2021 provided another crucial tool in reducing malaria morbidity and mortality. As countries introduce the RTS,S vaccine, there is an interest in exploring vaccination schedules that align with existing routine health touch points and to optimize vaccine coverage. MethodsThis study used OpenMalaria, an individual-based, stochastic model of malaria transmission and disease progression, to assess the impact of different vaccination timing schedules and coverage on uncomplicated malaria cases, severe malaria cases, and malaria-related deaths across different archetypal transmission settings. We ran simulations comparing fourth dose protection against infection and timings at six-, nine-, 12-, 15- and 18-month intervals following the primary series, including exploring ranges of plausible protection assumptions for many of the dose timings. ResultsThe primary series substantially reduces the malaria burden across transmission settings, regardless of timing of the fourth dose. While the number of cases averted varies by baseline prevalence, our modelling suggests that the primary series is responsible for around 54-93% of the total clinical and severe cases averted across transmission archetypes in perennial settings. Additionally, a fourth dose of the vaccine could avert additional 9-46% malaria cases and 7-41% severe cases in addition to the primary series alone. We find potential flexibility in timing this dose, especially when focused on 6 to 12 months following the primary series. ConclusionsIn addition to the primary series, use of a fourth dose of the RTS,S vaccine can be tailored to country specific context and linked to existing health touch points to ensure adequate coverage of this dose. In particular, a fourth dose delivered between 15- and 21-months of age with high population coverage will likely avert the largest proportion of cases of clinical malaria, severe malaria, and deaths in perennial settings, across transmission intensities. Trial registrationN/A