The first phase of a trial undertaken in young children in Burkina Faso and Mali to investigate the impact of combining vaccination with the RTS,S/AS01
E malaria vaccine with SMC has recently been completed [
7,
8]. In this study, conducted in areas of highly seasonal malaria transmission, 5920 children were enrolled at the age of 5–17 months and allocated to one of three groups. Children in one group received four, monthly courses of SMC with sulfadoxine-pyrimethamine plus amodiaquine (SP + AQ) each year during the malaria transmission season (the standard of care in both countries) plus control non-malarial vaccines (rabies and hepatitis A), those in a second group received RTS,S/AS01
E plus an SMC placebo, and those in a third group received both RTS,S/AS01
E and SMC. RTS,S/AS01
E was administered in three, monthly priming doses prior to the 2017 malaria transmission season, and then a single booster dose was given shortly before the start of the malaria transmission season during each of the following two years (2018 and 2019). All children were provided with an insecticide-treated bednet at the start of the trial. The primary trial endpoint was the incidence of clinical attacks of malaria; predefined secondary endpoints included hospital admissions with malaria and death from malaria [
7]. During three years of follow-up, RTS,S/AS01
E alone was non-inferior to SMC in preventing malaria and the combination of the two interventions led to a substantial reduction in the incidence of uncomplicated cases of malaria, hospital admissions with malaria and deaths from malaria over the level of protection obtained with either intervention given alone. A high level of protection was observed in the children in the group who received both interventions during the second and third years of the trial when children received only a single booster dose of RTS,S/AS01
E at the start of the malaria transmission season [
8]. Most breakthrough cases among children in the combined intervention group occurred during the last month of the malaria transmission season, and if these children had been given an additional fifth round of SMC, they would have been almost completely protected from clinical malaria. This trial is now being continued with an additional yearly pre-transmission season dose of RTS,S/AS01
E, given with or without SMC, until children reach the age of five years, the age after which SMC is no longer administered in Burkina Faso or Mali. A fifth round of SMC will be given in the study area in Burkina Faso in 2021 in concordance with a national strategy on the delivery of SMC in the country, which has one of the highest rates of malaria transmission in Africa. In Senegal, SMC is given up to the age of 10 years and here, and in any similar situation, consideration could be given to extending the age of seasonal vaccination beyond 5 years provided that it can be shown that many repeated doses of vaccine are safe and effective.
Combination of seasonal vaccination with an effective programme of chemoprevention could have a major impact on the malaria burden in the countries of the African Sahel and sub-Sahel where malaria transmission is markedly seasonal, and where six of the ten African countries included in the WHO’s ‘High burden-High Impact’ programme are located. However, further work is required to determine whether a programme of this kind could be deployed at scale and, if so, how this might be achieved most effectively. Potential approaches include utilization of targeted vaccination programmes to deliver both the priming and the booster doses with the latter given just prior to the malaria transmission season, as done during the first phase of the trial currently underway in Burkina Faso and Mali, utilizing the heath facilities and out reach clinics of the Expanded Programme of Immunization (EPI) to give both priming and booster doses, as is being done in the pilot RTS,S/AS01
E programmes currently underway in Ghana, Kenya and Malawi [
9] or using a combination of the two approaches with the three priming doses being delivered through the EPI clinic based programme and and pre-transmission season booster doses given through a mass vaccination campaign. Which approach might be optimal in a specific area is likely to be influenced by the vaccination coverage currently achieved through the routine EPI programme in a particular area, the duration of the transmission season, and the age pattern of malaria (particularly severe malaria) in the target population. Repeated mass campaigns would be demanding but might achieve higher coverage with the malaria vaccine than administration of priming and booster doses at routine EPI clinics or out-reach clinics in some areas. The feasibility, acceptability to the local population and health service providers, and the economic costs of different approaches to delivering the combination of seasonal vaccination and SMC need to be explored.