ICF: Seasonal R21 mass vaccination for malaria elimination
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: MRC Unit The Gambia at LSHTM
Abstract
Since 2000, the malaria burden in sub-Saharan Africa has substantially decreased thanks to the scale up of standard control interventions such as insecticide treated bed nets. However, progress has stalled since 2014, particularly in countries with moderate to high transmission. New interventions able to further reduce malaria transmission are needed.
Mathematical models suggest that mass vaccination with a pre-erythrocytic vaccine before the malaria transmission season could have a major impact on transmission. The development of malaria vaccines has targeted mainly infants as children under 5 are those at higher risk of severe malaria and death. The World Health Organization recently approved RTS,S/AS01, the first malaria vaccine recommended for children from 5 month of age. However, there are other malaria vaccine candidates under development, of which R21 is the most advanced as it has recently shown excellent protective efficacy against clinical malaria in children. Both RTS,S/AS01 and R21 are pre-erythrocytic vaccines as they target the stage of the malaria parasite that is injected by infected mosquitoes into humans. Therefore, if administered to the whole population, they could decrease transmission by reducing the proportion of successful infections by the vector. However, mass vaccination for malaria control has never been evaluated. The availability of R21 offers a unique opportunity for such an evaluation.
We propose to implement a community-based, cluster-randomized trial in two areas at the extremes of the malaria transmission spectrum, i.e., Upper River Region, eastern Gambia, with low to moderate seasonal transmission, and Central Plateau Region, Burkina Faso, with intense seasonal transmission. Fifty-four villages with 200-600 inhabitants (30 in The Gambia and 24 in Burkina Faso) will be randomized to either intervention or control arm. Mass vaccination with R21 (3 doses at 1 month interval) will be implemented in intervention villages just before the malaria transmission season (April-June). A booster vaccine dose will be administered the following year, in June, before the transmission season. Patients with clinical malaria will be diagnosed at local health facilities and in all study villages. At peak transmission season (November), a cross-sectional survey to determine the prevalence of malaria infection will be carried out in both study arms. Qualitative social science data on coverage, potential bottlenecks for the intervention, and acceptability will be collected; a health economics study on the cost-effectiveness of the intervention will be carried out. Following vaccination, the prevalence of malaria infection in all age groups at the peak transmission season in the intervention and control villages will be compared. Other outcomes include incidence of clinical malaria, prevalence of malaria infection in all age groups at peak transmission after the vaccine booster dose, safety and tolerability of R21, vaccination coverage at village level, cost-effectiveness of the intervention.
The capacity building component will include training on malaria modelling, a short course on malaria for regional health teams that will probably continue to be offered after completion of this project, a course on qualitative and mixed methods implemented by the Institute of Tropical Medicine, Antwerp, and at least 2 PhD scholarships.
Given the current stalling of progress towards the targets set up in the WHO Global Technical Strategy, it is important to determine the potential of any additional intervention able to accelerate progress towards malaria elimination. Results of the proposed trial will be essential for formulating a policy decision on mass vaccination against malaria. Results will be applicable to African countries with seasonal transmission and similar endemicity.
Mathematical models suggest that mass vaccination with a pre-erythrocytic vaccine before the malaria transmission season could have a major impact on transmission. The development of malaria vaccines has targeted mainly infants as children under 5 are those at higher risk of severe malaria and death. The World Health Organization recently approved RTS,S/AS01, the first malaria vaccine recommended for children from 5 month of age. However, there are other malaria vaccine candidates under development, of which R21 is the most advanced as it has recently shown excellent protective efficacy against clinical malaria in children. Both RTS,S/AS01 and R21 are pre-erythrocytic vaccines as they target the stage of the malaria parasite that is injected by infected mosquitoes into humans. Therefore, if administered to the whole population, they could decrease transmission by reducing the proportion of successful infections by the vector. However, mass vaccination for malaria control has never been evaluated. The availability of R21 offers a unique opportunity for such an evaluation.
We propose to implement a community-based, cluster-randomized trial in two areas at the extremes of the malaria transmission spectrum, i.e., Upper River Region, eastern Gambia, with low to moderate seasonal transmission, and Central Plateau Region, Burkina Faso, with intense seasonal transmission. Fifty-four villages with 200-600 inhabitants (30 in The Gambia and 24 in Burkina Faso) will be randomized to either intervention or control arm. Mass vaccination with R21 (3 doses at 1 month interval) will be implemented in intervention villages just before the malaria transmission season (April-June). A booster vaccine dose will be administered the following year, in June, before the transmission season. Patients with clinical malaria will be diagnosed at local health facilities and in all study villages. At peak transmission season (November), a cross-sectional survey to determine the prevalence of malaria infection will be carried out in both study arms. Qualitative social science data on coverage, potential bottlenecks for the intervention, and acceptability will be collected; a health economics study on the cost-effectiveness of the intervention will be carried out. Following vaccination, the prevalence of malaria infection in all age groups at the peak transmission season in the intervention and control villages will be compared. Other outcomes include incidence of clinical malaria, prevalence of malaria infection in all age groups at peak transmission after the vaccine booster dose, safety and tolerability of R21, vaccination coverage at village level, cost-effectiveness of the intervention.
The capacity building component will include training on malaria modelling, a short course on malaria for regional health teams that will probably continue to be offered after completion of this project, a course on qualitative and mixed methods implemented by the Institute of Tropical Medicine, Antwerp, and at least 2 PhD scholarships.
Given the current stalling of progress towards the targets set up in the WHO Global Technical Strategy, it is important to determine the potential of any additional intervention able to accelerate progress towards malaria elimination. Results of the proposed trial will be essential for formulating a policy decision on mass vaccination against malaria. Results will be applicable to African countries with seasonal transmission and similar endemicity.
Technical Summary
R21 is a safe and well tolerated novel pre-erythrocytic vaccine, with an overall protective efficacy in children of 75% against first or only clinical malaria episode and 74% against multiple episodes. Mathematical models suggest that mass vaccination with a pre-erythrocytic vaccine may substantially reduce malaria transmission. We will test this by implementing a cluster-randomized trial in two areas at the extremes of the malaria transmission spectrum, in The Gambia and in Burkina Faso. Study villages will be randomized to either the intervention (R21 mass vaccination) or control arm. An Information, Education and Communication campaign will be elaborated with the communities. Just before the malaria transmission, mass vaccination will be implemented for 2 years in intervention villages. In both study arms, a system of passive case detection to determine the incidence of clinical malaria will be set up at local health facilities and in all study villages, and a cross-sectional survey to determine malaria prevalence will be implemented at peak transmission season. Malaria prevalence in all age groups (determined by molecular methods) will be the primary outcome. Secondary outcomes will include clinical malaria incidence, malaria prevalence after the booster dose, safety and tolerability, intervention coverage. Mathematical modelling will be used to generalize the findings from the trial to provide direct support for policy decision-making. A cost-effectiveness evaluation will examine the value for money of the malaria vaccination campaign as part of the malaria control measures. Capacity building activities will include training in mathematical modelling, short courses on malaria and qualitative mixed methods, and PhD training.
