Seasonal R21 Mass Vaccination for Malaria Elimination

This is a cluster randomized trial to determine the impact of seasonal R21/MM mass vaccination (all ages) on malaria transmission and morbidity. Fifty-four villages (30 in The Gambia and 24 in Burkina Faso) will be randomized to either mass vaccination with R21 or no mass vaccination.

The primary objective is to compare in intervention and control clusters the prevalence of malaria (all age groups) at peak transmission after seasonal mass vaccination with R21 (3 monthly doses).

Secondary objectives are:

1. To assess the safety and tolerability of R21 through spontaneously reported adverse events.
2. To compare in intervention and control clusters the incidence of malaria infection (all age groups) during the malaria transmission season following seasonal mass vaccination with R21 (3 monthly doses).
3. To compare in intervention and control clusters the incidence of clinical malaria (all age groups) after seasonal mass vaccination with R21 (3 monthly doses).
4. To compare in intervention and control clusters the prevalence of malaria (all age groups) at peak transmission after one booster dose of R21.
5. To compare in intervention and control clusters the incidence of malaria infection (all age groups) during the malaria transmission season following one booster dose of R21.
6. To compare in intervention and control clusters the incidence of clinical malaria (all age groups), after one booster dose of R21.
7. To determine the coverage of seasonal mass vaccination with R21 (primary series of three vaccinations and booster) in intervention clusters and related socio-cultural factors
8. To estimate the cost of seasonal mass vaccination with R21 administration.
9. To estimate the cost-effectiveness of seasonal mass vaccination with R21 compared to standard malaria control measures.

The exploratory objective is to determine whether serological markers can detect changes in malaria transmission following mass vaccination with R21.

This is a cluster-randomized controlled trial. Fifty-four villages (30 in The Gambia and 24 in Burkina Faso) will be randomized to either mass vaccination with R21 or no mass vaccination. Therefore,15 medium-sized (200-600 people) villages in The Gambia and 12 medium-sized (200-600 people) villages in Burkina Faso will receive the intervention. All study villages will receive standard control intervention, e.g., seasonal malaria chemoprevention, insecticide-treated bed nets, implemented by the National Malaria Control Program and according the National Strategic Plan for malaria control. Mass vaccination will be completed before the start of the malaria transmission season, i.e. July.

A cross-sectional survey to estimate malaria prevalence will be implemented at peak transmission, both following the mass vaccination with 3 doses (first year) and the booster dose (second year). A blood sample will be collected during the malaria transmission season from a cohort of randomly selected individuals to determine the incidence of malaria infection. A system of passive case detection to determine the incidence of clinical malaria will be set up throughout the study period, with special attention to the malaria transmission season (July-December).

Eligibility Criteria:
Inclusion Criteria:

1. Age≥ 5 months.
2. Willingness to comply with trial procedures.
3. Individual written informed consent obtained at the beginning of the study.

Exclusion Criteria:

1. Pregnancy
2. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone.
3. Any history of anaphylaxis in relation to vaccination.
4. Known chronic illness.
5. Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.