R21-PD

The challenge

Anaemia is common among children in sub-Saharan Africa, due to malnutrition, malaria and other infections. Severe anaemia is treatable, but successfully treated children remain highly vulnerable after discharge from hospital, and at elevated risk of readmission and death.

In malaria-endemic areas, malaria is a major cause of readmission. High mortality after treatment of anaemia has been partially addressed through post-discharge malaria chemoprevention – provision of antimalarial drugs to children over the first few months after they leave hospital. This has been shown to reduce the risk of death by 77% and the risk of readmission by 55%. The WHO recommends this strategy and has been introduced in several African countries.

Despite its success, post-discharge malaria chemoprevention offers protection for only 3–4 months, while the elevated risk of death extends out to 12 months. Longer periods of preventive treatment could be considered, but this would be expensive, and adherence becomes a major challenge with long courses of drugs.

The project

Having pioneered the use of post-discharge malaria chemoprevention, the R21-PD project team is exploring whether an R21/Matrix-M malaria vaccine booster could provide longer-term protection after hospital discharge.

With malaria vaccination being rolled out widely in sub-Saharan Africa, many hospitalised children are now likely to have been vaccinated. A booster dose could generate an additional immune response during the post-discharge period of vulnerability. It takes 2–4 weeks for immune responses to peak after vaccination, during which time children would be protected by conventional malaria chemoprevention. 

To test this theory, the project is carrying out a clinical trial in moderate- to high-transmission areas of Kenya, Malawi, and Uganda. More than 600 children treated for severe anaemia will be randomised to either standard post-discharge malaria chemoprevention or ‘enhanced’ protection with the addition of an R21/Matrix-M vaccine boost. The trial will evaluate whether this approach further reduces mortality and the risk of readmission during the following year. 

The project will also explore the acceptability of the new approach to key groups, such as caregivers and health workers, and estimate its likely cost-effectiveness and budget impact.

Impact

The R21-PD project could help to protect a highly vulnerable group of children. It will:

• Determine whether R21/Matrix-M vaccination further reduces post-discharge mortality after treatment for severe anaemia.
• Show whether the strategy is feasible, acceptable and offers good value for money.

With more than half of all children in sub-Saharan Africa being affected by anaemia, enhancing protection against malaria during the critical first year after hospital recovery could not only significantly reduce mortality but also reduce pressures on health systems by preventing readmission.