By David Tellett
Sub-Saharan Africa is home to over 1 billion people, and according to WHO estimates for 2021, approximately 91.7% of the population there is at risk of contracting malaria.1World malaria report 2022, Annex 4G. Sum of all countries in the WHO African Region (AFRO) in the spreadsheet (Algeria, which is in AFRO but is not Sub-Saharan, is not listed) plus Somalia. 80% of malaria deaths on the continent are in children under the age of 5, and it is in young children that the R21 and RTS,S vaccines have been successfully tested. But with nearly 200m children under 5 living in sub-Saharan Africa and 40m born every year, not all can receive the vaccine, at least right away. Initial vaccine supplies are expected to be limited, particularly if there are delays with approvals and rollout plans for the R21 vaccine. Although Plasmodium falciparum, the most virulent species of the malaria parasite, is endemic in most parts of sub-Saharan Africa, some regions are affected significantly more than others.
Over half the world’s malaria deaths come from just four countries — Nigeria, the Democratic Republic of Congo, Uganda, and Mozambique2WHO Malaria Fact Sheet, July 2022 — in part due to high population (in Nigeria and the DRC), high prevalence of malaria parasites, and lack of effective use of other malaria prevention strategies. Over a quarter of the world’s malaria deaths are in Nigeria alone. The list of countries with some level of endemic malaria is much longer, and the WHO’s prioritization framework identifies 32 countries for vaccine rollout.3WHO 2022
Areas with the most children at risk from malaria are higher up the priority list, but the rollout will also depend on the finalization of local approvals and plans. The WHO has also promised some of the RTS,S vaccine supply to continue vaccinations in Kenya, Ghana, and Malawi, where the Malaria Vaccine Implementation Programme was conducted.
The framework prioritizes initial allocations based mainly on prevalence of malaria and child mortality in different regions of the 32 countries. Regions with the highest level of malaria prevalence, or moderate malaria prevalence combined with high child mortality, get a higher prioritization.
25 million children are born in these regions every year.4WHO 2022. Fortunately, production capacity is expected to be sufficient to supply over 25 million children per year. The Serum Institute of India has the capacity to manufacture 100m R21 vaccines per annum,5Serum Institute of India, October 2023 although as of March 2024, it is waiting on final local approval by the Indian regulator. The supply of RTS,S is initially limited to 18m vaccines up to 2025.6Gavi Malaria Vaccine Shipment FAQs Both plan to scale up production in future years.7Serum Institute, October 2023. There is also a technology transfer agreement in place to manufacture additional doses of RTS,S with a partner company in future years, but the size of an increase to future production is less certain.
Each child needs a course of four vaccinations using one of the vaccines, with three doses to be delivered from the ages of 5 months and upwards, and a booster vaccine a year later. As booster injections will not be delivered in the first year of vaccine rollout, only around 75 million vaccine doses are required initially to protect 25 million children born. Each subsequent year’s production will include booster vaccines to finish off the previous year’s course. If total available vaccine production in the first year consists of 100 million R21 doses and up to 6 million RTS,S doses, this potentially leaves over 30m additional doses to be allocated.
| Regions (by malaria prevalence) | Children born per year | Vaccines needed (per year, future years including boosters). | Vaccines needed (first year, when no boosters are delivered) |
| MVIP Area
Guaranteed RTS,S supply |
~900,000 | ~3,600,000 | 2,700,000 |
| Category 1
Most at risk, highest priority |
7,900,000 | 31,700,000 | 23,700,000 |
| Category 2 | 7,800,000 | 31,100,000 | 23,400,000 |
| Category 3 | 4,500,000 | 17,800,000 | 13,500,000 |
| Category 4 | 2,300,000 | 9,400,000 | 6,900,000 |
| Category 5
Least at risk, lower priority |
1,600,000 | 6,500,000 | 4,800,000 |
| Total | 25,000,000 | 100,000,000 | 75,000,000 |
| Other regions of 32 malaria infected countries not in initial allocation (lower risk) | 11,000,000 | Up to 33,000,000 | – |
Based on Table 1 and Table 2 in the appendix of Framework for the allocation of limited malaria vaccine supply, pages 20 and 21. “Vaccines needed” figure includes 100% uptake and no wastage. In practice, the number of vaccines not used because the children fail to complete a full course of vaccinations is likely to exceed numbers of vaccines wasted due to breakage, loss or storage failure – in line with numbers from large-scale trials.
This is a considerably more optimistic scenario than when only the production-constrained RTS,S was available, and 1DaySooner wants to ensure that all vaccines produced in the first year are used in the first year to maximize the number of lives saved.
One way to do this would be to vaccinate slightly older children in the highest risk areas (say, children aged 6-36 months). The current rollout plan recommends vaccinating children alongside other routine EPI vaccinations,8Gavi Malaria Vaccine Support Interim Guidelines, 2024 starting 5 months after they were born, which would mean older children missing out. As children under 5 years old are still at risk, and the R21 trials indicate the R21 vaccine is effective at protecting children up to the age of 36 months,9Schmit et al., (2024) it may be using vaccines produced in the first year to vaccinate older children in the highest-risk areas. If 75 million vaccinations are used to vaccinate 25 million children born in 2024 and there are ~30 million additional doses left over, there would be more than enough to provide a course of three vaccinations for the 7.9 million children born in the highest risk (Category 1) regions in 2023, for example.
There are also millions of children born every year outside the highest risk areas identified by WHO. Regions prioritized for vaccination (Category 1-5) only include those with a PfPR2-10 of 10%.10WHO 2022 This malaria prevalence measure means at least 10% of children between the ages of two and ten years old have malaria parasites in their bloodstream at any one time. Children in many areas below this threshold are still highly likely to contract malaria and are at risk of death. Even with malaria prevalence (PfPR2-10) as low as 3%, the Imperial study discussed in our status report estimates that a vaccination program could save over 38,000 cases of clinical malaria and 250 lives per 100,000 fully vaccinated children.11Schmit et al., (2024) Therefore a strong case can be made to vaccinate infants in lower risk regions when vaccine production is sufficient – up to another 11 million children annually in the 32 countries identified by the WHO, and other high-risk countries such as Rwanda and Senegal.
Vaccinating children is not a one time effort. Until malaria can be eradicated from more regions there will be an ongoing demand of at least 100 million vaccines every year. Other malaria vaccines are in development, but RTS,S and R21 are the only vaccines available now. Local health services and overseas funders will need to meet ongoing costs of vaccination programs, but current evidence suggests the vaccines are a cost effective way of saving lives that could reduce the huge burden malaria treatment places on local health services. Ensuring that all vaccines produced in the first year are delivered and used in the first year will maximize lives saved, and many more lives can be saved if production is scaled up and vaccines delivered in a cost effective manner to regions outside the scope of the initial rollout.