African countries embrace first malaria vaccine despite low efficacy

A child dies of malaria every two minutes. In line with global health’s “one death is one too many” mantra, in 2021 the World Health Organization recommended the expanded use of the first malaria vaccine among children living in regions with a high burden. The vaccine — RTS,S — has been criticized for its relatively high rollout costs and low 30% efficacy but WHO says it has resulted in a more than 10% drop in child deaths in three pilot countries: Ghana, Kenya, and Malawi. Gavi, the Vaccine Alliance has since opened up applications for the three pilot countries and other eligible countries to roll out the vaccine nationally. Health experts said African countries have responded positively to this call despite initial concerns. According to WHO, at least 28 African countries are planning to introduce the vaccine this year, and 13 have already applied for Gavi funding. “African ministers say this is the vaccine they want more than any other, and they demanded it,” Gavi CEO Seth Berkley said during a webinar. “They don't want to wait; they want it now.” Expanding coverage Since the RTS,S pilot began in 2019, more than 1.2 million children have received at least one dose of the vaccine. In Kenya, over a million jabs of the four-dose vaccine have been provided to children across eight counties and close to 400,000 children have received at least one dose. Susan Nakhumicha Wafula, Kenya's cabinet secretary for health, said this has resulted in “a dramatic reduction in the number of malaria cases and hospitalizations” in the 26 sub-counties where the vaccine has been administered. According to the health ministry, when the malaria vaccine was launched in Homa Bay county in 2019, the lake-endemic malaria region had a malaria prevalence of 27% but this has now dropped to 19%. “This can be attributed to the integrated malaria prevention strategies including utilization of long lasting insecticide treated nets, indoor residual spraying where available, prompt diagnosis and treatment, and the malaria vaccine as an additional and complementary malaria prevention tool,” the health ministry stated. This month the country expanded the coverage area to 25 more sub-counties. “In the coming years, our objective is to continue to expand malaria vaccination to other parts of the country, as more supplies of the vaccine become available,” Dr. Lucy Mecca, head of Kenya's national vaccines and immunization program, said. Similar developments are underway in Ghana where the Malaria vaccine implementation program was launched in May 2019 in 42 districts across seven regions. As of December 2022, a total of 1.4 million doses of the vaccine had been administered in the country and about 460,000 children received at least one dose, and nearly 185,000 completed all four doses. The expanded rollout — which began in February — will increase coverage to 51 additional districts in the seven regions. John Bawa, team lead for vaccine implementation in Africa at PATH, said they expect that the number of children in the country who would have received at least one dose of the vaccine would have exceeded 800,000 by the end of the year. In addition to increased access the pilot has also shown a strong acceptance of the vaccine and continued use of other prevention tools in the communities targeted. “The introduction of the malaria vaccine did not affect the use of insecticides at all. It rather increased access to malaria intervention,” Bawa said. “In the case of Ghana, for instance, we had some children that routine malaria interventions were not reaching them. The malaria vaccine reached them even when they were not receiving insecticide-treated bednets.” He added that a survey conducted among mothers in areas not included during the pilot in Ghana found that more than 60% were ready to bring their children to receive the vaccine once it became available. “So that shows the kind of enthusiasm that those who are not yet included already have, to be part of the process,” he said. Supply and pricing Bawa said there are plans to make doses available nationwide in Ghana and in other countries as early as next year but the vaccine’s limited supply will determine the rate of expansion. Kate O'Brien, director of the department of immunization, vaccines, and biologicals at WHO, said supply has been secured for wider use. “The initially limited supply will be allocated to children living in areas of highest need across endemic countries, with phased expansion to other countries as supply increases,” she said. GSK committed to supplying up to 15 million doses of the vaccine annually, in addition to 10 million doses already produced and donated for use in the pilot programs in Malawi, Kenya, and Ghana. In 2021, GSK announced a product transfer agreement with Bharat Biotech of India — which is meant to become the sole supplier of RTS,S by 2029, though GSK would still supply the adjuvant, a key ingredient in vaccines. In the meantime, Berkley said Gavi is working to get other manufacturers to step in and fill the supply gap. When supply eventually improves, Bawa said the relatively high $5-per-dose price tag is expected to reduce gradually. From January 2024, countries are expected to make co-payments for the vaccine and some countries such as Ghana have already agreed to this, he added. "This shows a significant demand for the vaccine and countries are quite enthusiastic. They know that they need to do the co-payment because they see the benefits that [the vaccine] will bring to them," he said. Scaling hurdles and considering other options One of the major challenges encountered during the pilots has been getting every child to receive the full four doses. In Ghana, for instance, Bawa said several mothers forgot to bring their children for the fourth dose and that health workers also forgot to remind them about it. This has resulted in sub-optimal coverage. “I would say that we have seen an average coverage of about 45% for the fourth dose, which is not so bad for a new vaccine, especially given the time of the rollout,” he said. In its new recommendation, WHO provided some flexibility for countries to consider what works best within their context. In line with this, Ghana has decided to move the timing for the fourth dose from 24 months to 18 months to coincide with the period when the children are receiving the second dose of the measles, mumps, and rubella, or MMR, vaccine. “As a minimum, we expect the coverage to be at par with the coverage for MMR 2 which is over 80% in the country already,” Bawa said. The Bill & Melinda Gates Foundation, a major funder of the RTS,S vaccine trials, is also working on a next-generation suite of anti-malarial tools including second-generation vaccines, monoclonal antibodies, and attractive targeted sugar baits. “Early-stage research already suggests that a low-cost, single-dose antibody treatment could protect children, and that a solution for all ages may be just one more breakthrough away,” Philip Welkhoff, director for Malaria at the Gates Foundation, wrote in a blog post. Berkley added that while Gavi is backing RTS,S rollout in Africa, it is also tracking progress regarding other vaccine options, especially those that may demonstrate higher efficacy. The most advanced is the R21/Matrix-M vaccine developed at the University of Oxford and currently manufactured by the Serum Institute of India. In 2022, it was reported that the vaccine reached the WHO goal of 75% or greater efficacy over 12 months. WHO said the R21/Matrix-M vaccine is in late-stage clinical development, and if recommended for use, could increase global supply and access. A phase 2 trial to demonstrate that the vaccine is well-tolerated and maintains its efficacy when administered with the antimalarial drug combination is also underway in Thailand.