Oct 16, 2021 Volume 398 Number 10309 p1381-1460
Malaria vaccine approval: a step change for global health
On Oct 6, WHO announced that it will be recommending widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine for children in sub-Saharan Africa and in other regions with moderate-to-high Plasmodium falciparum transmission. Malaria has ravaged people’s lives for centuries; today the burden falls disproportionately on children in tropical regions. 229 million cases were recorded in 2019, and 409 000 people lost their lives, two-thirds of whom were younger than 5 years and living in sub-Saharan Africa. Broad roll-out across the region is now eminently achievable. Challenges remain, but this scientific triumph could be one of the most monumental opportunities in child health for a generation.
RTS,S is the first parasite vaccine to have obtained regulatory approval. Designed to target the sporozoite phase of the lifecycle, it blocks infection of the liver, where the parasite would otherwise mature, multiply, re-enter the bloodstream, and infect erythrocytes. The first attempts at creating a malaria vaccine began in the 1960s, and the road to victory has been difficult. Most trials ended in disappointment and many observers doubted whether a malaria vaccine would ever become a reality. The success of RTS,S is the culmination of generations of scientific ingenuity, three decades of profitless research and development by GSK, the foresight of generous funders, and close collaboration within African communities.
Pivotal phase 3 trials in 2009–14 took place in Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania. The final results, published in The Lancet in 2015, showed that children in these regions receiving three doses of RTS,S plus a booster dose, between 5 and 17 months of age, would have a 29% reduced risk of severe malaria. Crucial implementation programmes in Kenya, Ghana, Malawi, Burkina Faso, and Mali, which will continue until 2023, have confirmed that, when combined with seasonal malaria chemoprevention, RTS,S can reduce death from malaria by over 70%. Compliance and acceptance are high, despite the complexity of the vaccination schedule, and implementation appears realistic, even in countries with under-resourced health-care infrastructure.
WHO’s endorsement of RTS,S comes at a crucial time in malaria control. Between 2000 and 2015, widespread deployment of simple but innovative control measures turned the tide against malaria. Insecticide-treated mosquito nets, indoor spraying of homes, rapid diagnostic tests, and new treatments and prophylactics are estimated to have averted 7·6 million deaths since 2000. But progress has stagnated over the past 6 years, especially in high-burden countries. Evolving mosquito and parasite populations are escaping detection by diagnostic tests and developing resistance to insecticides and antimalarials. Only last year, WHO warned that global targets of reducing malaria case incidence and mortality rates by at least 90% by 2030 would be missed. There is hope that the vaccine can turbocharge malaria control.
How the vaccine will fit into wider programmes of malaria control remains unclear. Understandably, there are questions over who will pay to make the vaccine available to all who need it, many of whom live in countries with fragile health systems. After a period of stalled development funding for malaria control, there is optimism that international donors will fund vaccination, as noted in a World Report. A reliance on international donors need not be the only option, however. The 2019 Lancet malaria eradication Commission noted that in addition to innovative technology, such as vaccines, domestic funding for malaria control would accelerate progress. Domestic spending on health is woefully low in the sub-Saharan region, and projections suggest that this is unlikely to improve over the next 30 years. But if countries could fund health system strengthening and overcome the barriers to ensure equitable access, they might avoid pitfalls that can come from narrow, vertical approaches to global health issues, which have a history of skewing incentives and neglecting the wider needs of population health.
A strong case for investment in health to reduce child and maternal mortality was made by the Lancet Commission on Investing in Health. For a disease that kills a child every 2 minutes, a vaccine with even a modest 30% efficacy could have a considerable effect on improving child survival. Wide availability of a malaria vaccine will mean that the prospect of ending preventable child mortality within a generation is now a step closer.