This article is part of a series of research impact stories related to our REF 2021 submission.
Malaria remains one of the world’s biggest killers, with an estimated 627,000 deaths from the disease in 2020 alone. A research team at St George’s, led by Professor Sanjeev Krishna, has set out to revolutionise the way the disease is treated, reducing both the number of deaths and cost of treatment.
Artemisinins are a group of antimalarial drugs, derived from the leaves of sweet wormwood (Artemisia annua). They have transformed how malaria was treated after their discovery in China in the 1970s. Further studies, leading to more easily used derivatives enabled malaria treatments that could be tested in clinical trials.
At the turn of the 21st Century, Professor Sanjeev Krishna and colleagues conducted a study of one such artemisinin derivative, artesunate, in combination with another drug called amodiaquine. The results showed that the new combination was both safe and more effective than taking amodiaquine on its own. This result triggered a run of further studies, testing the administration of the drug combination in parts of the world where multidrug-resistant malaria was emerging.
Following positive findings of the overall superiority of the combination and its safety, a new formulation of artesunate was developed, to be delivered via the rectal route.
“With millions of children around the world unable to access healthcare for hours or days, giving antimalarial treatments can be life-saving,” says Professor Krishna.
“Our research demonstrated not only that delivering the drug via the rectal route was simpler and safe, but that the dose used resulted in an up to 50% increase in survival rates for children delayed more than six hours in reaching clinics.”
As well as demonstrating the effectiveness of new treatments, the team also developed tools to help predict and overcome resistance to treatment.
“Drug resistance is a common cause of treatment failure,” explains Professor Krishna. “By building an assay that can predict whether a treatment is likely to stop working, we can optimise drug combinations for patients in a particular geographic area.” This assay is now used globally to assess potential drug resistance to some antimalarial combinations.
Thanks to the work of the team, rectal artesunate has since been added to the World Health Organization’s Model List of Essential Medicines for Children and is registered in 16 countries for use. The continuing impact on mortality rates of this treatment in children was demonstrated by a study in Zambia, which found that deaths in children with severe malaria decreased by 96% after treatment with the drug.
“Our research has provided the underpinning data showing that a simpler, cheaper and more convenient way of administering antimalarials can greatly improve the management of children in busy paediatric wards in malaria-affected regions,” says Professor Krishna.
“It has been an incredible privilege to see the implications of our work on saving the lives of children with malaria especially in some of the worst affected African countries,”
The research group has more recently found evidence showing that use of artemisinins is unlikely to lead to resistance and can continue to be used to treat malaria. You can find out more in our news story.