In the global fight against malaria, researchers have discovered how the malaria parasite protects itself by building resistance against the last-line in antimalarial medications and how a new medical treatment can overcome the parasite’s defenses.
University of Melbourne’s research shows that anti-malarial drugs known as artemisinins may function by chemically damaging the malaria parasite’s proteins, causing them to activate a cellular stress response. Parasites resistant to artemisinins have developed a more vigorous stress response, making them impervious to the normal drug treatments.
However, it appears that with prolonged artemisinin treatment, even this improved stress response can be overwhelmed, leading to parasite clearance, suggesting that extending artemisinin treatment or co-administering drugs that target the stress response can overcome drug resistance.
Lead researcher Leann Tilley, working with colleagues from Thailand, Singapore and the USA, demonstrates that resistant strains of Plasmodium falciparum sourced from the Pailin region of Cambodia can be made susceptible to artemisinin treatment either through extended drug treatment or through a combination therapy of artemisinins and clinically-used proteasome inhibitors.
Tilley added that their detailed kinetic observations are used to develop a mathematical model that allows, for the first time, a simulation of parasite responses to artemisinin chemotherapy in patients and this model can be used in a clinical setting to assess whether parasite strains have developed artemisinin resistance to a level that will cause clinical failures, thus improving detection and treatment options.
