Imatinib augments standard malaria combination therapy without added toxicity

Abstract

To exit its erythrocyte host, the malaria parasite Plasmodium falciparum must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Given that imatinib inhibits erythrocyte tyrosine kinases and has a favorable safety profile, we investigated whether combining imatinib with standard of care (SOC) for malaria could be both well tolerated and therapeutically effective. In a study conducted in Vietnam, where one-third of patients with uncomplicated P. falciparum malaria experience delayed parasite clearance (DPC), patients were treated for 3 days with either the region’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/day) or imatinib (400 mg/day) plus SOC. Participants receiving imatinib + SOC showed no increase in adverse events and experienced a significantly faster decline in parasite density and fever, with no cases of DPC. Notably, these benefits were most pronounced in patients with the highest parasite densities, who are at greater risk for severe complications and death. These findings suggest that imatinib enhances SOC therapy for P. falciparum malaria without introducing significant drug-related toxicities.