Multiple mechanisms of resistance in sickle cell trait (HbAS). Increased oxidative stress and host microRNAs in HbAS erythrocytes inhibit normal parasite development (1). This leads to inhibition of parasite transcription and protein expression (2). The formation of Maurer’s clefts is impaired due to aberrant actin morphology, which prevent normal protein trafficking (3). Binding of parasite proteins which reach the erythrocyte membrane is inhibited by haemichromes, resulting in reduced surface expression of PfEMP (4). Reduced PfEMP expression results in less cytoadherence, which results in increased susceptibility to splenic clearance via phagocytosis (5). Oxidative stress also results in increased haemachrome formation (6), inducing band 3 mediated senescence and phagocytosis (7). Enhanced phagocytosis promotes an immune response (8). Increased production of antibodies against parasite proteins further inhibits cytoadherence and amplifies the effect (9).