In vitro sensitivity of artemeter in Plasmodium falciparum-infected beta-thalassaemic trait erythrocytes

Abstract

Using an age-fractionated RBC model, we investigated the in vitro sensitivity of artemether in β-thalassaemic RBC infected with the K1 and FC27 strains of Plasmodium falciparum and, to study the role of oxidant stress in modulating the sensitivity pattern, pro-oxidant (riboflavin) and antioxidant (vitamin E) agents were added to cultures in the presence of artemether. With the FC27 strain, the artemether IC₅₀ doses in thalassaemic samples (whole blood and fractions) were significantly higher compared to equivalent normal RBC samples (P<0·05). However, with the K1 strain, such a significant difference was not demonstrable. The addition of vitamin E reduced the antimalarial effect of artemether in both the FC27 and K1 strains (P<0·0001). In contrast, the addition of riboflavin resulted in a significant increase in antimalarial activity (P<0·0001). This effect of the drug combinations was not influenced by the red cell type (P<0·0001) and there was no interaction between red cell type and drug type (P<0·0001). These findings show that reduced sensitivity to artemether occurs in whole blood and age-fractionated β-thalassaemic trait RBC. It appears that the RBC redox status does not influence the sensitivity to artemether.