Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review

Abstract

Artemisinin derivatives are widely used antimalarial drugs. There is some evidence from in vitro, animal and clinical studies that hemoglobinopathies may alter their disposition and antimalarial activity. This review assesses relevant data in α-thalassemia, sickle cell disease (SCD), β-thalassemia and hemoglobin E. There is no convincing evidence that the disposition of artemisinin drugs is affected by hemoglobinopathies. Although in vitro studies indicate that Plasmodium falciparum cultured in thalassemic erythrocytes is relatively resistant to the artemisinin derivatives, mean 50% inhibitory concentrations (IC50s) are much lower than in vivo plasma concentrations after recommended treatment doses. Since IC50s are not increased in P. falciparum cultures using SCD erythrocytes, delayed post-treatment parasite clearance in SCD may reflect hyposplenism. As there have been no clinical studies suggesting that hemoglobinopathies significantly attenuate the efficacy of artemisinin combination therapy (ACT) in uncomplicated malaria, recommended artemisinin doses as part of ACT remain appropriate in this patient group.

Figure 1.

Maximum plasma dihydroartemisinin concentrations after 2.4 mg/kg artesunate given intravenously to 266 patients with severe malaria (median and 2.5th to 97.5th percentiles) [27], and to 20 healthy volunteers with α-thalassemia or normal hemoglobin (HbAA) (mean and absolute range) [24]. The shaded area represents the 50% inhibitory concentration for DHA at 2 standard deviations above the mean for Plasmodium falciparum cultured in α-thalassemic erythrocytes.