EFFECT OF DIHYDROARTEMISININ (DHA) ON HUMAN ERYTHROID CELL DIFFERENTIATION : IMPLICATIONS FOR MALARIA TREATMENT IN PREGNANCY

Objectives: WHO does not recommend the use of Artemisinin Combination Therapy (ACT) to treat malaria during pregnancy, because animal studies showed a depletion of embryonic erythrocytes. We investigated the effect of Dihydroartemisinin (DHA), the metabolite of artemisinins, on an in vitro model reproducing human erythropoiesis. Methods: CD34+ cells differentiate towards erythroblasts under erythropoietin stimulus in 14 days. DHA, 0,5 or 2 M, was added on different erythroid stages. At different time cell growth, morphology, Glycophorin A expression as well as globin genes have been evaluated. Results: DHA added on stem cells or on early progenitors caused a transient inhibitory effect, which was then fully restored. On the contrary, DHA added on more differentiated erythroblasts significantly blocked the erythroid differentiation. This indicates that DHA specifically affects the primitive erythropoiesis, occurring in the yolk sac. Therefore, during the first trimester of pregnancy, ACT must be avoided. EU Antimal Project 18834 is acknowledged