Post-treatment Hemolysis in Severe Malaria: Elucidating the Biomechanical clearance of Pitted red cells for Prediction and Prevention – PHeSMalEBiPPP

Half of the world population is exposed to risk of malaria infection. Artemisinin derivatives are the most efficient and recommended treatment for malaria. Through their mode of action artemisinin derivatives induce pitting (expulsion of death parasite by the spleen without lysis of the host red blood cell). This transforms previous infected red blood cells to pitted red cells. Pitting is the major mechanism of parasite clearance in patients treated with artemisinine derivatives but not with other conventional antimalarial agents such as quinine. Some patients have a greater concentration of pitted red cells in circulation than do other patients. When many pitted red cells are produced during therapy, their delayed clearance few weeks later triggers post-artesunate delayed hemolysis (PADH). The early quantification of pitted red cells which express at least the Ring Erythrocyte Surface Antigen (RESA) and the P. falciparum Histidin Rich Protein 2 (HRP2), enables the prediction of PADH. Poor data are available for pitted red cells. How they trigger PADH remains unclear. Using HRP2-based dipsticks test, omics study, biochemical and cellular biology, we propose to optimize a simple test for the prediction of PADH that may improve the determination of the its incidence and facilitate the management of millions of patients. Moreover, we aim to characterize the changes induced by P. falciparum parasite in pitted red cells and the host responses in order to determine the mechanism of their clearance. This study would allow to define preventive approaches and increase the general knowledges on red blood cells biology and mechanisms of anemia.