Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria

摘要: Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized a 96-well microtiter plate format, retention in filters quantified by high-content imaging. stiffening activity of 40 pharmacological compounds assessed plates, using small molecule (calyculin) as positive control. calyculin spleen-mimetic microfluidic chips macrophage-depleted mice. Marked mechanical (80% 90%) mature obtained microplates following exposure at concentrations with no effect on parasite viability. Of tested, including 20 antimalarials, only 5 endoperoxides significantly increased (1.5- 2.5-fold; 24 h 1 μM). Mature exposed accumulated were cleared mice rapidly heat-stiffened erythrocytes, confirming results assay. An automated approach select gametocyte-stiffening has been established. Stiffening induces clearance both vitro vivo. Based physiologically validated tools, this screening cascade can identify novel uncover new targets block Innovative applications hematology also envisioned.