Gametocytes are loaded with hemozoin resulting from hemoglobulin consumption. Their voracious need of this food may explain why they hide in the bone marrow where they find a large supply of young red blood cells generated by erythropoiesis. Malaria leads to hemolysis and anemia, often severe, and this triggers and amplifies erythropoiesis. Over the years it became evident that not only intravenous artesunate often causes hemolysis, but also ACT therapy. In a recent large-scale clinical trial in Maniema, RDC, it was found that Artemisia afra void of artemisinin causes less hemolysis than Artemisia annua rich in artemisinin. This may explain why Artemisia afra rapidly and completely eliminates gametocytes and consequently blocks transmission to mosquitoes.
Jérôme Munyanga, Lucile Cornet-Vernet, Michel Idumbo, Chen Lu, Pierre Lutgen, Christian Perronne, Nadège Ngombe, Jacques Bianga, Bavon Mupenda, Paul Lalukala, Guy Mergeai, Dieudonné Mumba, Melissa Towler, Pamela Weathers. Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial. Phytomedicine, 2019, 57, 49-56
Hemolysates increase erythropoiesis in the bone marrow and this provides the large supply of hemoglobulin needed by young gametocytes. An additional hypothesis is that the hemolytic effect of the epoxide artemisinin ruptures the young erythrocytes in the bone marrow, and that the voracious gametocytes take advantage of the easy and increased supply of reticulocytes (young red blood cells) and hemoglobin. And create a large population of strong stage V gametocytes. It would be dramatic if ACTs recommended by WHO since 20 years, had increased malaria transmission.
A process of this complexity is of course difficult to elucidate and reproduce in vitro.
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