Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently.

Autor:	Portugaliza HP; ISGlobal, Hospital Clinic - Universitat de Barcelona, Barcelona, Spain.; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Department of Global Health, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands., Miyazaki S; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Geurten FJ; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Pell C; Department of Global Health, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, Netherlands., Rosanas-Urgell A; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Janse CJ; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Cortés A; ISGlobal, Hospital Clinic - Universitat de Barcelona, Barcelona, Spain.; ICREA, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Oct 21; Vol. 9. Date of Electronic Publication: 2020 Oct 21.
DOI:	10.7554/eLife.60058
Abstrakt:	Malaria transmission is dependent on the formation of gametocytes in the human blood. The sexual conversion rate, the proportion of asexual parasites that convert into gametocytes at each multiplication cycle, is variable and reflects the relative parasite investment between transmission and maintaining the infection. The impact of environmental factors such as drugs on sexual conversion rates is not well understood. We developed a robust assay using gametocyte-reporter parasite lines to accurately measure the impact of drugs on sexual conversion rates, independently from their gametocytocidal activity. We found that exposure to subcurative doses of the frontline antimalarial drug dihydroartemisinin (DHA) at the trophozoite stage resulted in a ~ fourfold increase in sexual conversion. In contrast, no increase was observed when ring stages were exposed or in cultures in which sexual conversion was stimulated by choline depletion. Our results reveal a complex relationship between antimalarial drugs and sexual conversion, with potential public health implications. Competing Interests: HP, SM, FG, CP, AR, CJ, AC No competing interests declared (© 2020, Portugaliza et al.)
Databáze:	MEDLINE
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