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Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes?

DOI: 10.1186/1475-2875-11-34

Keywords: Plasmodium falciparum, Gametocyte, Anti-malarial drugs

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Here the use of a simple robust assay to screen a panel of currently used and experimental anti-malarial drugs against mature P. falciparum gametocytes is described.Eight of 44 compounds tested reduced gametocyte viability by at least 50% and three showed IC50 values in nM range.There is a need to identify new compounds with activity against late stage gametocytes and the information provided by this in vitro assay is a valuable first step, which can guide future clinical studies.Gametocytes are the sexual stage of the malaria parasite, which develop in red blood cells and are essential for transmission to the mosquito vector. It has long been recognized that patients treated for malaria should be cleared of gametocytes in order to prevent them transmitting the infection to others [1]. This is particularly challenging in the case of Plasmodium falciparum infections as gametocytes of this species have a much longer lifespan than asexual stages. Late-stage gametocytes (stages IV-V) are more resistant to anti-malarial drugs and metabolic inhibitors [2] than early-stage gametocytes or asexual stage parasites. Primaquine is currently the only licensed anti-malarial drug that is effective against late stage P. falciparum gametocytes but has a number of drawbacks including its propensity to cause acute haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.With malaria eradication back on the global health agenda there is renewed emphasis on the identification of new and novel agents that can eliminate late-stage gametocytes in the patient's circulation and therefore block transmission of the parasite from its human host to the mosquito vector. However, evaluating the activity of promising anti-malarial drugs against Plasmodium gametocytes is difficult even in vitro. To this end a simple medium-high throughput assay suitable for assessing the potential of new and novel anti-gametocyte drugs has recently been described [3].Here a modification of


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