Abstract
BackgroundRecent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal. One high priority area is the need to determine the gametocytocidal activity of both currently used anti-malarial drugs and those in the development pipeline. However, testing the activity of compounds against Plasmodium falciparum gametocytes is technically challenging both in vivo and in vitro.MethodsHere 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.ResultsEight of 44 compounds tested reduced gametocyte viability by at least 50% and three showed IC50 values in nM range.ConclusionsThere 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.
Highlights
Recent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal
Gametocytes are the sexual stage of the malaria parasite, which develop in red blood cells and are essential for transmission to the mosquito vector
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
Summary
Recent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal. 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 challenging in the case of Plasmodium falciparum infections as gametocytes of this species have a much longer lifespan than asexual stages. 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 block transmission of the parasite from its human host to the mosquito vector. 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]
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