Last Updated: 11/06/2020
Development of an ex-vivo transmission blocking assay for clinical isolates of matured Plasmodium falciparum gametocytes through membrane feeding assays
Objectives
The objective of this proposal is to develop an ex-vivo transmission blocking assay of stage-V Plasmodium gametocyte clinical isolates.
This objective will be achieved through:
- To determine the optimal ex-vivo culture condition necessary to maintain viable and infectious parasites collected from malaria infected patients
- To establish a transmission-blocking assay using the gold standard Mosquito Feeding Assay following ex-vivo treatment of purified gametocytes with known gametocyte active and inactive compounds.
- To measure the transmission-blocking activity of clinical candidates compounds from MMV and H3D partners using our established assay.
University of Sciences Techniques and Technologies of Bamako (USTTB), Mali
The emphasis on malaria eradication has focused attention on malaria transmission with an increased effort for the development of drug and vaccine therapies targeting Plasmodium sexual stages. Artemisinin combination therapies (ACTs) are the front-line treatment for falciparum malaria and reduces gametocyte carriage. However, these regiments have little or no activity against the mature transmissible gametocytes, hence fail to block parasite transmission. The 8-aminoquinolines compounds primaquine or tafenoquine have potent gametocytocidal properties and have been shown to block transmission. However, these 8-aminoquinolines can be toxic to patients with glucose-6-phosphate dehydrogenase deficiency, a genetic condition with a high prevalence in malaria-endemic regions. For the successful control of malaria, there is an urgent need to identify safe transmission-blocking compounds.
The development of transmission blocking therapies does require appropriate tools to reliably measure the blocking properties of these therapies. The current tools for the assessment of gametocytocidal drug activity in vivo and in vitro are technically challenging for several reasons including ethical challenges for establishing clinical trials, the production of competent gametocytes in vitro, and the ability to measure transmission blocking efficacy and activities. Most experimental tools to measure the transmission blocking activity rely on conventional laboratories adapted strains which may not be fully reflective of the plasmodial population circulating in malaria-endemic regions. As such, the derived results may not anticipate the real gametocytocidal activities of tested compounds on clinical isolates. The development of robust transmission blocking assays based on Plasmodium clinical isolates to measure candidate compounds transmission blocking activity is a crucial component of drug discovery to support the global malaria eradication agenda.
Cross sectional study.
May 2019 — Apr 2021
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