Project: Understanding the biology of Plasmodium vivax and Plasmodium ovale for the development of a field-based anti-hypnozoite drug screening model

Acronym	HYPNOBIO (Reference Number: TMA2017CDF-1892)
Duration	01/01/2019 - 31/12/2020
Project Topic	Research focusing on Plasmodium vivax and Plasmodium ovale has been severely limited by logistical and biological obstacles while most of malaria control program have instead focused on falciparum malaria. P. vivax and P. ovale have unique attribute to cause malaria relapses, resulting from the activation of quiescent hepatic hypnozoites, hinder global efforts to control and eliminate malaria. Currently, Primaquine is the only licensed drug able to eradicate hypnozoite. However primaquine is not a well-tolerated drug. Unfortunately very few tools are available to support biological studies and screen efforts for P. vivax and P. ovale. Specifically, an optimized in vitro liver-stage model supporting biological studies and screen efforts and that would be easily accessible to all researchers is critically needed to enable the discovery of new drugs. We have previously used simian parasite, Plasmodium cynomolgi that is related to P. vivax to establish an in vitro culture system in which we have recapitulated the full liver stage life-cycle of the parasite including the hypnozoite stage. We have now demonstrated that this system could be used for testing candidate drugs or exploring the liver stage biology including hypnozoite. A further unique attribute is the absence of a reliable robust culture system for the blood stage forms of P. vivax and P. ovale, this is also the case for the most closely related simian malaria species, P. cynomolgi. Thus, access to P. vivax and P. ovale becomes depend to field isolates. These major obstacles have critically limited molecular and cellular investigation of P. vivax and P. ovale malaria biology. To leverage these promising results, the objective of this career development fellowship proposal is to accelerate the research toward an optimized drug assay in which to evaluate the anti-hypnozoite activity of candidate drugs through the achievement of the following aims: i) Field experimental infection of P. vivax and P. ovale to Anopheles spp in Addis Ababa and Bamako; ii) Routine production of sporozoites from P. vivax and P. ovale infected mosquitoes; iii) Establishment of in vitro optimized malaria liver stage infection and screen using field isolated sporozoites from P. vivax and P. ovale infected mosquitoes. These research activities will expose me to field and clinical works and thus better prepare me for clinical research. Achievement of these objectives will enable me publishing papers, developing young researchers and thus fulfil requirement for my university career development.
Network	EDCTP2
Call	Career Development Fellowships 2017

Project partner

Number	Name	Role	Country
1	Université des Sciences, des Techniques et des Technologies de Bamako	Coordinator	Mali