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Plasmodium falciparum et résistance aux antipaludiques : aperçu et conséquences des facteurs impliqués dans la sélection et la diffusion des parasites résistants

Abstract : Malaria remains one of the most terrible infectious diseases with more than 200 million infections and 430,000 deaths each year, mostly children under five years old in sub-Saharan Africa. Plasmodium falciparum is responsible for the vast majority of malaria mortality cases. Control of malaria still remains a major public health problem, in particular because of resistances to antimalarials that parasites developed. The apparition of these resistances is due to the drug pressure, and their progressive diffusion is mainly via the travelling of infected hosts. However, the dynamics of emergence, diffusion and persistence of resistant parasites result from complex interactions between the antimalarials, the Human, the parasite and the vector. The work presented here participates in the malaria control process by first proposing an inventory of Plasmodium resistance to antimalarials used in Cameroon, thanks to molecular, phenotypic and clinical tools. A second part explores the possible consequences of prolonged use of artemisinin derivatives on the P. falciparum phenotype, in areas where resistance to this molecule is already established. The in vitro model used showed that continuous artemisinin pressures induced a new pluri-resistance profile. Finally, a last part analyses the role of the mosquito in the epidemiology of resistances and shows that the sporogony favours the diffusion of minority alleles, resistant or not, presented in humans. All this work confirms the multiplicity of forces acting on the dynamics of resistances and the complexity of their interactions making any prediction very speculative. Even if better knowledge of the societal, epidemiological, biological and pharmacological phenomena involved in resistances is a priority, regular phenotypic and genotypic surveillance in the field remains the best tool for adapting malaria control strategies.
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Sandie Menard. Plasmodium falciparum et résistance aux antipaludiques : aperçu et conséquences des facteurs impliqués dans la sélection et la diffusion des parasites résistants. Maladies infectieuses. Université Paul Sabatier - Toulouse III, 2017. Français. ⟨NNT : 2017TOU30116⟩. ⟨tel-01919157⟩

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