Analyse des facteurs d’hôte et facteurs parasitaires dans le paludisme grave d’importation

Abstract : Malaria is a worldwide parasitic infection especially in tropical area where Plasmodium falciparum infection is responsible for hundreds of thousands annually mainly among children under five years old. Malaria is also a problem in France by the importation of malaria cases in travelers coming from endemic area. The Plasmodium falciparum infection in this population, considered at risk of developping severe malaria, can present different clinical forms more or less associated with mortality.While some risk factors for severity like age and immunity have been identified, this complex host-parasite interactions have been widely studied in children in endemic areas and few data are available for imported malaria. The aim of the thesis work is based on analysis of host factors and parasite factors in imported malaria.Through the monitoring network of the French National reference center of malaria, all the demographic, epidemiological, clinical and laboratory of imported malaria cases, notified between 2011 and 2015, were collected and also samples of the parasitological diagnosis. After diagnostic expertise, the plasma obtained after centrifugation was used for determinations of antimalarial drugs, for quantification of plasmatic HRP2 and for serological tests. RNA extracted by the Trizol® from red cells pellets was used to study the expression of var genes and domain cassettes by qRT-PCR. The pellet of parasitized red blood cells were cultured for maturation of parasitic forms for the study of phenotype cytoadherence on soluble receptor CD36, ICAM-1 and EPCR and for the study of the rosetting phenomenon. All of these studies was conducted in an imported malaria context,in a population of patients composed by first-generation migrants, second-generation migrants and travelers / expatriates and whose clinical presentation of imported malaria was classified into very severe (VSM), mild severe (MSM) and uncomplicated malaria (UM).All the epidemiological, clinical and biological data collected during the study identified the high age, ethnicity, depth of thrombocytopenia and no history of malaria as factors risk associated with the occurrence of very severe malaria, clinical entity characterized by high sequestered parasite biomass. The effect of pre-exposure to the parasite, reflected by the serological status of patients, seems to be the cause of the clinical presentation of the disease in particular by limiting parasite biomass sequestered during malaria. The study of the expression of var genes and domain cassettes performed in this population, according to clinical presentation, ethnicity and the serological status of patients, revealed an overexpression of the group of var genes A and B and protein patterns of the domain cassette DC4, DC8 and DC13 in mild severe and very severe malaria within this heterogeneous patient population. The study of cytoadherence phenotype and rosetting, made in another group of patients in imported malaria context, identified the rosetting as adhesion phenotype causing very severe malaria. The expression profile of var genes and domain cassettes corresponding to this population confirmed earlier observations and correlates rosetting phenotype to the expression of DBLß3 and DBLa2 of DC4 and DC8 (...)
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Nicolas Argy. Analyse des facteurs d’hôte et facteurs parasitaires dans le paludisme grave d’importation. Parasitologie. Université Sorbonne Paris Cité, 2015. Français. ⟨NNT : 2015USPCB093⟩. ⟨tel-01535631⟩

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