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Épidémiologie descriptive et analytique des orthohantavirus chez les rongeurs sauvages en France

Abstract : Orthohantavirus are viruses, mostly zoonotic, present in most places inhabited by rodents, which are the reservoir species. In Europe, Puumala virus (PUUV) is the orthohantavirus that causes the highest number of human disease cases, called nephropathia epidemica (NE). The virus is transmitted to humans indirectly via excretions of bank vole (Myodes glareolus), which is the reservoir species of PUUV. Infection of bank voles occurs by indirect contamination as in humans or by direct contact with another infected rodent. In France, the endemic area is located in the north-eastern part of the country. In this area, several outbreaks were identified among which the number of cases varies depending on locations, years and seasons. The epidemiology of human cases is closely related to PUUV infections in bank voles. However, the presence of an infected bank vole population alone does not explain the heterogeneous spatial distribution of human cases, with some areas remaining free of NE cases in spite of a high rodent seroprevalence. The main goal of this PhD was to better understand the factors that explain this discrepancy by comparing a low endemic area, that is Alsace, and a high endemic area, that is Ardennes. A first study evaluated the link between the risk for humans and the number of infected, and thus potentially excreting, rodents via the monitoring of rodent seroprevalence in space and time in Alsace. In comparison with studies conducted in highly endemic areas, our results show that in Alsace the limited number of human cases is associated with a low rodent seroprevalence. In addition to the number of infected rodents, the importance of environmental contamination and by this way the contamination risk for humans are impacted by the quantity of virus excreted by bank voles, which is partially modulated by the virus strain. Then, in a second phase, a phylogenetic study was conducted to assess the microevolution of virus in several sites in Ardennes. This microevolution was found to be very different depending on the number of NE cases associated to each site and was related to the characteristics of individual turnover (through survival and movements) in each rodent population. At last, the third phase of this thesis aimed to determine the impact of the environment on the demography and infection of rodents in Ardennes. This part started with an exhaustive literature review to identify the role of climatic conditions (temperatures, precipitations, snow) and food availability on rodent seroprevalence and on the number of human cases. Then, analyses with regression models allowed investigating the impact of these different factors on the risk of infection of rodents, estimated by two indicators: the seroprevalence, which is commonly used in such studies, and the incidence rate, which is a better indicator of the time of infection. Logically, our results showed that seroprevalence and incidence rate were not influenced by the same factors; the role of those factors is discussed in view of results from previous studies. Our studies suggested that the spatial heterogeneity of NE cases was partly related to the number of infected rodents and to the diversity of PUUV strains, which depend on the demographic characteristics of the rodent populations and their environment. These insights require further studies and other hypotheses need to be explored, such as the influence of rodent immunity on the level of viral excretion and the modulation of their contamination risk by their behaviour. All those inputs could be used in epidemiological models to better evaluate the risk for humans
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Élodie Monchâtre-Leroy. Épidémiologie descriptive et analytique des orthohantavirus chez les rongeurs sauvages en France. Microbiologie et Parasitologie. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1255⟩. ⟨tel-02500595⟩

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