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Rift Valley fever (RVF-V) is a viral, vector-borne, zoonotic disease. It affects multiple hosts, mainly livestock such as cattle, sheep, and goats. We aimed at enhancing knowledge on the relative contribution of host species to transmission, focusing on Senegal, a region with recurring RVFV circulation. With a systematic review of existing mechanistic models of RVFV transmission dynamics, we identified critical knowledge gaps and characterised the diversity of modelling approaches. We mapped RVF epidemic potential in northern Senegal for three consecutive rainy seasons (2014-2016), using the basic reproduction number. September was identified as a period of high risk of amplification following RVFV introduction. To quantify differences in infectiousness between host species, we developed the first within-host model of RVFV production by host cells, and estimated the relationship between host infectious viral loads and the probability to infect mosquitoes. The results showed that sheep were the most infectious host species, and that Aedes vectors were more likely to get infected than Culex when fed with similarly infectious bloodmeals. We incorporated this heterogeneity into a metapopulation model representing seasonal herd movements in northern Senegal. We quantified the delay between RVFV introduction through nomadic herds and infection of sedentary populations. We highlighted a systematic earlier infection in cattle than goats and sheep. This PhD used modeling to disentangle the complex transmission dynamics of a multi-host multivector pathogen, highlighting possible avenues for the development of efficient and targeted control strategies, crucial to ultimately prevent human cases.; La fièvre de la Vallée du Rift (FVR) est une maladie virale, vectorielle, et zoonotique. Elle touche principalement les animaux d’élevage : bovins, chèvres, moutons. Nous visions à mieux comprendre la contribution des différentes espèces d’hôtes à la transmission du virus de la FVR, en prenant comme zone d’étude le Sénégal. Une revue de la littérature nous a permis de caractériser la diversité des modèles mathématiques existants, et les questions que ces derniers n’ont pas encore abordé concernant la FVR. Nous avons ensuite cartographié le potentiel épidémique de la FVR au nord du Sénégal, et avons montré que pendant 3 saisons des pluies consécutives (2014-2016), le mois de Septembre était la période la plus à risque. Pour quantifier de potentielles différences d’infectiosité entre espèces d’hôtes à l’échelle individuelle, nous avons développé un modèle intra-hôte de la dynamique virale, et avons fait le lien avec la probabilité d’infecter les vecteurs. Nos résultats montrent que les moutons sont l’espèce la plus infectieuse, et que les moustiques du genre Aedes s’infectent plus facilement que les Culex. Enfin, nous avons incorporé cette hétérogéneité dans une métapopulation modélisant les mouvements de transhumance saisonniers au nord du Sénégal. Cela nous a permis de quantifier le délai entre l’introduction du virus de la FVR par les populations nomades et la propagation de l’infection chez les sédentaires. Nous avons également mis en évidence une infectionsystématiquement plus précoce chez les bovins que chez les petits ruminants. Cette thèse a ainsi permis de mieux comprendre la dynamique de transmission d’un pathogène multi-hôtes et d’identifier des pistes pourl’élaboration de stratégies de maitrise ciblées et efficaces.

International audience; Spatio-temporally heterogeneous environments may lead to unexpected population dynamics. Knowledge is needed on local properties favouring population resilience at large scale. For pathogen vectors, such as tsetse flies transmitting human and animal African trypanosomosis, this is crucial to target management strategies. We developed a mechanistic spatio-temporal model of the age-structured population dynamics of tsetse flies, parametrized with field and laboratory data. It accounts for density- and temperature-dependence. The studied environment is heterogeneous, fragmented and dispersal is suitability-driven. We confirmed that temperature and adult mortality have a strong impact on tsetse populations. When homogeneously increasing adult mortality, control was less effective and induced faster population recovery in the coldest and temperature-stable locations, creating refuges. To optimally select locations to control, we assessed the potential impact of treating them and their contribution to the whole population. This heterogeneous control induced a similar population decrease, with more dispersed individuals. Control efficacy was no longer related to temperature. Dispersal was responsible for refuges at the interface between controlled and uncontrolled zones, where resurgence after control was very high. The early identification of refuges, which could jeopardize control efforts, is crucial. We recommend baseline data collection to characterize the ecosystem before implementing any measures.; hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides', Cirad

This file has 8 sections and includes experimental data, model input data, model details, parameters, sensitivity analysis, addition information on control, and code sources and data files.

The tsetse fly complex (Glossina spp.) transmits the parasite responsible for African Animal Trypanosomiasis (AAT), or nagana, which is the most economically important livestock disease in Africa. The challenge of the last decades was to design programs that could sustainably control fly populations in different regions of the continent. Given the contrasted outcomes of these programs, there is still a need for a better understanding of the spatio-temporal dynamics of this vector.Mathematical models and computer-based simulations are relevant to assess which control measures should be used and when, accounting for the ecological complexity of the target pest and territorial specificities of the controlled area. They provide a useful tool, complementary to field observations and experiments, to suggest efficient vector management strategies.We developed a deterministic and mechanistic spatio-temporal model of the population dynamics of tsetse flies, structured by sex and age (pupae, teneral and non teneral adults). Temperature and fly density influenced the life-cycle, while spatial diffusion depended on density and relative quality of neighbouring locations. We applied the model on populations of Glossina palpalis gambiensis in the Niayes area of Senegal, for which biological and landscape data were available. The landscape was divided into 250m x 250m cells of heterogeneous carrying capacity, estimated by habitat suitability models. We transformed observed temperatures into “perceived” ones, to account for micro-environments where flies live. Dispersal, mortality, and development rates were calibrated on laboratory data, experts’ opinions and literature.The sensitivity analysis of the model identified the biological and environmental parameters influencing the most population dynamics. We showed that the mortality and development of adult females, along with temperature, were the key drivers of population persistence. Our predictions suggested that combining techniques to both increase mortality and decrease fecundity would be optimal to eradicate tsetse flies in targeted zones. Sequential aerosol technique (SAT), traps and targets (TT) and insecticide-treated livestock (ITL) increase daily mortality rates, whereas the sterile insect technique (SIT), by preventing egg-laying, slows down the development rate of the population. Furthermore, our results highlighted the need for more biological insights to achieve accurate model predictions. Additional field work and experiments are necessary to better infer the relationship between adult mortality and temperature, as well as differences between temperatures from weather stations and temperatures in tsetse fly resting places.

The contact structure between vertebrate hosts and arthropod vectors plays a key role in the spread of arthropod-borne viruses (arboviruses); thus, it is important to determine whether arbovirus infection of either host or vector alters vector feeding behavior. Here we leveraged a study of the replication dynamics of two arboviruses isolated from their ancestral cycles in paleotropical forests, sylvatic dengue-2 (DENV-2) and Zika (ZIKV), in one non-human primate (NHP) species from the paleotropics (cynomolgus macaques, Macaca fascicularis ) and one from the neotropics (squirrel monkeys, Saimiri boliviensis ) to test the effect of both vector and host infection with each virus on completion of blood feeding (engorgement) of the mosquito Aedes albopictus . Although mosquitoes were starved and given no choice of hosts, engorgement rates varied dramatically, from 0% to 100%. While neither vector nor host infection systematically affected engorgement, NHP species and body temperature at the time of feeding did. We also interrogated the effect of repeated mosquito bites on cytokine expression and found that epidermal growth factor (EGF) and macrophage migration inhibitory factor (MIF) concentrations were dynamically associated with exposure to mosquito bites. This study highlights the importance of incorporating individual-level heterogeneity of vector biting in arbovirus transmission models.

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic cycles involving monkey hosts, spilled over into human transmission, and were translocated to the Americas, creating potential for spillback into neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We exposed native (cynomolgus macaque) or novel (squirrel monkey) hosts to mosquitoes infected with either sylvatic DENV or ZIKV and monitored viremia, natural killer cells, transmission to mosquitoes, cytokines, and neutralizing antibody titers. Unexpectedly, DENV transmission from both host species occurred only when serum viremia was undetectable or near the limit of detection. ZIKV replicated in squirrel monkeys to much higher titers than DENV and was transmitted more efficiently but stimulated lower neutralizing antibody titers. Increasing ZIKV viremia led to greater instantaneous transmission and shorter duration of infection, consistent with a replication-clearance trade-off.