IntroTox

Toxoplasma gondii infection is a ubiquitous zoonosis that affects all warm-blooded species. It has a complex epidemiology due to the wide range of hosts and transmission pathways involved. In human, it is generally benign in immunocompetent persons, life-threatening cerebral and multivisceral forms, in addition to ocular forms, have been described. This clinical variability seems to be related to the patient’s immune status, but also to the virulence genetic determinants of the parasite strain. Over the last twenty years, a highly contrasted geographic distribution of the parasite populations in terms of genetic diversity has been demonstrated around the world. Determinants of this spatial structure are still poorly understood. In comparison to Europe and North America, a huge genetic diversity was found in South America, with highly pathogenic and even life-threatening strains described. Limited data is available about genetic diversity in Asia and Africa. However, the few studies conducted in Africa give insights of a high prevalence in human and animals, with an unusual severity of the human infection. A number of studies showed a link between the clinical expression and the causal strain, especially in South America. In a globalized world, understanding how the genetic diversity of the pathogen is structured becomes an emerging theme in the study of the toxoplasmosis epidemiology. It is an important public health issue and a priority to consider controlling this major parasitosis. Preliminary studies conducted by the project coordinator showed the role of human factors in the evolution of this diversity. A study conducted in French Guiana shows that the environment anthropization results in changes in the parasite’s local genetic diversity. It highlights the possibility of introgressions of wild strains (more genetically diverse and virulent for humans than anthropized strains) in the anthropized environment, causing potential risks for human health. These introgressions could favor the appearance of virulent recombinants. On a global scale, cases of severe toxoplasmosis, unusual among immunocompetent patients in Europe, were identified in metropolitan France following the consumption of horsemeat imported from the American continent. Trade globalization seems to create risk situations that are still unexplored and represent new challenges in human and animal health. The circulation of hosts, whether natural (bird migrations) or anthropogenic (transport of meat products, plants contaminated with oocysts, introduction of live animals such as cats or rodents) could be a source of introgression of T. gondii genotypes from one continent to another. These hypotheses suggested in the scientific literature remain to be demonstrated. The aim of the IntroTox project is to assess the impact of human and environmental disseminations of T. gondii strains on its genetic and genomic diversity among the animal reservoirs and their implications in human epidemiology in France and in West and Central Africa. These regions share a long history of commercial exchanges since the triangular trade period and important bird migratory corridors connect them. The extent of these exchanges and the diversity of flows observed between these two regions could thus favor the transfer of virulent genotypes from one region to another and the appearance of recombinant genotypes. In the context of health ecology, the specific objectives of this project will be: (i) to compare the genetic diversity of T. gondii populations in animals from France and West (Senegal and Benin) and Central (Gabon) Africa, (ii) to demonstrate gene flows and reconstruct the evolutionary history of T. gondii between these regions, (iii) to evaluate the virulence of isolated strains and (iv) to analyse genomic rearrangements (recombinations) within described genotypes in relation to their phenotypic expression (virulence in mice and pathogenicity in human).