Genetic and biological characterization of Toxoplasma gondii from Uganda

Toxoplasma gondii is a widely distributed protozoan parasite, estimated to infect 25-50% of the global human population. While most infections are asymptomatic, AIDS-associated toxoplasmic encephalitis causes a high level of morbidity and mortality and this is a particular problem in sub-Saharan Africa, where HIV affects a substantial part of the population. Despite the scale of the problem, virtually nothing has been known about the T. gondii strains present in Africa. The work presented in this thesis showed for the first time that all the three main clonal lineages of T. gondii are present and cause disease in African HIV-patients, and that genotype II was the most common in Uganda. Subsequent isolation of eight strains revealed that the T. gondii parasites in Uganda are highly similar to the strains found in Europe and North America, but over 1,200 novel mutations were identified and many of these were indicative of positive selection of genes active in the interface with the host. An important finding was the discovery of a rare natural recombinant strain, which possessed genetic elements from both genotype II and III and displayed an intermediate in vivo growth rate, compared with the genuine type II and III strains from the same area. Whole genome sequencing of this isolate revealed that sexual recombination may be more frequent than previously thought, but that selective pressures appear to favour a conserved genetic composition. The studies included in this thesis provide novel insight into the genotype and phenotype of T. gondii strains from Africa, and describe for the first time the genomics of a natural recombinant T. gondii strain.