Toxoplasma gondii: Deeper understanding of epidemiology, virulence and pathophysiology enhances diagnosis and informs vaccine design

Toxoplasma gondii is an extremely widespread intracellular obligate parasite that infects both animals and birds. This protozoan pathogen usually causes asymptomatic infection in humans but can cause significant disease in congenitally infected infants, immunodeficient patients and occasionally in immunocompetent individuals. In the complex life cycle of T. gondii, sexual development occurs uniquely in felines whereas asexual reproduction may take place in humans and other warm-blooded animals serving as intermediate hosts. The prevalence of infection varies considerably among different geographic areas and also among individuals, depending on a variety of factors, including culinary habits and cleanliness of surroundings. Studies to date show low genetic diversity of T. gondii, with three main lineages, designated types I, II and III, found at least within Europe and North America. T. gondii uses various mechanisms to invade host cells and to alter their signal pathways and gene expression. Kinases within the rhoptry, a unique apical organelle, and T. gondii granule proteins are key virulence factors that promote attachment to, and invasion of, host cells. Human Toxoplasma infection is acquired by ingestion of raw or undercooked meat that contains tissue cysts, or through the ingestion of water or food contaminated with oocysts. It is also transmitted congenitally from mother-to-foetus and less commonly by transfusion of contaminated blood or transplantation of an infected organ. Life-threatening toxoplasmosis can develop in immunocompromised patients. Diagnostic tests are critical to surveillance, control and prevention of toxoplasmosis. However, different technologies presently utilized around the world to detect different parasite stages are not of a uniformly sufficient standard to indicate clearly the epidemiology and severity of infection at global, regional and national levels. While a prophylactic vaccine is licensed for veterinary administration, no similarly efficacious preparation is available to prevent human infections. Here, we review the epidemiology and genotypes of T. gondii, as well as current detection methods and the state of vaccine development. In addition, the mechanisms by which this parasitic pathogen invades and overcomes the human immune system are considered.