Figure 3.16 Toxoplasma gondii tachyzoites. This protozoan parasite has an unusually large host range that encompasses most warm‐blooded vertebrates although sexual reproduction only occurs in the intestine of cats.
Figure 3.17 Life cycle of Toxoplasma gondii: 1: Cats acquire their infection by consuming either sporulated oocysts passed in another cat’s faeces or an intermediate host containing the tachyzoites and bradyzoites. Following ingestion, the parasites invade the epithelial cells lining the cat’s small intestine and multiply by endodyogeny followed by endopolygeny. Next, comes gametogenesis and the formation of microgametes and macrogametes. Fusion of the gametes results in the formation of a zygote, and this develops into an oocyst that is shed with the faeces whilst it is still unsporulated. 2: Sporogony happens outside the host. 3: When an infectious oocyst reaches the small intestine of an intermediate host, it releases the sporozoites and these then invade the gut epithelial cells. 4: They then leave these cells and invade macrophages and many other cell types within which they transform into tachyzoites which multiply by endodyogeny. 5: After a series of parasite division cycles, they form tissue cysts (zoitocysts) containing bradyzoites. If consumed, the tachyzoites and bradyzoites are infectious to both other intermediate hosts and to cats. 6: Virtually all warm‐blooded animals can act as intermediate hosts. Trans‐placental transmission in humans can lead to abortion and birth defects. The importance of birds as intermediate hosts in transmission dynamics is uncertain. Drawings not to scale.
Within infected cats, T. gondii also invades other tissues, including the muscles and nervous tissues where they divide asexually to produce tachyzoites and tissue cysts containing bradyzoites – just as in the intermediate hosts. If the cat is pregnant, in utero infection of the developing kittens may occur. Most cats, however, acquire their T. gondii infection through preying on mice, rats, and other rodents. As might be expected, the prevalence of infection is higher in stray cats and those that are good mousers. Many bird species, from sparrows and pigeons to ducks and owls, are naturally infected with T. gondii, but they are probably not as important as rodents as sources of infection to cats.
For T. gondii infection to circulate between cats and rodents, it is essential that the rodents ingest the oocysts. Domestic cats normally bury their faeces and although this could theoretically reduce the chances of contaminative transmission, it could contribute to oocyst survival by reducing exposure to environmental conditions such as desiccation and UV light. The smell of cat faeces repels mice and voles, so the oocysts must survive until the faeces breaks down and disperses in the soil. Dogs sometimes consume cat faeces (Lewin 1999), and therefore one might expect them to be at risk of serious infections. The seroprevalence of T. gondii in dogs is often high, especially in strays (e.g., Valenzuela‐Moreno et al. 2020), but this is probably due to their scavenging of dead animals and waste food rather than consumption of cat faeces – although the latter habit is unlikely to help.
Contaminated water sources are responsible for some outbreaks of toxoplasmosis in humans and many wild and domestic animals probably become infected in the same way. Presumably, the oocysts wash from the soil into ponds, streams, reservoirs, and they can survive the chlorination of drinking water and sewage treatment. The oocysts also survive for prolonged periods in brackish water and at least a year in seawater (Shapiro et al. 2019).
When an infectious oocyst reaches the small intestine of an intermediate host, it releases the sporozoites, and these then invade the gut epithelial cells. They then leave these cells and invade macrophages and many other cell types within which they transform into tachyzoites, which multiply by endodyogeny. Toxoplasma gondii does not invade the anucleate red blood cells of mammals. However, they do parasitize the nucleated red blood cells of birds. Within an infected cell, the parasites multiply until they consume the whole cell and all that is left is the cell membrane. At this point, the host cell is called a pseudocyst. Ultimately, the pseudocyst membrane breaks down, thereby releasing the tachyzoites that invade new host cells and repeat the process. As in other apicomplexan parasites, the tachyzoites actively invade their host cells. Having made initial contact with a suitable cell, the tachyzoites re‐orientate themselves and then discharge the contents of their micronemes, rhoptries, and dense granules. This enables the parasite to attach to the host cell surface after which it forces its way inside and becomes enclosed within a parasitophorous vacuole. Because T. gondii infects such a wide variety of types of cells and species of animal it presumably identifies host cell receptors that have a widespread distribution in warm‐blooded vertebrates. One of the microneme proteins, TgMIC1, has a cell binding motif called ‘microneme adhesive repeat’ (MAR) that binds to a group of carbohydrates called sialylated oligosaccharides. Sialic acid oligosaccharides are common components of cell surface membranes and play important roles in a variety of carbohydrate‐mediated cell surface interactions.
After a series of parasite division cycles, the host’s immune system starts to exert an effect, and this stimulates T. gondii to form tissue cysts (zoitocysts) containing bradyzoites. These tissue cysts develop predominantly within nervous (e.g., central nervous system and eyes) and skeletal and cardiac muscle tissue, but they may develop elsewhere. The tissue cysts probably persist for life in some intermediate hosts. Prolonged infections may also result from periodical re‐activation, transformation into tachyzoites, followed by the formation of new tissue cysts. In addition to infection through consuming oocysts, intermediate hosts may also acquire a T. gondii infection through consuming meat containing the tachyzoite and/or bradyzoites. In humans, this occurs through consuming raw or undercooked meat. In these instances, the parasites invade the gut epithelial cells, and the life cycle continues as described above. Human infections may also result from blood transfusions and organ transplants (Robert‐Gangneux et al. 2018).
In pregnant mammals, vertical transmission occurs when tachyzoites cross the placenta and infect the developing embryo. There is extensive documentation of transplacental transmission of T. gondii infections in humans but the extent to which it occurs in other animals, and its importance in the epidemiology of the parasite is uncertain. Acquisition of primary toxoplasmosis during pregnancy can be a significant cause of congenital infection. Consequently, in some countries, such as France, screening for the infection is a routine part of antenatal care. Although