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This genus contains only one species, Toxoplasma gondii. However, it has a remarkable host range and can probably infect all mammals and birds.

This intracellular parasite was initially described from a desert rodent, the North African gondi (Ctenodactylus gondi) [sometimes spelled ‘gundi’ – vowels are not used in written Arabic, so some words appear in various spellings when translated into English] in Tunisia 1908, but the life cycle was not established until 1969–1970. The name Toxoplasma has nothing to do with toxins but derives from the curved shape of the tachyzoite stage of the life cycle (Figure 3.16). ‘Toxon’ (Tόξoν) is the Greek word for a ‘bow or something that is crescent shaped and ‘plasma’ ( πλάσμα) is Greek for ‘creature’. Since these humble beginnings, it has become apparent that not only does T. gondii have a cosmopolitan distribution but also it has perhaps the widest host range of any parasite.

The life cycle of T. gondii has two parts and three infectious stages (Figure 3.17). The two parts of the life cycle are the sexual cycle that occurs within cats and other felines that are the definitive hosts and the asexual cycle that occurs in the intermediate hosts – which are virtually any warm‐blooded animal, including us. The three infectious stages are the sporulated oocysts that contain the sporozoites, the tachyzoites, and the tissue cysts that contain bradyzoites: all three stages are infectious to both the feline definitive hosts and the intermediate hosts. Cats acquire their infection by consuming either sporulated oocysts passed in another cat’s faeces (e.g., through contamination) or an intermediate host containing the tachyzoites and bradyzoites. Following ingestion, the parasites invade the epithelial cells lining the cat’s small intestine and undergo a complex series of asexual divisions. The first step is multiplication by endodyogeny – this involves two daughter cells developing within a mother cell and consuming her before separation takes place. After endodyogeny comes reproduction by endopolygeny in which the mother cell produces several daughter cells simultaneously. 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. Sporogony happens outside the host and takes about 2–3 days under ideal conditions. Fresh faeces are therefore not infectious because the oocysts first need to undergo sporogony to form sporocysts. The infectious sporulated oocysts are oval (10–13 × 9–11 μm) and contain two sporocysts each of which contains four sporozoites. The sporocysts can remain infectious in the environment for months and possibly even 1–2 years. The shedding of oocysts starts 3–10 days after initial infection and continues for only 1–2 weeks although some estimates suggest that a cat may shed up to 100 million oocysts in its faeces during that time. After an initial infection, a cat is usually resistant to re‐infection. The prolonged survival of the oocysts in the environment therefore compensates for the short period over which an infected cat sheds them in its faeces. In some cats, developmental stages may persist in a dormant state and give rise to another batch of oocysts following their subsequent reactivation. This could happen because of changes in the cat’s immune status. Immunity can also wane naturally with time and a cat may suffer another T. gondii infection several years after the first challenge.

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 there are sporadic calls for Toxoplasma testing for all pregnant women in the United Kingdom, the incidence is too low to make it cost effective. Instead, the emphasis is on identifying and treating individual women. Toxoplasma gondii is susceptible to treatment with antibiotics such as spiramycin that are relatively safe to administer during pregnancy and help to reduce the chances of congenital transmission, following the exposure of the mother to infection during the early stages of pregnancy. However, the outcome is often not a happy one; if that foetus is infected it can lead to spontaneous (or therapeutic) abortion or a severely handicapped baby.