The genera Theileria and Babesia belong to the order Piroplasmida and hence these parasites are referred to as piroplasmids. The genomes of Theileria species exhibit important differences from other apicomplexans (Nene et al. 2016). For example, although the T. parva genome is much smaller (36.5%) than that of P. falciparum, it contains 76.6% of the number of genes encoding proteins. This means its genes are packed extremely closely together. In addition, some metabolic pathways are abbreviated/absent, which indicates considerable metabolic dependence upon the host.
3.4.2.1 Theileria Life Cycle
The Theileria life cycle begins when a tick injects infectious sporozoites into the blood stream of a suitable mammal host (Figure 3.11). Theileria parva sporozoites are non‐motile and unlike those of many other apicomplexans, they do not actively invade the host cell. Instead, they make random contact with T and B‐lymphocytes and attach to host cell receptors. The host cell then internalizes the parasite and surrounds it with a vacuole membrane. The parasites do not orientate themselves in relation to the host cell, and they discharge the contents of their rhoptries and micronemes only after entering it. These chemicals cause the vacuole membrane to disperse so that the parasites lie free within the cytoplasm of the lymphocytes. The sporozoites then transform into multinucleate schizonts and induce the host cell to proliferate: the parasites are closely associated with the lymphocyte mitotic apparatus and divide with their host cell so that daughter lymphocytes are also infected. The first generation of schizonts are called ‘macroschizonts’ and these give rise to ‘macromerozoites’ that invade other lymphocytes and give rise to either more macroschizonts and macromerozoites or to microschizonts that give rise to micromerozoites. The micromerozoites may invade either lymphocytes or red blood cells. Those invading lymphocytes continue to multiply by schizogony, but those invading red blood cells differentiate into ‘piroplasms’ that do not divide any further but are infectious to the tick vector. The piroplasms are extremely small, typically 1.5–2 μm long and 0.5–1μm wide and rod‐shaped although oval, comma, and ring‐shaped forms also occur. They are a characteristic diagnostic feature of East Coast fever. The digestion of infected red blood cell within the tick gut lumen releases the piroplasms, and they differentiate into either microgametocytes or macrogametocytes. The microgametocytes and macrogametocytes fuse to form a diploid zygote, and this invades the tick gut epithelial cells where it transforms into a motile ‘kinete’ form. The kinetes make their way through the body to the tick salivary glands where they invade the type III acini cells and undergo sporogony to produce numerous infectious sporozoites.
Figure 3.11 Life cycle of Theileria parva. 1: An infected tick injects sporozoites into a cow’s bloodstream, and these are internalized by T‐ and B‐lymphocytes within which they transform into multinucleate schizonts. 2: Schizogony results in the formation of merozoites that are released when the host cell dies. 3: Infected lymphocytes are induced to divide and the parasites infect each new cell as it forms. The first generation of schizonts (macroschizonts) form ‘macromerozoites’ that invade other lymphocytes and give rise to either more macroschizonts and macromerozoites or to microschizonts that give rise to micromerozoites. The micromerozoites invade either lymphocytes or red blood cells. 4: Micromerozoites invading red blood cells differentiate into piroplasms that do not divide any further but are infectious to the tick vector. 5: The piroplasms are released within the tick gut lumen and differentiate into either microgametes or macrogametes. The microgametes and macrogametes fuse to form a diploid zygote, and this invades the tick gut epithelial cells where it transforms into a motile kinete. 6: The kinetes make their way through the tick’s body to its salivary glands where they undergo sporogony to produce sporozoites. The sporozoites are released into the saliva and are transmitted when the tick feeds. Drawings not to scale.
3.4.2.2 Theileria parva
Theileria parva is principally a disease of cattle. Ticks belonging to the genus Rhipicephalus (mainly Rhipicephalus appendiculatus and Rhipicephalus zambesiensis), transmit it, and its distribution is largely determined by the presence of its vectors.
Theileria parva exhibits considerable genotypic diversity. Indeed, a single cow may harbour several distinct genotypes. This complicates vaccine design because there is a lack of cross‐protection between different strains of the parasite (Katzer et al. 2010). The virulence of theileriosis varies between regions and probably relates to the ecology of the tick vector. Where the tick life cycle stages do not usually coincide (e.g., adults plus nymphs/nymphs plus larvae/adults plus larvae), the disease tends to be less virulent (Tindih et al. 2010). This is because a highly virulent parasite would kill its cattle host before there was an opportunity for the next generation of ticks to become infected. Rhipicephalus appendiculatus and R. zambesiensis are typical three host ticks and the larval, nymphal, and adult stages exploit different hosts. After feeding (engorging), the tick drops off to moult or in the case of the adult females to lay their eggs. In subtropical and southern regions of Africa, the ticks are seasonal with one generation per year (i.e., they are unimodal) but in tropical regions where there is high rainfall, up to three generations may occur.
3.4.3 Genus Babesia
Some reports state that there are over 100 species of Babesia, whilst others suggest that there are somewhat fewer. Most species are tick borne parasites of mammalian erythrocytes although some parasitize bird red blood cells. Some Babesia species also parasitize other blood cells, such as lymphocytes and histiocytes. The genus Babesia is primarily of economic importance as parasites of cattle, sheep, and other domestic animals (Table 3.2). The most important species are Babesia bigemina, Babesia bovis, and Babesia divergens. Babesia microti is primarily a parasite of rodents but it also infects other mammals and is the principal cause of human babesiosis. For example, between 2006 and 2015, the incidence of human infections in New York State, USA, increased from 1.7 cases per 100,000 persons to 4.5 cases per 100,000 persons. It has been isolated from ticks in Europe and human cases are increasingly reported – and not just in immunocompromised individuals. Because ticks are vectors for various bacterial and viral diseases, it is common for those who contract babesiosis to suffer from co‐infections such as Lyme disease. Rather confusingly, some literature refers to this parasite as Theileria microti. Even more confusingly, there is a parasite referred to as Babesia cf. microti, Babesia vulpes and Theileria annae that has a similar distribution and causes severe disease in dogs. The ‘cf’ denotes that it is uncertain whether it is actually B. microti, a sub‐species, or a closely related but different species. In addition to tick vectors, transmission of B. microti, and B. cf. microti is also possible across the placenta. Dogs and other canines infected with babesiosis are reportedly capable of directly transmitting the infection in their bites.
3.4.3.1 Babesia Life Cycle
The life cycle begins when ticks inject infective sporozoites are into the mammal bloodstream and these then invade the red blood cells (Figure 3.12). Initially, the host cell encloses the sporozoites within a membrane‐bound vacuole. However, the parasites escape from this and therefore come into intimate contact with the erythrocyte cytoplasm. The sporozoites now transform into the merozoite stage that divides by binary fission and accumulates within the cell and eventually kill it. The merozoites are usually pear shaped (in Babesia bigemina they are 4–5 μm