Parasitology. Alan Gunn

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.

      Population structure of Toxoplasma gondii

      The population structure of T. gondii is highly clonal (Galal et al. 2019). In Europe and North America, most strains of T. gondii belong to one of three distinct genotypes: Types I, II, and III. However, other genetically distinct strains exist in Brazil and French Guiana. There is limited variability within genotypes I, II, and III, and this suggests that they probably arose relatively recently. Furthermore, this polymorphism appears limited to just two alleles called A and E – short for Adam and Eve – on the basis that all extant strains derive from mixtures of two ancestral founder strains. The continued existence of these separate strains probably results from the parasite’s ability to maintain asexually reproducing populations, possibly indefinitely, by horizontal and vertical transmission between intermediate hosts and the limited opportunity for genetic mixing during sexual reproduction within the cat definitive host. Because T. gondii is haploid, genetic mixing only occurs if a cat has simultaneous infections with two different strains of the parasite. Furthermore, the development of the two strains would have to be synchronous because the production of gametes occurs over a relatively short period. This scenario might occur if the cat consumed a mouse harbouring two or more strains of the parasite or two mice harbouring different strains in a short period. There is limited evidence of intermediate hosts harbouring mixed strain T. gondii infections, but there is a need for more work in this area.

3.5.7 Genus Neospora

      This is a genus of emerging parasites. The first description was in Norway in 1984 when a cyst‐forming protozoan parasite was associated with the development of encephalomyelitis and myositis in a litter of puppies. Since then, the parasite responsible has been given the name Neospora caninum although Heydorn and Melhorn (2002) consider this to be a ‘nomen nudum’ – that is it fails to conform to International Code of Zoological Nomenclature. Despite the taxonomic uncertainty, most workers continue to refer to the parasite as N. caninum and we shall do the same. Presumably, up until 1984, the parasite was overlooked because it rapidly became recognised as having a cosmopolitan distribution and being a major cause of abortion in cattle. Another species of Neospora, Neospora hughesi, causes myeloencephalitis in horses and donkeys but we currently know very little about its biology.

      3.5.7.1 Neospora caninum

      Neospora caninum is essentially a disease (neosporosis) of dogs and cattle although many other mammals may also be infected. On a worldwide basis, it causes losses of hundreds of millions of pounds per year and is a particular problem in cattle‐breeding countries (Liu et al. 2020). It parasitises many wild animals from mice to dugongs although the consequences of infection for wild animals are uncertain.

The life cycle of N. caninum resembles that of T. gondii. Apart from having different definitive hosts, the two parasites occupy a very similar ecological niche. It is therefore not surprising that competition probably exists between the two species in the intermediate hosts (Sundermann and Estridge 1999). Sexual reproduction in N. caninum occurs within dogs and other canines (rather than cats in the case of T. gondii) and they are therefore the definitive host. A separate asexual cycle occurs within cattle, particularly dairy cattle, but also within several other mammals, including dogs, in which transmission takes place vertically via the placenta, rodents, shrews, pigs, and camels. Although the parasite will grow in laboratory human cell line cultures, and some reports mention finding low antibody titres to the parasite in human serum samples, there are no confirmed cases of human infection to date (Calero‐Bernal et al. 2019).

      Dogs normally acquire an infection by consuming meat containing the tissue cysts. When these cysts reach the small intestine, they release bradyzoites that invade the intestinal cells and reproduce by schizogony to form schizonts. The subsequent stages leading to the formation of the oocysts are a bit uncertain. Presumably, the schizonts give rise to microgametes and macrogametes that then fuse and develop into oocysts. The oocysts (10–11 μm) are subsequently shed with the dog’s faeces and sporulate in the environment to produce two sporocysts, each containing four sporozoites.

      A cow (or other intermediate host) acquires an infection when it ingests a sporulated oocyst – for example, whilst grazing or through contaminated water. The oocyst releases the sporozoites when it reaches the cow’s small intestine, and these invade the intestinal epithelium and ultimately find their way to a wide variety of cell types around the body. The majority of parasites locate themselves in the reticulo‐endothelial system where they transform into tachyzoites that multiply asexually by endodyogeny until they kill their host cell after which they invade other cells. Healthy cows usually do not exhibit any signs of infection. The parasites induce a strong gamma‐interferon‐based cell‐mediated immune response, and this causes N. caninum to form tissue cysts containing bradyzoites. These tissue cysts are approximately 100 μm in size and occur predominantly in nervous tissue, but they may be located elsewhere. If the cow is pregnant at the time of her initial infection, the tachyzoites can cross the placenta and infect the developing embryo. Alternatively, if she becomes pregnant after being infected, the resting tissue cysts are activated because of the normal reduction in cell‐mediated immunity that happens during the first trimester of pregnancy. Within the tissue cysts, the bradyzoites transform into tachyzoites that find their way to the developing calf. The consequences for the developing calf depend upon the number of invading tachyzoites and the stage of pregnancy. The earlier in pregnancy that the calf is infected the worse the prognosis. Infection during the first and second trimester is most likely to result in abortion, whilst infection during the third trimester may apparently have no harmful effects – although 80–95% of calves born to infected mothers are infected at birth. Occasionally, a calf infected during the third trimester may abort or be born with neurological symptoms, such as paralysis. Within infected but otherwise healthy calves, the parasite forms dormant tissue cysts. When infected female calves reach adulthood and become pregnant, these cysts are activated and the parasite transfers to the next generation. Although N. caninum can cause abortion and birth defects in sheep and goats, there are fewer published reports on this than in cattle.

      The colostrum of infected cows may contain N. caninum tachyzoites, but these are unlikely to be important for the transmission of the infection. This is because over 80% of calves born to infected mothers are already infected at birth. Similarly, although the parasite is detectable in the semen of infected bulls, it is uncertain whether it is sexually transmissible – and if it is whether it happens sufficiently often to be a significant epidemiological factor.

      Because so many calves are born infected, this is probably the principal means by which the infection is maintained within herds. This would occur through the normal farm practice of retaining a proportion of the female calves as replacement heifers (female cows). However, modelling studies suggest that this is not sufficient to maintain the infection over prolonged periods and there must be periodic horizontal transmission from infected dogs. Because farm dogs are often closely associated with cattle herding, dog: cow transmission cycles are probably common.

      Within dogs, tissue tachyzoite stages also form and neurological symptoms occur if nervous tissues are infected. In addition, in pregnant bitches, the tachyzoites can invade across the placenta and infect the developing pups. The consequences of congenital infection in dogs can result in the pups being born with serious damage to nervous and skeletal muscle tissue that results in paralysis.

3.5.8 Genus