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The coccidia are members of the suborder Eimeriina. They are typically highly host-, organ-, and tissue-specific. Under natural conditions, most mammals pass small numbers of coccidial oocysts in their faeces, without apparent clinical effect. Coccidiosis becomes important as a disease when animals are reared under conditions that permit the build-up of high numbers of infective oocysts in the environment. This is because the degree of damage caused by coccidia depends upon the numbers of parasites able to replicate in any given site, which depends firstly upon the numbers of infective stages (oocysts) ingested. This is different from other protozoa which may reproduce indefinitely by binary fission, until halted by host immunity or death. Eimeria infections are self limiting because the parasites only pass through a limited number of asexual multiplications. Coccidiosis involves (extensive) destruction of the intestinal epithelia. The effects of intestinal coccidiosis in mammals vary with the host-parasite system. They are mainly related to malabsorption induced by villous atrophy and reduction of brush border enzymes, or to anaemia, hypoproteinaemia and dehydration due to exudative enteritis and colitis caused by epithelial erosion and ulceration. High mortality may occur in ruminants infected by the most pathogenic species (see also Nervous System Diseases, Ruminants).
About 15 species of Eimeria parasitize cattle; of these E. zuernii and E. bovis are potentially highly pathogenic. Other species, such as E. auburnensis may at times contribute to the general clinical picture. In general, the infection occurs in calves or weaned feeder cattle under one year of age, but clinical disease occasionally occurs in adults, especially if massive infections are acquired during stressful situations. The diseases caused by E. zuernii and E. bovis are very similar; they are characterized by a haemorrhagic diarrhoea which may become so severe that pure blood is passed instead of faeces. Tenesmus is marked, and there is anaemia, weakness, anorexia and emaciation. In severe infections death may occur. The first clinical signs appear just before the peak in oocysts output (day 18–19). At that moment there is maximal loss of epithelium in the large intestine due to destruction of cells by second generation schizogony and gamogony. This causes the exposure of the lamina propria and the formation of diphtheritic membranes. The destruction of the epithelium leads to reduction in the reabsorption of water, Na+ and Cl- from the intestinal contents. The abrupt loss of weight and the reduction of the plasma concentration of these two ions support this contention. Exposed capillaries of the large intestinal lamina propria may rupture, leading to loss of erythrocytes and plasma.
Coccidial infection is virtually universal in sheep and goats, and large numbers of oocysts may be found in the faeces of clinically normal animals. Coccidiosis in small ruminants is chiefly restricted to young animals up to 4–10 weeks of age. Close morphological similarity between the oocysts of Eimeria species from sheep and goats has caused some confusion in the literature. Relatively little is known about the pathogenicity of the different species, but it has been established that E. ovinoidalis in sheep and its analogue in goats, E. ninakohlyakimovae can be very pathogen. Other species such as E. bakuensis (E. ovina) and E. crandallis in sheep, and E. arloingi and E. christenseni in goats may exacerbate the symptoms of the former two species. Outbreaks of coccidiosis are usually acute and characterized by moderate morbidity and low mortality. There is a green or yellow watery diarrhoea with a fetid odour, occasionally with blood. Abdominal pain, some anaemia (macrocytic, hypochromic), loss of appetite, dehydration, tenesmus, weakness and loss of weight occur. Depression, inactivity, and recumbency are prominent. Pathological changes include thickening of the caecum and colon mucosa, oedema, haemorrhage and hyperaemia. Myiasis, bacterial diarrhoea, and bacterial septicaemia often accompany coccidiosis outbreaks.
The only species occurring in horses, Eimeria leuckarti, is not known to cause disease.
At least 12 species of Eimeria are thought to occur in swine, and a single species of Isospora. Eimeria spp are not considered a major cause of disease in pigs and many animals are asymptomatic carriers. Isospora suis is the only important species. It causes porcine neonatal coccidiosis, a disease of piglets from about 5–6 days to about 2–3 weeks of age. It is characterized by a yellow, foul smelling diarrhoea, dehydration, occasional vomiting, loss of condition and death, or at the least a temporary check in growth. Morbidity is usually high, mortality low or moderate. Necropsy reveals villous atrophy and a marked, sometimes necrotizing, enteritis of the small intestine. Simultaneous infection of I. suis with viruses and E. coli results in more severe lesions and clinical disease than with coccidia alone.
There are at least 14 species of coccidia in canine faeces: Isospora canis, Isospora (Cystoisospora) ohioensis, I. burrowsi, I. neorivolta, Hammondia heydorni, Neospora caninum and eight species of Sarcocystis. A total of at least 15 species exist in cats: Isospora felis, I. rivolta, five species of Besnoitia, Hammondia hammondi, Toxoplasma gondii, and six species of Sarcocystis. In relation to pathogenicity, it is usually the intermediate hosts rather than the dog or cat that are adversely affected. Clinical coccidiosis in dogs or cats is apparently caused by certain species of Isospora and by Toxoplasma gondii. For example I. ohioensis can cause clinical disease in newborn pups. Diarrhoea is caused by inflammation of the intestinal crypts, with necrosis and massive desquamation of the tips of villi, especially in the lower part of the small intestine.
Reports from the literature suggest that immunity to coccidia is short-lived in young animals. In contrast, repeated coccidian infections induce a more long-lasting immunity than a single (primary) infection. An increasing infection pressure may cause a deterioration of immunity that is evident by an enhanced number of intracellular developmental stages and so output of oocysts, and possibly the development of clinical signs. The effect of immunity can range from complete (or close on zero) inhibition of oocysts production (premunition) to the passage of smaller numbers of oocysts in the faeces (partial immunity). It is assumed that premunition (immunity of the non sterile type) to coccidia depends upon the persistence of some (occult, extraintestinal) development stages in the immune host from initial infection and/or reinfection. Thus, the acquired (often) species- or even life-cycle-stage specific immunity of the host to coccidia plays an important role in the control of parasites and may depend on various host factors such as individual immune status, age of the host and its genetic background (breed type: innate immunity). It seems that development of natural immunity to coccidiosis through digestion of sporulated oocysts is rather slow and may take several weeks or even longer. Therefore, using vaccines to prevent coccidiosis in the short life span of fattening young animals appears problematic because protective immunity resulting from vaccination may be insufficient. This is true particularly in case of broilers, which life span lasted about 35–40 days only. On the other hand, breeder replacement chicks and commercial layers are able to profit from the immunity protection against coccidiosis. They may be exposed to a controlled number of sporulated coccidia oocysts, i.e., to live virulent vaccines. Today, various types of live vaccine for the control of poultry coccidiosis are available (see Table 1). Coccivac® or Immucox® (sporulated oocysts of wild-type) has been used mainly for replacement birds, which represent a relatively small market in comparison with that of the broiler industry. In using such vaccines it appears economically acceptable to have some loss of performance as result of immunization. However, live virulent Eimeria vaccines for control of coccidiosis in broiler chicken have rarely been used because loss of body weight, and its effect on feed conversion is not acceptable. Attenuated parasites for delivery in the drinking water are `sub-lines' of sporulated oocysts from chicken derived from the progeny of single oocysts. They may be attenuated after long-term passages through the chorioallantoic membranes of embryonating eggs (Livacox®), or they may be recovered after only a few passages with selection for early development by passages through chickens (Paracox®, Livacox®) or rabbits. Precocious lines of coccidia species are drug sensitive and thus any use of anticoccidial drugs should be avoided during the month following vaccination. Precocious lines are characterized by a shorter life cycle, i.e., decrease in prepatent period, number and size of endogenous stages (e.g., deletion of the terminal generation of schizonts of the wild-type parents). They can induce protective immunity against coccidiosis in spite distinct attenuation of their virulence. Such parasites (oocysts) are no longer able to cause infections with severe clinical signs in chickens or rabbits (the production of precocious lines in cattle obviously failed). Problems arising from vaccination in the poultry industry or elsewhere may be the delivery and application practice of such live vaccines. Thus the application management of vaccines seems to be more sophisticated than that of feed-in products in widely used chemoprophylaxis. Another problem may arise through genetic instability in precocious sublines. In addition, cost of production of live “cocktail”-vaccines containing all (Paracox®) or only certain Eimeria spp. (Livacox®) may be considerable and above that of in-feed delivered anticoccidial drugs.
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The chances for developing protective recombinant vaccines against coccidiosis in chickens appear promising though E. maxima shows antigenic diversity, and live Eimeria vaccines may show differences in their virulence and immunogenicity in the individual recipient and different breeds of poultry. The development of effective recombinant vaccines (genetically engineered Eimeria antigens) against poultry and farm livestock coccidiosis has become a major goal in modern parasitology. Since coccidiosis involves the intestinal immune system, understanding of the complex gut-associated immune system is most important in the development of immunological control strategies to coccidian parasites. Different types of antigens (surface-, internal-, secretory antigens of sporozoites, merozoites, gamonts) that induce parasite-specific immunity have been identified by means of monoclonal antibodies against various Coccidia species. Recombinant proteins derived from these antigens have been shown to induce either humoral or cellular response or both, whereas protection against live challenge (sporulated oocysts) proved to be insufficient to weak or partial only. For instance, responses of different poultry breeds vary considerably to such recombinant antigens (epitopes). Sub-unit vaccines developed so far lack epitopes that induce strong protection and this seems to be also true for optimal delivery systems that release these epitopes at the site of infection. Suitable live recombinant vectors derived from bacteria or viruses will be necessary to induce a persistent stimulation of the local immune system by presentation of `perfect' recombinant target antigens to adequate immune effectors. Such approaches are only possible by using biotechnology that requires great skills of molecular biology as well as a profound knowledge of host immune responses to coccidian infection. Until now, there are large gaps in our existing knowledge concerning precise definition of target antigens and immune effectors. Consequently, the development of protective recombinant coccidiosis vaccines will be in any case a long-term and high-risk research project. Furthermore, such a vaccine must not only confer resistance but also be cheap and fit in with current management practice in the poultry industry and farm livestock. An exiting new approach to vaccine development may be highly attenuated bacterial vectors that have the ability to enter epithelial cells and directing plasmid DNA to the cytoplasm of the host cell for protein synthesis and processing for antigen presentation. Delivery of DNA-encoded antigens should permit mucosal immunization against the parasite simultaneously with multiple antigens that can stimulate T helper cells and antibody production, especially the proper folding and conformational epitopes for the immunoglobulins A (IgA) and G (IgG). Aside from the practical oral application of bacterial DNA delivery, this type of vaccines does not need DNA purification and can be produced for the fermentation, lyophilization and packaging.
