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The equine cyathostomin problems- A case of anthelmintic resistance or change in diversity of species

It has been reported that horses have been suffering from the pathogenic parasites that cause a lot of challenges in their health. Cyathostomins has been found to be the most dominant parasite in the horses today that causes the syndrome in them. Cyathostomins is a small red worm that has a capsule-cylindrical shape (*Brady, Nichols, Blanek, & Hutcheson, 2008). They are approximately 25mm in length. According to Lichtenfels (1975), Cyathostomins occur differently depending on the areas where they are found around the world. Their occurrences are morphologically based. Moreover, he creates awareness that there are different types of Cyathostomins. He outlines that there are over forty-one species and grouped them in eight genera; Caballonema, Cyathostomum, Cylicocyclus, Cylicodontophorus, Cylicostephanus, Cylindropharynx, Gyalocephalusn and Poteriostomum.

Cyathostomins species life cycle is still not clear in details. However, a general life cycle of all the species has been developed and assumed to fit all the Cyathostomins species. The larvae in the third stage (L3) that have not undergone ingestion remove their outer sheath while still in the small intestine before they penetrate into the Lieberkuhn glands that are found in the colon and the caecum. At the lower part of the Lieberkuhn glands, the larvae penetrate the Lieberkuhn layer known as the mucosa. After the L3s have penetrated into the mucosa layer, it is then hemmed in by the fibroblast leading to the formation of the capsule in that layer. Ogbourne (1978), narrates that, the different species of the Cyathostomins penetrates the mucosal layer at different depths. The bigger species normally penetrates deeper into the submucosa layer while the smaller ones just penetrate the mucosa layer only. While in the wall of the large intestine the L3s shades off the older sheath and starts a new growth. During this period the L3s matures, and they enter another level of stage known as the forth stage larvae (L4). During the development of the L4s, a stage is reached where it breaks the capsule and then it penetrates into the gut lumen. In the gut lumen, the L4s develops as it removes the outer sheath. Different mature Cyathostomins species have been found to migrate to different parts of the large intestine depending on the type of the species (Ogbourne, 1978).

During the L3 early stages, there is always a dormancy period on its development in the mucosa or submucosa layer (Eysker, Jansen & Mirck, 1984). This period of dormancy is regarded to be part of the development life circle of the Cyathostomins (Coles et al., 2003), and it may occur for a longer period. Gibson (1953) confirmed that the dormant larvae that are not going through any development could still continue with the development process in a live horse after three years. According to Barker (2009), there are factors that lead to the dormancy of the Cyathostomins larvae stage. This was carried out experimentally based on the infections of the nematodes. According to the experiment, the following factors were observed to influence the dormancy period of the Cyathostomins; immunity of the host, the size of the horse population and the larval condition depending on the season. In Northern Hemisphere, it has been noted that the dormancy period of the Cyathostomins larvae is higher during the cold seasons when the pasture conditions are severe promoting the larvae infection. The period of prepatency for the Cyathostomins is approximately 2-3 months, even though, this varies depending on the inhibition of the larval stage (Brady, & Nichols, 2009). Also, it has been found that the aged horse has got some effect on the period of the prepatency, and it is longer in the aged horses than in the younger ones (Smith, 1978). According to the study that was conducted in Scotland, it was found that the period of prepatency that infects the horses was between 54 – 64 days (Love & Duncan, 1992b).

Almost all the horses are Cyathostomins infected. The highest number of this parasite are found in the small intestine and the large intestine on the mucosa and the submucosa. The Cyathostomins numbers vary in the gut lumen up to greater numbers of above 1.2 million (Ogbourne, 1975a). From these large numbers of the larval and the adult, ninety percent of the adults are found in the dorsal, and the ventral colon and the ten percent that is remaining are distributed in the caecum  (Reinemeyer, 1986; Gawor, 1995; Collobert-Laugier et al., 2002).

The study on the prevalence of the Cyathostomins species worldwide shows that over forty Cyathostomins species can infect the horse and at any particular time the number of species that are active in the infected horse are approximately ten (Lichtenfels et al., 2001). Moreover, Lichtenfels, Gibbons & Krecek (2002) states that one horse can be infected with approximately five to ten different species of Cyathostomins. Different authors have outlined the most common species that are common, however, the study that was carried out in Scotland identified Cylicocyclus ashworthi as the most common infectious species (Lichtenfels et al., 2001).

On the epidemiology study of the Cyathostomins, the eggs that are laid by these pathogens are passed out with the faeces. When the conditions are favorable for them, they are hatched into the first stage larvae (L1) within a period of 2-4 days. The laid eggs are adaptable to low temperatures where this will only postpone the development of these eggs (Uhlinger, 1991). The percentage of the egg hatching increases with increasing temperature of the surrounding (Mfitilodze & Hutchinson, 1987). Mfitilodze & Hutchinson, (1987) demonstrates that the optimum temperature for the complete hatching of these eggs is between 25-350C and at this temperature all the eggs hatch within twenty-four hours. They continue to say that the temperatures below five 0C hinders hatching, in spite of this, the eggs remain viable. The Li are vulnerable to the lower temperatures as well as to desiccation extremely dry conditions. During the hot seasons, the faecal materials dry fast. Therefore, the hatched L1s does not survive since they normally feed on the bacteria that are found in the faecal materials. L1s develop into the second stage larvae (L2). The L2s are resistance to the hot and dry environment but are vulnerable to the cold environment just like L1s (Ogbourne, 1972). During the larval development, their infective starts at the L3s stage. Their survival is affected by the faecal material conditions, temperature range and the interaction of the moisture.

In the past, the Cyathostomins was regarded to be a non-pathogenic organism, although there were some of the parasites that were visible in the large intestines of the horses that were assumed to be causing diarrhea in the horses (Love, Murphy & Mellor, 1999). This was 150 years ago. Fifty years later the Cyathostomins pathogens were identified, and a comprehensive description was given by the clinical scientists (Velichkin, 1952). The veterinary specialists previously flouted the effects of the Cyathostomins pathogens. This lead to a more rampant case of the symptoms seen in the horses that were anguished from the infection of S.vulgaris. However, there is a fading out of the S.vulgaris giving the upsurge of anthelmintic resistance Cyathostomins. Currently, the cyathostomin has been regarded as one of the infectious nematode pathogens in the horses (Love, Murphy & Mellor, 1999)

The horses that have been infected by the adult cyathostomin are normally diagnosed with diarrhea. The larval developments at different stages are responsible for the damages that are caused in the mucosa and sub-mucosa layers. The surrounded larvae by the fibrous capsule normally cause the inflammation due to the reaction that takes place with the eosinophils that are usually severe in the submucosa (Palmer, 1985).  When the larvae emerge from the gut wall of the lumen, this triggers the rupture of the muscular mucosae and severe eosinophilia and oedema. During the inflammation of the muscularis mucosae, the neutrophils, and the macrophages undergoes infiltration at the same time. According to Palmer (1985), the horses that are greatly infected may have 55-65 larvae per centimeter square of the mucosa layer in the large intestine.

According to Lichtenfels, Gibbons & Krecek (2002), the clinical syndrome may occur due to the synchronized revival of the dormant larvae, and this may as well lead to the massive emergence of the fourth stage larvae (L4s) into the intestine lumen. Moreover, there are factors that are linked to the growth of the clinical disease. These risk factors include; the age of the horse, season and the anthelmintic treatment (Reid et al., 1995). Larvae cyathostomins is serious disease that commonly affects the younger horses that are of approximately of up to six years, although, it also attacks the aged horses. It has been observed that the cyathostomins infection is seasonal depending on the climatic conditions at a particular time of the year. In the temperate climatic areas, it often takes place between January and May when the larval development resumes from dormancy (Giles, Urquhart & Longstaffe, 1985). The larval cyathostomins infection can attack a single horse, but when there is an outbreak most of the horses on the farm might be infected (Soulsby, 1986). There are various clinical symptoms that are associated with the cyathostominosis. They include; profuse, loss in weight, prolonged severe diarrhea, body loss conditions; the horse becomes weak and loses appetite and the swelling of the limbs due to the collection of water in limb tissues. They infection may as well lead to the death of the infected horse(s) (Love, 1995). A study that was carried out in the UK showed that the chronic diarrhea was viewed to be common in younger horses that were of the age older than one year. Therefore, the larval cyathostominosis was seen to be infecting these young horses than the aged ones (Love, Mair & Hillyer, 1992).

Younger horses are vulnerable to cyathostomins infections than the ones that are old. However, there has been studies on the immunity of the horses against this infectious disease due to its complexity. However, the studies that have been carried out indicates that immunity in horses increases as it grows (Klei & Chapman, 1999). There is a high number of eggs in the faeces, and the clinical cyathostominosis are regularly seen in the younger horses mostly the ones below six years. There is also differences in age in the period of prepatency for the cyathostomins and the required time for the eggs to reemerge on the faeces of the horse after their deworming. These characteristics are shorter in the younger horses as compared to the older horses. Also, the studies of cyathostomins show that the horses that have been infected naturally increase the cyathostomins species diversity. This was evident in the foals and yearling as compared to the horses that were above eight years (Klei & Chapman, 1999).

Dopfer, Kerssens, Meijer, Boersema, & Eysker (2004), outlined that the horses that were previously infected by the cyathostomins develop immunity that helps the resist the re-infection and the clinical signs are also reduced. Tizard (2000) states that the young horses that were exposed to cyathostomins infected pastures developed the immunity against the infections of the L3s. Although observations that have been made indicates that development of immunity in the horses increases by with the increase in age of the horse.

During the diagnosis of the infections in the horses, the number of the parasites eggs are determined per germ of faeces. However, this method does not show the sex immaturity of the eggs at stages of the L5s and L4s in the horse lumen, the growth of the L4s an L3s in the mucosa and the inactive L3s in the mucosa. Therefore this method is used to determine the presence of the larvae and worms in the horse. The density of the worms and their distribution should be determined as these factors influence the reproduction of these parasites. However, the determination of the egg count in the faeces helps in the comparison of the effectiveness of the anthelmintic compounds, resistance to drug detection and the determination of the anthelmintic treatment interval (Herd, 1992; Warnick, 1992).

In the recent past, some of the control measures have been undertaken to reduce the cyathostomins infection in the horses.  One of the controls was to reduce the number of the eggs and the resulting L3s on the pasture areas which result in the clinical diseases (Denwood, Reid, Love, Nielsen, Matthews, McKendrick, & Innocent, 2010). This could be achieved by frequent treatment of the horses with the anthelmintic medicines and the spraying of the grazing areas to kill these pathogens (Back, Nyman, & Lind, 2013). The cyathostomins infection has been reported to have decreased over the recent past year. However, these parasites are gradually developing the resistance against the drug that is being used in the treatment of the infection DiPietro, & Todd, 1987). The anthelmintic drugs that are have been used in the treatment of the cyathostomins infections include; Benzimidazoles (BZ), Tetrahydropyrimidines and Macrocyclic lactones (ML) (*Bolwell, Rosanowski, Scott, & Sells, 2014). When these drugs were initially introduced, they were very effective in the treatment of the nematode infections. In spite of these drugs effectiveness, these nematodes species of the cyathostomins have with time developed resistance against them. Chandler, Collins & Love (2000) have stipulated that more research is still being carried out to come up with the most effective drugs that can kill these resistant cyathostomins species.

There are some of the anthelmintic treatments that can be done as a precaution measures to prevent the horses from being infected which may increase the cost of the treatment during that time (Chandler, & Love, 2002). These routine treatments include; interval dosing of the horses after every six to eight weeks, treatment of the horses depending on the seasons that encourages the development and the survival of the parasites especially the L3 on the pasture. Treatment of horses that have a higher number of eggs count per gram above a certain limit was then administered (Bishop, Scott, Gee, Rogers, Pomroy, & Mayhew, 2014). Frequent treatment of the infections reduces the reproduction of these parasites by killing them hence cuts the life cycle of these nematodes thus reducing the number. To improve the rate of the infection in horses, vaccination has also been practiced by the oral administration and injection. This was observed to be helpful in both the young and the older horses as it improved their immunity system.

Continuous and extensive use of the anthelmintic compound drug has resulted in the parasite resistance to the drugs that are administered to the horses (Andersen, Howe, Dangoudoubiyam, Toft, Reinemeyer, Lyons, Olsen, Monrad, Nejsum, & Nielsen, 2013). This has made it even hard to treat the infections since almost all the drugs that are being used ineffective due to the resistance developed by these parasites (Allison, Taylor, Wilsmore & Garforth, 2011. In some of the Southern Hemisphere countries, anthelmintic resistance has reached a point that it is hard to control due to the complete resistance of the parasites against the drugs that are being used (Coles, Bauer, Borgsteede, Geerts, Klei, Taylor, & Waller, 1992). Anthelmintic resistance is the loss of change in the sensitivity of the worms due to their genetic revolution from being sensitive to insensitive to the drugs being used to kill them when using the same drug over a period (Köhler, 2001). Therefore, it is important to rotate the usage of the drugs that are being used to avoid the intensive and extensive of one drug which will lead to the development of resistance by the parasites (Craig, Diamond, Ferwerda, & Thompson, 2007). To reduce the rate at which these parasites genetically develops the resistance to the drugs that are being used horse farmers should embrace some of the non-chemical methods to control the parasite (Bartram, Leathwick, Taylor, Geurden, & Maeder, 2012). Such methods would include the frequent removal of the faecal material from the areas that are being used for grazing (Bairden, Davies, Gibson, Hood, & Parker, 2006). This would reduce the contact between the horses and the cyathostomins parasites (Chapman, French, Monahan, & Klei, 1996). In spite of the development of the resistance against the anthelmintic drugs, macrocyclic lactones have been recommended to be used as it is still effective on the equine establishment where the nematode parasites have developed resistance to Benzimidazole and other anthelmintic drugs (Bairden, Brown, McGoldrick, Parker, & Talty, 2001).

Due to the consistency of the researches that are being done, various in vivo and in-vitro tests methods have been found to be used in the detection of the anthelmintic resistance (Boersema, Eysker, Nas, 2002). Nevertheless, the method has got their merits and demerits. These tests methods include; controlled test, critical test, and faecal egg count reduction test (FECRT). These are in vivo test methods. Moreover, in vitro test methods are also used in the detection of the anthelmintic resistance developed by nematode parasites in the horses (Brady, & Nichols, 2009). The in vitro test methods includes; larval development assay (LDA), genetic tests, and egg hatch assay (EHA).

 

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