what is used to control coccidiosis in poultry

1. Introduction

Coccidiosis is a disease acquired by parasites of the genus Eimeria and Isospora belonging to the phylum Apicomplexa with a complex life cycle, affecting mainly the intestinal tract of many species of mammals and birds. It is of slap-up economic significance in subcontract animals, especially chickens. Most knowledge on coccidiosis has been obtained from chickens, where the disease has been studied most intensively as it is in commercial poultry that this parasite causes the near damage due to the fact that birds are reared together in large numbers and high densities. The economic significance of coccidiosis is attributed to decreased animal production (college feed conversion, growth low and increased mortality) and the costs involved in treatment and prevention. Worldwide, the annual costs inflicted by coccidiosis to commercial poultry have been estimated at 2 billion €, stressing the urgent need for more efficient strategies to control this parasite.

ii. Anticoccidial products

Numerous anticoccidial drugs have been introduced since 1948, when sulphaquinoxaline and nitrofurazone were first canonical by the American Food and Drug Administration (Chapman 1997; McDougald 2003; Conway and McKenzie 2007). Most of the anticoccidial products currently approved in dissimilar regions of the world for the prevention of coccidiosis in chickens are listed in Table 1. Moreover, national regulatory limitations may apply to some products. A number of anticoccidials have been withdrawn overtime because of safe or efficacy bug; yet, many of these drugs are still available and used.

Table 1. Contemporary anticoccidial products and recommended doses for safety treatment of coccidiosis in chickens (modified from Conway and McKenzie 2007).

2.1. Categories

The anticoccidial products tin exist classified in three categories according to their origin (Chapman 1999a, 1999b; Allen and Fetterer 2002).

1.

Constructed compounds. These compounds are produced past chemical synthesis and often referred to as 'chemicals'. Synthetic drugs accept a specific mode of action against the parasite metabolism. For example, amprolium competes for the absorption of thiamine (vitamin Bone) by the parasite.

ii.

Polyether antibiotics or ionophores. These products are produced by the fermentation of Streptomyces spp. or Actinomadura spp. and destroy coccidia by interfering with the balance of of import ions like sodium and potassium. The post-obit groups of ionophores exist:

Monovalent ionophores (monensin, narasin and salinomycin).

Monovalent glycosidic ionophores (maduramicin and semduramycin).

Divalent ionophores (lasalocid).

1.

Mixed products. A few drug mixtures, consisting of either a synthetic chemical compound and ionophore (nicarbazin/narasin (Maxiban®)) or ii synthetic compounds (meticlorpindol/methylbenzoquate (Lerbek®)), are as well used confronting coccidiosis.

2.2. Mode of activity

Although detailed knowledge on the selective activeness of anticoccidial compounds against specific stages of the parasite is often lacking (Wang 1982), a wide categorization of the mode of action of anticoccidials on the parasite metabolism has been undertaken (Chapman 1997).

2.2.1. Products affecting cofactor synthesis

Several anticoccidial products influence essential biochemical pathways of the parasitic cell by affecting an of import cofactor (Greif et al. 2001).

Ethopabate, which is often used in combination with amprolium to improve the spectrum of efficacy, is a folate antagonist and blocks a step in the synthesis of para-aminobenzoic acid (PABA) and prevents the formation of nucleic acids of vitamins (Rogers et al. 1964). It is about active against Eimeria maxima and Eimeria brunetti.

Similar to ethopabate, sulphonamides prevent the synthesis of dihydrofolate by interfering with the dihydropteroate synthetase reaction, blocking the conjugation of pteridine and PABA. Dihydropteroate synthetase is only present in the parasite. They are very effective against E. brunetti, E. maxima and Eimeria acervulina and to a much lower caste against Eimeria tenella and Eimeria necatrix (Ryley and Betts 1973). A major drawback of sulphonamides is their small-scale prophylactic margin, which easily leads to intoxications particularly if they are used as handling for coccidiosis outbreaks.

A third product affecting the folate pathway of coccidia is pyrimethamine. It prevents the reduction of dihydrofolate to tetrahydrofolate past inhibiting the enzyme dihydrofolate reductase. Pyrimethamine has a clear synergistic effect with sulphonamides (Kendall and Joyner 1956). Ethopabate, sulphonamides and pyrimethamine bear upon the second generation of schizonts (Reid 1973, 1975).

Thiamine analogues, like amprolium, block the absorption of thiamine completely and have probably an combative effect on the vitamin B1 supply. Amprolium seems especially efficacious during schizogony equally then the demand of thiamine is at its highest (James 1980). There is a difference in sensitivity of the thiamine transport organization of host and parasite (more than sensitive) to amprolium. Information technology affects the get-go generation of schizonts and to a bottom extent the gametogony (Reid 1973) assuasive allowed response to develop.

ii.2.2. Products affecting mitochondrial office

Quinolone drugs, amongst which buquinolate, decoquinate and nequinate (methyl benzoquate) are listed, bear witness anticoccidial activeness at very low concentrations. These products inhibit the respiration of coccidia by blocking the electron transport in their mitochondria (Wang 1975). Quinolones arrest the development of sporozoites (Yvoré 1968; Reid 1973).

Meticlorpindol is the most of import compound of the pyridone grouping. Similar to the quinolones, information technology inhibits electron transport in mitochondria, but maybe at another level every bit cantankerous-resistance with quinolones does non occur. A synergistic outcome betwixt meticlorpindol and iv-hydroxiquinolones has been described (Challey and Jeffers 1973). A widely used pyridone–quinolone combination drug is Lerbek®, consisting of meticlorpindol and methyl benzoquate.

The true style of action of nicarbazin (4,four′-dinitrocarbanilide) is unknown. The product has been shown to inhibit both the succinate-linked NAD reduction in mitochondria of beef hearts and the energy dependent transhydrogenase and accumulation of Catwo+ ions by rat liver mitochondria (Dougherty 1974). It is non suitable for layers as information technology negatively affects the egg production and quality.

The verbal anticoccidial mechanism of robenidine (a guanidine derivative) is still unknown. However, from studies in mammals, information technology is assumed that it inhibits the oxidative phosphorylation of mitochondria (Wong et al. 1972).

Another anticoccidial drug possibly affecting mitochondrial function is the triazinetrione compound toltrazuril, which is applied in drinking water for preventive and therapeutic treatment. Harder and Haberkorn (1989) showed that activities of some enzymes of the respiratory chain, such every bit succinate-cytochrome C reductase, nicotinamide adenine dinucleotide (NADH) oxidase and succinate oxidase from mouse liver, were reduced in the presence of toltrazuril. They also showed an inhibitory effect on the dihydroorotate-cytochrome C reductase from mouse liver. More than recently, it has been suggested that toltrazuril might affect plastid-like organelles (Hackstein et al. 1995). Toltrazuril is efficacious confronting all intracellular stages (schizogony and gametogony) of all important Eimeria spp. in the chicken (Mehlhorn et al. 1984, 1988). It induces cidal changes in the organelles of the parasite at multiple levels and does not seem to impair the evolution of natural immunity (Greif and Haberkorn 1997; Greif 2000).

2.2.three. Products affecting jail cell membrane office

Polyether antibiotics influence the transport of mono- or divalent cations (Na+, K+ and Ca++) across jail cell membranes inducing osmotic damage (Berger 1951; Shumard and Callender 1967). These drugs are accumulated by extracellular stages (like sporozoites and merozoites) of the parasite in the lumen of the intestine (Long and Jeffers 1982).

Depending on the dose given, ionophore anticoccidials allow the development of immunity against coccidia (Jeffers 1989; Chapman and Hacker 1993; Chapman 1999b).

2.2.four. Products with unknown mode of action

Diclazuril is a nucleoside analogue thought to be involved in nucleic acid synthesis, perhaps affecting later phases of coccidia differentiation (Verheyen et al. 1988). It has been shown to touch parasite wall synthesis resulting in the germination of an abnormally thickened, incomplete oocyst wall and zygote necrosis in both E. brunetti and Due east. maxima (Verheyen et al. 1989).

Halofuginone is a quinazolinone derivative with an unknown style of action, which peculiarly affects the showtime generation of the schizogony.

2.three. Antimicrobial and growth-promoting properties

Ionophores have been plant to inhibit Gram-positive organisms and mycoplasmas (Shumard and Callender 1967; Dutta and Devriese 1984; Stipkovits et al. 1987). Monensin and narasin were shown to inhibit Clostridium perfringens (types A and C) in chickens and turkeys (Elwinger et al. 1992; Vissiennon et al. 2000). Ionophores may therefore take contributed in some cases to the command of necrotizing enteritis (Martel et al. 2004).

Salinomycin has been shown to reduce the number of resistant coliforms (sulphadiazine) and Streptococci (erythromycin and lincomycin; George et al. 1982). It as well seemed to reduce the number of resistant Salmonella typhimurium bacteria (Ford et al. 1981).

2.iv. Incompatibilities

Ionophores are incompatible with some therapeutic antibiotics like tiamulin, chlorampheniol, erythromycin, oleandromycin and certain sulphonamides. Ionophores are too incompatible with some antioxidants (XAX-G, Duokvin, TD; Umemura et al. 1984; Prohaszka et al. 1987; Dowling 1992; Von Wendt et al. 1997).

ii.5. European Union regulations

The future status of anticoccidial drugs is uncertain at this moment: their electric current status equally feed additives may be maintained or new legislation and phasing-out of these drugs every bit feed additives could exist proposed. Commodity eleven of Regulation 1831/2003 chosen for a report of the European Commission on this subject field. In Apr 2008, the commission submitted a report (COM 2008) in which it clearly recommends the maintenance of the use of anticoccidial products, including ionophores as feed additives, due to a lack of alternatives and to safeguard the economical feasibility of the poultry industry. It is not clear whether the European Council will follow this recommendation or not.

Actual and forthcoming data of the obtained regulations tin can exist found on the website of the European Commission animate being diet feed additives (http://ec.europa.eu/food/nutrient/animalnutrition/feedadditives/legisl_en.htm).

2.6. Resistance

The Earth Health System (WHO) defines drug resistance in antimalarial chemotherapy, which tin also exist applied to coccidiology, every bit 'the ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug in doses equal to or higher than those commonly recommended merely within the limits of tolerance of the subject area' (WHO 1965).

Generally, drug resistance in coccidia can be complete, in which case increasing doses up the maximum tolerated by the host is ineffective (i.e. diclazuril and nicarbazin). In contrast, relative resistance to anticoccidial drugs is characterized by the fact that increasing doses tolerated by the host withal will show efficacy (i.e. ionophores).

The worldwide intensive use of anticoccidial drugs to prevent coccidiosis has inevitably led to the evolution of resistance to all anticoccidial drugs as long-term exposure to any drug will event in loss of sensitivity. The widespread occurrence of resistance has been described in the United States of America, South America, Europe and People's republic of china (Jeffers 1974a, 1974b, 1989; Chapman 1978, 1982, 1984, 1997; Ryley 1980; Hamet 1986; Litjens 1986; McDougald et al. 1986, 1987; Zeng and Hu 1996; Zhou et al. 2000; Peek and Landman 2003; Peek and Landman 2004). In some cases resistance is induced very quickly, as in the example of quinolones and pyridinols, which led to a pass up in their use, while in other instances information technology may take several years as in the case of the ionophores.

Despite the widespread occurrence of resistance, at least in Europe, coccidiosis outbreaks seem to have had limited bear on so far. This is explained by the fact that resistance in many cases will have allowed the occurrence of trickle infections, which are essential in the building upward of immunity (Jeffers 1989; Chapman 1998; Peek and Landman 2003; McDougald and Shirley 2009).

2.half-dozen.1. Direction of resistance

To minimize the occurrence of resistance, rotation (a given anticoccidial product is used during a maximum of 2 months or two fattening periods) of various anticoccidial drugs or shuttle programmes (two or more anticoccidial drugs are used inside a fattening period) is used. The rationale backside this is the fact that, every bit said previously, the loss of sensitivity is correlated to the length of drug exposure, which should exist kept short if possible. Due to the occurrence of cross-resistance between anticoccidial drugs, anticoccidial drugs with singled-out manner of action should be used within rotation and shuttle programmes.

In social club to optimize the use of safe medication in the field, scientific information on the drug-sensitivity profiles of Eimeria spp. apropos field isolates is vital. This information can simply be obtained past performing an in vivo Anticoccidial Sensitivity Examination (AST) in battery cages. Despite the fact that the AST is the simply accurate tool to find anticoccidial drug resistance, the procedure is slow and expensive; isolates frequently originate from disease outbreaks (and may not always be representative for the field) and need to be propagated commencement in specified pathogen-gratuitous chickens for multiplication (which may effect in the selection of non-relevant coccidia). All the same, it is generally accepted by the scientific community that ASTs provide valuable information and should be given more than attention in coccidiosis prevention programmes.

A more recent development in managing anticoccidial drug resistance is the rotation of anticoccidial drugs with alive Eimeria spp. vaccines. Several studies take documented a higher incidence of sensitive Eimeria spp. field isolates when live anticoccidial vaccines and anticoccidial products are rotated. The exact machinery resulting in an increase of sensitivity of Eimeria spp. field isolates is currently unknown, but it is explained by the fact that chicken houses are seeded with drug-sensitive vaccine oocysts (Jeffers 1976; Mathis and McDougald 1989; Chapman 1994, 1996; Newman and Danforth 2000; Mathis and Broussard 2006; Peek and Landman 2006). This may lead to the outgrowth of resistant strains by reproductively more advantageous drug-sensitive coccidia, interbreeding betwixt field and vaccine parasites resulting in (more than) sensitive interbreeds or a combination of both. Moreover, in case live adulterate coccidiosis vaccines are used, less virulent interbreed field isolates may be produced (Shimura and Isobe 1994; Williams 2002a).

three. Vaccines

Immunity to coccidiosis, which can be induced by passive or agile immune responses, is generally defined as the occurrence of 'resistance' to a challenge infection with an Eimeria spp. and can exist determined by a reduction of the pathogenic effects of coccidiosis: less macroscopically visible lesions and/or a subtract in oocyst production, and increased performance of birds.

The first study showing that chickens infected with E. tenella were resistant to homologous challenge was reported by Embankment and Corl (1925) and formed the basis of modern coccidiosis vaccinology. Still, information technology took some other 27 years before the first commercial alive coccidiosis vaccine CocciVac® was registered in the USA (Edgar and King 1952).

During the past twenty years, diverse reports describing coccidiosis vaccines and their use in poultry have been published (Shirley 1988; Williams 1992, 1996, 1998, 1999, 2000; 2002a, 2002b; Dalloul and Lillehoj 2006; Shirley et al. 2007). In Table 2, an overview showing about available coccidiosis vaccines and their usage is given (Williams 2002a; Shirley et al. 2005).

Tabular array 2. Overview of anticoccidial vaccines that are being used or being registered for use in chickens (modified from Williams 2002a; Shirley et al. 2005; manufacturer's technical information bulletins and websites).

Vaccination can be alternated with anticoccidial drugs in feed inside rotation programmes and in combination with biosecurity.

three.1. Subunit vaccines

Subunit vaccines are composed of a purified antigenic determinant that is separated from the virulent organism. Such vaccines can be obtained past unlike technologies and may consist of native antigens or of recombinant proteins expressed from Dna of diverse developmental stages (sporozoites, merozoites and gametes) of the Eimeria parasite.

Despite an increasing number of manuscripts on exploring the feasibility of subunit vaccines against coccidiosis, no commercial products, except CoxAbic®, have been marketed to date (Brother et al. 1988; Jenkins et al. 1989; Miller et al. 1989; Jenkins et al. 1990; Crane et al. 1991; Bhogal et al. 1992; Jenkins 1998; Vermeulen 1998; Jenkins 2001; Vermeulen et al. 2001; Dalloul and Lillehoj 2006). A major limiting cistron has been that until at present no antigens able to induce potent protective immune response against Eimeria have been isolated. Systematic and detailed analysis of host–parasite interactions at the molecular and cellular levels including studies of basic immunology need to exist completed before successful subunit vaccine products will be fabricated available. In this regard, the E. tenella genome project may help to further understand how protective immune responses against Eimeria spp. are adult and help to identify antigens of vital importance in coccidial immunology (Shirley et al. 2007).

iii.1.1. Maternal immunization, transmission blocking amnesty

CoxAbic® is a vaccine confronting coccidiosis, which induces maternally derived antibodies to protect broiler chickens (Michael 2003, 2007; Finger and Michael 2005; Ziomko et al. 2005). It is an inactivated, subunit vaccine (oil emulsion) containing affinity-purified proteins (56, 82 and 230 kDa) from the oocyst wall-forming bodies of E. maxima gametocytes. Cross-protection resulting in lower oocyst shedding of E. maxima, E. acervulina and East. tenella has been described later the administration of low-dose challenge inocula using the aforementioned Eimeria spp. (Wallach et al. 1995; Wallach 1997). This is remarkable because subsequently natural Eimeria infections, cross-immunity has not been described (Rose and Long 1962). However, Crane and co-workers (1991) found cross-protection against 4 Eimeria spp. (E. acervulina, E. maxima, E. necatrix and Eastward. tenella) after administration of a single recombinant antigen.

Offspring originating from vaccinated parent birds are fed an anticoccidial drug-free diet in order to ensure natural exposure to the parasites and subsequent development of active immunity after maternal antibodies have disappeared.

iii.ii. Alive vaccines

Live Eimeria vaccines consist of sporulated oocysts and are either not-attenuated (wild-blazon strains of Eimeria spp.) or adulterate. Further differentiation is based on the Eimeria spp. included, their anticoccidial drug sensitivity profile and application. Protective immunity tin be accomplished if chickens are infected with either a single high dose or multiple low doses (trickle infections) of Eimeria (vaccine) parasites (Joyner and Norton 1973, 1976; Long et al. 1986). It is crucial that anticoccidial drugs are withdrawn from feed in case chicken flocks are vaccinated with drug-sensitive live vaccine parasites in guild to avert vaccination failures.

three.2.ane. Not-attenuated (or wild-type strains of Eimeria spp.) vaccines

Non-attenuated vaccines consist of Eimeria parasites, which have not been modified in any mode to change their pathogenicity and originate from laboratory or field strains. Examples of such vaccines are: CocciVac®, Immucox®, Inovocox® and Advent®.

Some of these vaccines (CocciVac® and Immucox®) are available equally ii dissimilar products and the choice of products depends on the poultry to be vaccinated, e.g. broilers versus breeders and layers.

During the usage of non-adulterate coccidiosis vaccines, information technology is crucial that all birds are given the required dose and the occurrence of clinical coccidiosis is avoided. Therefore, application protocols should exist followed strictly (Chapman et al. 2002). In guild to diminish the risk of coccidiosis outbreaks following vaccination, attenuated vaccines have been developed.

3.2.two. Adulterate vaccines

Attenuated vaccines consist of Eimeria spp. strains, which have been manipulated in the laboratory in order to decrease their virulence. Reduced virulence has been performed by series passages of the parasite in craven embryos; e.g. E. tenella in Livacox® vaccines. Selection for precocity is the second described method for attenuation; e.g. remaining Eimeria spp. in Livacox® and all lines in Paracox® vaccines (McDonald and Shirley 1984; Shirley and Millard 1986; Shirley et al. 1995; Shirley and Bedrnik 1997). Precocity is characterized past a shortened endogenous life-bicycle due to the fact that the number of generations of schizogony is decreased because last generations of schizogony disappear by selecting early oocysts. As a consequence, the number of oocysts produced during infection is reduced. However, the immunizing potential is maintained (Jeffers 1975, 1986; McDonald et al. 1986; Shirley and Millard 1986).

A major drawback of live coccidiosis vaccines is their loss of infectivity with time affecting their expiry (Jeston et al. 2002). Other concerns are their loftier production costs and management shortcomings during their application such as dosage errors that may result in bereft immune response or clinical coccidiosis in case non-adulterate vaccines are used, the erroneous add-on of anticoccidial drugs to the feed frustrating effective vaccination of drug-sensitive strains and vaccination of ill birds. Furthermore, reversal of virulence of alive vaccines may be another point of concern. Subunit vaccines offer possibilities to circumvent mentioned drawbacks and could provide a sustainable solution for the coccidiosis trouble in commercial poultry if with the help of new technologies their immunogenicity tin be increased.

A full listing of anticoccidial vaccines, including, amid others, their composition and route of administration, has been given in Tabular array ii.

4. Other preventive strategies confronting coccidiosis

The prevention and control of coccidiosis in commercial poultry and mainly broilers is largely based on the assistants of anticoccidial drugs in feed, although in some cases an anticoccidial drug administered shortly via drinking h2o is applied (Mathis et al. 2004). Moreover, biosecurity measures aiming at preventing the introduction of the parasite to the farm can be of additional strategic value confronting clinical coccidiosis. During the past decade, live coccidiosis vaccination has get increasingly popular equally an alternative strategy to command Eimeria spp. In feed, products with supposed anticoccidial activeness like herbs, essential oils, probiotics and prebiotics have been added more recently.

The development of resistance against all anticoccidial drugs used in feed to date and a loud call for residue-gratuitous poultry products, which in Europe has been translated first into a re-evaluation of all existing anticoccidial products and regulations safeguarding lower residues, take prompted the search for alternative control and prevention strategies.

4.1. Management and biosecurity

Good health and hence optimal immune response are essential in order to minimize the impact of infectious diseases. General management measures safeguarding the basic requirements of poultry should therefore always exist implemented: birds should be provided with proper feed and drinking h2o intake, acceptable bedding, temperature, humidity, lighting and ventilation.

Direction and biosecurity measures for the command of coccidiosis should focus on the prevention of the introduction of the parasite into the premises, and command of its multiplication and spread in example flocks have been infected. However, strict biosecurity leading to coccidiosis-free flocks is well-nigh impossible to attain in practice. Therefore, already in the early on days of coccidiosis research gradual edifice upwardly of amnesty through repeated light (trickle) infections was advocated every bit a hateful to control this affliction (Chapman 2003).

four.one.1. Fugitive the introduction of the parasite

Eimeria parasites are ubiquitous and have enormous reproduction capabilities leading to high contamination levels of infected poultry houses and their environs. Moreover, the oocyst wall protects the parasite from desiccation and chemical disinfectants, ensuring long-term survival in the environs, from which it may exist introduced to a farm through a diversity of ways. On the other hand, oocysts may already exist present in the farm house if cleaning and disinfection was not adequate.

Biosecurity measures aiming to prevent the introduction of Eimeria parasites to the farm are similar to those applied for the prevention of other infectious poultry diseases and should focus on:

one.

Isolation. Birds should be separated from the environment by fencing and other animals including rodents and insects should be kept out.

ii.

Traffic control should non merely exist performed at the farm, but also the traffic betwixt farms should be restricted.

three.

Sanitation includes disinfection of materials, people and equipment entering the farm and poultry house.

4.i.ii. Environmental factors

In case coccidiosis infections occur, their multiplication cannot be restricted by influencing the climate environment of the chicken house as Eimeria spp. thrives in atmospheric weather condition that are beneficial to the birds also.

In order for Eimeria spp. to become infective, it must sporulate after excretion in the faeces. The degree and rate of sporulation of excreted oocysts make up one's mind the infection pressure in a craven flock. Sporulation of the oocyst depends mainly on the following bones factors: temperature, humidity and aeration (access to oxygen) (Kheysin 1972).

The best sporulation temperature is approximately 24–28°C (Edgar 1955), while a temperature to a higher place 35°C is lethal for oocysts (Schneider et al. 1979). Due to the fact that the platonic sporulation temperature is within the range of temperatures frequently encountered in the poultry environs and that high temperatures are detrimental to the birds, temperature is non a factor that can be used to control parasite multiplication.

A full general misconception, regarding humidity is the belief that the drier the climate, the less coccidiosis occurs. Inquiry data have shown that in the field sporulation in wet litter is suboptimal possibly due to the occurrence of ammonia and bacteria (Williams 1995); in fact, dry litter showed better sporulation rates (Graat et al. 1994; Waldenstedt et al. 2001). However, increasing the litter humidity as a control measure to reduce sporulation does not seem feasible as information technology might cause footpad lesions and pare burns in the birds.

Adequate ventilation of the poultry house is essential for good performance and health of the birds although proper aeration will likewise favour sporulation.

Theoretically, a higher bird density will event in greater oocyst accumulation in the litter and increase the chances of clinical coccidiosis (Williams et al. 2000). Thus, reducing bird density could aid to command Eimeria infections.

4.1.3. Cleaning and disinfection

Cleaning and disinfection betwixt flocks and maximizing the downtime period is of import in order to significantly reduce the number of parasites in contaminated chicken houses. Withal, there are mixed points of view regarding the apply of cleaning and disinfection for the control of coccidiosis. Some consider that the presence of oocysts in the poultry environment enabling early institution of immunity in club to avoid outbreaks at afterward age is beneficial. In instance coccidiosis vaccines are used to repopulate the houses with drug-sensitive strains, survival of vaccine parasites betwixt vaccinated and non-vaccinated flocks is desired and therefore cleaning and disinfection should be skipped. Nevertheless, in case of severe clinical coccidiosis outbreaks especially due to anticoccidial drug-resistant strains, it is customary in Europe, where birds are non housed on deep litter, to clean and disinfect the chicken houses in society to reduce infection pressure.

Ammonium hydroxide has been reported as a highly effective disinfectant against sporulated and non-sporulated oocysts. It has been shown to be effective at a concentration of ≥5% in both fluid and vapour forms (Chroustova and Pinka 1987). Also, products that generate ammonia after mixing 2 components (ammonium table salt and sodium hydroxide) have shown to be oocidal (Oocide®, Antec International Ltd, Uk). More than recently, a cresol-based product (Neopredisan® 135-1, Menno Chemie, Norderstedt, Deutschland) has been marketed in Germany for the control of coccidiosis by chemical disinfection. It has been shown to exist efficient against diverse Eimeria spp. (Daugschies et al. 2002; Houdek et al. 2002). In a contempo written report, the efficacy of 8 disinfectants against Eastward. tenella unsporulated oocysts isolated from broilers was studied in vitro. The best disinfection efficacy was observed for the combination formol 37% and sodium dodecylbenzene sulphonate 12% (Gumarães et al. 2007).

In do, poultry houses in the Netherlands are ofttimes disinfected using calcium hydroxide in combination with ammonium sulphate (per 500 g2 40 kg calcium hydroxide is spread and subsequently moisturized with approximately 500 L h2o, after which 80 kg ammonium sulphate is added).

4.ii. Alternative coccidiosis control

Various alternative methods like homeopathy, phytotherapy and aromatherapy have been used during the past decennia for the handling of various poultry diseases. Homeopathy is a system for treating disease based on the administration of minute doses of a drug that in massive amounts produces clinical signs in healthy individuals similar to those of the illness itself. The treatment is thus based on law of similars, i.e. similia similibus curentur = the most similar remedy will cure (Saine 2000). Information technology is thought to enhance the body's natural defenses. Homeopathy is often confused with herbalism also known as botanical medicine, medicinal botany, medical herbalism, herbal medicine, herbology and phytotherapy. It is based on the utilize of plant and establish extracts for the handling and prevention of disease. Its scope is sometimes extended to include fungi, bee products, minerals, shells and certain animal parts. Aromatherapy, which is closely related to phytotherapy, is the treatment or prevention of disease by means of essential oils, and other scented compounds from plants. Information technology involves the apply of distilled plant volatiles, a twentieth century innovation. Essential oils differ in chemical limerick from other herbal products because the distillation procedure just recovers lighter phytomolecules.

Although many papers have been published on the efficacy of homeopathic treatment in humans, its effectiveness has remained a matter of debate to the scientific community. Studies assessing the methodological quality of a big number of human homeopathic experiments report a lack of testify for efficacy of homeopathic treatments because of frequent low methodological quality and publication bias (Kleynen et al. 1991; Linde et al. 2001). Co-ordinate to Velkers et al. (2005), 'Efficacy of medicines should be beyond placebo effect and observation and interpretation should be without subjective elements. Therefore, all medicines, including homeopathic remedies, should be tested in a double blind randomized clinical trial'. Published studies on homeopathy in poultry are rare and similar to homo studies, are frequently afflicted by depression methodological quality (Velkers et al. 2005). There are no scientific reports on the homeopathic handling of coccidiosis.

Some plant products or derived pharmaceutical drugs have been incorporated into mainstream medicine; still, virtually herbal treatments have been developed without modern scientific assessment. Although subsequently many herbs have been found efficacious in in vitro animal models and/or clinical studies (Srinivasan 2005), there are also many studies showing negative results (Pittler et al. 2000). However, evaluation of the literature on complementary/alternative therapies is difficult due to the occurrence of location bias in the corresponding controlled clinical trials. More than positive than negative trials are published, except in high-impact mainstream medical journals. Furthermore, in complementary/alternative medicine journals, positive studies are of poorer quality than corresponding negative studies. The latter was non the case in mainstream medical journals publishing on a wider range of therapies.

Pre- and probiotics take too been included inside alternative coccidiosis control strategies although they are quite distinct from phytotherapy and aromatherapy. Probiotics consist of live bacteria or yeasts administered in feed, which are supposed to be beneficial for the individual'south health. In contrast, prebiotics are non-digestible food ingredients, which also have a beneficial outcome on the host'southward health.

four.2.1. Plant (herb) extracts

Many different herbal compounds have been investigated for their potential use every bit a dietary supplement to control coccidiosis and are reported next in alphabetical lodge. The main conclusions obtained in the research of alternative coccidiosis command have been summarized in Table 3 and Effigy one.

Figure one. Artemisinin extracts, citric fruits and different herb extracts seem to have an inhibitory effect on the development of Eimeria spp. Prebiotics and oregano accept an indirect inhibitory upshot on the development of Eimeria parasite. Betaine has an indirect effect on the development of the parasite through its osmoprotective properties on the intestinal mucosa and stimulation of the intraepithelial lymphocytes. Echinacea purpurea, mushrooms extracts, turmeric and probiotics accept an indirect inhibitory effect on the development of Eimeria spp. through stimulation of the immune organisation.

Table 3. Overview of the influence of alternative feed additives, including the active compound, dose per kg feed and mode of action, on a coccidiosis infection in poultry.

4.2.1.1. Artemisinin

Artemisinin is an herbal extract, which can be obtained from Artemisia annua (almanac wormwood) and Artemisia sieberi. Positive effects were found for E. tenella (Oh et al. 1995; Allen et al. 1997b), mixed results for E. acervulina (Allen et al. 1997b; Arab et al. 2006) and negative results for E. maxima (Allen et al. 1997b; Arab et al. 2006).

four.2.1.2. Betaine

Betaine is a sweet crystalline alkaloid (trimethylglycine C5H11NO2), choline counterpart and methyl donor occurring in sugar beets and other plants, which is used in the treatment of certain metabolic disorders (muscular weakness and degeneration). It has been shown to protect cells against osmotic stress past stabilizing cell membranes enabling the maintenance of osmotic pressure in the cells and ensuring normal metabolic activity (Rudolph et al. 1986). The osmoprotective effect of betaine is not restricted to the abdominal cells, but too affects the developing stages of the coccidia. Information technology protects different prison cell types against chemical and ecology stresses (Kunin and Rudy 1991), including the asexual stages (sporozoites) of E. acervulina against the destructive action of salinomycin (Augustine and Danforth 1999). However, feed efficacy and weight proceeds were significantly improved in birds infected with a mixture of E. acervulina, Due east. maxima and E. tenella if betaine (0.xv%) and salinomycin (44 or 66 ppm) were supplemented separately, but much more than if both components were given together suggesting a palliative outcome of betaine on the coccidiosis infection. Betaine alone did non influence the severity of lesion scores and mortality (Augustine et al. 1997). Both products alone or in combination inhibited the invasion of E. acervulina and E. tenella (sporozoites) and the development of Due east. acervulina (second generation schizonts).

The ionophore-amplifying effect of betaine was only observed once and could not be found with other anticoccidial ionophore drugs similar monensin and narasin (Matthews et al. 1997; Waldenstedt et al. 1999), while other scientists plant contradictory results (Fetterer et al. 2003).

The weight gain and feed conversion-promoting capabilities found in some studies may be explained by betaine'southward osmoprotectant properties ensuring normal metabolism of abdominal cells. This may warrant normal development of the chicks despite the fact that the coccidiosis infection is not fully halted. Another contributing cistron to the positive effect of betaine on coccidiosis infection may be the fact that information technology increases intraepithelial lymphocytes in the duodenum and the functional backdrop of phagocytes of Eimeria-infected chickens (Klasing et al. 2002).

4.2.one.3. Citric extracts

A product based on citric extracts and organic acids amid others supplemented to broilers showed a moderate efficacy against a challenge with various Eimeria spp. considering coccidiosis lesion scores and oocyst production (Tamasaukas et al. 1996, 1997).

4.2.1.iv. Echinacea purpurea

The anticoccidial effect of E. purpurea has been attributed to its immunomodulating properties, which have been widely documented (Stimple et al. 1984; Burger et al. 1997; See et al. 1997; Sunday et al. 1999; Currier and Miller 2001; Goel et al. 2002). Ground root preparations of E. purpurea (0.ane–0.5%) supplemented to broilers during two weeks reduced weight gain retardation and coccidial lesions after a mixed infection at the historic period of 28 days with Due east. acervulina, Due east. maxima, E. tenella and E. necatrix (Allen 2003).

4.2.1.v. Gentian violet

Gentian violet, besides named crystal violet, methyl violet and hexamethyl pararosaniline chloride, is derived from coal tar and known for its antifungal and antibacterial properties. It has been shown to reduce coccidiosis lesion scores in the duodenum and better weight gain in Eimeria spp. challenged birds. In combination with anticoccidial drugs, it improved feed conversion (Sharkey 1978).

iv.2.i.six. Mushrooms and their extracts

Mushrooms and their extracts have gained interest in medicine and as dietary supplement due to their immune enhancing and antitumour properties. However, they should exist used charily as mushrooms may harbour toxic levels of metals (arsenic, lead, cadmium and mercury) and radioactive contamination with 137Cs (Borchers et al. 2004).

Polysaccharide extracts originating from Lentinus edodes and Tremella fuciformes as well equally the herb Astragalus membranaceus showed a positive effect on the cellular and humoural immunity of E. tenella infected female broilers (Guo et al. 2004). In another study, the birds treated with the same extracts had better growth during immunization in comparison with the non-treated vaccinated birds and had lower E. tenella oocyst countings later on challenge (Guo et al. 2005).

Extracted lectin from the mushroom Fomitella fraxinea injected in eighteen-day-quondam embryos, protected broilers inoculated with Due east. acervulina at 1 week post-hatch against weight loss and was associated with a significant reduction in oocyst shedding compared to untreated embryos (Dalloul et al. 2006).

four.2.1.7. Oregano

The essential oils of Origanum vulgare are known for their antibacterial activity (Hammer et al. 1999) and outcome against some parasites (Milhau et al. 1997). Furthermore, some essential oils of oregano, mainly carvacrol and thymol, have an anticoccidial outcome against E. tenella although lower than lasalocid (Giannenas et al. 2003). However, in subsequently performed studies with diets supplemented with a mixture of the essential oils, oregano, thymol, eugenol, curcumin and piperin, a beneficial issue of these oils on a coccidiosis vaccination was non found (Oviedo-Rondón et al. 2006).

iv.2.1.8. Turmeric (Curcuma longa)

Turmeric is a spice and colourant fabricated from the rhizomes of the plant C. longa, a leafy plant belonging to the ginger family unit. Its phenolic compound curcumin has been shown to have antioxidative, anti-inflammatory and antitumour properties (Mukhopadhyay et al. 1982; Conney et al. 1991; Ammon et al. 1993; Brouet and Ohshima 1995).

Eimeria maxima-infected chicks fed with diets supplemented with 1% curcumin showed an improved weight gain and a reduction in the lesion scores and oocyst excretion. Nevertheless, the activity was simply shown against East. maxima and not confronting Due east. tenella. A meaning reduction of plasma and concentrations was but constitute in E. maxima-infected and curcumin-treated birds and provide a possible explanation for the difference in anticoccidial activity found for both Eimeria spp. (Allen et al. 1998). A similar result on lesion scores, oocyst shedding, growth, and plasma and concentrations was found for γ-tocopherol. The antioxidative backdrop of curcumin past inhibiting NOS consecration by macrophages stimulated with lipopolysaccharide and interferon-γ has been shown previously (Brouet and Ohshima 1995). Although NO is an of import defence mechanism against the invasion of different Apicomplexa parasites (Adams et al. 1990; Mellouk et al. 1991), it was suggested more recently that NO might itself promote the development of coccidial lesions (Allen 1997a, 1997b).

4.ii.ane.9. Incidental reports on the anticoccidial action of other herb(southward) extracts

The anticoccidial effect of a number of herbs and extracts has been documented in single manuscripts and summarized in Table three for convenience. Although anticoccidial activity was reported, to our knowledge, none of these studies was repeated and has not led to the large-scale application of any of these compounds in exercise.

iv.ii.two. Pre- and probiotics

The term prebiotic was introduced past Gibson and Roberfroid (1995), who defined it every bit 'a not-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a express number of leaner in the colon, and thus improves the host'due south wellness. The positive influence of prebiotics on the intestinal flora has been confirmed by a number of studies (Van Loo et al. 1999). Recently, the definition of the prebiotics was narrowed with the introduction of a prebiotic index by Roberfroid (2005), who stated that a grooming might be called prebiotic if it is capable to produce at to the lowest degree 4 × 10eight colony-forming units of Bifidobacteria/gram faeces per daily dose (gram) ingested. Only three large groups meet this criterion: inulin and oliogofructose, galactose oligosaccharides and xylooligosaccharides.

Probiotics consist of beneficial live bacteria or yeasts supplemented to the diet. Co-ordinate to the Food and Agriculture Organisation (FAO) and WHO probiotics are 'live microorganisms, which when administrated in adequate amounts confer a wellness benefit on the host' (FAO/WHO 2002). The most often used probiotics in humans are species of the genera Lactobacillus and Bifidobacteria, whereas species of Bacillus, Enterococcus and Saccharomyces yeasts have been the almost commonly used organisms in livestock. In poultry production, probiotics are known for their chapters to restore the intestinal microflora later on beingness disrupted by antibody handling or enteric infections (Rada and Rychly 1995; Line et al. 1998; Pascual et al. 1999). They are also known for their ability to boost the immune system and used against allergies and other allowed diseases (Zulkifli et al. 2000; Dalloul et al. 2003b; Kabir et al. 2004; Koenen et al. 2004).

A treatment with prebiotics can exist easily combined with a probiotic in a then-called 'synbiotic' approach (Gibson and Roberfroid 1995). An advantage of this combination is the improved survival of probiotics when given in a medium of prebiotics. The use of pre- and probiotics in poultry has been reviewed by Patterson and Burkholder (2003).

four.2.ii.ane. Prebiotics

Mannan oligosaccharides (MOS) are derived from the cell wall of the yeast Saccharomyces cerevisiae and are widely used in animal feed to promote gastrointestinal health and performance. MOS have been described as a prebiotic, just are idea to block the binding of pathogens to mannan receptors on the mucosal surface and stimulate the immune response (Leap et al. 2000).

In an experiment performed with coccidia, dietary MOS (i thousand/kg feed) were able to reduce the severity of a single E. tenella infection with 3500 or 5000 sporulated oocysts (Elmusharaf et al. 2006). In some other experiment, a dietary supplementation of MOS at a concentration of x k/kg feed reduced the oocyst excretion and macerated the severity of East. acervulina lesions in birds infected orally with a mixture of E. acervulina, E. maxima and E. tenella at subclinical doses of 900, 570 and 170 sporulated oocysts, respectively (Elmusharaf et al. 2007).

In dissimilarity, in a study performed by McCann et al. (2006) supplementation of MOS (0.5 g/kg feed) or tannin (0.5 k/kg feed) either individually or in combination did not reduce the severity of a mixed coccidiosis infection of E. acervulina, E. maxima and E. tenella given orally at clinical doses of 50,000, 15,000 and 15,000 sporulated oocysts, respectively. These contradictory results are perchance explained by the differences in MOS concentrations in feed and the magnitude of Eimeria spp. inoculation doses.

iv.2.2.2. Probiotics

Lower intestinal invasion, development of coccidia and oocyst production, explained by enhanced local cell-mediated amnesty, were observed with a Lactobacillus-based probiotic supplemented diet in Eastward. acervulina-infected broilers (Dalloul et al. 2003a, 2003b, 2005).

More recently, in a written report performed with a Pediococcus-based commercial probiotic (MitoGrow®) given to birds infected with either E. acervulina or E. tenella, increased resistance of birds against coccidiosis and a partial protection against growth retardation were demonstrated (Lee et al. 2007a). In another study, performed with a Pediococcus- and Saccharomyces-based probiotic (MitoMax®), less E. acervulina and Eastward. tenella oocyst shedding and a better antibiotic response were plant (Lee et al. 2007b).

v. Conclusions and perspectives

To appointment, coccidiosis control has relied mainly on chemoprophylaxis. Nevertheless, the occurrence of resistance, consumer concerns and the increasing regulations as well equally possible upcoming bans on the use of anticoccidial drugs every bit feed additives, have prompted the quest for alternative control strategies, amongst which vaccines, phytotherapy, aromatherapy, pre- and probiotics have been quite extensively studied. So far, live vaccines take proved to be the most solid and successful anticoccidiosis alternative arroyo. Although a number of drawbacks are associated with the product and use of alive coccidiosis vaccines, their efficacy and ability to increase the sensitivity of Eimeria spp. isolates to anticoccidial drugs, take farther stimulated their utilise. If the immunogenicity of subunit vaccines can be improved, they could represent the next generation of highly efficient and low-cost anticoccidial strategies.

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Source: https://www.tandfonline.com/doi/full/10.1080/01652176.2011.605247

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