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Coccidiosis is a realistic problem and one of the most important diseases of poultry worldwide. It is caused by a protozoan parasite known as Eimeria that invade the cells of the poultry intestine. Species of coccidia which commonly affect poultry are Eimeria tenella, E. acervulina, E. necatrix, E. maxima and E. brunetti. The disease is characterized by enteritis, diarrhoea and mortality. The bird develops a disability to absorb nutrients, which results in weight loss and eventually death. Subclinically, it is manifested by poor performance, impaired feed conversion, poor flock uniformity and poor growth. Coccidia can also damage the immune system and leave poultry more vulnerable to pathogens like Salmonella and E. coli. The disease is considered as one of the most severe health and economical problems in poultry that causes an enormous loss to poultry producers worldwide.


The History of Coccidiosis

Even though coccidiosis is known to affect almost every species of animal on earth, our first attempts at treating coccidiosis dates back to an outbreak in poultry some 60 years ago. Poultry was still one of the most important sources of meat at the time. The drug of choice for the treatment of coccidiosis then, based on availability, was the sulphonamides.

Through further experimentation, poultry producers in the United States found in the late 1940s that the most economical method of preventing the disease and controlling the problem was via continuous usage of sulphaquinoxalines in the feed of the chickens. This not only reduced the mortality caused by the protozoan parasite but also lessened the morbidity of the disease in poultry.

Since the 1950s, various types of anticoccidials have been produced from different drugs and chemicals. Some of the older chemicals such as amprolium and nicarbazine are still being used today. Most are no longer in use or allowed in various countries due to proven toxicological findings or a lack of efficacy due to the development of resistance by the coccidia it was designed to treat.

In the 1970s, a new class of antibiotics was discovered. These were named the ionophores, and eventually replaced the earlier chemical compounds. Ionophores are unique, because they permit a small amount of coccidia to survive and complete their life cycle within the intestines of the bird, enabling the birds to develop a certain level of immunity. This allows a greater degree of protection against the parasite and is a very efficient method of control. However, these more recent developments were still not able to address the issue of resistance, and soon enough, each species of coccidia had developed resistance to all the ionophores available in the industry. Many of these ionophore coccidiostats simply await their potential ban as feed additives in year 2009.


The Battle Against Coccidiosis

An outbreak of coccidiosis in a poultry flock has a very high negative and economical impact on the flock as well as for the poultry producer. There is an immediate and considerable drop in production figures and the recovery and reestablishment period after treatment is slow. Some flocks never fully recover or regain their full production potential. Hence, it is a well recognised fact that treatment alone cannot prevent the economical losses. It is well established within the poultry sector that the only choice is therefore prevention of the disease. However, an effective and sustainable prevention and control programme against the disease is not easy.

Coccidiosis is particularly difficult to combat because several different species of Eimeria exist in the field. Poultry may become infected with different species because the immunity that develops after infection is specific only to one species. Eimeria have a very complex life cycle which involves many developmental stages inside the host cells. Each Eimeria parasite is able to infect only one host species, and they each attack different segments of the intestine in each specific host species.

Avian coccidiosis has become increasingly prevalent in the worldwide poultry industry. These occur in the form of mortalities, reduced market value of the affected birds and sometimes culling or delayed slaughter time. Another predisposing factor is the confined host-rearing conditions, which lead to an increase in the numbers of oocysts, which are ingested by poultry via the litter. These lead to destruction of the integrity of the intestinal mucosae and interfere with nutrient absorption, ultimately causing diarrhoea, which in turn causes high medication costs. Ultimately, all these setbacks point to huge losses of profit for the poultry producer.

Another factor is the increasing incidence of drug resistance to field strains of coccidia. The conventional methods to control the disease are by using certain coccidiostats or coccidiocidal drugs. Producers are adding a number of anticoccidial drugs to commercial feed in a frantic struggle to control the recurring coccidial challenge. In the case of salinomycin, it is known that at approximately day 28 of the broiler production period, performance declines in birds receiving the anticoccidial due to the presence of subclinical coccidiosis. Under normal management conditions, this is a typical occurrence when this ionophore is used.

To prevent widespread resistance to the narrow range of anticoccidial drugs available in the field, nutritionists and veterinarians have resorted to devising and implementing many different forms of complicated anticoccidial shuttle and rotational programmes in an attempt to achieve optimal efficacy with minimal side effects. However, the design, implementation and monitoring of such programmes has become extremely complicated and fraught with obstacles and risks. For example, poultry flocks cannot be treated with nicarbazine during early autumn or spring because sudden heat waves can result in high mortality, even in young birds. Albeit still valuable to the industry, ionophores also have it own share of dangers. In Northern Ireland, for instance, detectable residual levels of the coccidiostat lasalocid were found in commercial table eggs. The contaminated eggs were traced back to a feed mill that also produced broiler feed.

A relatively common problem that poses devastating consequences is the accidental feeding of diets containing coccidiostats to non-target animals. For instance, turkeys fed rations containing salinomycin may encounter an increase in mortality, whereas broiler breeders fed rations containing nicarbazine may be affected by a drop in egg production and infertility.

Last but not least, producers need to consider the extra time and money spent by the feed mill for flushing systems of coccidiostat residues, the planning and mixing of various different batches of medicated feed, and attempts to avoid cross contamination of drug-free withdrawal feed. Residual effects, if ever found in the poultry meat or eggs, may pose a serious problem for producers who wish to export their produce to countries where legislation requires drug and residue-free chicken meat and eggs and where demands for such healthy produce are on the rise.


Fighting a Losing Battle

Due to an explosive growth of the human population over the past century, there has been a higher demand for food and an increase in the supply of meat, milk and eggs to meet these needs. Livestock farming has thus developed to an intensive level in an attempt to conform to such demands and this has brought about more diseases of varying intensities and public health concerns with regards to food safety issues.

Financial losses due to coccidiosis are costing the industry a lot of money every year, and in the European Union, this amounts to £500 million a year. In the United States, the poultry industry loses more than $800 million annually from coccidiosis alone and drug-based control measures cost the industry more than $300 million annually.

Also, possible overuse of anticoccidial drugs adds to the public concern over chemical residues in the food supply and issue of food safety. Furthermore, non-discretionary use of anticoccidial drugs including monensin, amprolium, ionophores and nicarbazine has resulted in the emergence of drug-resistant strains, which has reduced the efficacy of many of the currently used coccidiostats. Confounding this problem is the absence of new drugs to replace the older, ineffective anticoccidials. During the recent years, pharmaceutical industries throughout the world have not marketed any new anticoccidials.

The European Union has already banned antibiotics used in human medicine from being added to animal feed. The new regulation will complete this ban on antibiotic growth promoters in feed by prohibiting the use of four drugs not used in human medicine that are still currently allowed in the EU market, which are monensin sodium, salinomycin sodium, avilamycin and flavophospholipol. The Scientific Steering Committee of the EU has recommended the progressive phasing out of the use of all antibiotics as growth promoters, while preserving animal health. The EU said the recommendation was a precautionary measure, as the experts say there are fears that people eating the meat of antibiotic-fed animals and birds may lower their resistance to medicines.

So as the European Union begins to implement its ban on the four remaining feed grade antibiotics growth promoters this year, poultry producers in Europe are on their toes, ameliorating their search for alternatives that are able to assist them in their laborious battle against the disease. The ban includes usage of the two most widely used ionophore coccidiostats, salinomycin sodium and monensin sodium, as feed additives. Apart from these, the other coccidiostats too, will be banned as feed additives by year 2009.

As a result, leading poultry integrators in Europe who are proactive and who desire to remain competitive in this fast-changing industry have currently stepped up their research and development endeavours in an effort to better understand the common and prevalent diseases which affect them, to improve their nutrition, management, hygiene and biosecurity and to minimize any possible negative impact that may be brought upon by the ban. These poultry producers have been using coccidiostats for many decades, and have grown to be dependant on such substances for the control and prevention of coccidiosis, so much so that they would feel crippled and unable to raise their birds if these were ever taken away from them.


Coccidial Vaccinations: A Boon or a Bane?





Obviously an alternative system to control coccidiosis is by vaccination. Currently, a number of coccidial vaccines have been developed and used commercially. Most coccidial vaccines include a low dose of the live parasite as a key ingredient to stimulate protective immunity. These have been used in millions of chickens. However, the parasite can still cause disease in vaccinated chickens if their immune systems are already compromised, damaged or suppressed by other infectious agents.

In the field, once birds have been exposed to coccidia, they develop immunity after approximately three cycles of oocyst production. Although live or attenuated parasites have been widely used as a commercial vaccine, antigenic variability between the Eimeria species present in the vaccine and those in the field restricts the effectiveness of commercial vaccines.

There is also a price to be paid for protection against a potential threat. This could be in the form of the high cost of vaccines, time spent to administering the vaccines and losses due to vaccine reactions in live vaccines and localized tissue damage in killed vaccines.





The disadvantages associated with the live vaccines are problems with uniform vaccine application, excessive vaccine reactions, unwanted spread of the vaccinal viruses, extreme handling requirements needed to maintain viability of the vaccinal organisms and last but not least, the emergence of necrotic enteritis, an enterotoxaemic disease that usually accompanies coccidiosis, caused by Clostridium perfringens. The disadvantages of the killed vaccines are increased costs in terms of labour and the product itself, slower onset of immunity, a narrow spectrum of protection and localized tissue damage at the site of injection.

Furthermore, one cannot totally eliminate the risk of vaccination failure. A vaccination failure occurs when, following vaccine administration, the chickens do not develop adequate protection and are susceptible to a field disease outbreak. There are several factors, including high levels of maternal antibodies, various stressors such as environmental extremes, inadequate nutrition, parasitism and other concurrent diseases that can also contribute towards vaccine failure. Improper handling or administration of the vaccine should also be considered.


A New Natural Weapon: Botanical Warfare!

But now we have the very solution, a benchmark product that is competitively priced which functions not only as a replacement for coccidiostats and antibiotic growth promoters, but which can also provide many other benefits that lead to supreme productivity and animal health, which in turn spells better profit and a higher return of investment for the poultry producer.

Orego-Stim® is an oregano-based product that is used as a feed additive in poultry production worldwide. It has been extensively researched and tested, and is able to increase the performance of poultry production by improving the Feed Conversion Ratio (FCR) as well as increasing the body weight gain of broilers. It also helps to reduce mortality caused by gastrointestinal diseases by preventing the occurrences of gastrointestinal pathogen invasion. The phenolic compounds within oregano, carvacrol and thymol effectively kill these microorganisms, which include both gram positive and gram negative bacteria upon contact within the gut of the animals.

Diagram (a) shows unspecified bacteria before treatment with essential oil from Oreganum vulgare.	Diagram (b) shows the same bacteria after treatment with essential oil from Oreganum vulgare. Complete cell lysis is clearly visible.

Orego-Stim® is also able to control coccidiosis in all phases of poultry production. In contrast to antibiotic growth promoters and coccidiostats, there has been no evidence of bacterial or coccidial resistance from using oregano, simply because of the main constituents being largely phenolic, its mode of action is a straightforward and primitive one. Description tests from Campden and Chorleywood Food Research Association suggest that Orego-Stim® is not absorbed from the intestines into the bloodstream, therefore there are no residues found in the meat or eggs. Hence, there is no withdrawal period and Orego-Stim® can be safely used right until the slaughter period.

In humans and animals, the upper layer of enterocytes is constantly shed and replenished every 4 to 7 days. Orego-Stim® speeds up this natural renewal process, creating an environment that is hostile to the coccidial life cycle. The sporozoite-infected cells are thus shed before development of the merozoite stage, which causes the main clinical signs of coccidiosis outbreaks. This disrupts the life cycle of the coccidia, resulting in effective control and prevention of coccidiosis.









_{Figure 1. The effect of Orego-Stim® on sporozoite-infected enterocytes within the lumen.}

The rapid shedding of the intestinal cells also prevents thickening of the intestines caused by E. coli and other pathogenic bacteria that may be potential secondary invaders. Hence, the accelerated rate of epithelial cell turnover results in lesser contamination of the emerging enterocytes and improved absorption capacity for nutrients.

On the other hand, Orego-Stim® encourages the building up of immunity against coccidiosis, by allowing small amounts of oocysts to undergo and complete their lifecycle in the intestinal cells. This is often just enough to stimulate an immune response via activation of the Bursa-derived cell-mediated immunity, which releases macrophages, lymphocytes and natural killer cells to provide a longer-lasting immunity against coccidiosis with each cycle of oocyst production.

At the same time, Orego-Stim® can prevent incidences of necrotic enteritis that usually accompany outbreaks of coccidiosis in poultry. Intestinal colonisation by Clostridium perfringens not only decreases growth and feed utilization, but can also result in high mortality. Orego-Stim® is easily able to kill Clostridium perfringens in the gut, thus preventing further complications of superinfection.
 
In a trial conducted in the USA by Colorado Quality Research Incorporated, Orego-Stim® was fed to chicks that had been challenged with coccidiosis oocysts in order to evaluate the ability of this product to protect against a coccidiosis challenge in comparison to a commonly used ionophore coccidiostat, which was salinomycin. The results indicate that the Orego-Stim® gave effective protection against the coccidiosis challenge.  The level of protection achieved by the Orego-Stim® group was similar to the protection provided by salinomycin at 55 grams per tonne.



<sub>Figure 2.  Orego-Stim® Weight Gain (Bar) & Feed Conversion (Line), 11-19 Days




Figure 3.  Orego-Stim® Coccidiosis Lesion Scoring, Day 19</sub>


In the same experiment, the performance of chicks fed Orego-Stim® in the presence of a necrotic enteritis challenge was also evaluated. Orego-Stim® was compared with Bacitracin Methylene Disalicylate (BMD) in this part of the experiment. The results indicated that the Orego-Stim® gave effective protection against the necrotic enteritis challenge model. The level of protection achieved by the Orego-Stim® was similar to the protection provided by BMD at 27.5 grams per tonne.



<sub>Figure 4.  Orego-Stim® Weight (Bar) & Feed Conversion (Line), 0-11 Days




Figure 5.  Orego-Stim® Weight (Bar), Feed Conversion (Line), 11-29 Days




Figure 6.  Orego-Stim® Necrotic Enteritis Score, 29 Days</sub>



Orego-Stim® Application Rate for Control of Coccidiosis in Poultry

It is our recommendation that Orego-Stim® be applied continuously as a prophylaxis for control and prevention of coccidiosis, rather than at higher dosages for treatment. There are currently two application schemes, one using only the Orego-Stim Liquid® (OSL) and the second using mainly Orego-Stim Powder® (OSP) plus some OSL.


Scheme A (Orego-Stim Liquid® only):

Week 1: Add OSL at 300ml per 1000L of water.
Week 2 onwards: Add OSL at 150ml per 1000L of water.
Critical periods*: Increase the OSL dosage to 300ml per 1000L of water.


Scheme B (Orego-Stim Powder® plus Orego-Stim Liquid®):

Week 1: Add OSP at 300g per tonne of feed together with OSL at 150ml per 1000L of water.
Week 2 onwards: Add OSP at 300g per tonne of feed.

Critical periods*: Add extra OSL at 150ml per 1000L of water.

Orego-Stim® is the world’s leading product in the field of nutraceuticals, a product of blending science and nature. A product that would help to sustain intensive livestock rearing in a competitive environment and be able to see through all the changes in legislations to reach a common goal of promoting healthy animals for healthy people the natural way.

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