ANTIOXIDANT, ANTIFUNGAL & ANTIVIRAL PROPERTIES OF OREGO-STIM®

ANTIOXIDANT PROPERTIES
A major preventive measure of lipid oxidation is the use of synthetic or natural antioxidants that function either by scavenging chain-carrying peroxyl radicals or by diminishing the formation of initiating lipid radicals. Synthetic antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) have long been used to control oxidation of lipids and vitamins in the feed, but recent concern over their use has created a need and prompted research for alternative antioxidants.
In the last few years, a range of naturally occurring antioxidants including extracts of herbs and spices have been studied for their potential to protect lipids and vitamins in feed from the process of peroxidation. Herbs of the Labiatae family exhibit substantial antioxidant activity and might be useful in animal diets. Orego- Stim® contains bioflavonoids which act as antioxidants that prevent the process of peroxidation and the degradation of lipids and vitamins within the feed.
The ability of Orego-Stim® to replace synthetic antioxidants can be observed and self-experimented in feedmills. If the feedmills could measure the level of vitamins in the feed with and without the inclusion of Orego-Stim®, they would be able to see a difference. Based on this difference, the levels of synthetic antioxidants such as BHT and BHA used in the feed could be reduced. Orego-Stim® also helps reduce spoilage in the long-term storage of feed.

ANTIFUNGAL PROPERTIES
The antifungal properties of essential oils from medicinal as well as other edible plants have been recognized since ancient times. Orego-Stim® possesses a broad spectrum of antifungal activities attributed to the high content of its phenolic derivatives, carvacrol and thymol. In a study conducted by Stiles et al in 1995, its antifungal properties were examined against three different strains of the yeast Candida albicans using agar diffusion and serial broth methods. The minimum inhibitory concentration (MIC) was found to be at less than 0.2 μg per ml against each of the Candida strains studied. In a separate study, the MIC of Orego-Stim® was tested against Candida albicans (strain reference R3251) at the Veterinary Laboratories Agency (VLA) in the United Kingdom, and it was found to be only 0.195 μg per ml.
Orego-Stim® can kill or inhibit the growth of virtually any fungus. It is known that Orego-Stim® acts as a mould inhibitor at inclusion rates as low as 40g per tonne. Therefore, when Orego-Stim® is used at the normally recommended inclusion rates, there would be mould inhibiting properties in the feed. However, Orego-Stim® should not be mistaken as a toxin binder, as it cannot bind to toxins. There will always be a need for toxin binders once the toxins are produced by fungus which grows in the grain.

ANTIVIRAL PROPERTIES
Very few know of the antiviral properties of Orego-Stim®. Orego-Stim® acts against enteric viruses the same way it acts against coccidiosis and ileitis. As the enteric virus needs a host cell (in this case, it is the enterocyte) to undergo the process of replication, therefore Orego-Stim® can control viral enteric diseases such as those caused by rotavirus and coronavirus.

Porcine Rotavirus
Rotaviruses belong to the Reoviridae family of viruses. They are typically 70 nm in diameter, non-enveloped viruses comprising a triple layered protein capsid. Rotaviral infections are one of the most common causes of diarrhoea in piglets aged more than one week old.
Antigenically, there are seven distinct groups based on the presence of a common group antigen which is part of the structural inner core of the virus. Of these seven, only four antigens (A, B, C and E) have been known to infect pigs. Within each group, there may be several serotypes that have different external antigens. Hence there may not be cross protection between serotypes within a group.
Rotaviruses have been found worldwide and are enzootic to all pig breeding farms. The virus has been known to be highly resistant to even the most adverse of environments and eradicating it is therefore extremely difficult and close to impossibility.
Rotaviral diarrhoea generally occurs in an enzootic form under natural conditions. Most adult pigs already have acquired rotaviral antibodies. The severity of clinical disease in piglets is influenced by the immune status of the lactating sow. Litters born to gilts which have little or no antibodies in the milk may suffer from severe rotaviral diarrhoea with high mortality if piglets are infected during the first few days of life. This is why severe outbreaks of diarrhoea with high mortality have been reported in newly established farms where the majority of the breeding population consists of gilts.
The level of antibodies in the colostrum and milk drop rapidly within a few days after farrowing. Clinical disease occurs when the infective dose of rotavirus exceeds the level of lactogenic immunity. Although the clinical disease usually occurs between one and five weeks of age, piglets less than one week old can also be infected. Usually the severity of the infection is inversely related to the age of the pig.

Pathogenesis
Pigs are infected via the oral-faecal route of transmission. During rotaviral infection, large numbers of viral particles are shed in the faecal material. Upon ingestion of contaminated faeces, the virus infects the mature epithelial cells of the small intestinal. Destruction and subsequent loss of the epithelial cells result in the shortening of the intestinal villi, a condition known as villous atrophy. The loss of mature absorptive cells leads to maldigestion and malabsorption as the remaining immature cells lack enterokinase at their microvillus border. The enterokinase enzyme is necessary to convert pancreatic trypsin into an active form. The presence of other enteric pathogens exacerbates the severity of infection while the presence of antibodies in the milk lessens its severity.

Clinical Signs
Most infections are subclinical or associated with only mild diarrhoea followed by rapid recovery. Gilt litters are more severely affected. Piglets affected are usually those between 1-5 weeks of age. The highest incidence is between one and three weeks of age. In most cases, not more than 20-30% of a litter is affected. The diarrhoea lasts for mostly 2-3 days. The colour of the faeces is usually yellowish or whitish and often contains white material known to be curdled, undigested milk. The consistency may be watery or pasty. Some pigs may vomit prior to the onset of diarrhoea. Occasionally there is mild dehydration.
There are however, situations that differ from the usual pattern described above. In breeding farms that often import new pigs into the farm from endemically infected countries, the morbidity and severity of rotaviral diarrhoea can be higher due to the regular introduction of new serotypes towards which the resident herd has little or no immunity. Where most of the sows have no lactogenic immunity, rotaviral diarrhoea may occur in pigs shortly after birth. A similar situation can occur in pigs shortly after birth. A similar situation can occur in newly established farms where nearly all the sows are in their first parity.

Coronaviral Gastroenteritis
Coronaviruses belong to the Coronaviridae family of the genus Coronavirus. Epizootics of viral gastroenteritis due to coronavirus are Transmissible Gastro-Enteritis (TGE) or Porcine Epidemic Diarrhoea (PED). Both diseases are clinically indistinguishable. Both are highly contagious enteric diseases of pigs, characterized by profuse watery diarrhoea, weight loss, transient vomiting and a high mortality in pigs less than two weeks of age. Both are caused by coronaviruses that are antigenically distinct from each other.
TGE has been reported in many pig-rearing countries such as USA, Canada, Europe, West Africa and Asia. PED was first clinically recognized back in the early seventies after outbreaks of acute diarrhoea were reported in England and Belgium with clinical features similar to TGE. This disease is present in several countries in Europe, United Kingdom, Taiwan and China. In the United States and Europe, TGE appears to be a seasonal disease with outbreaks occurring during the winter months.

Pathogenesis
The causative organism is a coronavirus. Transmission of infection is via the faecal-oral route, usually taking place through the ingestion of infected faeces. During coronaviral infection large numbers of viral particles are shed in the faeces. Upon ingestion of the contaminated faecal material, the virus infects the epithelial cells of the small intestine especially at the tips of the villi. There is rapid destruction of the mature absorptive cells leading to their replacement by immature cells from the base of the crypts. This results in severe villous atrophy especially in the jejunum and to a lesser extent in the ileum. The rapid destruction of the intestinal epithelial cells results in a reduction in the enzymatic activity in the small intestine which disrupts digestion and cellular transport of nutrients and electrolytes, causing an acute malabsorption syndrome. The presence of undigested lactose exerts an osmotic force in the lumen of the intestine which causes retention of fluid and even a withdrawal of fluids from the tissues of the body and thus contributes to diarrhoea and dehydration. The lower mortality rate in older pigs as compared to newborn pigs is believed to be due to the replacement rate of the infected epithelial cells. It has been reported that 3-week-old pigs normally replace villous absorptive cells in the small intestine about three times more rapidly than do newborn pigs.

Clinical Signs
There are two main forms of coronaviral gastroenteritis, namely, the epizootic and the enzootic form. The clinical signs of the epizootic disease are most characteristic. The disease has a short incubation period of 18 hours to 3 days. Because of this, epizootic TGE begins with a sudden outbreak of diarrhoea which spreads rapidly to involve pigs of all ages within a few days. In temperate countries, the rapidity of spread is greater in winter.
The diarrhoea in young pigs is usually profuse and watery and the faeces often contain small curds of undigested milk. The odour of the diarrhoea is very offensive. Vomiting may occur in pigs under three weeks of age. Affected pigs become rapidly dehydrated. Death may occur within two to four days in pigs aged less than one week. Lactating sows become very sick with inappetance and agalactia. However, the severity of the disease varies inversely with the age of the pig. In TGE, the mortality in pigs less than one week old is almost 100% but gradually declining with age. Deaths are rare in pigs older than three weeks. Clinical signs in adult pigs are limited to diarrhoea and inappetance. Occasionally there is transient vomiting. Adult pigs usually recover within a week or so.
While the clinical features of both diseases are very similar, the differences are that PED spreads somewhat slower and the mortality rate in suckling pigs less than one week old can range from 50% to 90%. The disease spreads through the farm over a period of 4-5 weeks or longer. While TGE outbreaks seldom last for more than 1-2 months, an outbreak of PED can linger on in the farm for as long as 6 months.
In some farms, a few months after the initial outbreak, acute diarrhoea may be encountered in post-weaned pigs. These susceptible pigs were born from immune mothers and were protected from infection by the antibodies in the milk of the sow. Following weaning, when exposed to the virus, they developed clinical disease. The presence of the disease in post-weaned pigs indicates that the virus is still present in the environment of the farm and that there is a danger of the disease becoming enzootic.

In most countries, the prevention of viral diarrhoea in piglets seemed to be limited to promoting the spread of infection to gilts and sows to ensure they develop a high level of antibodies prior to farrowing. However, in a breakthrough of technological advancement, the latest solution to this problem is Orego-Stim®.
Orego-Stim® is a natural feed additive for use in pig diets as an appetiser, to enhance feed flavour and increase feed intake. Orego-Stim® prevents viral replication in the intestinal epithelial cells by speeding up the shedding process of these enterocytes, ensuring a quick replenishment of these cells and thus creating an environment that is hostile to viral replication. The multiplication of the virus is disrupted and therefore, viral gastroenteritis in piglets can be thus controlled.
Studies performed in pigs have shown that Orego-Stim® also increases intestinal dimensions and the villus height-crypt depth ratio. The lengthening of the villi creates more surface area for absorption of nutrients and electrolytes, thus combating villous atrophy and preventing maldigestion and malabsorption.
Orego-Stim® has also shown to significantly increase intestinal enzyme activity such as alkaline phosphatase, leucine aminopeptidase, maltase, sucrase and lactase within the gut. This further aids in the digestion and absorption of the nutrients and the electrolytes. Its ability to kill pathogens within the gastrointestinal tract also prevents secondary bacterial invaders such as Salmonella and E. coli from causing infection and diarrhoea to complicate the primary viral infection.
Orego-Stim®, when included in the ration of lactating sows, preserves the lactation production rate. The milk yield of the sow is crucial for suckling piglet survivability, especially during the first two weeks of life, as it contains all the essential antibodies needed by the piglet to combat intestinal infections and diarrhoea. Field observations suggest that adding Orego-Stim® in lactating sow diets results in more efficient utilization of the feed offered and helps the sow to preserve lactation production rate.
The recommended inclusion rate for Orego-Stim® in pre-weaned piglets (from farrowing up to 15 kg bodyweight) is 1 kg per tonne of feed, followed by 500 grams per tonne of feed up to 25 kg bodyweight. Grower and finisher pigs (25 kg to slaughter weight) require only 250 grams per tonne of feed. In lactating sows, the recommended inclusion rate is also 250 grams per tonne of feed.

Neonatal Diarrhoea in Calves
Neonatal diarrhoea in calves, which occurs mostly during the first four weeks of life, is very common. Various microbiological agents have been associated with the syndrome such as Salmonella and E. coli, but the two most important, and certainly most studied viruses are rotavirus and coronavirus. Both these viruses will produce diarrhoea in colostrum-deprived calves, although strain differences do exist.
The relative importance of E. coli and the enteric viruses in the aetiology of neonatal calf diarrhoea has not been fully ascertained. E. coli is not often isolated from calves more than 10 days old, whereas rotavirus and coronavirus are mainly detected in the faeces of calves between 5 and 15 days old. These two viruses can be demonstrated in up to 60% of calves with diarrhoea. We therefore suspect that coronavirus and rotavirus are the main or primary cause of neonatal calf diarrhoea, whereas E. coli comes in as a secondary invader.
Orego-Stim® in this case acts both against the viruses as well as against the secondary bacterial invaders. How do we know this? In the field, many have tried various forms of antibiotic treatment to control the bacteria, but were still unable to control the diarrhoea, but once Orego-Stim® was used, the disease was under control. Therefore by first treating the primary cause of the diarrhoea, which is the enteric viruses, Orego-Stim® can control neonatal calf diarrhoea. The inclusion rate of Orego-Stim® for calves is 1-2 grams or ml per 10kg of bodyweight.