Antiviral properties of Orego-Stim

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.

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. During infection, large numbers of viral particles are shed in the faeces. Upon ingestion of contaminated faeces, the virus infects mature epithelial cells of the small intestines. Destruction and subsequent loss of epithelial cells result in the shortening of the intestinal villi, a condition known as villus atrophy. The loss of mature absorptive cells leads to maldigestion and malabsorption, as the remaining immature cells lack enterokinase at their microvillus border. Enterokinase 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.

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.

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.

Transmission is via the faecal-oral route, usually taking place via ingestion of contaminated faeces. During infection large numbers of viral particles are shed in the faeces. Upon ingestion, 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 villus 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 3 times more rapidly compared to newborn pigs.

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 spread is faster in winter. Diarrhoea in young pigs is usually profuse and watery. The faeces often contain small curds of undigested milk. The odour of the diarrhoea is very offensive. Vomiting may occur in pigs under 3 weeks of age. Affected pigs become rapidly dehydrated. Death may occur within 2-4 days in piglets aged less than a 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, mortality in piglets aged less than a week old is almost 100% but gradually declines with age. Deaths are rare in pigs older than 3 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 sows and were protected from infection by the antibodies in the milk of the sow. When exposed to the virus after weaning, 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® 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, 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 viruses as well as against secondary bacterial invaders. How do we know this? In the field, various forms of antibiotic treatments have been attempted, 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.