Taking a Fresh Look at Necrotic Enteritis02 October 2013
Necrotic enteritis remains a challenge to the poultry industry but the progress on a vaccine represents a promising new development on the horizon, according to Professor Van Immerseel of Ghent University, speaking at a recent veterinary conference. Senior editor, Jackie Linden reports.
Necrotic enteritis is an emerging problem, explained molecular biologist, Professor Filip Van Immerseel, and its study reflects the work in his lab in the Faculty of Veterinary Medicine at the University of Ghent in Belgium.
He was presented with an award by the Houghton Trust and invited to present the Avian Pathology Lecture at the 18th World Veterinary Poultry Association (WVPA) Congress in Nantes, France in August 2013.
Clostridium perfringens: Causative Bacterium
Gut inflammation with necrosis is the main feature of necrotic enteritis, explained Professor Van Immerseel. It is caused by Clostridium perfringens, a Gram-positive, spore-forming bacterium that is hard to eradicate. It is unable to synthesise for itself more than 10 amino acids. It is the toxins produced by the bacterium that result in the tissue damage. These characteristics explain why the bacterium is both hard to eradicate and associated with high-protein diets. It causes disease in both Man and animals.
The different Cl. perfringens types are currently classified according to which of five toxins types they produce, although this method is not ideal as scientists have now identified 14 different toxins produced by this species. Some of the toxins are enzymes.
The different types of Cl. perfringens produce specific symptoms in the species affected, which include horses, cattle, sheep and pigs as well as Man and poultry. In poultry, the necrotic foci are initially found in the gut. The clinical form is rarely seen; it is the subclinical form that represents significant economic cost to producers, which has been estimated to cost between $300 and $1,500 per flock in the US.
Diagnosis is based on recognition of lesions in the gut. The first sign is a reduction in villus length, which then develops into necrotic areas.
Pre-disposing Factors: an Opportunistic Pathogen
The host and bacteria will not always lead to disease, even where numbers are high, said Professor Van Immerseel. In 2005, a complex scheme was published covering all the factors involved. However, the main one is the presence of coccidiosis, so the use of dietary anticoccidials is generally effective to control necrotic enteritis.
A pathogenic form of Cl. perfringens must be present, of course.
Among the dietary factors involved, necrotic enteritis is associated with high-protein diets, especially those including animal protein (particularly fishmeal), along with non-starch polysaccharides, complex carbohydrates present in wheat, barley and rye. Feed enzymes can reduce the risk of necrotic enteritis, while other components that cause gut damage, such as mycotoxins, may pre-dispose towards the disease.
Management factors exacerbating the risk of disease include wet litter and high stocking density, because of their association with increased stress in the birds.
"NetB toxin is the key virulence factor"
Pathogenesis of Necrotic Enteritis
The early work on the disease was started in 1974, when the pathogen was called Bacillus welchii but most of our knowledge has been generated since about 2003. The first report of necrotic enteritis in poultry was actually in 1967 in Australia and the first good description was reported four years later.
The ban on antimicrobial growth promoters in the EU in 2006 boosted research into alternatives.
Typing of Cl. perfringens has resulted in molecular pathogenesis and the development of vaccines as the main topics of research.
Investigations into how Cl. perfringens causes damage to the gut have shown that the bacteria become attached to the mucus layer of the villi that line the intestine wall, where they multiply, causing damage to the epithelial cells. This causes a release of proteins into the gut lumen, on which the bacteria feed.
The gut does repair itself but this is the reason for the drop in performance associated with subclinical infections.
The alpha-toxins were for some time thought to be the main virulence factor for Cl. perfringens but it has since been found in healthy flocks too. It appears that it is the isolate that is important rather than the expression of alpha-toxin in itself. An alpha-toxin mutant from one outbreak has been found to cause disease in a trial at Monash University.
The same team isolated necrotic enteritis toxin B (NetB). Its mutants did not lead to gut lesions.
NetB toxin is the key virulence factor and appears to be crucial in the development of disease in poultry, said Professor Van Immerseel. Its crystal structure has now been established.
Cl. perfringens is known to secrete a number of enzymes, which include proteases that break open the epithelial cells and lead to infection and the leaking of nutrients into the gut lumen.
Immunoglobulins play an important role, he said, likely related to the decline in material antibodies at three to four weeks of age, which is the peak time for the occurrence of necrotic enteritis.
The link to coccidiosis is thought to be the characteristics of its causative pathogens, Eimeria spp., to boost the production of mucus (mucogenesis) in the gut. This leads to an overgrowth of Cl. perfringens.
One clone is always found in the gut of birds with necrotic enteritis and it appears to inhibit other clones.
Other bacterial factors may also be involved, said Professor Van Immerseel. For example, some strains of Cl. perfringens stimulate the production of the volatile fatty acid, butyrate, which stimulates enteric cell regeneration.
Controlling Necrotic Enteritis
Effective control can be achieved by killing the bacteria so antibiotics work, as do organic acids and essential oils, he explained.
Vaccination - either in-ovo or at day-old - with the NetB toxin seems to be a promising development.
Dr Van Immerseel summed up by saying that necrotic enteritis remains a challenge. Whilst its pathogenicity is not yet fully understood, useful progress is being made in this area.
He said that the identification of the NetB toxin was a breakthrough. While some tools to control the disease are already available, a vaccine based on the NetB toxin is under investigation and represents a promising new development, he added.
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