{"id":59010,"date":"2020-12-03T09:09:17","date_gmt":"2020-12-03T08:09:17","guid":{"rendered":"https:\/\/ew-nutrition.com\/necrotic-enteritis-the-complete-overview\/"},"modified":"2023-03-27T08:59:51","modified_gmt":"2023-03-27T06:59:51","slug":"necrotic-enteritis-the-complete-overview","status":"publish","type":"post","link":"https:\/\/ew-nutrition.com\/en-uk\/necrotic-enteritis-the-complete-overview\/","title":{"rendered":"Necrotic enteritis: The complete overview"},"content":{"rendered":"

byInge Heinzl, Marisabel Caballero, Ajay Bhoyar<\/strong>, EW Nutrition<\/em><\/p>\n

Eliminating necrotic enteritis from your operations starts from a good understanding of what it is, how to prevent it, and how to mitigate its effects on your poultry production.<\/strong><\/p>\n

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Necrotic enteritis is a poultry disease caused by an overgrowth of Clostridium perfringens<\/em> type A, and to a lesser extent type C, in the small intestine. The toxins produced by C. perfringens<\/em> also damage the intestinal wall. In general, it occurs in broiler chickens of 2-6 weeks of age. In subclinical forms, it is characterized by impaired digestion. Clinical forms lead to severe problems and increased flock mortality in a very short time.<\/p>\n

Necrotic enteritis is the cause of USD 6 billion annual losses in global poultry production and this controllable disease is on the rise. One reason is the voluntary or legally required reduction of antibiotics in animal production. This trend is driven by the increasing occurrence of antimicrobial resistance, as well as by consumer demand. Another reason is the reduction of ionophores which, besides their activity against coccidia, also show efficacy against clostridia. When anticoccidial live vaccines are used, the application of these ionophores is not possible and clostridia \/ necrotic enteritis increase (Williams, 2005).<\/p>\n

While this is a widespread problem in all poultry, for broilers in particular, necrotic enteritis and coccidiosis are the most significant health problem.<\/p>\n

Clinical and subclinical forms of NE<\/h2>\n

The clinical form<\/h3>\n
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(c) Rob Moore<\/figcaption><\/figure>\n

…is characterized by acute, dark diarrhea resulting in wet litter and suddenly increasing flock mortality of up to 1% per day after the first clinical signs appear (Ducatelle and Van Immerseel, 2010), sometimes summing up to mortality rates of 50% (Van der Sluis, 2013). The birds have ruffled feathers, lethargy, and inappetence.<\/p>\n

Necropsy typically shows ballooned small intestines with a roughened mucosal surface, lesions, and brownish (diphtheritic) pseudo-membranes. There is a lot of watery brown, blood-tinged fluid and a foul odor during post-mortem examination. The liver is dark, swollen, and firm, and the gall bladder is distended (Hofacre et al., 2018).<\/p>\n

In the case of peracute<\/strong> necrotic enteritis, birds may die without showing any preliminary signs.<\/p>\n

The subclinical form<\/h3>\n

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When birds suffer\u00a0from the subclinical form, chronic damage to the intestinal mucosa and an increased quantity of mucus in the small intestine lead to\u00a0\u00a0impaired digestion and absorption of nutrients resulting in poor growth performance.<\/p>\n

The deteriorated feed conversion and the resulting decreased performance become noticeable around day 35 of age. As feed contributes approximately 65-75% of the input cost to produce a broiler chicken, poor feed conversion increases production costs and significantly influences profitability. Often, due to a lack of clear symptoms, this subclinical disease remains untreated and permanently impacts the efficiency of production.<\/p>\n

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Pathogens<\/h2>\n

Responsible for necrotic enteritis are Gram-positive, anaerobic bacteria, specific strains of Clostridium perfringens<\/em> type A and, to a lesser extent, type C (Keyburn et al., 2008).<\/strong><\/p>\n

Clostridia primarily occur in the soil where organic substances are degraded, in sewage, and the gastrointestinal tract of animals and humans<\/a>. These bacteria produce spores, which are extremely resistant to environmental impact (heat, irradiation, exsiccation) as well as some disinfectants, and can survive for several years. Under suitable conditions, C. perfringens<\/em> spores can even proliferate in feed or litter.<\/p>\n

Clostridium perfringens<\/em> is a natural inhabitant of the intestine of chickens. In healthy birds, it occurs in a mixture of diverse strains at 102<\/sup>-104<\/sup> CFU\/g of digesta (McDevitt et al., 2006). The disease starts when C. perfringens<\/em> proliferates in the small intestine, usually due to a combination of factors such as high amount protein, low immunity, and an imbalance in the gut flora. Then, the number rises to 107<\/sup>-109<\/sup> CFU\/g of digesta (Dahiya et al., 2005).<\/p>\n

NetB, a key virulence factor for NE<\/h3>\n

To establish in the host, Clostridium<\/em> Spp. and other pathogens depend on virulence factors (see infobox). These virulence factors include, for example, \u201ctools\u201d for attachment, evasion or suppression of the host\u2019s immune system, \u201ctools\u201d for getting nutrients, and \u201ctools\u201d for entry into intestinal cells. Over the years, the \u03b1-toxin produced by C. perfringens<\/em> was assumed to be involved in the development of the disease and a key virulence factor. In 2008, Keyburn and coworkers found another key virulence factor by using a C. perfringens<\/em> mutant unable to produce \u03b1-toxin, yet still causing necrotic enteritis.<\/p>\n

Thus, another toxin was identified occurring only in chickens suffering from necrotic enteritis: C. perfringens<\/em> necrotic enteritis B-like toxin (NetB). NetB is a pore-forming toxin. Pore-forming toxins are exotoxins usually produced by pathogenic bacteria, but may also be produced by other microorganisms. These toxins destroy the integrity of gut wall cell membranes. The leaking cell contents serve as nutrients for the bacteria. If immune cells are destroyed, an immune reaction might be partially impacted (Los et al., 2013).<\/p>\n

Additionally, pathogenic strains of C. perfringens<\/em> produce bacteriocins \u2013 the most important being Perfrin (Timbermont et al., 2014) \u2013 to inhibit the proliferation of harmless Clostridium<\/em> Spp. strains and to replace the normal intestinal flora of chickens (Riaz et al., 2017).<\/p>\n

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Examples of virulence factors<\/h4>\n

1. Adhesins<\/strong>
\nEnable the pathogen to adhere or attach within the target host site, e.g. via fimbria. Pili enable the exchange of RNA or DNA between pathogens.<\/p>\n

2. Invasion factors<\/strong>
\nFacilitate the penetration and the distribution of the pathogens in the host tissue (invasion and spreading enzymes). For example: hyaluronidase attacking the hyaluronic acid of the connective tissue or flagella enabling the pathogens to actively move.<\/p>\n

3. Toxins<\/strong>
\nDamage the function of the host cells or destroy them (e.g. endotoxins – lipopolysaccharides, exotoxins)<\/p>\n

4. Strategies of evasion<\/strong>
\nEnable the pathogen to bypass the strategies of defense of the immune system (e.g. antiphagocytosis factors provide protection against an attack by phagocytes; specific antibodies are inactivated by enzymes).<\/p>\n<\/div>\n

 <\/p>\n

A chicken with optimal gut health<\/strong> may be less susceptible to NE<\/strong>. Additional predisposing factors<\/strong> are necessary to allocate nutrients and make the gut environment suitable for the proliferation of these pathogens, \u00a0enabling them to cause disease (Van Immerseel et al., 2008; Williams, 2005).<\/p>\n

Predisposing factors<\/h2>\n

Feed: composition and particle size<\/h3>\n

The role of feed in the development of necrotic enteritis should not be underestimated. This is where substances creating an intestinal environment favorable for C. perfringens<\/em> come into play.<\/p>\n

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Mycotoxin contamination<\/h3>\n

Mycotoxins harm gut integrity and crea<\/strong>te ideal conditions for the proliferation of Clostridium perfringens<\/em>.<\/strong><\/p>\n

Mycotoxins do not have a direct effect on C. perfringens<\/em> proliferation, toxin production, or NetB transcription. However, mycotoxins disrupt gut health integrity, creating a favorable environment for the pathogen. For example:<\/p>\n

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  1. DON provides good conditions for proliferation of C. perfringens<\/em> by disrupting the intestinal barrier and damaging the epithelium. The possibly resulting permeability of the epithelium and a decreased absorption of dietary proteins can lead to a higher amount of proteins in the small intestine. These proteins may serve as nutrients for the pathogen (Antonissen et al., 2014).<\/li>\n
  2. DON and other mycotoxins decrease the number of lactic acid producing bacteria indicating a shift in the microbial balance (Antonissen et al., 2016.).<\/li>\n<\/ol>\n

    Eimeria ssp.<\/h3>\n

    An intact intestinal epithelium is the best defense against potential pathogens such as C. perfringens<\/em>. Here, Coccidiosis comes into play. Moore (2016) showed that by damaging the gut epithelium, Eimeria<\/em> species give C. perfringens<\/em> access to the intestinal basal domains of the mucosal epithelium. Then, the first phase of the pathological process takes place and from there, C. perfringens<\/em> invades the lamina propria. Damage to the epithelium follows (Olkowski et al., 2008). The plasma proteins leaking to the gut and the mucus produced are rich nutrient sources (Van Immerseel et al., 2004; Collier et al., 2008).\u00a0 A further impact of Coccidiosis is shifting the microbial balance in the gut by decreasing the number of e.g., Candidatus savagella<\/em> which activates the innate immune defense.<\/p>\n

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      \n
    1. Eimeria<\/em> induce leakage of plasma proteins by killing epithelial cells<\/li>\n
    2. They enhance mucus production in the intestine<\/li>\n<\/ol>\n

      1+2 lead to an increase in available nutrients and create an environment favorable for the proliferation of C. perfringens.<\/em><\/p>\n

      Not only Eimeria <\/em>Spp., also other pathogens (e.g. Salmonella<\/em> Spp., Ascarid larvae, viruses) and agents, such as mycotoxins damaging the intestinal mucosa can pave the way for a C. perfringens<\/em> infection.<\/p>\n

      Predisposing factors like wet litter, the moisture of which is essential for the sporulation of Eimeria <\/em>Spp. oocysts, must also be considered as promoting factors for necrotic enteritis (Williams, 2005).<\/p>\n

      Immunosuppressive factors<\/h3>\n

      Besides the already explained influencers feed, mycotoxins and coccidia, also other predisposing factors must be mentioned. In general, any factor which induces stress in the animals disrupts the balance of the intestinal flora. The resulting suppression of the immune system contributes to the risk of necrotic enteritis (Tsiouris, 2016). These factors include:<\/p>\n

      Bacteria<\/strong>: Shivaramaiah and coworkers (2011) investigated a neonatal Salmonella typhimurium<\/em> infection as a predisposing factor for NE. The early infection causes significant damage to the gut (Porter et al., 1998) Additionally, Hassan et al. (1994) showed that the challenge with Salmonella typhimurium negatively impacted the development of lymphocytes which might also promote a colonization of Clostridium perfringens<\/em>.<\/p>\n

      Viruses<\/strong>: Infectious Bursal Disease is known to increase the severity of infections with salmonella, staphylococci, but also clostridia. Another clostridia-promoting viral disease is Marek\u2019s Disease.<\/p>\n

      Stress<\/strong>: The intestinal tract is particularly sensitive to any type of stress. This stress can be caused by e.g. too high temperatures, high stocking densities, an abrupt change of feed.<\/p>\n

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      Treatment<\/h2>\n

      In acute cases, the farmer should consult a veterinarian and treat his birds.<\/p>\n

      It must be mentioned that, as the treatment takes place via feed or water, only birds which still consume water or feed may be treated.<\/p>\n

      Antibiotics<\/h3>\n

      Antibiotics targeting Gram-positive bacteria are commonly used for the treatment of acute NE. The antibiotic choice shall be addressed by a veterinarian, taking into account mode of action and the presence of resistance genes in the farm\/flock.<\/p>\n

      The prophylactic use of antibiotics is not recommened and many countries have already banned it in order to reduce antimicrobial resistance<\/a> (AMR).<\/p>\n

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      Antimicrobial Resistance (AMR)<\/strong><\/h4>\n

      Some bacteria are less sensitive to certain antibiotics due to genetic mutations. They are able to:<\/span><\/p>\n