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Necrotic enteritis is one of the world’s most common and financially crippling poultry diseases affecting approximately 40% of commercial broiler flocks. Clinical outbreaks can cause mortality rates of up to 50% and has been estimated to cost the global broiler industry upwards of US$5-6 billion annually. However, it is the sub-clinical form that often goes undetected and thus, untreated.
Necrotic enteritis is commonly seen in 2- to 5-week old broiler chickens raised on litter and in 7-to 12-week-old turkeys. The disease will remain in the flock for 5 to 10 days, causing 2% to 50% mortality (Merck Veterinary Manual, 1998).
Necrotic enteritis is usually described in broiler chickens; however, layers and turkeys are also affected by this condition (Broussard et al., 1984; Gazdzinski and Julian, 1991; Droual et al., 1994, 1995; Dhillon et al., 2004).
Necrotic enteritis can lead to a significant effect on performance through its ability to impair nutrient absorption, growth rate, and feed conversion as well as animal welfare, and likely causes a far greater impact on profitability than the clinical disease. On average, the estimated economic cost per bird to producers due to necrotic enteritis ranges from USD$0.050 to $0.063 per bird.
Figure 1. Necrotic enteritis costs producers USD$0.050 to $0.063 per bird
Overpopulation of Clostridium perfringens causes necrotic enteritis
Necrotic enteritis is a result of over proliferation of Clostridium perfringens, a sporulated Gram-positive bacteria that is considered a member of the normal intestinal microbiota. Spores are a dormant form of life extremely resistant to desiccation, heat, disinfectants, and UV radiation. Due to the resistant nature of spores, Clostridia are virtually ubiquitous in poultry houses around the world.
Most of the time C perfringens is present in chicken's intestines without causing disease. Predisposing factors are needed to exacerbate this bacterium, stimulate toxin production and cause the clinical disease. Intestinal protozoa and parasites; immune suppressor diseases; sudden changes in diet; wheat, diets containing rye or fishmeal (viscous diets); and changes in the normal intestinal microflora due to antibiotic treatment or vaccination exacerbate the replication of C perfringens (Branton et al., 1987).
During acute outbreaks of necrotic enteritis birds do not present obvious external signs. A frequent observation is that dead birds that suffered this disease tend to decompose rapidly.
Hepatitis and Colangiohepatitis associated with necrotic enteritis has been described (Randal et al, 1983; Hutchincon and Ridell 1990, Loveland and Kaldhusdal 1999; Sasaki et al 2000). Cholangiohepatitis induction by bile duct ligation and inoculation of C. perfringens (Onderka et al 1990, and Sasaki et al 2000 ), necrotic hepatitis due to C. perfringens in newly hatched broiler chicks (Sasaki et al 2003), cholecystitis, lesions in the bursa of fabricius, spleen and gizzard might also happen.
In the sub-acute form of necrotic enteritis the clinical signs are:
Necrotic enteritis can also be present in a sub-clinical form in which sub-optimal production can be the sole sign of the disease.
During postmortem examinations the small intestine is usually distended with gas. Intestinal lesions are more prevalent in the jejunum and ileum; however, lesions usually extend to the adjacent regions of the small intestine and could even compromise the large intestine (Long et al., 1974). Advanced macroscopic lesions consist of patches of diphtheritic membrane lining the intestinal mucosa. The diphtheritic embrane is composed by degenerated epithelial cells, red blood cells, heterophils, macrophages, lymphocytes, fibrin, and bacteria.
Microscopically the beginning of the condition is characterized by local destruction of the enterocytes at the apices of the villi. Sloughing of the epithelium is visible and it is accompanied by colonization of the lamina propria by Gram- positive bacilli. Necrotic areas are surrounded by inflammatory infiltrate (heterophils and macrophages). Advanced necrosis of the intestine can progress to the submucosal and muscular layers of the intestine.
When dead birds are opened, it might look like the bird has coccidiosis, but the intestines are ballooned with gas, friable and contain a foul-smelling brown fluid. Early in the disease progression, intestines may contain ulcers or light yellow spots on the surface. Later, the interior surface of intestines may contain what seems to be a tan to yellow colored membrane that is often said to resemble a “turkish towel.” Livers may show foci of necrosis.
Necrotic enteritis is caused by toxins produced by Clostridium perfringens type A, and into a lesser extent by C. perfringens type C.
Alpha-toxin from C. perfringens type A, and alpha- and beta-toxins from C. perfringens type B have usually been linked with the generation of the clinical disease. Claims exist that alpha-toxin is not essential to reproduce the disease in poultry; however, the experimental model used to support this observation included a diet composed of 50 % fish meal with no mortality recorded after the replication of the disease (Keyburn et al., 2006).
More recent data have proposed a novel NetB toxin as the causative agent for necrotic enteritis in poultry. This finding was supported by a knockout mutant of the bacteria that was only able to reproduce the disease when complemented with the wild type NetB gene.
Apparently, NetB toxin is a pore forming protein able to bore 1.6 — 1.8 nm diameter hydrophilic pores into cell membranes. Even though there is strong evidence supporting the role of this toxin in the disease not all Clostridia able to reproduce necrotic enteritis were found to have this gene (Keyburn et al., 2008).
Regardless of the toxin responsible for the generation of the disease, it seems that necrotic enteritis is produced when Clostridia reach high numbers within the intestine. Quorum sensing (the ability of these bacteria to detect extracellular signals derived from other bacteria) is apparently involved in the production/exacerbation of the extracellular toxins. In the case of Clostridium the secreted quorum sensing substances consist of peptides called autoinducers that function as ligands for signal receptors (Kaori et al, 2002).
Figure 2. Factors influencing the development of necrotic enteritis
Several factors can have a considerable impact on the proliferation of C. perfringens, including management practices, nutritional factors, coccidiosis, and mycotoxin contamination.
Contributing factors that can lead to necrotic enteritis:
Diet constitutes a key risk factor having a strong impact on the incidence of necrotic enteritis in broiler chickens. Indigestible dietary protein, such as that found in animal proteins like meat and bone meal or fishmeal, cannot be digested and absorbed in the upper part of the intestinal tract.
Instead, protein builds up in the lower portion of the intestinal tract, which can then act as a substrate for the gut microbiota. The fermentation of protein produces unfavorable by-products such as amines and ammonia, increasing intestinal pH and encouraging the proliferation of pathogenic bacteria.
A variety of feed composition and digestibility factors can predispose birds to necrotic enteritis, including:
Coccidial infection, resulting either from natural disease outbreak or from introduction at low levels through live coccidiosis vaccination, can damage the intestinal epithelium, allowing the leakage of plasma proteins into the intestinal lumen –a rich nutrient substrate that C. perfringens can exploit for proliferation and toxin production. This can reduce performance and predispose birds to necrotic enteritis.
Mycotoxins – toxic fungal metabolites produced by common molds found in many components of poultry diets— can directly reduce gut integrity, thus leading to decreased absorption and digestion of dietary nutrients and increased intestinal barrier permeability. Reduced nutrient uptake and leakage of plasma proteins into the lumen due to this breach results in increased protein concentration in the intestinal lumen, providing a substrate for C. perfringens proliferation.
Mycotoxins also adversely affect immunity and have a strong correlation with enteric infections (Table 1). Given the numerous harmful effects of mycotoxins, a proper mycotoxin management program is essential to protect intestinal integrity.
Contamination of broiler feed with Fusarium mycotoxins like deoxynivalenol or fumonisins or a combination of the two is a predisposing factor for necrotic enteritis in broiler chickens.
|% of animals with NE lesions
|C. perfringens alone
|20 ± 2.6b
|C. perfringens + DON
|47 ± 3.0a
|0 ± 0.0
|0 ± 0.0
Table 1. The impact of DON on the percentage of birds affected by necrotic enteritis
These mycotoxins negatively influence the intestinal barrier. For example, duodenal villi gets shorter and enterocytes tight junctions are disrupted resulting in leakage of proteins from the plasma to the gut, less absorption of nutrient from the feed, and increasing the level of intestinal nutrients that are available for Clostridium perfringens.
Figure 3. Impacts of low level deoxynivalenol on intestinal barrier
The bacteria load in drinking water matters a great deal. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Additionally, C. perfringens biofilm can protect the bacterial cells from the action of most disinfectants (University of Montreal). C. perfringens biofilm is an effective in vitro protection mechanism to antibiotics and most disinfectants commonly used on farms and in food processing.
Since C. perfringens is almost ubiquitous it cannot be controlled by standard biosecurity procedures. Reducing of the exacerbating factors plus the reduction of C. perfringens itself are the key factors to reduce the incidence of necrotic enteritis. A reduced number of Clostridium perfringens within the intestinal tract may lead to the prevention or alleviation of necrotic enteritis.
Strategies to treat and prevent necrotic enteritis include:
Mortality associated with necrotic enteritis usually subsides after 24 to 48 hours of antibiotic
treatment. A number of antibiotics have been successfully used in water and feed in therapeutic doses to treat necrotic enteritis. The control of coccidia is also considered a key aspect to decrease the incidence of necrotic enteritis in poultry (Ficken, 1991).
Conventional prevention of necrotic enteritis is based on the constant inclusion of low doses of antimicrobials in the feed or water plus adequate control of coccidia. This practice has been used with success for decades in the worldwide poultry industry. However, subtherapeutic application of antibiotics in poultry production is increasingly falling out of favor as a result of consumer and regulatory demand.
One solution to reduce bacterial growth and activity is to limit their access to protein, a key nutrient source. Many producers switch to an all-vegetable diet, for example. Increasing digestibility of nutrients so they are absorbed and utilized by the bird instead of the microbiota is another option. Some phytogenic feed additives are capable of increasing endogenous digestive enzyme activity so the bird is better able to break down and absorb protein and other nutrients making them unavailable to the microbiota (Figure 4). Supplementation of exogenous proteolytic enzymes is another method that can help break down excess protein.
Figure 4. The effect of phytogenic feed additives on apparent ileal digestibility in broiler chickens. (Hafeez et al., 2015)
The immediate post-hatch period is a critical time for the development of a chick’s intestinal tract. The changes occurring during this period depend entirely upon appropriate microbial colonization. Application of probiotics in the hatchery and as soon as they reach the broiler house provides an ideal opportunity for beneficial bacteria to colonize the digestive tract before chicks are exposed to potentially pathogenic bacteria and fungi in the broiler house, aiding the development of the digestive tract and helping to protect against enteric infections (Table 2).
Probiotics and phytogenic feed additives, with or without the use of coccidiostats or vaccines, can help alleviate the negative effects of coccidial infection. They have been shown to reduce oocyst shedding, severity of intestinal lesions, and adverse effects on performance, demonstrating their status as a promising ‘anticoccidial’ (Figures 5 and 6).
Figure 5. The effect of probiotics with and without coccidia vaccine on intestinal lesion scores during a coccidial challenge. (Ritzi et al., 2016)
Figure 6. The effect of Digestarom® on broiler performance during a coccidial challenge. (Reisinger et al., 2011)
Several management steps can be taken to reduce the risk of necrotic enteritis. For example:
Early exposure of chicks with C. perfringens-contaminated litter decreased the severity of the controlled necrotic enteritis challenge. More severe outbreaks in first flocks follow a complete cleanout and in first flocks in a new broiler house.
Antonissen G, Martel A, Pasmans F, Ducatelle R, Verbrugghe E, Vandenbroucke V, Li S, Haesebrouck F, Van Immerseel F, Croubels S. The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases. Toxins. 2014; 6(2):430-452.
Branton, S.L., F.N. Reece, and W.M. Hagler. 1987. Influence of a wheat diet on mortality of broiler chickens associated with necrotic enteritis. Poult. Sci. 66:1326-1330.
Broussard, C.T., C.L. Hofacre, R.K. Page, and OJ. Fletcher. 1986. Necrotic enteritis in cage-reared commercial layer pullets. Avian Dis. 30(3):617-619.
Dhillon A.S., P. Roy, L. Lauerman, D. Schaberg, S. Weber, D. Bandli, and F. Wier. High mortality in egg layers as a result of necrotic enteritis. Avian Dis. 48:675-680.
Droual, R., H.L Shivaprasad, and R.P. 1994. Coccidiosis and necrotic enteritis in turkeys. Avian Dis. 38:177-183.
Droual, R. T.B. Farver, and A.A. Bickford. 1995. Relationship of sex, age, and concurrent intestinal disease to necrotic enteritis in turkeys. Avian Dis. 39:599-605.
Ficken, M.D. 1991. Necrotic enteritis. In: Diseases of Poultry, ninth edition. Iowa State University Press, Iowa.
Gazdzinski and R.J. Julian. 1992. Necrotic enteritis in turkeys. Avian Dis. 36:792-798. Hafeez A., Männer K., Schieder C., Zentek J.; Effect of supplementation of phytogenic feed additives (powdered vs. encapsulated) on performance and nutrient digestibility in broiler chickens, Poultry Science, Volume 95, Issue 3, 1 March 2016, Pages 622–629, doi.org/10.3382/ps/pev368
Kaori, O., H. Hayashi, and T. Shimizu. 2002. The luxS gene is involved in cell-cell signaling for toxin production in Clostridium perfringens. Mol. Microb. 44(1): 171-179.
Keyburn, A.L., S.A. Sheddy, M.E. Ford, M.M. Williamson, M.M. Awad, J.I. Rood, and R.J. Moore. 2006. Alpha-toxin of Clostridium perfringens is not an essential virulence factor in necrotic enteritis in chickens. Infection and Immunity, 74(ll):6496-6500.
Keyburn, A.L., J.D. Boyce, P. Vaz, T.L. Bannam, M.E. Ford, D. Parker, A. Di Rubbo, J.I. Rood, and J. Moore. 2008. NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens. Plos Pathogens 4(2): 1-11. Long, J.R., J.R. Pettit, and D.A. Barnum. 1974. Necrotic enteritis in broiler chickens II. Pathology and proposed pathogenesis. Can. J. comp. Med. 38:467-474.
Kaldhusdal, M. and A. Lovland. 2000. The economical impact of Clostridium perfringens is greater than anticipated. World Poult. 16:50-51.
Lovland, A. and M. Kaldhusdal. 2001. Severely impaired production performance in broiler flocks with incidence ofClostridium perfringens-associated hepatitis. Avian Pathol. 30:73-81.
McReynolds J., Waneck C., Byrd J., Genovese K., Duke S., Nisbet D.; Efficacy of multistrain direct-fed microbial and phytogenetic products in reducing necrotic enteritis in commercial broilers, Poultry Science, Volume 88, Issue 10, 1 October 2009, Pages 2075–2080, doi.org/10.3382/ps.2009-00106
Reisinger, R., Steiner, T., Nitsch, S., Schatzmayr, G., Applegate, T.J. (2011) Effects of a blend of essential oils on broiler performance and intestinal morphology during vaccine exposure. J. Appl. Poult. Res. 20, 272–283.
Ritzi, M. M., Abdelrahman, W., van-Heerden, K., Mohnl, M., Barrett, N. W., & Dalloul, R. A. (2016). Combination of probiotics and coccidiosis vaccine enhances protection against an Eimeria challenge. Veterinary Research, 47, 111. doi.org/10.1186/s13567-016-0397-y
Teo A.Y. and H. Tan. 2005. Inhibition of Clostridium perfringens by a novel strain of Bacillus subtilis isolated from the gastrointestinal tract of healthy chickens. Appl.
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