By Dr. Inge Heinzl, Editor, Madalina Diaconu, Produt Manager Pretect D, and Dr. Ajay Awati, Global Category Manager Gut Health & Nutrition, EW Nutrition

Often you have an extensive coccidiosis control program in place. You don’t observe any clinical signs of coccidiosis. However, at the end of the cycle, you record significantly lower body weight and a higher FCR. There is a high probability that your animals have subclinical coccidiosis. This article digs deeper into understanding why birds don’t perform as they should, why subclinical coccidiosis occurs on the farm, and why drug resistance is an important factor.

Subclinical coccidiosis – a silent enemy

Clinical coccidiosis is clearly characterized by severe diarrhea, high mortality rates, reduced feed/water intake, and weight loss. By contrast, subclinical Coccidiosis does not display any visual signs and often remains undetected.

According to De Gussem (2008), the damages caused by subclinical coccidiosis can reach up to 70% of the total cost of coccidiosis control treatments, ranging from US$ 2.3 billion to US$ 13.8 billion/year in 2020 worldwide (De Gussem, 2008; Ferreira da Cunha, 2020; Blake et al., 2020).

Monitoring coccidiosis occurrence on the farm

There are several tools available to evaluate the level of infection. The most common ones are:

Lesion scoring – is used to evaluate the damages caused by coccidiosis in the intestinal tract. Lesion scoring gives insight into the severity of the infection. Furthermore, based on the location of lesions in the GI tract, it is possible to determine the plausible Eimeria spp. responsible for the infection.

OPG (Oocyst per gram) – the number of oocysts per gram of feces indicates the level of shedding of oocysts in the manure, litter, and, eventually, in the farm environment. OPG levels may not give the exact severity of the infection in the bird but certainly provide a clear idea of its likely spread within the flock.

Ways to deal with coccidiosis on the farm

Different tools are widely used to prevent and treat coccidiosis:

Anticoccidials:                  Chemicals, ionophores

Vaccination:                       Natural strains, attenuated strains

Bio-shuttle:                        Vaccine + ionophore

Natural anticoccidials:   Phytomolecules

These coccidiosis control programs are used depending on the farm history and the severity of the infection. Traditionally, treatment was heavily dependent on chemicals and ionophores. However, rampant and unbridled use of ionophores leads to resistance in Eimeria spp. on the farm, the failure of the control program, and significant performance losses, with high mortality due to coccidiosis. Therefore, the tools mentioned above are inserted in rotation or shuttle programs to minimize the generation of resistances. In a rotation program, the anticoccidial changes from flock to flock. In a shuttle program, the anticoccidial changes within one cycle according to the feed (Chapman, 1997).

However, this strategy is often not 100% effective due to a lack of diversity and overuse of certain tools within programs. The rigorous financial optimization of the program leads to the use of cost-effective but marginally effective solutions. These factors over the period weaken the program, which seems to work well but leads to resistance to anticoccidial drugs and sets up subclinical coccidiosis.

Resistances have been reported in the US (Jeffers, 1974, McDougald, 1981), South America (McDougald, 1987; Kawazoe and Di Fabio, 1994), Europe (Peeters et al., 1994; Bedrník et al., 1989; Stephan et al., 1997), Asia (Lan et al., 2017; Arabkhazaeli et al., 2013), and Africa (Ojimelukwe et al., 2018). Chapman and co-workers (1997) even stated that resistances were documented for all anticoccidial drugs employed at this time, and new products have not been approved for decades.

Resistance and subclinical coccidiosis can be approached naturally

When an anticoccidial has lost its effectiveness due to excessive use, some resistant coccidia survive. They can cause a mild course of the disease, subclinical coccidiosis, driving the costs high. Reducing the occurrence of resistance and subclinical coccidiosis can significantly decrease the expenses of coccidiosis control programs and, eventually, the cost of production.

Increasing consumer pressure to reduce the overall usage of drugs in animal production has driven innovation efforts to find natural solutions that can be effectively used within coccidiosis control programs. However, this shift was not easy for the producers. Lack of reliable data, poor understanding of the mode of action, lack of quality optimization, and unsubstantiated claims led to the failure of many earlier-generation natural solutions.

However, the consumer-driven movement to find natural solutions to animal gut health issues has recently led to relentless innovation in this area. Knowledge, research, and technological developments are now ready to offer solutions that can be an effective part of the coccidia control program and open opportunities to make poultry production even more sustainable by reducing drug dependency.

For centuries, phytomolecules have been used for their medicinal properties and effects on the health and well-being of animals and humans. In the case of coccidiosis, tannins and saponins have been proven to support animals in coping with this disease. Tannic acids and tannic acid extracts strengthen the intestinal barrier by reducing oxidative stress and inflammation (Tonda et al., 2018). On the other hand, saponins lessen the shedding of oocysts, improve the lesion score, and, in the case of an acute infection, the occurrence of bloody diarrhea (Youssef et al., 2021).

These natural substances can be integrated into shuttle or rotation programs to reduce the use of anticoccidials and, therefore, minimize resistance development.

Pretect D: Coccidiosis programs can be strengthened naturally!

In an EU field trial conducted with more than 200 000 birds, Pretect D (a natural phytogenic-based product designed to increase the efficacy of coccidiosis control) was used in the shuttle program together with ionophores. The trial provided excellent results on zootechnical performance (figures 1-4).

Figures 1-4: Zootechnical performance of broilers with Pretect D included in the shuttle program

Trials show that Pretect D supports the efficiency of coccidiosis control programs by impairing the Eimeria development cycle when used in combination with vaccines, ionophores, and chemicals as part of the shuttle or rotation program:

• It protects the epithelium from inflammatory and oxidative damage
• It promotes the restoration of the mucosal barrier function

Table 1 exemplifies one way of including a natural solution (Pretect D) in actual coccidiosis control programs.

Table 1: Exemple of including Pretect D into coccidiosis control programs

Natural solutions suit both farmers and consumers

With phytomolecules partly replacing anticoccidials in rotation or shuttle programs, the use of anticoccidials in poultry production can be decreased. On the one hand, this answers consumers’ demand; on the other hand, it leads to a push-back of resistances in the long run. The returning effectiveness of the anticoccidials can reduce subclinical coccidiosis, leading to lower costs spent on this disease and a higher profit for the farmers.

References:

Arabkhazaeli, F., M. Modrisanei, S. Nabian, B. Mansoori, and A. Madani. “Evaluating the Resistance of Eimeria spp. Field Isolates to Anticoccidial Drugs Using Three Different Indices.” Iran J Parasitol. 8, no. 2 (2013): 234–41.

Bedrník, P., P. Jurkovič, J. Kučera, and A. Firmanová. “Cross Resistance to the IONOPHOROUS Polyether Anticoccidial Drugs IN Eimeria Tenella Isolates from Czechoslovakia.” Poultry Science 68, no. 1 (1989): 89–93. https://doi.org/10.3382/ps.0680089

Blake, Damer P., Jolene Knox, Ben Dehaeck, Ben Huntington, Thilak Rathinam, Venu Ravipati, Simeon Ayoade, et al. “Re-Calculating the Cost of Coccidiosis in Chickens.” Veterinary Research 51, no. 1 (2020). https://doi.org/10.1186/s13567-020-00837-2

Chapman, H. D. “Biochemical, Genetic and Applied Aspects of Drug Resistance in Eimeria Parasites of the Fowl.” Avian Pathology 26, no. 2 (1997): 221–44. https://doi.org/10.1080/03079459708419208.

De Gussem, M., and S. Huang. “The Control of Coccidiosis in Poultry.” International Poultry Production 16, no. 5 (2008): 7–9.

Ferreira da Cunha, Anderson, Elizabeth Santin, and Michael Kogut. “Editorial: Poultry Coccidiosis: Strategies to Understand and Control.” Frontiers in Veterinary Science 7 (2020). https://doi.org/10.3389/fvets.2020.599322

Jeffers, T. K. “Eimeria Acervulina and E. Maxima: Incidence and Anticoccidial Drug Resistance of Isolants in Major Broiler-Producing Areas.” Avian Diseases 18, no. 3 (1974): 331. https://doi.org/10.2307/1589101

Kawazoe, Urara, and J. Di Fabio. “Resistance to DICLAZURIL in Field Isolates OfEimeriaspecies Obtained from Commercial BROILER Flocks in Brazil.” Avian Pathology 23, no. 2 (1994): 305–11. https://doi.org/10.1080/03079459408418998

Lan, L.-H., B.-B. Sun, B.-X.-Z. Zuo, X.-Q. Chen, and A.-F. Du. “Prevalence and Drug Resistance of Avian Eimeria Species in Broiler Chicken Farms of Zhejiang PROVINCE, CHINA.” Poultry Science 96, no. 7 (2017): 2104–9. https://doi.org/10.3382/ps/pew499

McDougald, L. R. “Anticoccidial Drug Resistance in the Southeastern United STATES: POLYETHER, IONOPHOROUS Drugs.” Avian Diseases 25, no. 3 (1981): 600. https://doi.org/10.2307/1589990

McDougald, Larry R., Jose Maria Silva, Juan Solis, and Mauricio Braga. “A Survey of Sensitivity to Anticoccidial Drugs in 60 Isolates of Coccidia from Broiler Chickens in Brazil and Argentina.” Avian Diseases 31, no. 2 (1987): 287. https://doi.org/10.2307/1590874

Ojimelukwe, Agatha E., Deborah E. Emedhem, Gabriel O. Agu, Florence O. Nduka, and Austin E. Abah. “Populations of Eimeria Tenella Express Resistance to Commonly Used Anticoccidial Drugs in Southern Nigeria.” International Journal of Veterinary Science and Medicine 6, no. 2 (2018): 192–200. https://doi.org/10.1016/j.ijvsm.2018.06.003

Peeters, Johan E., Jef Derijcke, Mark Verlinden, and Ria Wyffels. “Sensitivity of AVIAN EIMERIA Spp. to Seven Chemical and Five Ionophore Anticoccidials in Five Belgian INTEGRATED Broiler Operations.” Avian Diseases 38, no. 3 (1994): 483. https://doi.org/10.2307/1592069

Stephan, B., M. Rommel, A. Daugschies, and A. Haberkorn. “Studies of Resistance to Anticoccidials IN Eimeria Field Isolates and Pure Eimeria Strains.” Veterinary Parasitology 69, no. 1-2 (1997): 19–29. https://doi.org/10.1016/s0304-4017(96)01096-5

Tonda, RM, J.K. Rubach, B.S. Lumpkins, G.F. Mathis, and M.J. Poss. “Effects of Tannic Acid Extract on Performance and Intestinal Health of Broiler Chickens Following Coccidiosis Vaccination and/or a Mixed-Species Eimeria Challenge.” Poultry Science 97, no. 9 (2018): 3031–42. https://doi.org/10.3382/ps/pey158

Youssef, Ibrahim M., Klaus Männer, and Jürgen Zentek. “Effect of Essential Oils or Saponins Alone or in Combination on Productive Performance, Intestinal Morphology and Digestive Enzymes’ Activity of Broiler Chickens.” Journal of Animal Physiology and Animal Nutrition 105, no. 1 (2020): 99–107. https://doi.org/10.1111/jpn.13431

byInge Heinzl, Marisabel Caballero, Ajay Bhoyar, EW Nutrition

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.

Necrotic enteritis is a poultry disease caused by an overgrowth of Clostridium perfringens type A, and to a lesser extent type C, in the small intestine. The toxins produced by C. perfringens 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.

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).

While this is a widespread problem in all poultry, for broilers in particular, necrotic enteritis and coccidiosis are the most significant health problem.

Clinical and subclinical forms of NE

The clinical form

…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.

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).

In the case of peracute necrotic enteritis, birds may die without showing any preliminary signs.

The subclinical form

When birds suffer from the subclinical form, chronic damage to the intestinal mucosa and an increased quantity of mucus in the small intestine lead to  impaired digestion and absorption of nutrients resulting in poor growth performance.

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.

 

Pathogens

Responsible for necrotic enteritis are Gram-positive, anaerobic bacteria, specific strains of Clostridium perfringens type A and, to a lesser extent, type C (Keyburn et al., 2008).

Clostridia primarily occur in the soil where organic substances are degraded, in sewage, and the gastrointestinal tract of animals and humans. 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 spores can even proliferate in feed or litter.

Clostridium perfringens is a natural inhabitant of the intestine of chickens. In healthy birds, it occurs in a mixture of diverse strains at 10²-10⁴ CFU/g of digesta (McDevitt et al., 2006). The disease starts when C. perfringens 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 10⁷-10⁹ CFU/g of digesta (Dahiya et al., 2005).

NetB, a key virulence factor for NE

To establish in the host, Clostridium Spp. and other pathogens depend on virulence factors (see infobox). These virulence factors include, for example, “tools” for attachment, evasion or suppression of the host’s immune system, “tools” for getting nutrients, and “tools” for entry into intestinal cells. Over the years, the α-toxin produced by C. perfringens 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 mutant unable to produce α-toxin, yet still causing necrotic enteritis.

Thus, another toxin was identified occurring only in chickens suffering from necrotic enteritis: C. perfringens 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).

Additionally, pathogenic strains of C. perfringens produce bacteriocins – the most important being Perfrin (Timbermont et al., 2014) – to inhibit the proliferation of harmless Clostridium Spp. strains and to replace the normal intestinal flora of chickens (Riaz et al., 2017).

 

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

Predisposing factors

Feed: composition and particle size

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 come into play.

Mycotoxin contamination

Mycotoxins harm gut integrity and create ideal conditions for the proliferation of Clostridium perfringens.

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

1. DON provides good conditions for proliferation of C. perfringens 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).
2. DON and other mycotoxins decrease the number of lactic acid producing bacteria indicating a shift in the microbial balance (Antonissen et al., 2016.).

Eimeria ssp.

An intact intestinal epithelium is the best defense against potential pathogens such as C. perfringens. Here, Coccidiosis comes into play. Moore (2016) showed that by damaging the gut epithelium, Eimeria species give C. perfringens 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 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).  A further impact of Coccidiosis is shifting the microbial balance in the gut by decreasing the number of e.g., Candidatus savagella which activates the innate immune defense.

1. Eimeria induce leakage of plasma proteins by killing epithelial cells
2. They enhance mucus production in the intestine

1+2 lead to an increase in available nutrients and create an environment favorable for the proliferation of C. perfringens.

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

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

Immunosuppressive factors

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:

Bacteria: Shivaramaiah and coworkers (2011) investigated a neonatal Salmonella typhimurium 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.

Viruses: Infectious Bursal Disease is known to increase the severity of infections with salmonella, staphylococci, but also clostridia. Another clostridia-promoting viral disease is Marek’s Disease.

Stress: 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.

Treatment

In acute cases, the farmer should consult a veterinarian and treat his birds.

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.

Antibiotics

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.

The prophylactic use of antibiotics is not recommened and many countries have already banned it in order to reduce antimicrobial resistance (AMR).

 

Bacteriophages

Experimental use of phage treatments have shown to be effective in reducing disease progression and symptoms of necrotic enteritis (Miller et al., 2010). By oral application of a bacteriophage cocktail, Miller and coworkers could reduce mortality by 92% in C. perfringens challenged broilers compared to the untreated control.

Mode of action: the endolysins, highly evolved enzymes produced by bacteriophages, are able to digest the bacterial cell wall for phage progeny release (Fischetti, 2010). However, phages are still not approved by the EFSA.

Prevention

Preventing a disease is always better – and more cost-effective – that its treatment.

How, then, should it be done?

Preventing the conditions that favor the proliferation of Clostridium perfringens and strengthening the host’s immune response lowers the probability of disease.

Besides eliminating the predisposing factors, the main targets are:

• Balance of the gut flora
• Optimization of gut function and integrity
• Maintenance of immunity

Biosecurity

There is evidence that most Clostridium strains isolated from birds suffering from necrotic enteritis could induce the disease experimentally, while strains isolated from healthy birds cannot. This confirms that only specific strains are problematic (Ducatelle and Van Immerseel, 2010).

It is therefore of the highest importance to avoid introducing these pathogenic strains to the farm.

• Strict biosecurity measures!

• Separate clothing, boots, and hand washing/disinfecting facilities in each poultry house
• More than 14 days of down time between flocks

Specific measures against coccidiosis

1. Vaccination

According to parasitologists, 7 to 9 Eimeria species are found in chickens, and they do not cross-protect against each other. An effective vaccination must contain sporulated oocysts of the most critical pathogenic Eimeria species (E. acervulina, E. maxima, E. tenella, E. necatrix, and E. brunetti). The more species contained in the vaccine, the better. However, if not applied the correct way, vaccines can be ineffective or cause reactions in the birds that might lead to NE (Mitchell, 2017).

2. Anticoccidials

Alternate use of chemicals (synthetic compounds) and ionophores (polyether antibiotics) with different modes of action is important to avoid  development of resistance.

Ionophores have a specific mode of action and kill oocysts before they are able to infect birds. Being very small, ionophore molecules can be taken up and diffused into the outer membrane of the sporozoite. There, it decreases the concentration gradient leading to an accumulation of water within the sporozoite causing its bursting.

Diet

Minimizing non-starch polysaccharides (NSPs) in cereals

To prevent a “feeding” of Clostridium perfringens, high content of water-soluble but indigestible NSPs such as wheat, wheat by-products, and barley should be avoided or at least minimized. Additionally, xylanases should be included in the feed formulation to reduce the deleterious effects of NSPs and improve feed energy utilization. Instead of these cereals, maize could be included in the diet. It is considered a perfect ingredient in broiler diets due to its high energy content and high nutrient availability.

Formulating low protein diets/diets with highly digestible amino acids

Feeding low-protein diets supplemented with crystalline amino acids might be beneficial to reduce the risk of necrotic enteritis (Dahiya et al., 2007). To improve protein digestibility and therefore reduce the proliferation of C. perfringens, proteases may be added to the feed.

Avoiding/Minimizing poor quality fats / animal fats in the diet

These fats tend to increase the count of Clostridium perfringens; thus, they should be replaced by higher quality and/or vegetable fats, respectively.

Feed form

In terms of feed form, Engberg et al. (2002) found that birds fed pellets showed a reduced number of Clostridium perfringens in the caeca and the rectum than mash-fed birds. Branton and co-workers (1987) reported a lower mortality by feeding roller-milled (coarsely ground) than hammer-milled feed.

Additives

Additives can be used either to prevent the proliferation of Clostridium perfringens or to change the environmental conditions in a way that  proliferation of C. perfringens is prevented.

Probiotics

These live microbial supplements can be used to help to establish, maintain or re-establish the intestinal microflora.

Mode of action:

• compete with pathogenic bacteria for substrates and attachment sites
• produce antimicrobial substances inhibiting the growth of pathogenic bacteria (Gillor et al., 2008)
• bind and neutralize enterotoxins (Mathipa and Thantsha, 2017)
• promote immune function of the host (Yang et al., 2012)

Prebiotics

• These feed ingredients serve as substrates to promote beneficial bacteria in the intestine.

Mode of action:

• D-mannose or fructose, starches non-digestible by birds, selectively stimulate the growth and the activity of the “good” gut flora
• Fructooligosaccharides decrease C. perfringens and E. coli in the gut and increase the diversity of Lactobacillus Spp. (Kim et al., 2011)
• Galactooligosaccharides, in combination with a B. lactis based probiotic, have been reported to selectively promote the proliferation of Bifidobacterium ssp. (Jung et al., 2008).

Organic acids

Organic acids are often used in animal diets to improve intestinal health.

Mode of action:

• decreased pH promotes beneficial bacteria
• caprylic acid suppresses C. perfringens, but also Salmonella Spp. by inhibiting their utilization of glucose (Skrivanova et al., 2006)
• lauric, citric, oleic and linoleic acid as well as medium-chain fatty acids (C8-C14) impede the growth of C. perfringens

Phytomolecules

Phytomolecules, also known as secondary plant compounds, have been used against pathogens for centuries. In general, two subgroups of these substances are known as effective against Clostridium perfringens:

Tannins

• Many studies have shown the efficacy of tannins against different pathogens such as helminths, Eimeria, viruses, and bacteria
• Extracts from the chestnut and quebracho trees are effective not only against C. perfringens, but also its toxins (Elizando et al., 2010)
• Activity of tannins against Eimeria (Cejas et al., 2011) and Salmonella Sp., two predisposing factors for NE.

Essential Oils

• Their hydrophobic characteristic enables them to interact with the lipids of the membrane of C. perfringens.
• They can incorporate into the bacterial membrane and disrupt its integrity.
• This increases the permeability of the cell membrane for ions and other small molecules such as ATP, leading to the decrease of the electrochemical gradient above the cell membrane and the loss of the cell’s energy equivalents.

Besides their direct effect on Clostridium Spp., a lot of phytomolecules improve gut health and help to prevent a proliferation of Clostridium ssp. and therefore necrotic enteritis.

Mycotoxin/bacterial toxin binders

These binders have two modes of action:

• Binding mycotoxins, damage of the intestinal epithelium can be reduced or even prevented, so that the preconditions for Clostridium proliferation are not generated.
• Binding toxins produced by Clostridium perfringens can reduce the occurrence or severity of lesions:

Alpha-toxin (phospholipase C) hydrolyses membrane phospholipids and damages erythrocytes, leucocytes, myocytes, and endothelial cells and causes their lysis (Songer, 1996). This leads to necrosis and tissue damage.

• Binding NetB toxin, the key virulence factor, could reduce the severity of necrotic enteritis.

Conclusion

The ever-growing trend of reduced antibiotic and ionophore use is contributing to an increased incidence of necrotic enteritis in poultry production.

The subclinical form of necrotic enteritis generally goes unnoticed, resulting in poor feed efficiency and is a major cause of financial losses to poultry producers.

Maintaining optimum gut health is key to preventing the occurrence of necrotic enteritis. In the era of antibiotic-free poultry production, alternatives acting against this pathogenic bacterium and also against its predisposing factors must be considered to control this devastating disease.

 

References

Annett, C.B., J. R. Viste, M. Chirino-Trejo, H. L. Classen, D. M. Middleton, and E. Simko. “Necrotic enteritis: effect of barley, wheat and corn diets on proliferation of Clostridium perfringens type A.” Avian Pathology 31 (2002): 599– 602. https://doi.org/10.1080/0307945021000024544

Antonissen G, F. Van Immerseel, F. Pasmans, R. Ducatelle, F. Haesebrouck, L. Timbermont, M. Verlinden, G.P.J. Janssens, V. Eeckhaut, M. Eeckhout, S. De Saeger, S. Hessenberger, A. Martel, and S. Croubels. “The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-Induced necrotic enteritis in broiler chickens. PLoS ONE 9 no. 9 (2014): e108775. https://doi.org/10.1371/journal.pone.0108775

Antonissen, G., V. Eeckhaut, K. Van Driessche, L. Onrust , F. Haesebrouck, R. Ducatelle, R.J. Moore, and F. Van Immerseel. “Microbial Shifts Associated With Necrotic enteritis.” Avian Pathol. 45 no. 3 (2016): 308-312. https://doi.org/10.1080/03079457.2016.1152625

Branton, S.L., F.N. Reece, and W.M. Hagler. “Influence of a wheat diet on mortality of broiler chickens associated with necrotic enteritis.” Poultry Sci. 66 (1987): 1326-1330. https://doi.org/10.3382/ps.0661326

Cejas, E., S. Pinto, F. Prosdócimo, M. Batalle, H. Barrios, G. Tellez, and M. De Franceschi. “Evaluation of quebracho red wood (Schinopsis lorentzii) polyphenols vegetable extract for the reduction of coccidiosis in broiler chicks.” International Journal of Poultry Science 10 no. 5 (2011): 344–349. https://doi.org/10.3923/ijps.2011.344.349

Collier, C.T., C.L. Hofacre, A.M. Payne, D.B. Anderson, P. Kaiser, R.I. Mackie, and H.R. Gaskins. “Coccidia-induced mucogenesis promotes the onset of necrotic enteritis by supporting Clostridium perfringens growth.” Veterinary Immunology and Immunopathology 122 (2008):104–115.

https://doi.org/10.1016/j.vetimm.2007.10.014

https://www.academia.edu/12692646/Coccidia-induced_mucogenesis_promotes_the_onset_of_necrotic_enteritis_by_supporting_Clostridium_perfringens_growth

Dahiya, J.P., D. Hoehler, A.G. Van Kessel, and M.D. Drew. “Effect of different dietary methionine sources on intestinal microbial populations in broiler chickens.” Poultry Science 86 (2007):2358–2366

https://doi.org/10.3382/ps.2007-00133

Dahiya, J.P., D. Hoehler, D.C. Wilkie, A.G. van Kessel, and M.D. Drew. “Dietary glycine concentration affects intestinal Clostridium perfringens and Lactobacilli populations in broiler chickens.” Poultry Science 84 no.12 (2005):1875-85. https://doi.org/10.1093/ps/84.12.1875

Diaz Carrasco, J.M., L.M. Redondo, E.A. Redondo, J.E. Dominguez, A.P. Chacana, and M.E. Fernandez Miyakawa. “Use of plant extracts as an effective manner to control Clostridium perfringens induced necrotic enteritis in poultry.” BioMed Research International (2016): Article ID 3278359. https://dx.doi.org/10.1155/2016/3278359

Ducatelle, R. and F. van Immerseel. “Necrotic enteritis: emerging problem in broilers.” WATTAgNet.com – Poultry Health and Disease (April 9, 2010).

https://www.wattagnet.com/articles/5523-necrotic-enteritis-emerging-problem-in-broilers

Elizondo, A.M.,  E.C. Mercado, B.C. Rabinovitz, and M.E. Fernandez-Miyakawa. “Effect of tannins on the in vitro growth of Clostridium perfringens.” Veterinary Microbiology 145 no. 3-4 (2010): 308–314. https://doi.org/10.1016/j.vetmic.2010.04.003

Engberg, R.M., M.S. Hedemann, and B.B. Jensen. “The influence of grinding and pelleting of feed on the microbial composition and activity in the digestive tract of broiler chickens.” · British Poultry Science 43 no. 4 (2002):569-579. https://doi.org/10.1080/0007166022000004480

Fischetti, V.A. “Bacteriophage endolysins: A novel anti-infective to control Gram-positive pathogens.” J Med Microbiol. 300 no. 6 (2010): 357–362. https://doi.org/10.1016/j.ijmm.2010.04.002

Gillor, O., A. Etzion and M.A. Riley. “The dual role of bacteriocins as anti- and probiotics.” Appl Microbiol Biotechnol. 81 no. 4 (2008): 591–606. https://doi.org/10.1007/s00253-008-1726-5

Hassan, J. O., and R. Curtiss III. “Virulent Salmonella typhimurium induced lymphocyte depletion and immunosuppression in chickens.” Infect. Immun. 62 (1994):2027–2036 https://doi.org/10.1128/IAI.62.5.2027-2036.1994

Hofacre, C.L., J.A. Smith, and G.F. Mathis. “Invited Review. An optimist’s view on limiting necrotic enteritis and maintaining broiler gut health and performance in today’s marketing, food safety, and regulatory climate.” Poultry Science 97 (2018):1929–1933. https://dx.doi.org/10.3382/ps/pey082

Jung, S.J., R. Houde, B. Baurhoo, X. Zhao, and B. H. Lee. “Effects of galacto-oligosaccharides and a bifidobacteria lactis-based probiotic strain on the growth performance and fecal microflora of broiler chickens.” Poultry Science 87 (2008):1694–1699. https://doi.org/10.3382/ps.2007-00489

Kaldhusdal and Skjerve. “Association between cereal contents in the diet and incidence of necrotic enteritis in broiler chickens in Norway.” Preventive Veterinary Medicine 28 (1996):1-16. https://doi.org/10.1016/0167-5877(96)01021-5

https://www.academia.edu/17521917/Association_between_cereal_contents_in_the_diet_and_incidence_of_necrotic_enteritis_in_broiler_chickens_in_Norway

Keyburn, A. L., S. A. Sheedy, M. E. Ford, M. M. Williamson, M. M. Awad, J. I. Rood, and R. J. Moore. “Alpha-toxin of Clostridium perfringens is not an essential virulence factor in necrotic enteritis in chickens.” Infect. Immun. 74 (2006): 6496–6500. https://doi.org/10.1128/IAI.00806-06

Keyburn, A.L., J.D. Boyce, P. Vaz, T.L. Bannam, M.E. Ford, D. Parker, A. Di Rubbo, J.I. Rood, and R.J. Moore. “NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens.” PLoS Pathog 4 no. 2, e26 (2008): 0001-0011. https://doi.org/10.1371/journal.ppat.0040026

Kim, G.-B., Y. M. Seo , C. H. Kim , and I. K. Paik. “Effect of dietary prebiotic supplementation on the performance, intestinal microflora, and immune response of broilers.” Poultry Science 90 (2011):75–82. https://doi.org/10.3382/ps.2010-00732

Knap, I., B. Lund, A. B. Kehlet, C. Hofacre, and G. Mathis. “Bacillus licheniformis prevents necrotic enteritis in broiler chickens.” Avian Diseases 54 no. 2 (2010):931-935. https://doi.org/10.1637/9106-101509-ResNote.1

Knarreborg, A., M.A. Simon, R.M. Engberg, B.B. Jensen, and G.W. Tannock. “Effects of Dietary Fat Source and Subtherapeutic Levels of Antibioticon the Bacterial Community in the Ileum of Broiler Chickensat Various Ages.” Applied and Environmental Microbiology 68 no. 12 (2002): 5918-5924. https://doi.org/0.1128/AEM.68.12.5918–5924.2002

Kocher, A. and M. Choct. “Improving broiler chicken performance. The efficacy of organic acids, prebiotics and enzymes in controlling necrotic enteritis.” Australian Government-Rural Industries Research and Development Corporation. Publ. no. 08/149 (2008).

https://www.agrifutures.com.au/wp-content/uploads/publications/08-149.pdf

Kondo, F. “In vitro lecithinase activity and sensitivity to 22 antimicrobial agents of Clostridium perfringens isolated from necrotic enteritis of broiler chickens.” Research in veterinary Science 45 (1988): 337-340. https://doi.org/10.1016/S0034-5288(18)30961-5

Kubena, L.F., J.A. Byrd, C.R. Young, and D.E. Corrier. “Effects of tannic acid on cecal volatile fatty acids and susceptibility to Salmonella typhimurium colonization in broiler chicks.” Poultry Science 80, no. 9 (2001): 1293–1298. https://doi.org/10.1093/ps/80.9.1293

Los, F.C.O., T.M. Randis, R.V. Aroian, and A.J. Ratner. “Role of pore-forming toxins in bacterial infectious diseases.” Microbiology and Molecular Biology Reviews 77 (2013): 173-207 https://doi.org/10.1128/MMBR.00052-12

M’Sadeq S.A., Shubiao Wu, Robert A. Swick, Mingan Choct. “Towards the control of necrotic enteritis in broiler chickens with in-feed antibiotics phasing-out worldwide.” Animal Nutrition 1 (2015): 1-11. https://dx.doi.org/10.1016/j.aninu.2015.02.004

Mathipa, M.G. and M.S. Thantsha. “Probiotic engineering: towards development of robust probiotic strains with enhanced functional properties and for targeted control of enteric pathogens.” Gut Pathog. 9 no. 28 (2017). https://doi.org/10.1186/s13099-017-0178-9

McDevitt, R.M., J.D. Brooker, T. Acamovic, and N.H.C. Sparks. “Necrotic enteritis, a continuing challenge for the poultry industry.” World’s Poultry Science Journal 62; World’s Poultry Science Association (June 2006). https://doi.org/10.1079/WPS200593

Miller, R.W., J. Skinner, A. Sulakvelidze, G.F. Mathis, and C.L. Hofacre. “Bacteriophage therapy for control of necrotic enteritis of broiler chickens experimentally infected with Clostridium perfringens.” Avian Diseases 54 no. 1 (2010): 33-40. https://doi.org/10.1637/8953-060509-Reg.1

Mitsch, P., K. Zitterl-Eglseer, B. Köhler, C. Gabler, R. Losa, and I. Zimpernik. “The Effect of Two Different Blends of Essential Oil Components on the Proliferation of Clostridium perfringens in the Intestines of Broiler Chickens.” Poultry Science 83 (2004):669–675. https://doi.org/10.1093/ps/83.4.669

Mitchell, A. “Choosing the right coccidiosis vaccine for layer and breeder chickens.” The Poultry Site March 21 (2017). https://thepoultrysite.com/articles/choosing-the-right-coccidiosis-vaccine-for-layer-and-breeder-chickens

Olkowski, A.A., C. Wojnarowicz, M. Chirino-Trejo, B. Laarveld, and G. Sawicki. “Sub-clinical necrotic enteritis in broiler chickens: Novel etiological consideration based on ultra-structural and molecular changes in the intestinal tissue.” Veterinary Science 85 (2008): 543–553. https://doi.org/10.1016/j.rvsc.2008.02.007

Pan, D. and Z. Yu. “Intestinal microbiome of poultry and its interaction with host and diet.” Gut Microbes 5 no. 1 (2014): 108–119. https://dx.doi.org/10.4161/gmic.26945

Porter, R., Jr. “Bacterial enteritides of poultry.” Poult. Sci. 77 (1998):1159–1165 https://doi.org/10.1093/ps/77.8.1159

Robert Koch Institut. “Grundwissen Antibiotikaresistenz“. https://www.rki.de/DE/Content/Infekt/Antibiotikaresistenz/Grundwissen/Grundwissen_inhalt.html#:~:text=Wenn%20ein%20neues%20Antibiotikum%20auf,%C3%BCberleben%20und%20vermehren%20sich%20weiter.

Rougière, N. and B. Carré. “Comparison of gastrointestinal transit times between chickens from D + and D- genetic lines selected for divergent digestion efficiency.” Animal 4 no. 11 (2010): 1861-1872. https://doi.org/10.1017/S1751731110001266

Santos, F.B.O., B.W. Sheldon, A.A. Santos Jr., and P.R. Ferket. ”Influence of housing system, grain type, and particle size on Salmonella colonization and shedding of broilers fed triticale or corn-soybean meal diets.” Poultry Science 87 (2008): 405-420. https://dx.doi.org/10.3382/ps.2006-00417

Schiavone, A. , K. Guo, S. Tassone, L .Gasco, E. Hernandez, R. Denti, and I. Zoccarato. “Effects of a Natural Extract of Chestnut Wood on Digestibility, Performance Traits, and Nitrogen Balance of Broiler Chicks.”  Poult Sci. 87 no. 3 (2008): 521-527. https://doi.org/10.3382/ps.2007-00113

Shivaramaiah, S., R. E. Wolfenden, J. R. Barta, M. J. Morgan, A. D. Wolfenden, B. M. Hargis, and G. Téllez. „The role of an early Salmonella typhimurium infection as a predisposing factor for necrotic enteritis in a laboratory challenge model.” Avian Diseases 55 (2011): 319-323. https://doi.org/10.1637/9604-112910-ResNote.1

Singh, Y., V. Ravindran, T.J. Wester, A.L. Molan, and G. Ravindran. “ Influence of feeding coarse corn on performance, nutrient utilization, digestive tract measurements, carcass characteristics, and cecal microflora counts of broilers.” Poultry  Science 93 (2014): 607–616. https://dx.doi.org/10.3382/ps.2013-03542

Skrivanova, E., M. Marounek, V. Benda, and P. Brezina. “Susceptibility of Escherichia coli, Salmonella sp. and Clostridium perfringens to organic acids and monolaurin.” Veterinarni Medicina 51 no. 3 (2006): 81–88. https://doi.org/10.17221/5524-VETMED

Songer, J.G. “Clostridial Enteric Diseases of Domestic Animals.” Clinical Microbiology Reviews 9 no. 2 (1996): 216-234. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC172891/pdf/090216.pdf

Stanley D., Wu S.-B., Rodgers N., Swick R.A., and Moore R.J. “Differential Responses of Cecal Microbiota to Fishmeal, Eimeria and Clostridium perfringens in a Necrotic Enteritis Challenge Model in Chickens.” PLoS ONE 9 no. 8 (2014): e104739. https://doi.org/10.1371/journal.pone.0104739

Tan, L., D. Rong, Y. Yang, and B. Zhang. “Effect of Oxidized Soybean Oils on Oxidative Status and Intestinal Barrier Function in Broiler Chickens.” Brazilian Journal of Poultry Science 18 no. 2 (2018): 333-342. http://dx.doi.org/10.1590/1806-9061-2017-0610

Tan, L., D. Rong, Y. Yang, and B. Zhang. “The Effect of Oxidized Fish Oils on Growth Performance, Oxidative Status, and Intestinal Barrier Function in Broiler Chickens.” J. Appl. Poult. Res. 28 (2019): 31-41. http://dx.doi.org/10.3382/japr/pfy013

ThePoultrySite. “Necrotic Enteritis. Disease Guide”. https://thepoultrysite.com/disease-guide/necrotic-enteritis

Timbermont L., A. Lanckriet, J. Dewulf, N. Nollet, K. Schwarzer, F. Haesebrouck, R. Ducatelle, and F. Van Immerseel. “Control of Clostridium perfringens-induced necrotic enteritis in broilers by target-released butyric acid, fatty acids and essential oils.” Avian Pathol. 39 no. 2 (2010): 117-21. https://doi.org/10.1080/03079451003610586

Tsiouris, V. “Poultry management: a useful tool for the control of necrotic enteritis in poultry.” Avian Pathol. 45 no. 3 (2016):323-325. https://doi.org/10.1080/03079457.2016.1154502

Van der Most, P.J., B. de Jong, H.K. Parmentier and S. Verhulst. “Trade-off between growth and immune function: a meta-analysis of selection experiments.” Functional Ecology 25 (2011): 74-80. https://doi.org/0.1111/j.1365-2435.2010.01800.x

Van der Sluis, W. “Clostridial enteritis is an often underestimated problem.” Worlds Poult. Sci. J. 16 (2000):42–43.

Van der Suis, W. “Necrotic enteritis kills birds and profits.” Poultry World Apr5 (2013). https://www.poultryworld.net/Health/Articles/2013/4/necrotic-enteritis-kills-birds-and-profits-1220877W/

Van Immerseel, F., J. De Buck, F. Pasmans, G. Huyghebaert, F. Haesebrouck, and R. Ducatelle. “Clostridium perfringens in poultry: an emerging threat of animal and public health.” Avian Pathology 33 (2004): 537-549. https://doi.org/10.1080/03079450400013162

Van Immerseel, F., J.I. Rood, R.J. Moore, and R.W. Titball. “Rethinking our understanding of the pathogenesis of necrotic enteritis in chickens.” Trends in Microbiology 17 no. 1 (2008):32-36. https://doi.org/10.1016/j.tim.2008.09.005

Wade, B., A. Keyburn. “The true cost of necrotic enteritis.” World Poultry 31 no. 7 (2015): 16–17. https://www.poultryworld.net/Meat/Articles/2015/10/The-true-cost-of-necrotic-enteritis-2699819W/

Wade, B., A.L. Keyburn, T. Seemann, J.I. Rood, and R.J. Moore. “Binding of Clostridium perfringens to collagen correlates with the ability to cause necrotic enteritis in chickens.” Veterinary Microbiology 180 no. 3–4 (2015): 299-303. https://doi.org/10.1016/j.vetmic.2015.09.019

Williams, R.B. “Intercurrent coccidiosis and necrotic enteritis of chickens: rational, integrated disease management by maintenance of gut integrity.” Avian Pathology 34 no. 3 (2005):159-180. https://doi.org/10.1080/03079450500112195

Yang , C.M., G.T. Cao, P.R. Ferket, T.T. Liu, L. Zhou, L. Zhang, Y.P. Xiao, and A. G. Chen. “ Effects of probiotic, Clostridium butyricum, on growth performance, immune function, and cecal microflora in broiler chickens.” Poultry Science 91 (2012): 2121–2129. https://dx.doi.org/10.3382/ps.2011-02131