Water is a main nutrient and carrier for vaccines, medicine – including antibiotics, but also for pathogens

Chemistry

pH and pKa

Acidity and dissociation index
Target: pH 3,5-3,8 Important for acids application (E.g. organic acids, etc), and ORP

Hardness

Content of Ca, sometimes plus Mg
Target: better TDS Important for acid binding capacity (ABC, buffer capacity)

Oxidation Reduction Potential (ORP)

Target: 650 mV>700 mV » reduces water intake Important for biocides application (E.g. chlorination)

Total Dissolved Solids (TDS)

Sum of dissolved salts, minerals, metals, carbonates, organics Target: 2000 ppm>3000 ppm » laxation Important for buffer capacity and ORP

Microbiology

Yeast

Target: < 5000 cfu/gr

Enterobacterias

Target: < 100 cfu/gr

Moulds

Target: < 100 cfu/gr

Conference report 

At the recent EW Nutrition Poultry Academy in Jakarta, Indonesia, Dr Steve Leeson, Professor Emeritus, University of Guelph, Canada, opened his presentation by stating that “it is obvious that any nutrient deficiency will impact bird health, but not so obvious is that nutrition per se can positively impact immunity and health in an otherwise healthy and high-producing bird.”

Modern high-performing broilers are characterized by extremely high feed intake. This puts a lot of stress on the physiology of the entire gastrointestinal tract, but particularly so on the absorptive epithelial cells of the small intestine. Any organism requires a nutrient source for survival and reproduction. Dr Leeson asked “can we significantly reduce nutrient supply to pathogens, while sustaining bird productivity?”

He reminded the audience that no cellular function comes for free: so there is always a “cost”. A general conclusion is that 10% of nutrients can be used for immune function during disease challenge, and always get priority. Therefore, you don’t want to overstimulate the immune system, which in extreme situations leads to an inflammatory response. In his presentation, Dr Leeson considered factors determining gut health and nutritional tools which are available to support gut health.

Gut microflora

Gut pathogens impact the bird and/or the consumer. Clostridia and E. coli are the major concerns regarding bird health and productivity, whereas Salmonella and Campylobacter are major pathogens important for human health.

The chick hatches with a gut virtually devoid of microbes, so early colonizers tend to predominate quite quickly. Microbial species present on the hatching tray, during delivery and during the first few days at the farm will likely dictate early gut colonization. In some instances, the chick’s microflora may be established by the time it gets to the farm, so the probiotic faces more of a challenge to establish itself as the predominant species.

Antibiotic alternatives

Gut villi development matures at around 10-15 days of age. The broiler pre-starter diet therefore is a target for feed additives that positively impact gut structure and development.

• Among the short chain fatty acids, butyric acid is considered the prime energy source for enterocytes and it is also necessary for the correct development of the gut-associated lymphoid tissue (GALT). Butyric acid can also be added indirectly via fermentation of judicious levels of soluble fiber to encourage optimal gut villi development. Dr Leeson added that he is a big believer in butyric acid, encouraging a good gut structure at 10 days, which can be worth about 50 kcal.
• Exogenous enzymes should also be considered in an attempt to maximize digestion and limit the flow of nutrients to the large intestine and ceca. Protease enzymes have great potential in this regard, since they allow nutritionists to reduce dietary crude protein and hopefully reduce the supply of nitrogen that fuels proteolytic Clostridia bacteria in the large intestine and ceca.
• Amino acids, particularly threonine, play a critical role in the maintenance of intestinal mucosal integrity and barrier function, especially for mucin synthesis, which protects enterocytes from adherence by pathogenic bacteria, and from attack by endogenous enzymes and acids.
• Polyunsaturated fatty acids (PUFAs) – Omega-3s and especially DHA from fish oil help to reduce inflammatory response (overstimulation). Omega-3s are poorly converted to DHA by the chicken, so conventional sources such as flax are of limited application for immunity.
• Blood plasma from pigs or cattle is a complex spray-dried mixture of proteins and amino acids, many of which are immunoglobulins that “temper” the immune system, much like PUFAs.
• Vitamins A, D, E and C have vital roles in the normal function of the immune system and have antioxidant capacity.
• Certain complex carbohydrates, such as ß-glucans, influence gut health due to their fermentation, leading to the production of short-chain fatty acids, such as butyrate.
• Antioxidants – to firstly control oxidation of fats and fat-soluble vitamins in feed, and secondly to optimize birds’ cellular oxidative capacity, to prevent cell damage, therefore maintaining healthy cellular and immune function.
• Betaine increases intracellular water retention, reducing “dehydration” of microvilli and increasing their volume/surface area.
• Fiber – moderate levels (1-2%) of soluble (fermentable) and insoluble fiber can be beneficial to early gut development by stimulating gizzard development and endogenous enzyme production.
• Phytogenics are becoming very common in combination with acidifiers (upper tract) and probiotics. Essential oils are becoming more mainstream the more we know about them.

Recommendations for optimizing gut health and immunity

Fast growth rate and high egg output are negatively correlated with immune response. Consequently, nutrient-dense diets are not optimal for immunity. With bacteria, it’s a numbers game – but these numbers quickly multiply. The first 7 days are important, therefore probiotics must be established early. Consider the role of targeted feed additives, such as butyrate, phytogenics, antioxidants, PUFAs etc.

Also, maximize feed particle size – the limit is usually pellet quality. Mitigate nutrient transition at any diet change. Review the supply of trace minerals, as there is a trend to lower levels of organic minerals. With all the factors that weigh into production performance, any support that can be rallied through nutrition needs to be considered.

***

EW Nutrition’s Poultry Academy took place in Jakarta and Manila in early September 2023. Dr. Steve Leeson, an expert in Poultry Nutrition & Production with nearly 50 years’ experience in the industry, was the distinguished keynote speaker.

Dr. Leeson had his Ph.D. in Poultry Nutrition in 1974 from the University of Nottingham. Over a span of 38 years, he was a Professor in the Department of Animal &Poultry Science at the University of Guelph, Canada. Since 2014, he has been Professor Emeritus at the same University. As an eminent author, he has more than 400 papers in refereed journals and 6 books on various aspects of Poultry Nutrition & Management. He also won the American Feed Manufacturer’s Association Nutrition Research Award (1981), the Canadian Society of Animal Science Fellowship Award (2001), and Novus Lifetime Achievement Award in Poultry Nutrition (2011).

By Dr. Inge Heinzl, Editor, EW Nutrition

Salmonellosis is third among foodborne diseases leading to death (Ferrari, 2019). More than 91,000 human cases of Salmonellosis are reported by the EU each year, generating overall costs of up to €3 billion a year (EFSA, 2023), 10-20% of which are attributed to pork consumption (Soumet, 2022). The annual costs arising from the resulting human health losses in 2010 were about €90 million (FCC Consortium, 2010). Take the example of Ireland, where a high prevalence of Salmonella in lymph nodes still shows a severe issue pre-slaughter and a big challenge for slaughterhouses to stick to the process hygiene requirements (Deane, 2022).

Several governments already have monitoring programs in place, and the farms are categorized according to the salmonella contamination of their pigs. In some countries, e.g., Denmark, an economic penalty of 2% of the carcass value must be paid if the farm has level 2 (intermediate seroprevalence) and 4-8% if the level is 3. Other countries, e.g., Germany, the UK, Ireland, or the Netherlands, use quality assurance schemes. The farmers can only sell their carcasses under this label if their farm has a certain level.

Let’s take a quick look at the genus of Salmonella

Salmonellas are rod-shaped gram-negative bacteria of the family of enterobacteria that use flagella for their movement. They were named after the American vet Daniel Elmer Salmon. The genus of Salmonella consists of two species (S. bongori and S. enterica with seven subspecies) with in total more than 2500 serovars (see Figure 1). The effects of the different serovars can range from asymptomatic carriage to severe invasive systemic disease (Gal-Mor, 2014). All Salmonella serovars generally can cause disease in humans; the rosa-marked ones already showed infections.

Figure 1: the genus of Salmonella with Salmonella serovars relevant for pigs (according to Bonardi, 2017: Salmonella in the pork production chain and its impact on human health in the European Union)

Within the group of Salmonella, some serovars can only reside in one or few species, e.g., S. enterica spp. enterica Serovar Dublin (S. Dublin) in bovines (Waldron, 2018) or S. Cholerasuis in pigs (Chiu, 2004). An infection in humans with these pathogens is often invasive and life-threatening (WHO, 2018). On the contrary, serovars like S. Typhimurium and S. Enteritidis are not host-specific and can cause disease in various species.

The serotypes S. Typhi and S. Paratyphi A, B, or C are highly adapted to humans and only for them pathogenic; they are responsible for the occurrence of typhus.

Serovars occurring in pigs and relevant for humans are, for example, S. Typhimurium (Hendriksen, 2004), S. Serotype 4,[5],12:I (Hauser et al., 2010), S. Cholerasuis (Chiu, 2004), S. Derby (Gonzalez-Santamarina, 2021), S. Agona (Brenner Michael, 2006) and S. Rissen (Elbediwi, 2021).

Transmission of Salmonella mostly happens via contaminated food

The way of transmission to humans depends on the serovar:
Human-specific and, therefore, only in humans and higher primates residing serovars S. Typhi and Paratyphi A, B, or C (typhoidal) are excreted via feces or urine. Therefore, any food or water contaminated with the feces or urine of infected people can transmit this disease (Government of South Australia, 2023). Typhoid and paratyphoid Salmonellosis occur endemic in developing countries with the lack of clean water and, therefore, inadequate hygiene (Gal-Mor, 2014).

Serovars which can cause disease in humans and animals (non-typhoidal), can be transmitted by
– animal products such as milk, eggs, meat
– contact with infected persons/animals (pigs, cows, pets, reptiles…) or
– other feces- or urine-contaminated products such as sprouts, vegetables, fruits….

Farm animals take salmonellas from their fellows, contaminated feed or water, rodents, or pests.

Symptoms of Salmonellosis can be severe

In the case of typhoid or paratyphoid Salmonellosis, the onset of illness is gradual. People can suffer from sustained high fever, unwellness, severe headache, and decreased appetite, but also from an enlarged spleen irritating the abdomen and dry cough.

A study conducted in Thailand with children suffering from enteric fever caused by the typhoid serovars S. Typhi and Paratyphi showed a sudden onset of fever and gastrointestinal issues (diarrhea), rose spots, bronchitis, and pneumonia (Thisyakorn et al., 1987)

The non-typhoid Salmonellosis is typically characterized by an acute onset of fever, nausea, abdominal pain with diarrhea, and sometimes vomiting (WHO, 2018). However, 5% of the persons – children with underlying conditions, e.g., babies, or people who have AIDS, malignancies, inflammatory bowel disease, gastrointestinal illness caused by non-typhoid serovars, and hemolytic anemia, or receiving an immunosuppressive therapy can be susceptible to bacteremia. Additionally, serovars like S. Cholerasuis or S. Dublin are apt to develop bacteremia by entering the bloodstream with little or no involvement of the gut (Chiu, 1999). In these cases, consequences can be septic arthritis, pneumonia, peritonitis, cutaneous abscess, mycotic aneurysm, and sometimes death (Chen et al., 2007; Chiu, 2004, Wang et al., 1996).

In pigs, S. Cholerasuis causes high fever, purple discolorations of the skin, and thereinafter diarrhea. The mortality rate in pigs suffering from this type of Salmonellosis is high. Barrows orally challenged with S. Typhimurium showed elevated rectal temperature by 12h, remaining elevated until the end of the study. Feed intake decreased with a peak at 48h after the challenge and remained up to 120h after the challenge. Daily gain reduced during the following two weeks after infection. A higher plasma cortisol level and a lower IGF-I level could also be noticed. All these effects indicate significant changes in the endocrine stress and the somatotropic axis, also without significant alterations in the systemic pro-inflammatory mediators (Balaji et al., 2000)

To protect humans, Salmonella in pork must be restraint

There are three main steps to keep the contamination of pork as low as possible:

1. Keeping Salmonella out of the pig farm
2. Minimizing spreading if Salmonella is already on the farm
3. Minimizing contamination in the slaughterhouse

1. How to keep Salmonella out of the pig farm?

To answer this question, we must look at how the pathogen can be transported to the farm. According to the Code of Practice for the Prevention and Control of Salmonella on Pig Farms (Ministry of Agriculture, Fisheries and Food and the Scottish Executive Rural Affairs Department), there are several possibilities to infiltrate the pathogen into the farm:

• Diseased pigs or pigs which are ill but don’t show any symptoms
• Feeding stuff or bedding contaminated with dung
• Pets, rodents, wild birds, or animals
• Farm personnel or visitors
• Equipment or vehicles

Caution with purchased animals!

To minimize/prevent the entry of Salmonella into the livestock, bought-in animals must come from reputable breeding farms with a salmonella monitoring system in place. As possible carrier animals are more likely to excrete Salmonella when stressed; they should be kept in isolation after purchasing. Additionally, the animals must go through a disinfectant foot bath before entering the farm.

Keep rodents, wild animals, and vermin in check!

Generally, the production site must be kept clean and as unattractive as possible for all these animals. Rests of feed must be removed, and dead animals and afterbirths must be promptly and carefully disposed of. A well-planned baiting and trapping policy should be in place to effectively control rodents.

Only selected people should enter the hog houses

In any case, the number of persons entering the hog house must be kept as low as possible. Farmworkers should be trained in the principles of hygiene. They should wear adequate clothing (waterproof boots and protective overalls) that can be easily cleaned/laundered and disinfected. The clothes/shoes should always be used only at this site. Thorough hand washing and the disinfection of the boots when entering and leaving the pig unit are a must.

If visits are necessary, the visitors should take the same measures as the farm workers. And, of course, they should not have had contact with another pig farm during the last 48 hours.

Keep pens, farm equipment, and vehicles clean!

Farm equipment should not be shared with other farms. If this cannot be avoided, it must be cleaned and disinfected before re-entering the farm. Also, the vehicles for the transport of the animals must be cleaned and disinfected as soon as possible after usage, as contaminated transporters always pose the risk of infection.

Feed should be Salmonella-free!

To get high feed quality, the feed should be purchased from feed mills/sources with a well-functioning bacterial control to guarantee the absence of Salmonella. It is essential that birds, domestic and wild animals cannot enter the feed stores.
It is also advised to keep dry feed dry as possibly contaminating Salmonella can multiply in such humid conditions. Additionally, all feed bins and delivery pipes for dry and wet feed must be consciously cleaned, and the damp feed pipes also disinfected.
The change from pellets to mash could be helpful as the pellets facilitate Salmonella colonization by stimulating the secretion of mucins (Hedemann et al., 2005).

For sanitation of the feed, we offer organic acids (Acidomix product range) or mixtures of organic acids and formaldehyde in countries where formaldehyde products are allowed (Formycine) to decrease the pathogenic load of the feed materials. In vitro trials show the effectiveness of the products:

For the in vitro trial with Formycine, autoclaved feed samples were inoculated with Salmonella enteritidis serovar Typhimurium DSM 19587 strain to reach a Salmonella contamination of 10⁶ CFU/g of feed. After incubating at room temperature for three hours, Formycine Liquido was added to the contaminated feed samples at 0, 500, 1000, and 2000 ppm. The control and inoculated feed samples were further incubated at room temperature, and Salmonella counts (CFU/g) were carried out at 24, 48, 72 hours and on day 15. The limit of Salmonella detection was set at 100 CFU/g (10²). Results are shown in figure 2.

Fig. 2: Effect of treatment time and different inclusion levels of Formycine Liquido on the Salmonella count in feed

As important as uncontaminated feed is clean water for drinking. It can be achieved by taking the water from a main or a bacteriologically controlled water borehole. Regular cleaning/disinfection of the tanks, pipes, and drinkers is essential.

Bedding should be Salmonella-free

Straw material containing feces of other animals (rodents, pets) always carries the risk of Salmonella contamination. Also, wet or moldy bedding is not recommended because it is an additional challenge for the animal. To optimize the quality of bedding, the straw should be bought from reliable and as few as possible sources. The material must be stored dry and as far as practicable from the pig buildings (Ministry of Agriculture, Fisheries and Food & Scottish Executive Rural Affairs Department, 2000).

Vaccination is a beneficial measure

For the control of Salmonella in swine herds, vaccination is an effective tool. De Ridder et al. (2013) showed that an attenuated vaccine reduced the transmission of Salmonella Typhimurium in pigs. The vaccination with an attenuated S. Typhimurium strain, followed by a booster vaccination with inactivated S. Cholerasuis, showed better effects than an inactivated S. Cholerasuis vaccine alone (Alborali et al., 2017). Bearson et al. (2017) could delimitate transmission through less shedding and protect the animals against systemic disease.
To achieve the best effects, the producer must understand the diversity of Salmonella serovars to choose the most promising vaccination strategy (FSIS, 2023).

2. How to minimize the spreading of Salmonella on the farm?

If there are already cases of Salmonella on the farm, infected animals must be separated from the rest of the herd. Small batch sizes are beneficial, as well as not mixing different litters after weaning. If feasible, separate units for different production phases with an all-in/all-out system could break the reinfection cycle and help reduce Salmonella contamination on the farm. And also in this case, vaccination is helpful.

Salmonella doesn’t like acid conditions

An effective tool is acidifying the feed with organic acids, as Salmonella doesn’t like acid conditions. A trial was conducted with Acidomix AFG and Acidomix AFL to show their effects against Salmonella. For the test, 10⁵ CFU/g of Salmonella enterica ser. Typhimurium was added to feed containing 1000 ppm, 2000 ppm, and 3000 ppm of Acidomix AFG or AFL. The stomach and intestine were simulated in vitro by adjusting the pH with HCl and NaHCO3 as follows:
Stomach              2.8
Intestine              6.8-7.0

After the respective incubation, the microorganisms were recovered from feed and plated on an appropriate medium for CFU counting. The results are shown in figures 3 and 4.

Figures 3 + 4: Effects of different concentrations of Acidomix AFG and Acidomix AFL against Salmonella enterica ser. Typhimurium in feed

Phytomolecules can support pigs against Salmonella

Plant compounds or phytomolecules can also be used against Salmonella in pigs. Some examples of phytomolecules to be used are Piperine, Allicin, Eugenol, and Carvacrol. Eugenol, e.g., increases the permeability of the Salmonella membrane, disrupts the cytoplasmic membrane, and inhibits the production of bacterial virulence factors (Keita et al., 2022; Mak et al., 2019). Thymol and Carvacrol interact with the cell membrane by H bonding, also resulting in a higher permeability.

An already published in vitro trial conducted with our product Ventar D also showed excellent effects against Salmonella while sparing the beneficial gut flora. A further trial once more demonstrated the susceptibility of Salmonella to Ventar D. It showed that Ventar D controls Salmonella by suppressing their motility and, at higher concentrations, inactivating the cells (see figures 5 + 6):

Figure 5: S. enterica motility test: on the left side – control; on the right side – motility medium containing.750 µg/mL of Ventar

Fig 6 . Disk diffusion assay employing S. enterica. upper left side – disk containing 10 µL of Ventar; upper right – 5 µL; lower left – control; lower right – 1µL.

In addition to the direct Salmonella-reducing effect, essential oils / secondary plant compounds / phytomolecules improve digestive enzyme activity and digestion, leading to increased nutrient absorption and better feed conversion (Windisch et al., 2008).

3. How can the farmer keep Salmonella contamination low in the slaughterhouse?

In general, the slaughterhouse personnel is responsible for adequate hygiene management to prevent contamination of carcasses and meat. However, also the farmer can make his contribution to maintain the risk of contamination in the slaughterhouse as low as possible. A study by Vieira-Pinto (2006) revealed that one Salmonella-positive pig can contaminate several other carcasses.

According to a trial conducted by Hurd et al. (2002), infection and, therefore, “contamination” of other pigs can rapidly occur, meaning that cross-contamination is a topic during transport to the slaughterhouse and in the lairages when the pigs come together with animals from other farms. The stress to which the pigs are exposed influences physiological and biochemical processes. The microbiome and animal’s immunity are affected, leading to higher excretion of Salmonella during transport and in the lairages. So, the animals should not be stressed during loading and unloading or transportation. The trailer poses a further risk of infection if it was not cleaned and disinfected before. So, reliable people who treat the animals well and keep their trailers clean should be chosen for transportation.

Pig producers are obliged to keep Salmonella in check – phytomolecules can help

At least in the EU, pig producers have the big duty to keep Salmonella low in their herds; otherwise, they will have financial losses. They are not only responsible for their farm, but also the slaughterhouses count on them. Besides the standard strict hygiene management and vaccination, farmers can use products provided by the industry to sanitize feed but also to support their animals directly with phytomolecules acting against pathogens and supporting gut health.

All these measures together should be a solution to the immense challenge of Salmonella, to protect people and prevent economic losses.

References:

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Vieira-Pinto, M, R Tenreiro, and C Martins. “Unveiling Contamination Sources and Dissemination Routes of Salmonella Sp. in Pigs at a Portuguese Slaughterhouse through Macrorestriction Profiling by Pulsed-Field Gel Electrophoresis.” International Journal of Food Microbiology 110, no. 1 (2006): 77–84. https://doi.org/10.1016/j.ijfoodmicro.2006.01.046.

Waldron, P. “Keeping Cows and Humans Safe from Salmonella Dublin.” Cornell University College of Veterinary Medicine, December 25, 2018. https://www.vet.cornell.edu/news/20181218/keeping-cows-and-humans-safe-salmonella-dublin.

Wang, J.-H., Y.-C. Liu, M.-Y. Yen, J.-H. Wang, Y.-S. Chen, S.-R. Wann, and D.-L. Cheng. “Mycotic Aneurysm Due to Non-Typhi Salmonella: Report of 16 Cases.” Clinical Infectious Diseases 23, no. 4 (1996): 743–47. https://doi.org/10.1093/clinids/23.4.743.

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By Dr Merideth Parke BVSc, Regional Technical Manager Swine, EW Nutrition

We care for our animals, and antibiotics are a crucial component in the management of disease due to susceptible pathogens, supporting animal health and welfare.  However, the administration of antibiotics in pig farming has become a common practice to prevent bacterial infections, reduce economic losses, and increase productivity.

All antibiotic applications have collateral consequences of significance, bringing a deeper consideration to their non-essential application. This article aims to challenge the choice to administer antibiotics by exploring the broader impact that antibiotics have on animal and human health, economies, and the environment.

Antibiotics disrupt microbial communities

Antibiotics do not specifically target pathogenic bacteria. By impacting beneficial microorganisms, they disrupt the natural balance of microbial communities within animals. They reduce the microbiota diversity and abundance of all susceptible bacteria – beneficial and pathogenic ones… many of which play crucial roles in digestion, brain function, the immune system, and respiratory and overall health. Resulting microbiota imbalances may present themselves in animals showing health performance changes associated with non-target systems, including the nasal, respiratory, or gut microbiome ^{7, 8, 14}. The gut-respiratory microbiome axis is well-established in mammals. Gut microbiota health, diversity, and nutrient supply directly impact respiratory health and function¹³. In pigs specifically, the modulation of the gut microbiome is being considered as an additional tool in the control of respiratory diseases such as PRRS due to the link between the digestion of nutrients, systemic immunity, and response to pulmonary infections¹¹.

The collateral effect of antibiotic administration disrupting not only the microbial communities throughout the animal but also linked body systems needs to be considered significant in the context of optimal animal health, welfare, and productivity.

Antibiotic use can lead to the release of toxins

The consideration of the pathogenesis of individual bacteria is critical to mitigate potential for direct collateral effects associated with antibiotic administration. For example, in cases of toxin producing bacteria, when animals are medicated either orally or parenterally, mortality may increase due to the associated release of toxins when large numbers of toxin producing bacteria are killed quickly².

Modulation of the brain function can be critical

Numerous animal studies have investigated the modulatory role of intestinal microbes on the gut-brain axis. One identified mechanism seen with antibiotic-induced changes in fecal microbiota is the decreased concentrations of hypothalamic neurotransmitter precursors, 5-hydroxytryptamine (serotonin), and dopamine⁵. Neurotransmitters are essential for communication between the nerve cells. Animals with oral antibiotic-induced microbiota depletion have been shown to experience changes in brain function, such as spatial memory deficits and depressive-like behaviors.

Processing of waste materials can be impacted

Anaerobic treatment technology is well accepted as a feasible management process for swine farm wastewater due to its relatively low cost with the benefit of bioenergy production. Additionally, the much smaller volume of sludge remaining after anaerobic processing further eases the safe disposal and decreases the risk associated with the disposal of swine waste containing residual antibiotics⁴.

The excretion of antibiotics in animal waste, and the resulting presence of antibiotics in wastewater, can impact the success of anaerobic treatment technologies, which already could be demonstrated by several studies ^{6, 11}. The degree to which antibiotics affect this process will vary by type, combination, and concentration. Furthermore, the presence of antibiotics within the anaerobic system may result in a population shift towards less sensitive microbes or the development of strains with antibiotic-resistant genes^{1, 12}.

Antibiotics can be transferred to the human food chain

Regulatory authorities specify detailed withdrawal periods after antibiotic treatment. However, residues of antibiotics and their metabolites may persist in animal tissues, such as meat and milk, even after this period. These residues can enter the human food chain if not adequately monitored and controlled.

Prolonged exposure to low levels of antibiotics through the consumption of animal products may contribute to the emergence of antibiotic-resistant bacteria in humans, posing a significant public health risk.

Contamination of the environment

As mentioned, the administration of antibiotics to livestock can result in the release of these compounds into the environment. Antibiotics can enter the soil, waterways, and surrounding ecosystems through excretions from treated animals, inappropriate disposal of manure, and runoff from agricultural fields. Once in the environment, antibiotics can contribute to the selection and spread of antibiotic-resistant bacteria in natural bacterial communities. This contamination poses a potential risk to wildlife, including birds, fish, and other aquatic organisms, as well as the broader ecological balance of affected ecosystems.

Every use of antibiotics can create resistance

One of the widely researched concerns associated with antibiotic use in livestock is the development of antibiotic resistance. The development of AMR does not require prolonged antibiotic use and, along with other collateral effects, also occurs when antibiotics are used within recommended therapeutic or preventive applications.

Gene mutations can supply bacteria with abilities that make them resistant to certain antibiotics (e.g., a mechanism to destroy or discharge the antibiotic). This resistance can be transferred to other microorganisms, as seen with the effect of carbadox on Escherichia coli⁵ and Salmonella enterica² and the carbadox and metronidazole effect on Brachyspira hyodysenteriae¹⁵. Additionally, there is an indication that the zinc resistance of Staphylococcus of animal origin is associated with the methicillin resistance coming from humans³.

Consequently, the effectiveness of antibiotics in treating infections in target animals becomes compromised, and the risk of exposure to resistant pathogens for in-contact animals and across species increases, including humans.

Alternative solutions are available

To successfully minimize the collateral effects of antibiotic administration in livestock, a unified strategy with support from all stakeholders in the production system is essential. The European Innovation Partnership – Agriculture⁹ concisely summarizes such a process as requiring…

1. Changing human mindsets and habits: this is the first and defining step to successful antimicrobial reduction
2. Improving pig health and welfare: Prevention of disease with optimal husbandry, hygiene, biosecurity, vaccination programs, and nutritional support.
3. Effective antibiotic alternatives: for this purpose, phytomolecules, pro/pre-biotics, organic acids, and immunoglobulins are considerations.

In general, implementing responsible antibiotic stewardship practices is paramount. This includes limiting antibiotic use to the treatment of diagnosed infections with an effective antibiotic, and eliminating their use as growth promotors or for prophylactic purposes.

Keeping the balance is of crucial importance

While antibiotics play a crucial role in ensuring the health and welfare of livestock, their extensive administration in the agricultural industry has collateral effects that cannot be ignored. The development of antibiotic resistance, environmental contamination, disruption of microbial communities, and the potential transfer of antibiotic residues to food pose significant challenges.

Adopting responsible antibiotic stewardship practices, including veterinary oversight, disease prevention programs, optimal animal husbandry practices, and alternatives to antibiotics, can strike a balance between animal health, efficient productive performance, and environmental and human health concerns.

The collaboration of stakeholders, including farmers, veterinarians, policymakers, industry and consumers, is essential in implementing and supporting these measures to create a sustainable and resilient livestock industry.

References

1. Angenent, Largus T., Margit Mau, Usha George, James A. Zahn, and Lutgarde Raskin. “Effect of the Presence of the Antimicrobial Tylosin in Swine Waste on Anaerobic Treatment.” Water Research 42, no. 10–11 (2008): 2377–84. https://doi.org/10.1016/j.watres.2008.01.005.
2. Bearson, Bradley L., Heather K. Allen, Brian W. Brunelle, In Soo Lee, Sherwood R. Casjens, and Thaddeus B. Stanton. “The Agricultural Antibiotic Carbadox Induces Phage-Mediated Gene Transfer in Salmonella.” Frontiers in Microbiology 5 (2014). https://doi.org/10.3389/fmicb.2014.00052.
3. Cavaco, Lina M., Henrik Hasman, Frank M. Aarestrup, Members of MRSA-CG:, Jaap A. Wagenaar, Haitske Graveland, Kees Veldman, et al. “Zinc Resistance of Staphylococcus Aureus of Animal Origin Is Strongly Associated with Methicillin Resistance.” Veterinary Microbiology 150, no. 3–4 (2011): 344–48. https://doi.org/10.1016/j.vetmic.2011.02.014.
4. Cheng, D.L., H.H. Ngo, W.S. Guo, S.W. Chang, D.D. Nguyen, S. Mathava Kumar, B. Du, Q. Wei, and D. Wei. “Problematic Effects of Antibiotics on Anaerobic Treatment of Swine Wastewater.” Bioresource Technology 263 (2018): 642–53. https://doi.org/10.1016/j.biortech.2018.05.010.
5. Köhler, Bernd, Helge Karch, and Herbert Schmidt. “Antibacterials That Are Used as Growth Promoters in Animal Husbandry Can Affect the Release of Shiga-Toxin-2-Converting Bacteriophages and Shiga Toxin 2 from Escherichia Coli Strains.” Microbiology 146, no. 5 (2000): 1085–90. https://doi.org/10.1099/00221287-146-5-1085.
6. Loftin, Keith A., Cynthia Henny, Craig D. Adams, Rao Surampali, and Melanie R. Mormile. “Inhibition of Microbial Metabolism in Anaerobic Lagoons by Selected Sulfonamides, Tetracyclines, Lincomycin, and Tylosin Tartrate.” Environmental Toxicology and Chemistry 24, no. 4 (2005): 782–88. https://doi.org/10.1897/04-093r.1.
7. Looft, Torey, Heather K Allen, Brandi L Cantarel, Uri Y Levine, Darrell O Bayles, David P Alt, Bernard Henrissat, and Thaddeus B Stanton. “Bacteria, Phages and Pigs: The Effects of in-Feed Antibiotics on the Microbiome at Different Gut Locations.” The ISME Journal 8, no. 8 (2014a): 1566–76. https://doi.org/10.1038/ismej.2014.12.
8. Looft, Torey, Heather K. Allen, Thomas A. Casey, David P. Alt, and Thaddeus B. Stanton. “Carbadox Has Both Temporary and Lasting Effects on the Swine Gut Microbiota.” Frontiers in Microbiology 5 (2014b). https://doi.org/10.3389/fmicb.2014.00276.
9. Nasralla, Meisoon. “EIP-Agri Concept.” EIP-AGRI – European Commission, September 11, 2017. https://ec.europa.eu/eip/agriculture/en/eip-agri-concept.html.
10. Niederwerder, Megan C. “Role of the Microbiome in Swine Respiratory Disease.” Veterinary Microbiology 209 (2017): 97–106. https://doi.org/10.1016/j.vetmic.2017.02.017.
11. Poels, J., P. Van Assche, and W. Verstraete. “Effects of Disinfectants and Antibiotics on the Anaerobic Digestion of Piggery Waste.” Agricultural Wastes 9, no. 4 (1984): 239–47. https://doi.org/10.1016/0141-4607(84)90083-0.
12. Shimada, Toshio, Julie L. Zilles, Eberhard Morgenroth, and Lutgarde Raskin. “Inhibitory Effects of the Macrolide Antimicrobial Tylosin on Anaerobic Treatment.” Biotechnology and Bioengineering 101, no. 1 (2008): 73–82. https://doi.org/10.1002/bit.21864.
13. Sikder, Md. Al, Ridwan B. Rashid, Tufael Ahmed, Ismail Sebina, Daniel R. Howard, Md. Ashik Ullah, Muhammed Mahfuzur Rahman, et al. “Maternal Diet Modulates the Infant Microbiome and Intestinal Flt3l Necessary for Dendritic Cell Development and Immunity to Respiratory Infection.” Immunity 56, no. 5 (May 9, 2023): 1098–1114. https://doi.org/10.1016/j.immuni.2023.03.002.
14. Slifierz, Mackenzie Jonathan. “The Effects of Zinc Therapy on the Co-Selection of Methicillin-Resistance in Livestock-Associated Staphylococcus Aureus and the Bacterial Ecology of the Porcine Microbiota,” 2016.
15. Stanton, Thaddeus B., Samuel B. Humphrey, Vijay K. Sharma, and Richard L. Zuerner. “Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira Hyodysenteriae” Applied and Environmental Microbiology 74, no. 10 (2008): 2950–56. https://doi.org/10.1128/aem.00189-08.
16. Toledo Castillo, Manuel, Rocío García Espejo, Alejandro Martínez Molina, María Elena  Goyena Salgado, José Manuel Pinto, Ángela Gallardo Marín “Clinical Case: Edema Disease – the More I Medicate, the More Pigs Die!” $this->url_servidor, October 15, 2021. https://www.pig333.com/articles/edema-disease-the-more-i-medicate-the-more-pigs-die_17660/.

By Madalina Diaconu, Product Manager Pretect D, EW Nutrition and

With costs of over 14 billion USD per year (Blake, 2020), coccidiosis is one of the most devastating enteric challenges in the poultry industry. With regard to costs, subclinical forms of coccidiosis account for the majority of production losses, as damage to intestinal cells results in lower body weight, higher feed conversion rates, lack of flock uniformity, and failures in skin pigmentation. This challenge can only be tackled, if we understand the basics of coccidiosis control in poultry and what options producers have to manage coccidiosis risks.

Current strategies show weak points

Good farm management, litter management, and coccidiosis control programs such as shuttle and rotation programs form the basis for preventing clinical coccidiosis. More successful strategies include disease monitoring, strategic use of coccidiostats, and increasingly coccidiosis vaccines. However, the intrinsic properties of coccidia make these parasites often frustrating to control. Acquired resistance to available coccidiostats is the most difficult and challenging factor to overcome.

Optimally, coccidiosis control programs are developed based on the farm history and the severity of infection. The coccidiostats traditionally used were chemicals and ionophores, with ionophores being polyether antibiotics. To prevent the development of resistance, the coccidiostats were used in shuttle or rotation programs, at which in the rotation program, the anticoccidial changes from flock to flock, and in the shuttle program within one production cycle (Chapman, 1997).

The control strategies, however, are not 100% effective. The reason for that is a lack of diversity in available drug molecules and the overuse of some molecules within programs. An additional lack of sufficient coccidiosis monitoring and rigorous financial optimization often leads to cost-saving but only marginally effective solutions. At first glance, they seem effective, but in reality, they promote resistance, the development of subclinical coccidiosis, expressed in a worsened feed conversion rate, and possibly also clinical coccidiosis.

Market requests and regulations drive coccidiosis control strategies

Changing coccidiosis control strategies has two main drivers: the global interest in mitigating antimicrobial resistance and the consumer’s demand for antibiotic-free meat production.

Authorities have left ionophores untouched

Already in the late 1990s, due to the fear of growing antimicrobial resistance, the EU withdrew the authorization for Avoparcin, Bacitracin zinc, Spiramycin, Virginiamycin, and Tylosin phosphate, typical growth promoters, to “help decrease resistance to antibiotics used in medical therapy”. However, ionophores, being also antibiotics, were left untouched: The regulation (EC) No 1831/2003 [13]of the European Parliament and the Council of 22 September 2003 clearly distinguished between coccidiostats and antibiotic growth promoters. Unlike the antibiotic growth promoters, whose primary action site is the gut microflora, coccidiostats only have a secondary and residual activity against the gut microflora. Furthermore, the Commission declared in 2022 that the use of coccidiostats would not presently be ruled out “even if of antibiotic origin” (MEMO/02/66, 2022) as “hygienic precautions and adaptive husbandry measures are not sufficient to keep poultry free of coccidiosis” and that “modern poultry husbandry is currently only practicable if coccidiosis can be prevented by inhibiting or killing parasites during their development”. In other words, the Commission acknowledged that ionophores were only still authorized because it believed there were no other means of controlling coccidiosis in profitable poultry production.

Consumer trends drove research on natural solutions

Due to consumers’ demand for antibiotic-reduced or, even better, antibiotic-free meat production, intensified industrial research to fight coccidiosis with natural solutions has shown success. Knowledge, research, and technological developments are now at the stage of offering solutions that can be an effective part of the coccidia control program and open up opportunities to make poultry production even more sustainable by reducing drug dependency.

Producers from other countries have already reacted. Different from the handling of ionophores regime in the EU, where they are allowed as feed additives, in the United States, coccidiostats belonging to the polyether-ionophore class are not permitted in NAE (No Antibiotics Ever) and RWE (Raised Without Antibiotics) programs. Instead of using ionophores, coccidiosis is controlled with a veterinary-led combination of live vaccines, synthetic compounds, phytomolecules, and farm management. This approach can be successful, as demonstrated by the fact that over 50% of broiler meat production in the US is NAE. Another example is Australia, where the two leading retail store chains also exclude chemical coccidiostats from broiler production. In certain European countries, e.g., Norway, the focus is increasingly on banning ionophores.

The transition to natural solutions needs knowledge and finesse

In the beginning, the transition from conventional to NAE production can be difficult. There is the possibility to leave out the ionophores and manage the control program only with chemicals of different modes of action. More effective, however, is a combination of vaccination and chemicals (bio-shuttle program) or the combination of phytomolecules with vaccination and/or chemicals (Gaydos, 2022).

Coccidiosis vaccination essentials

When it is decided that natural solutions shall be used to control coccidiosis, some things about vaccination must be known:

1. There are different strains of vaccines, natural ones selected from the field and attenuated strains. The formers show medium pathogenicity and enable a controlled infection of the flock. The latter, being early mature lower pathogenicity strains, usually cause only low or no post-vaccinal reactions.
2. A coccidiosis program that includes vaccination should cover the period from the hatchery till the end of the production cycle. Perfect application of the vaccines and effective recirculation of vaccine strains amongst the broilers are only two examples of preconditions that must be fulfilled for striking success and, therefore, early and homogenous immunity of the flock.
3. Perfect handling of the vaccines is of vital importance. For that purpose, the personnel conducting the vaccinations in the hatchery or on the farms must be trained. In some situations, consistent high-quality application at the farm has shown to be challenging. As a result, interest in vaccine application at the hatchery is growing.

Phytochemicals are a perfect tool to complement coccidiosis control programs

As the availability of vaccines is limited and the application costs are relatively high, the industry has been researching supportive measures or products and discovered phytochemicals as the best choice. Effective phytochemical substances have antimicrobial and antiparasitic properties and enhance protective immunity in poultry infected by coccidiosis. They can be used in rotation with vaccination, to curtail vaccination reactions of (non-attenuated) wild strain vaccines, or in combination with chemical coccidiostats in a shuttle program.

In a recent review paper (El-Shall et al., 2022), natural herbal products and their extracts have been described to effectively reduce oocyst output by inhibiting Eimeria species’ invasion, replication, and development in chicken gut tissues. Phenolic compounds in herbal extracts cause coccidia cell death and lower oocyst counts. Additionally, herbal additives offer benefits such as reducing intestinal lipid peroxidation, facilitating epithelial repair, and decreasing Eimeria-induced intestinal permeability.

Various phytochemical remedies are shown in this simplified adaptation of a table from El-Shall et al. (2022), indicating the effects exerted on poultry in connection to coccidia infection.

Table 1: Bioactive compounds and their anticoccidial effect exerted in poultry

Consumers vote for natural – phytochemicals are the solution

Due to still rising antimicrobial resistance, consumers push for meat production without antimicrobial usage. Phytomolecules, as a natural solution, create opportunities to make poultry production more sustainable by reducing dependency on harmful drugs. With their advent, there is hope that antibiotic resistance can be held in check without affecting the profitability of poultry farming.

By Lea Poppe, Regional Technical Manager On-Farm Solutions Europe, and Dr. Inge Heinzl, Editor

One of the ten global public health threats is antimicrobial resistance (AMR). Jim O’Neill predicted 10 million people dying from AMR annually by 2050 (O’Neill, 2016). The following article will show the causes of antimicrobial resistance and how antibodies from the egg could help mitigate the problem of AMR.

Global problem of AMR results from the incorrect use of antimicrobials

Antimicrobial substances are used to prevent and cure diseases in humans, animals, and plants and include antibiotics, antivirals, antiparasitics, and antifungals. The use of these medicines does not always happen consciously, partially due to ignorance and partially for economic reasons.

There are various possibilities for the wrong therapy

1. The use of antibiotics against diseases that household remedies could cure. A recently published German study (Merle et al., 2023) confirmed the linear relationship between treatment frequency and resistant scores in calves younger than eight months.
2. The use of antibiotics against viral diseases: antibiotics only act against bacteria and not against viruses. Flu, e.g., is caused by a virus, but doctors often prescribe an antibiotic.
3. Using broad-spectrum antibiotics instead of determining an antibiogram and applying a specific antibiotic.
4. A too-long treatment with antimicrobials so that the microorganisms have the time to adapt. For a long time, the only mistake you could make was to stop the antibiotic therapy too early. Today, the motto is “as short as possible”.

Let’s take the example of neonatal calf diarrhea, one of the most common diseases with a high economic impact. Calf diarrhea can be caused by a wide range of bacteria, viruses, or parasites. This infectious form can be a complication of non-infectious diarrhea caused by dietary, psychological, and environmental stress (Uetake, 2012). The pathogens causing diarrhea in calves can vary with the region. In Switzerland and the UK, e.g., rotaviruses and cryptosporidia are the most common pathogens, whereas, in Germany, E. coli is also one of the leading causes. To minimize the occurrence of AMR, it is always crucial to know which pathogen is behind the disease.

Prophylactic use of antibiotics is still a problem

1. The use of low doses of antibiotics to promote growth. This use has been banned in the EU now for 17 years now, but in other parts of the world, it is still common practice. Especially in countries with low hygienic standards, antibiotics show high efficacy.
2. The preventive use of antibiotics to help, e.g., piglets overcome the critical step of weaning or to support purchased animals for the first time in their new environment. Antibiotics reduce pathogenic pressure, decrease the incidence of diarrhea, and ensure the maintenance of growth.
3. Within the scope of prophylactic use of antimicrobials, also group treatment must be mentioned. In veal calves, group treatments are far more common than individual treatments (97.9% of all treatments), as reported in a study documenting medication in veal calf production in Belgium and the Netherlands. Treatment indications were respiratory diseases (53%), arrival prophylaxis (13%), and diarrhea (12%). On top, the study found that nearly half of the antimicrobial group treatment was underdosed (43.7%), and a large part (37.1%) was overdosed.

However, in several countries, consumers request reduced or even no usage of antibiotics (“No Antibiotics Ever” – NAE), and animal producers must react.

Today’s mobility enables the spreading of AMR worldwide

Bacteria, viruses, parasites, and fungi that no longer respond to antimicrobial therapy are classified as resistant. The drugs become ineffective and, therefore, the treatment of disease inefficient or even impossible. All the different usages mentioned before offer the possibility that resistant bacteria/microorganisms will occur and proliferate. Due to global trade and the mobility of people, drug-resistant pathogens are spreading rapidly throughout the world, and common diseases cannot be treated anymore with existing antimicrobial medicines like antibiotics. Standard surgeries can become a risk, and, in the worst case, humans die from diseases once considered treatable. If new antibiotics are developed, their long-term efficacy again depends on their correct and limited use.

Different approaches are taken to fight AMR

There have already been different approaches to fighting AMR. As examples, the annually published MARAN Report compiled in the Netherlands, the EU ban on antibiotic growth promoters in 2006, “No antibiotics ever (NAE) programs” in the US, or the annually published “Antimicrobial resistance surveillance in Europe” can be mentioned. One of the latest approaches is an advisory “One Health High-Level Expert Panel” (OHHLEP) founded by the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Program (UNEP), and the World Health Organization (WHO) in May 2021. As AMR has many causes and, consequently, many players are involved in its reduction, the OHHLEP wants to improve communication and collaboration between all sectors and stakeholders. The goal is to design and implement programs, policies, legislations, and research to improve human, animal, and environmental health, which are closely linked. Approaches like those mentioned help reduce the spread of resistant pathogens and, with this, remain able to treat diseases in humans, animals, and plants.

On top of the pure health benefits, reducing AMR improves food security and safety and contributes to achieving the Sustainable Development Goals (e.g., zero hunger, good health and well-being, and clean water).

Prevention is better than treatment

Young animals like calves, lambs, and piglets do not receive immunological equipment in the womb and need a passive immune transfer by maternal colostrum. Accordingly, optimal colostrum management is the first way to protect newborn animals from infection, confirmed by the general discussion on the Failure of Passive Transfer: various studies suggest that calves with poor immunoglobulin supply suffer from diarrhea more frequently than calves with adequate supply.

Especially during the immunological gap when the maternal immunoglobulins are decreasing and the own immunocompetence is still not fully developed, it is crucial to have a look at housing, stress triggers, biosecurity, and the diet to reduce the risk of infectious diseases and the need for treatments.

Immunoglobulins from eggs additionally support young animals

Also, if newborn animals receive enough colostrum in time and if everything goes optimally, the animals suffer from two immunity gaps: the first one occurs just after birth before the first intake of colostrum, and the second one occurs when the maternal antibodies decrease, and the immune system of the young animal is still not developed completely. These immunity gaps raise the question of whether something else can be done to support newborns during their first days of life.

The answer was provided by Felix Klemperer (1893), a German internist researching immunity. He found that hens coming in contact with pathogens produce antibodies against these agents and transfer them to the egg. It is unimportant if the pathogens are relevant for chickens or other animals. In the egg, the immunoglobulins usually serve as an immune starter kit for the chick.

Technology enables us today to produce a high-value product based on egg powder containing natural egg immunoglobulins (IgY – immunoglobulins from the yolk). These egg antibodies mainly act in the gut. There, they recognize and tie up, for example, diarrhea-causing pathogens and, in this way, render them ineffective.

The efficacy of egg antibodies was demonstrated in different studies (Kellner et al., 1994; Erhard et al., 1996; Ikemori et al., 1997; Yokoyama et al., 1992; Marquart, 1999; Yokoyama et al., 1997) for piglets and calves.

Trial proves high efficacy of egg immunoglobulins in piglets

One trial conducted in Germany showed promising results concerning the reduction of mortality in the farrowing unit. For the trial, 96 sows and their litters were divided into three groups with 32 sows each. Two of the groups orally received a product containing egg immunoglobulins, the EP -1 + 3 group on days 1 and 3 and the EP – 1 + 2 + 3 group on the first three days. The third group served as a control. Regardless of the frequency of application, the egg powder product was very supportive and significantly reduced mortality compared to the control group. The measure resulted in 2 additionally weaned piglets than in the control group.

Egg immunoglobulins support young dairy calves

IgY-based products were also tested in calves to demonstrate their efficacy. In a field trial conducted on a Portuguese dairy farm with 12 calves per group, an IgY-containing oral application was compared to a control group without supplementation. The test product was applied on the day of birth and the two consecutive days. Key observation parameters during a two-week observation period were diarrhea incidence, onset, duration, and antibiotic treatments, the standard procedure on the trial farm in case of diarrhea. On-farm tests to check for the pathogenic cause of diarrhea were not part of the farm’s standards.

In this trial, 10 of 12 calves in the control group suffered from diarrhea, but in the trial group, only 5 calves. Total diarrhea and antibiotic treatment duration in the control group was 37 days (average 3.08 days/animal), and in the trial group, only 7 days (average 0.58 days/animal). Additionally, diarrhea in calves of the Globigen Calf Paste group started later, so the animals already had the chance to develop an at least minimally working immune system.

The supplement served as an effective tool to support calves during their first days of life and to reduce antibiotic treatments dramatically.

Conclusion

Antimicrobial reduction is one of the biggest tasks for global animal production. It must be done without impacting animal health and parameters like growth performance and general cost-efficacy. This overall demand can be supported with a holistic approach considering biosecurity, stress reduction, and nutritional support. Feed supplements such as egg immunoglobulins are commercial options showing great results and benefits in the field and making global animal production take the right direction in the future.

References upon request.

By Tingting Fan, Regional Technical Manager Poultry, EW Nutrition

Chicken coccidiosis is a common and important disease in poultry production, with an incidence of infection as high as 50-70%. The mortality rates are around 20-30% or higher in highly severe cases. In addition to losses due to mortality, producers lose money due to poor growth as well as decreased meat yield and quality. Additionally, the birds get more susceptible to secondary infections, e.g., necrotic enteritis (Moore, 2016).

The costs caused by coccidiosis in poultry are about 13 billion US $ (Blake, 2020). These costs globally divide into 1 billion costs for prophylaxis/treatment and 12 billion due to performance losses. Until now, only 5% of the prophylaxis costs have been created by natural solutions. That means that there is still a high potential to be tapped.

Natural solutions, unfortunately, are only used by a minority

For a long time, ionophores fitting the classical definition of antibiotics and chemicals were used in coccidia-fighting programs – and contributed to the development of antimicrobial resistance (Nesse et al., 2015). Nowadays, the combination with vaccination in rotation or shuttle programs has reduced this danger, but there is still potential. Meanwhile, some natural solutions are available that can be integrated into coccidiosis-fighting programs. However, producers using natural solutions are still a minority.

For thousands of years, plants have been used in human and veterinary medicine. Before the discovery of antibiotics in 1928, diseases were fought with plants. To regain the effectiveness of antibiotics, using natural solutions for prophylaxis should be once more standard, and the use of antibiotics is the treatment only for critical cases.

How does Eimeria damage broilers

The pathogenic mechanism of coccidia or Eimeria spp. is mainly the massive destruction of host intestinal cells when it reproduces, resulting in severe damage to the intestinal mucosa. On the one hand, the damaged gut wall loses its capability for effective digestion and absorption of nutrients, leading to worse feed conversion and lower weight gain.

On the other hand, this damage reduces the chicken’s immunity and paves the way for other infections, such as necrotic enteritis, and raises mortality.

Table 1:The seven most known Eimeria species in broilers and their main site of occurrence

Concerning their pathogenicity, for poultry, the Eimeria species must be ordered in the following way: E. necatrix> E. tenella > E. brunetti > E. maxima > E. acervulina > Eimeria mitis, and Eimeria praecox.

Prevention is better than treatment

Thanks to its bi-layered wall with a robust structure, the oocysts of coccidia are extremely resilient. They can survive 4 to 9 months in the litter or soil and are resistant to common disinfectants. Farm personnel and visitors are also important vectors, so good biosecurity practices can reduce the number of oocysts contaminating the premises and help prevent clinical out-brakes. Coccidiosis control in poultry should focus on “prevention” rather than “treatment”, combining biosecurity practices, feed additives, and/or vaccination.

Effective hygiene on the farm is crucial

To prevent coccidia infections, one of the most critical points is hygiene. Biosecurity practices are crucial and include cleaning and disinfection of the poultry houses and their surroundings, pest control and prevention, restriction, control, and management of the entry of personnel, visitors, vehicles, and equipment, among others.

Coccidia oocysts are ubiquitous and survive for a long time, and even effective cleaning and disinfection cannot completely remove them. After a severe outbreak, it is recommended to take drastic biosecurity measures such as flame or caustic soda disinfection to prevent further spread of the disease.

When there are birds in the house, it must be paid attention that the litter is not excessively humid. Litter moisture should be maintained around 25%; turning and replacing moist litter are the best practices to follow. For keeping the litter dry, adequate ventilation and appropriate stocking density are beneficial.

To avoid unnecessary stress and gut health issues, the birds must be fed according to their requirements with high-quality feed so that the animals build up good immunity and resilience.

Coccidiosis can be controlled with effective programs

Anticoccidial drugs were the first means of preventing and controlling coccidiosis in chickens and once achieved very good results. Since Sulfaquinoxaline was found to be effective in the 1850s, about fifty other drugs have been developed for the prevention and control of coccidiosis. Generally, the anticoccidials used for years to prevent the disease can be divided into ionophores and chemicals.

Ionophores, produced as by-products of bacterial fermentation, are technically antibiotics. The great benefits of ionophores are that they kill the parasite before it can infect the bird and thus prevent damage to the host cells. Eimeria species also take a long time to develop resistance to ionophores (Chapman, 2015). Well-established ionophores are products that contain monensin, lasalocid, salinomycin, narasin, or maduramycin; the trade names are Coban/Monensin, Avatec, Coxisstac, Monteban, and Cygro.

Chemicals, these molecules, are produced by chemical synthesis. They differ from each other and ionophores as each one has a unique mode of action against coccidia. In general, they act by interfering with one or more stages of the life cycle of Eimeria, e.g., supplying fake nutrients (Amprolium, Vit. B1) to the parasite, starving them out. The active components here are nicarbazin, amprolium, zoalene, decoquinate, clopidol, robenidine and diclazuril, and the respective trade names Nicarb, Amprol, Zoamix, Deccox, Coyden, Robenz and Clinacox. Eimeria species develop resistance to these chemical molecules; therefore, they must be used carefully and with strict planning. However, cross-resistance does not develop, making them highly valuable in rotation programs.

Vaccination against coccidiosis is accepted by many farmers as a good solution to control coccidiosis in chickens. Vaccination aims to replace resistant field strains with vaccine strains, which are sensitive to anticoccidials. Currently, commercial chicken vaccines are available in natural and attenuated strains; research to obtain safer and more efficient vaccines is also ongoing.

Non-attenuated vaccines are less expensive and make for good immunity, but as they may mildly damage the intestinal epithelium, the risk of necrotic enteritis can increase. On the contrary, attenuated strains – usually “precocious” strains with shorter reproduction cycles, cause less intestinal damage and thus have a lower risk of provoking bacterial or necrotic enteritis. The immunity is like after normal infections; however, you have a controlled epidemiology, fewer coccidiosis outbreaks, and an improved uniformity of the flock.

Phytomolecules-based natural anticoccidials saponins and tannins are natural components that can also help control coccidiosis (e.g., Pretect D, EW Nutrition GmbH). These ingredients act in different ways: the tannins improve the intestinal barrier function locally and systemically. The saponins directly impact the oocysts by preventing their growth, interacting with the cholesterol in the cell membrane (triterpenoid saponin), or hindering further sporulation and causing cell death by causing pores in the cell membrane of the parasite. Altogether, Pretect D promotes the beneficial microbial population and reduces the harmful one, improves the gut barrier function, reduces mucosal inflammation, inhibits growth and replication of Eimeria, preventing their lesions, and fosters birds’ immune response against Eimeria spp.

To prove Pretect D’s effectiveness in the reduction of coccidiosis, several trials were conducted. One of the trials was carried out in Poland with 360.000 broilers in commercial conditions. The animals were divided into ten houses, and two cycles were tested. Half of the birds served as control and received Narasin and Nicarbazin in the starter and grower I diet and salinomycin in the grower II diet. The other half also were fed Narasin and Nicarbazin in the starter and grower I diet, but Pretect D @1kg/t in grower II and 0.5kg/t in the finisher diet. The results are shown in figure 1: The application of Pretect D in the grower II and finisher diet decreased the number of oocysts in the droppings more than the application of salinomycin and, therefore, reduced the spreading of coccidiosis. In addition, the performance of the broilers receiving Pretect D was nothing short of the control’s performance showing Pretect as an optimal completion in shuttle or rotation programs (see more HERE).

Figure 1: Reduction of oocysts in the droppings by Pretect D

Managing coccidiosis without promoting antimicrobial resistance is not easy, but feasible

Coccidiosis is a challenge aggravated by our current high level of production. Tools such as ionophores, chemicals, but also vaccines, and natural products are available to fight coccidiosis. However, due to the high probability of resistance development, these tools must be used carefully and in structured programs. The phytomolecules-based product Pretect D gives the possibility to reduce antimicrobial resistance as part of programs against coccidiosis.

References upon request

By Dr. Ajay Bhoyar, Global Technical Manager Poultry, EW Nutrition

Gut health is a critical challenge in antibiotics-free (ABF) production as it plays a vital role in the overall health and well-being of animals. Antibiotics have long been used as a means of preventing and treating diseases in animals, but their overuse has led to the development of antibiotic-resistant bacteria. As a result, many farmers and producers are shifting towards antibiotics-free production methods. This shift presents a significant challenge as maintaining gut health without antibiotics can be difficult. It is, however, not impossible.

One of the main challenges in antibiotics-free production is the prevention of bacterial infections in the gut. The gut microbiome plays a crucial role in the immune system and overall health of animals. When the balance of microbes in the gut is disrupted (dysbiosis), it can lead to poor nutrient absorption which subsequently results in reduced live bird performance including feed efficiency and weight gain in broiler chicken. In the absence of antibiotics, farmers and producers must rely on other methods to maintain a healthy gut microbiome.

Antibiotic reduction – a major global trend

The trend in recent years has been for poultry producers to reduce their use of antibiotics to promote public health and improve the sustainability of their operations. This has been driven by concerns about the development of antibiotic-resistant bacteria and the potential impact on human health, as well as by consumer demand for meat produced without antibiotics. Many countries now have regulations in place that limit the use of antibiotics in food and animal production.

Challenges to antibiotics-free poultry (ABF) production

1. Disease control. Antibiotic-free poultry production requires farmers to rely on alternative methods for controlling and preventing diseases, such as stepped-up biosecurity practices. This can be more labor-intensive and costly.
2. Higher mortality rates. Without antibiotics, poultry farmers may experience higher mortality rates due to disease outbreaks and other health issues. This can lead to financial losses for the farmer and a reduced supply of poultry products for consumers.
3. Feeding challenges. Antibiotic growth promotors (AGPs) are often used in feed to promote growth and prevent intestinal disease in poultry. Without AGPs, poultry producers can find alternative ways to ensure expected production performance.
4. Increased cost. Antibiotic-free poultry production can be more expensive than conventional production methods, as farmers must invest in additional housing, equipment, labor, etc.

Phasing out AGPs will likely lead to changes in the microbial profile of the intestinal tract. It is hoped that strategies such as infectious disease prevention programs and using non-antibiotic alternatives minimize possible negative consequences of antibiotic removal on poultry flocks (Yegani and Korver, 2008).

Gut health is key to overall health

A healthy gastrointestinal system is important for poultry to achieve its maximum production potential. Gut health in poultry refers to the overall well-being and functioning of the gastrointestinal tract in birds. This includes the balance of beneficial bacteria, the integrity of the gut lining, and the ability to digest and absorb nutrients. Gut health is important for maintaining the overall health and well-being of the birds. A healthy gut helps to improve feed efficiency, nutrient absorption, and the overall immunity of the birds.

The gut is host to more than 640 different species of bacteria and 20+ different hormones. It digests and absorbs the vast majority of nutrients and makes up for nearly a quarter of body energy expenditure. It is also the largest immune organ in the body (Kraehenbuhl and Neutra, 1992). Consequently, ‘gut health’ is highly complex and encompasses the macro and micro-structural integrity of the gut, the balance of the microflora, and the status of the immune system (Chot, 2009).

Poultry immunity is mediated by the gut

The gut is a critical component of the immune system, as it is the first line of defense against pathogens that enter the body through the digestive system. Chickens have a specialized immune system in the gut, known as gut-associated lymphoid tissue (GALT), which helps to identify and respond to potential pathogens. The GALT includes Peyer’s Patches, which are clusters of immune cells located in the gut wall, as well as the gut-associated lymphocytes (GALs) that are found throughout the gut. These immune cells are responsible for recognizing and responding to pathogens that enter the gut.

The gut-mediated immune response in chickens involves several different mechanisms, including the activation of immune cells, the production of antibodies, and the release of inflammatory mediators. The GALT and GALs play a crucial role in this response by identifying and responding to pathogens, as well as activating other immune cells to help fight off the infection.

The gut microbiome also plays a critical role in gut-mediated immunity in chickens. The gut microbiome is made up of a highly varied community of microorganisms, and these microorganisms can have a significant impact on the immune response. For example, certain beneficial bacteria can help to stimulate the immune response and protect the gut from pathogens.

Overall, the gut microbiome, GALT, and GALs all work together to create an environment that is hostile to pathogens while supporting the growth and health of beneficial microorganisms.

Dysbiosis/Dysbacteriosis impacts performance

Dysbiosis is an imbalance in the gut microbiota because of an intestinal disruption. Dysbacteriosis can lead to wet litter and caking issues. Prolonged contact with the caked litter can lead to pododermatitis (feet ulceration) and hock-burn, resulting in welfare issues as well as degradation of the carcass (Bailey, 2010). Apart from these issues, the major economic impact comes from reduced growth rates, FCR, and increased veterinary treatment costs. Coccidiosis infection and other enteric diseases can be aggravated when dysbiosis is prevalent. Generally, animals with dysbiosis have high concentrations of Clostridium that generate more toxins, leading to necrotic enteritis.

Fig.1: Dysbiosis – a result of challenging animal’s microbiome. Source: Charisse Petersen and June L. Round. 2014

It is believed that both non-infectious and infectious factors can play a role in dysbacteriosis (DeGussem, 2007). Any changes in feed and feed raw materials, as well as the physical quality of feed, influence the balance of the gut microbiota. There are some risk periods during poultry production when the bird will be challenged, for example during feed change, vaccination, handling, transportation, etc. During these periods, the gut microbiota can fluctuate and, in some cases, if management is sub-optimal, dysbacteriosis can occur.

Infectious agents that potentially play a role in dysbacteriosis include mycotoxins, Eimeria spp., Clostridium perfringens, and other bacteria producing toxic metabolites.

Factors affecting gut health

The factors affecting broiler gut health can be summarized as follows:

1. Feed and water quality: The form, type, and quality of feed provided to broilers can significantly impact their gut health. Consistent availability of cool and hygienic drinking water is crucial for optimum production performance.
2. Stress: Stressful conditions, such as high environmental temperatures or poor ventilation, can lead to an imbalance in the gut microbiome and an increased risk of disease.
3. Microbial exposure: Exposure to pathogens or other harmful bacteria can disrupt the gut microbiome and lead to gut health issues.
4. Immune system: A robust immune system is important for maintaining gut health, as it helps to prevent the overgrowth of harmful bacteria and promote the growth of beneficial bacteria.
5. Sanitation: Keeping the broiler environment clean and free of pathogens is crucial for maintaining gut health, as bacteria and other pathogens can easily spread and disrupt the gut microbiome.
6. Management practices: Proper management practices, such as proper feeding and watering, and litter management can help to maintain gut health and prevent gut-related issues.

Fig. 2. Key factors affecting broilers’ gut health

Key approaches for managing gut health without antibiotics

Two key approaches for managing gut health in poultry without the use of antibiotics are outstandingly successful.

Proper nutrition and management practices

Ensuring the birds have access to clean water, high-quality feed, and a stress-free environment is crucial for ABF poultry production. A balanced diet in terms of protein, energy, and essential vitamins and minerals is essential for maintaining gut health.

The environment in which birds have kept plays a major role in maintaining gut health. Proper sanitation and ventilation, as well as the right temperature and humidity, are crucial to prevent the spread of disease and infection. There is no alternative to the strict implementation of stringent biosecurity measures to prevent the spread of disease.

Early detection and treatment of diseases can help to prevent them from becoming more serious problems affecting the profitability of ABF production. It is important to keep a close eye on birds for signs of disease, such as diarrhea, reduced water, and feed consumption.

Gut health-promoting feed additives

Another approach to maintaining gut health in antibiotics-free poultry production is using gut health-supporting feed additives. A variety of gut health-supporting feed additives including phytochemicals/essential oils, organic acids, probiotics, prebiotics, exogenous enzymes, etc. in combination or alone are used in animal production. Particularly, phytogenic feed additives (PFAs) have gained interest as cost-effective feed additives with already well-established effects on improving broiler chickens’ intestinal health.

Plant secondary metabolites and essential oils (generically called phytogenics, phytochemicals, or phytomolecules) are biologically active compounds that have recently garnered interest as feed additives in poultry production, due to their capacity to improve feed efficiency by enhancing the production of digestive secretions and nutrient absorption. This helps reduce the pathogenic load in the gut, exert antioxidant properties and decrease the microbial burden on the animal’s immune status (Abdelli et al. 2021).

Plant extracts – Essential oils (EOs) /Phytomolecules

Phytochemicals are naturally occurring compounds found in plants. Many phytomolecules have been found to have antimicrobial properties, meaning they can inhibit the growth or kill microorganisms such as bacteria, viruses, and fungi. Examples of phytomolecules with antimicrobial properties include compounds found in garlic, thyme, and tea tree oil. Essential oils (EOs) are raw plant extracts (flowers, leaves, roots, fruit, etc.) whereas phytomolecules are active ingredients of essential oils or other plant materials. A phytomolecule is clearly defined as one active compound. Essential oils (EOs) are important aromatic components of herbs and spices and are used as natural alternatives for replacing antibiotic growth promoters (AGPs) in poultry feed. The beneficial effects of EOs include appetite stimulation, improvement of enzyme secretion related to food digestion, and immune response activation (Krishan and Narang, 2014).

A wide variety of herbs and spices (thyme, oregano, cinnamon, rosemary, marjoram, yarrow, garlic, ginger, green tea, black cumin, and coriander, among others), as well as EOs (from thyme, oregano, cinnamon, garlic, anise, rosemary, citruses, clove, ginger), have been used in poultry, individually or mixed, for their potential application as AGP alternatives (Gadde et al., 2017).

Fig. 3: Phytomolecule-based feed additive outperforms AGPs with improved broiler performance (42 Days field study)

One of the primary modes of action of EOs is related to their antimicrobial effects which allow for controlling potential pathogens (Mohammadi and Kim, 2018).

Fig. 4: Effectivity of phytomolecule-based feed additive (Ventar D) against enteropathogenic bacteria (MIC value in PPM)

Phytomolecules have been shown to have anti-inflammatory properties. These compounds include flavonoids, polyphenols, carotenoids, and terpenes, among others. One of the ways in which phytomolecules exhibit anti-inflammatory effects is through their ability to inhibit the activity of pro-inflammatory enzymes and molecules. For example, polyphenols have been shown to inhibit the activity of nuclear factor-kappa B (NF-kB), a transcription factor that plays a key role in regulating inflammation.

Phytomolecules also have antioxidant properties, which can help to protect cells from damage caused by reactive oxygen species (ROS) and other reactive molecules that can contribute to inflammation. Plant extracts are also proposed to be used as antioxidants in animal feed, protecting animals from oxidative damage caused by free radicals. The presence of phenolic OH groups in thymol, carvacrol, and other plant extracts act as hydrogen donors to the peroxy radicals produced during the first step in lipid oxidation, thus retarding the hydroxyl peroxide formation (Farag et al., 1989, Djeridane et al., 2006). Thymol and carvacrol are reported to inhibit lipid peroxidation (Hashemipour et.al. 2013) and have strong antioxidant activity (Yanishlieva et al., 1999).

Overall, the anti-inflammatory effects of phytomolecules are thought to be due to a combination of their ability to inhibit the activity of pro-inflammatory enzymes and molecules, their antioxidant properties, and their ability to modulate the immune system. Plant extracts (i.e. carvacrol, cinnamaldehyde, eugenol. etc.) inhibit the production of pro-inflammatory cytokines and chemokines from endotoxin-stimulated immune cells and epithelial cells (Lang et al., 2004, Lee et al., 2005, Liu et al., 2020). It has been indicated that anti-inflammatory activities may be partially mediated by blocking the NF-κB activation pathway (Lee et al., 2005).

Fig. 5: Anti-inflammatory effect of phytomolecule-based feed additive (Ventar D) – the reduced activity of inflammatory cytokines

Proper protection of EOs/Phytomolecules is key to optimum results

Several phytogenic compounds have also been shown to be largely absorbed in the upper GIT, meaning that without proper protection, the majority would not reach the lower gut where they would exert their major functions (Abdelli et al. 2021). The benefits of supplementing the broiler diet with a mixture of encapsulated EOs were higher than the tested PFA in powdered, non-protected form (Hafeez et al. 2016). Novel delivery technologies have been developed to protect PFAs from the degradation and oxidation process during feed processing and storage, ease the handling, allow a slower release, and target the lower GIT (Starčević et al. 2014). The specific protection techniques used during the commercial production of an EO/phytomolecule blend are crucial in delivering on all the objectives with remarkable consistency.

Fig. 6: Pelleting stability of phytomolecule – based feed additive (Ventar D) at high temperature and longer conditioning time

Phytomolecule blend optimizes production performance

Removal of antibiotics in poultry production can be challenging for controlling mortality and maintaining the production performance of the birds. Phytogenic feed additives have been shown to improve production performance of chicken due to their antimicrobial, anti-inflammatory, antioxidant, and digestive properties. Possible mechanisms behind improved nutrient digestibility by phytogenic feed additives (PFAs) supplementation could be attributed to the ability of these feed additives to stimulate appetite, saliva secretion, intestinal mucus production, bile acid secretion, and activity of digestive enzymes such as trypsin and amylase as well as to positively affect the intestinal morphology (Oso et al. 2019). EOs are perceived as growth promoters in poultry diets, with strong antimicrobial and anticoccidial activities (Zahi et al., 2018). PFAs have positive effects on body weight gain and FCR in chickens (Khattak et al. 2014, Zhang et el. 2009).

Fig. 7: Phytomolecule-based feed additive improved broiler FCR and mortality in field trial

Conclusion

In conclusion, managing gut health is a significant challenge in ABF broiler production that must be addressed to achieve optimal performance and welfare of the birds. The use of antibiotics as a preventative measure in broiler production has been widely used, but with the increasing demand for antibiotic-free products, alternative methods to maintain gut health must be implemented. These include using gut health-supporting feed additives, and proper management practices such as implementing biosecurity measures, maintaining optimal environmental conditions, providing adequate space and ventilation, and reducing stress. However, it is essential to note that there is no one-size-fits-all solution for gut health management in ABF broiler production. It is important to continuously monitor and assess their flock’s gut health and make adjustments as necessary. Additionally, research and development in this field should be encouraged to identify new and innovative ways to maintain gut health in ABF broiler production.

Overall, managing gut health is a critical challenge that requires a multi-faceted approach and ongoing monitoring and management. By implementing the appropriate strategies and utilizing new technologies, poultry operators can ensure the health and well-being of their flocks while meeting the growing demand for antibiotic-free products sustainably.

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Gadde U., Kim W.H., Oh S.T., Lillehoj H.S. Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: A review. Anim. Health Res. Rev. 2017;18:26–45.

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By Dr. Inge Heinzl, Editor, EW Nutrition 

For a long time now, IgY technology has been used to provide clear benefits in diagnostics, human medicine, and animal production. To give you a deeper insight into this topic, in the following, we will show you some steps of production, the benefits, and the applications of IgY.

IgY – what is it?

A short time later, Klemperer (1892) documented that the serum antibodies were also transferred into the egg. For this purpose, he did a similar trial with hens but collected the eggs. He fed mice a solution containing the egg yolk, and afterward, he infected them with tetanus. All mice with a higher dosage of egg yolk remained healthy, the others receiving a low dosage or no egg yolk died.

IgY production is a non-invasive and highly effective process

The “usual” production of antibodies in mammals includes pain and stress-causing procedures such as immunization, bleeding, and sacrifice. The only stress factor in producing egg antibodies is the hyper-immunization with the pathogen or parts of it; the rest -collecting the eggs- is non-invasive (Ikemori et al., 1993). The European Centre for the Validation of Alternative Methods (ECVAM) ), one of Europe’s health and consumer protection institutes, strongly recommends egg immunoglobulins as an alternative to mammalian antibodies (Schade et al., 1996).

IgY production is also advantageous in terms of quantitative and qualitative output. Usually, one egg (with 15 mL of yolk) contains about 100-150 mg IgY  (Pereira et al., 2019). Assuming that a hen lays about 300 eggs per year, one bird can produce between 30 and 45 g IgY in this period. After the isolation of the IgY from the egg yolk and the extraction from the remaining proteins, a final purification step that includes chromatography could achieve IgY with >90 % purity (Morgan et al., 2021).

Hyperimmunized hens provide more effective IgY

The targeted confrontation of the animal with specific pathogens or antigens leads to the production of specific antibodies. In a field trial with piglets, Kellner et al. (1994) compared three groups of piglets suffering from diarrhea on day 1 of the test. One group received egg powder originating from hens hyperimmunized with diarrhea-causing pathogens, the second group egg powder from regular eggs, and the third didn’t receive any egg powder. The following results they achieved in one of two farms. The trial shows that, after applying egg powder with selected antibodies, the animals completely recovered within three days. In the group receiving egg powder of regular eggs, still, 9.1% suffered from severe diarrhea and in the control group without any egg powder, only 27.3 % recovered.

Figure 1: Comparison of eggs originating from regular and hyperimmunized hens

Preconditions for and benefits of industrially produced IgY

A process must meet specific requirements to be suitable for industrial production. In the case of IgY production, the crucial preconditions are that…

• hens produce antibodies also against pathogens non-specific to them
• the antibodies produced and transferred to the egg also are effective in mammals (Yokoyama et al., 1993)
• due to their phylogenetic distance from mammals, hens can produce antibodies even against structurally highly conserved proteins, which is not always possible in rabbits, guinea pigs, and goats (Gassman and Hübscher, 1992).

Industrially produced IgY can target selected pathogens, e.g., enteric bacteria or viruses, respiratory pathogens, SARS-COV-2, etc. As the antibodies act not only in birds but also in other animals, such as mammals including humans, they can be used to prevent disease or support persons/animals in the case of illness. IgY is safe for animals and humans.

Concerning the economic benefits of IgY production, it can be said that it is a cost-effective method due to the high concentration of IgY in the egg yolk and the relatively simple process of the purification of the antibodies. Additionally, feeding and handling are easier and more cost-effective for hens than for many other animals.

Not all IgY products are the same

There are different methods of IgY production. One possibility is to hyperimmunize the hens simultaneously with multiple antigens. This method seems to be convenient but does not deliver standardized products concerning the content of immunoglobulins.

The other possibility is the immunization of different groups of hens, each with one antigen (e.g., Rotavirus, Salmonella, E. coli). The content of immunoglobulins is determined, and the different egg powders are mixed. The result is an IgY product with standardized amounts of specific immunoglobulins.

Where can we use IgY?

There are different application areas for IgY or IgY products. In human medicine, egg immunoglobulins can be used against the toxin of rattlesnakes or scorpions, or Streptococcus mutans bacteria, causing dental caries (Gassmann and Hübscher, 1992) Egg immunoglobulins are important for diagnostic tests such as radioimmunoassay (RIA) and enzyme-linked immunoassay (ELISA).

A further application area is animal nutrition. Young animals, such as calves or piglets, but also young dogs or cats, are born with immature immune systems. If they, additionally, are deprived of maternal colostrum in adequate quantity and/or quality, they suffer from immunity gaps during their first weeks of life and are susceptible to pathogens in their environment.

Antibiotics have been used prophylactically for a long time to protect young animals in this critical phase. With increasing antibiotic resistance, this procedure is not allowed anymore.

Products based on egg immunoglobulins against enteric pathogens, e.g., support young animals against newborn or weaning diarrhea (e.g., Yokoyama et al., 1992; Ikemori et al., 1992; Ikemori et al., 1997, Yokoyama et al., 1998).

IgY – a fascinating technology that should be better recognized

IgY technology is an animal-friendly technology with high output. Its various applications make IgY a helpful tool for human medicine as well as animal production. To get the best results, attention must be paid to quality, meaning, amongst others the standardization of the products.

IgY is an optimal tool to help young animals such as calves and piglets cope with pathogenic challenges in early life. Consequently, IgY technology enables us to limit (preventive) antimicrobial use in critical periods of animal rearing and, therefore, reduce antimicrobial resistance.

References:

Gassmann, M., and U. Hübscher. “Use of Polyclonal Antibodies from Egg Yolk of Immunised Chickens .” ALTEX – Alternatives to animal experimentation 9, no. 1 (1992): 5–14.

Ikemori, Yutaka, Masahiko Kuroki, Robert C. Peralta, Hideaki Yokoyama, and Yoshikatsu Kodama. “Protection of Neonatal Calves against Fatal Enteric Colibacillosis by Administration of Egg Yolk Powder from Hens Immunized with K99-Piliated Enterotoxigenic Escherichia Coli.” Amer. J. Vet. Res. 53, no. 11 (1992): 2005–8. https://doi.org/PMID: 1466492.

Ikemori, Yutaka, Masashi Ohta, Kouji Umeda, Faustino C. Icatlo, Masahiko Kuroki, Hideaki Yokoyama, and Yoshikatsu Kodama. “Passive Protection of Neonatal Calves against Bovine Coronavirus-Induced Diarrhea by Administration of Egg Yolk or Colostrum Antibody Powder.” Veterinary Microbiology 58, no. 2-4 (1997): 105–11. https://doi.org/10.1016/s0378-1135(97)00144-2.

Ikemori, Yutaka, Robert C. Peralta, Masahiko Kuroki, Hideaki Yokoyama, and Yoshikatsu Kodama. “Research Note: Avidity of Chicken Yolk Antibodies to Enterotoxigenic Escherichia Coli Fimbriae.” Poultry Science 72, no. 12 (1993): 2361–65. https://doi.org/10.3382/ps.0722361.

Kellner, J., M.H. Erhard, M. Renner, and U. Lösch. “Therapeutischer Einsatz Von Spezifischen Eiantikörpern Bei Saugferkeldurchfall – Ein Feldversuch.” Tierärztliche Umschau 49, no. 1 (January 1, 1994): 31–34.

Klemperer, Felix. “Ueber Natürliche Immunität Und Ihre Verwerthung Für Die Immunisirungstherapie.” Archiv für Experimentelle Pathologie und Pharmakologie 31, no. 4-5 (1893): 356–82. https://doi.org/10.1007/bf01832882.

Pereira, E.P.V., M.F. van Tilburg, E.O.P.T. Florean, and M.I.F. Guedes. “Egg Yolk Antibodies (Igy) and Their Applications in Human and Veterinary Health: A Review.” International Immunopharmacology 73 (2019): 293–303. https://doi.org/10.1016/j.intimp.2019.05.015.

Schade, R., C. Staak, C. Hendriksen, M. Erhard, H. Hugl, G. Koch, A. Larsson, et al. “The Production of Avian (Egg Yolk) Antibodies: IgY,” 1996. https://www.researchgate.net/publication/281466059_The_production_of_avian_egg_yolk_antibodies_IgY_The_report_and_recommendations_of_ECVAM_workshop_21.

Schade, R., C. Staak, C. Hendriksen, M. Erhard, H. Hugl, G. Koch, A. Larsson, et al. “The Production of Avian (Egg Yolk) Antibodies: IgY. The Report and Recommendations of ECVAM Workshop 21.” ATLA (Alternatives to Laboratory Animals) 24 (1996): 925–34. https://doi.org/https://www.researchgate.net/publication/281466059_The_production_of_avian_egg_yolk_antibodies_IgY_The_report_and_recommendations_of_ECVAM_workshop_21.

Yokoyama, H, R C Peralta, R Diaz, S Sendo, Y Ikemori, and Y Kodama. “Passive Protective Effect of Chicken Egg Yolk Immunoglobulins against Experimental Enterotoxigenic Escherichia Coli Infection in Neonatal Piglets.” Infection and Immunity 60, no. 3 (1992): 998–1007. https://doi.org/10.1128/iai.60.3.998-1007.1992.

Yokoyama, Hideaki, Robert C. Peralta, Kouji Umeda, Tomomi Hashi, Faustino C. Icatlo, Masahiko Kuroki, Yutaka Ikemori, and Yoshikatsu Kodama. “Prevention of Fatal Salmonelosis in Neonatal Calves, Using Orally Administered Chicken Egg Yolk Salmonella-Specific Antibodies.” Amer. J. Vet. Res. 59, no. 4 (1998): 416–20. https://doi.org/PMID: 9563623.

Yokoyama, Hideaki, Robert C. Peralta, Sadako Sendo, Yutaka Ikemori, and Yoshikatsu Kodama. “Detection of Passage and Absorption of Chicken Egg Yolk Immunoglobulins in the Gastrointestinal Tract of Pigs by Use of Enzyme-Linked Immunosorbent Assay and Fluorescent Antibody Testing.” American Journal of Veterinary Research 54, no. 6 (1993): 867–72. https://doi.org/PMID: 8323054.

Zhang, Xiao-Ying, Ricardo S. Vieira-Pires, Patricia M. Morgan, Rüdiger Schade, Xiao-Ying Zhang, Rao Wu, Shikun Ge, and Álvaro Ferreira Júnior. “Immunization of Hens.” Essay. In IGY-Technology: Production and Application of Egg Yolk Antibodies. Basic Knowledge for a Successful Practice., 116–34. Cham, Switzerland: Springer Nature, 2021.

Zhang, Xiao-Ying, Ricardo S. Vieira-Pires, Patricia M. Morgan, Schade Rüdiger, Patricia M. Morgan, Marga G. Freire, Ana Paula M. Tavares, Antonysamy Michael, and Xiao-Ying Zhang. “Extraction and Purification of IgY .” Essay. In IGY-Technology: Basic Knowledge for a Successful Practice, 135–60. Cham: Springer International Publishing AG, 2021.

Zhang, Xiao-Ying, Ricardo S. Vieira-Pires, Patricia M. Morgan, Schade Rüdiger, Patricia M. Morgan, Xiao-Ying Zhang, Antonysamy Michael, Ana Paula M. Tavares, and Marga G. Freire. “Extraction and Purification of IgY (Chapter 11).” Essay. In IGY-Technology: Basic Knowledge for a Successful Practice, 135–60. Cham: Springer International Publishing AG, 2021.

Antimicrobial resistance is a natural process but this is accelerated by inappropriate prescribing of antimicrobials, poor infection control practices and the unnecessary use of antimicrobials in agriculture (Barber and Sutherland, 2017).

Antimicrobial resistance – a threat to humanity

Resistance to specific antibiotics occurs through mutations that enable the bacteria to withstand an antibiotic treatment. One mechanism is the production of enzymes degrading or altering the antibiotic, rendering them harmless. The elimination of entrances for antibiotics or the development of pumps discharging them is another possibility. A further option is the elimination of the targets the antibiotic would attack.

So-called “resistance genes” are responsible for resistance. These genes can be transferred from one bacterium to another and also from beneficial bacteria to harmful ones. When antibiotics are used, “normal” bacteria are killed; the resistant ones survive and have all possibilities to proliferate. The Dutch Government has been tracking resistant bacteria in poultry flocks for the last two decades. A clear correlation between antibiotic use and the percentage of resistance could be observed. The good thing: according to the 2020 MARAN report (De Greeff et al., 2020), by reducing the use of antibiotics, the occurrence of resistances can be pushed back.

Figure 1. Sales of antibiotics from 1999 to 2016 and the development of resistances (MARAN report, 2018)

Antibiotic use in animal production

In pig production, antibiotics are often used in stressful situations such as weaning or moving. Antibiotics decrease the pathogenic pressure in animals and help them overcome these critical periods. Disadvantage: Antibiotics do not differentiate between good and bad but between susceptible and resistant. Therefore, also the beneficial gut flora gets destroyed through antibiotic treatment, and resistance is spread.

After the ban of antibiotic growth promoters in Europe in 2006, the US has also made considerable efforts to reduce the use of antibiotics.

Is performance at risk without antibiotics?

When antibiotics are taken out of livestock production, measures in different areas must be implemented to keep performance and profitability high. Without supporting the animals by other means, they will get sick and even die in acute cases. Subclinical disease forms reduce their feed intake, and growth performance consequently decreases. According to literature, losses due to decreased average weight gain can be up to $40 per pig (Hao et al., 2014).

Goal: reducing antibiotics while maintaining performance

To support pigs, especially during the afore-mentioned critical periods, alternatives focusing on the maintenance of gut health and, therefore, also overall health must be chosen. This goal can only be achieved by balancing the intestinal flora with reducing pathogenic bacteria occurrence.

Phytomolecules are an effective solution

Phytomolecules are produced by plants to defend themselves against predators or pathogens. Farmers use the substances in animal feeds to support digestion, improve palatability, but also to reduce pathogenic pressure (Baser and Buchbauer, 2010).

In animal feeding, different application forms are available:

• As premixes containing microencapsulated phytomolecules with a slow release. This version is mixed into the feed in the feed mill and constitutes continuous long-term support for the animals. Due to microencapsulation, the active substances are released where they are needed – in the gut.
• As liquid complementary feeds for the application via the waterline. The application of the liquid form to the animals can be decided from one day to the other. It is an optimal additional tool to support the pigs in challenging situations such as weaning.

Scientific trials show: In-feed phytomolecules support performance

A trial conducted at the Federal University of Lavras (Brazil) evaluated if phytomolecules as a regular diet component can deliver the same effects on growth performance as AGPs in pig production.

For the trial, 108 castrated newborn male pigs were allocated to 3 groups (control, AGP (antibiotic growth promoters), and Activo). Pigs were weaned at 23 days of age with an average weight of 6.3 kg. They were fed a 3-phase diet (nursery, growing, and finishing). The inclusion rates of the additives (antibiotics and phytomolecules-based product – Activo) are shown in table 1.

On days 0, 1, and 2 of the experiment, the animals were challenged by applying a solution containing 10⁷ CFU of E. coli K88, producing the toxins LT, Sta, and bST. Additionally, during the two last days before the growing phase, the animals were exposed to 5h of heat stress, using infrared lamps and closed windows. The parameters weight gain, final weight, FCR, and gut flora composition in the cecum were evaluated.

Table 1. Inclusion rate of the additives in the feed
AGP: Antibiotic growth promoter; Activo: product based on phytomolecules, microencapsulated (EW Nutrition)

Results

The results of this trial are shown in figure 2.

Concerning growth performance, the group fed the phytomolecules-based product Activo showed a 4.36 kg higher final weight after 126 days than the group provided AGPs (p=0.11), resulting in a 3.28 kg higher weight gain (p=0.21) and a 13 points better feed conversion.

Figure 2. Data of growth performance including final weight, weight gain and FCR adjusted to 100kg

The evaluation of some bacteria naturally occurring in the gut flora showed that, in contrast to the antibiotic prophylaxes, Activo has no negative impact on E. coli, Lactobacillus and Bifidobacterium. However, the antibiotic group showed a slight decrease in the population of Lactobacilli (Figure 3).

Figure 3. Impact of antibiotics and phytomolecules (Activo) on the composition of the gut flora

This trial shows Activo increasing growth performance and feed conversion without any negative impact on gut flora. The addition of phytomolecules (Activo) to the feed is documented as optimal long-term support instead of antibiotic growth promoters.

Trial shows: Phytomolecules support animals in critical situations like weaning

In a trial conducted in the USA, a product containing phytomolecules and organic acids (Activo Liquid, EW Nutrition) was compared to an antibiotic for controlling bacterial diseases in US pig production (Mecadox). For the trial, a total of 360 weanling pigs, about 19 days old and weighing 5.70 kg, were divided into four groups. Each group consists of 9 pens with 10 animals per pen. All groups were fed a 3-phase diet.

To the different trial groups, the following products were added (table 2):

These performance parameters were evaluated: live weight, daily gain, daily feed intake, feed:gain ratios, and mortality.

Table 2. Feeding and inclusion of the additives

Results

The results of the trial are shown in figure 4. Concerning growth, no significant differences could be seen between the groups, only numerical differences. Live weight in the antibiotic group was 25.95 kg, and in the Activo Liquid groups, it ranges from 25.77 kg (shortest period of application) to 26.20 kg (see below). This resulted in calculated values for an average daily gain of 473 g in the Mecadox fed animals and 463 to 487g in the Activo Liquid groups. Due to a lower feed intake per kg of weight gain, all groups fed Activo Liquid showed a significantly (p=0.05) better feed conversion than the Mecadox group.

Figure 4. Live weight in the groups fed the antibiotic Mecadox and the phytomolecules-based product Activo Liquid for different periods
Average daily gain in the different trial groups
Average daily feed intake in the different trial groups (P=0.05)

Concerning mortality, the group fed Activo Liquid for 5 days showed the lowest mortality rate of 1.1% (figure 5).

Figure 5. Feed:gain ratio in the different trial groups (P=0.05) & Mortality rates

Considering all parameters, the group fed Activo Liquid for five days provided the best results: numerically the lowest mortality rate, highest daily gain, and one of the two lowest feed:gain ratios. This trial concludes that Activo Liquid with an application period of five days can safely replace antibiotic growth promoters in the diet. Therefore, Activo Liquid is an interesting tool to additionally support pigs during critical periods of life.

Phytomolecules help keep health and performance together

The trials conducted with two types of phytomolecules-based products show that phytomolecules efficiently support pigs to achieve their genetic potential. A basic supply of these substances within the feed yields results similar to those of animals receiving antibiotic growth promoters (AGPs). In challenging situations like weaning, additional short-term supply is recommended, which can be done with liquid products via the waterline.

With this strategy, the use of antibiotic growth promoters and, therefore, antibiotics in general can be drastically reduced. This approach can help decrease antimicrobial resistance and, not to be forgotten, accommodates final customers’ requests for the lower usage of antibiotics in livestock.

References

Barber, Sarah, and Nikki Sutherland. “O’Neill Review into Antibiotic Resistance.” House of Commons Library, March 6, 2017. https://commonslibrary.parliament.uk/research-briefings/cdp-2017-0074/.

Baser, Kemal Hüsnü Can, and Gerhard Buchbauer. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: Taylor & Francis distributor, 2010.

Davies, Dame Sally. “Antibiotic Resistance ‘Big Threat to Health’.” BBC News. BBC, November 16, 2012. https://www.bbc.co.uk/news/health-20354536.

De Greeff, S.C., A.F. Schoffelen, and C.M. Verduin. “MARAN Reports.” WUR. National Institute for Public Health and the Environment – Ministery of Health, Welfare and Sport, June 2020. https://www.wur.nl/en/Research-Results/Research-Institutes/Bioveterinary-Research/In-the-spotlight/Antibiotic-resistance/MARAN-reports.htm.

Hao, Haihong, Guyue Cheng, Zahid Iqbal, Xiaohui Ai, Hafiz I. Hussain, Lingli Huang, Menghong Dai, Yulian Wang, Zhenli Liu, and Zonghui Yuan. “Benefits and Risks of Antimicrobial Use in Food-Producing Animals.” Frontiers in Microbiology 5, no. Art. 288 (2014): 1–11. https://doi.org/10.3389/fmicb.2014.00288.

Marquardt, Ronald R, and Suzhen Li. “Antimicrobial Resistance in Livestock: Advances and Alternatives to Antibiotics.” Animal Frontiers 8, no. 2 (2018): 30–37. https://doi.org/10.1093/af/vfy001.

O’Neill, J. “Tackling Drug-Resistant Infections Globally.” Review on Antimicrobial Resistance. Wellcome Trust / HM Government, May 19, 2016. https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf.