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^{10, 9, 16}. The gut-respiratory microbiome axis is well-established in mammals. Gut microbiota health, diversity, and nutrient supply directly impact respiratory health and function¹⁵. 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 infections¹².

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 quickly³.

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 dopamine⁶. 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 antibiotics⁵.

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^{8, 13}. 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, 14}.

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 already mentioned before, 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 coli⁷ and Salmonella enterica² and the carbadox and metronidazole effect on Brachyspira hyodysenteriae¹⁶. Additionally, there is an indication that the zinc resistance of Staphylococcus of animal origin is associated with the methicillin resistance coming from humans⁴.

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 – Agriculture¹¹ 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. Castillofollow, Manuel Toledo, Rocío García Espejofollow, Alejandro Martínez Molinafollow, María Elena  Goyena Salgadofollow, José Manuel Pintofollow, Ángela Gallardo Marínfollow, M. Toledo, et al. “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/.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Nasralla, Meisoon. “EIP-Agri Concept.” EIP-AGRI – European Commission, September 11, 2017. https://ec.europa.eu/eip/agriculture/en/eip-agri-concept.html.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.

By Madalina Diaconu, Product Manager Pretect D, EW Nutrition and
Twan van Gerwe, Ph.D., Technical Director, EW Nutrition

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.

Bioactive compound	Effect
Saponins	Inhibition of coccidia: By binding to membrane cholesterol, the saponins disturb the lipids in the parasite cell membrane. The impact on the enzymatic activity and metabolism leads to cell death, which then induces a toxic effect in mature enterocytes in the intestinal mucosa. As a result, sporozoite-infected cells are released before the protozoa reach the merozoite phase.Support for the chicken: Saponins enhance non-specific immunity and increase productive performance (higher daily gain and improved FCR, lower mortality rate). They decrease fecal oocyst shedding and reduce ammonia production.
Tannins	Inhibition of coccidia: Tannins penetrate the coccidia oocyst wall and inactivate the endogenous enzymes responsible for sporulation.Support for the chicken: Additionally, they enhance anticoccidial antibodies’ activity by increasing cellular and humoral immunity.
Flavonoids and terpenoids	Inhibition of coccidia: They inhibit the invasion and replication of different species of coccidia.Support for the chicken: They bind to the mannose receptor on macrophages and stimulate them to produce inflammatory cytokines such as IL-1 through IL-6 and TNF. Higher weight gain and lower fecal oocyst output are an indication of suppression of coccidiosis.
Artemisinin	Inhibition of coccidia: Its impact on calcium homeostasis compromises the oocyst wall formation and leads to a defective cell wall and, in the end, to the death of the oocyst. Enhancing the production of ROS directly inhibits sporulation and also wall formation and, therefore, affects the Eimeria life cycle.Support for the chicken: Reduction of oocyst shedding
Leaf powder of Artemisia annua	Support for the chicken: Protection from pathological symptoms and mortality associated with Eimeria tenella infection. Reduced lesion score and fecal oocyst output. The leaf powder was more efficient than the essential oil, which could be due to a lack of Artemisinin in the oil, and to the greater antioxidant ability of A. annua leaves than the oil.
Phenols	Inhibition of coccidia: Phenols change the cytoplasmic membrane’s permeability for cations (H+ and K+), impairing essential processes in the cell. The resulting leakage of cellular constituents leads to water unbalance, collapse of the membrane potential, inhibition of ATP synthesis, and, finally, cell death. Due to their toxic effect on the upper layer of mature enterocytes of the intestinal mucosa, they accelerate the natural renewal process, and, therefore, sporozoite-infected cells are shed before the coccidia reaches the merozoite phase.

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

Eimeria species	Predilection site
E. tenella	Ceca
E. acervulina	Duodenum and prox. jejunum
E. maxima	Central jejunum
E. mitis	Distal jejunum and ileum
E. necatrix	Central jejunum and ceca
E. brunetti	Ileum, entrance of the ceca and rectum
E. praecox	Duodenum and prox. jejunum

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.

References:

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Bailey R. A. 2010. Intestinal microbiota and the pathogenesis of dysbacteriosis in broiler chickens. PhD thesis submitted to the University of East Anglia. Institute of Food Research, United Kingdom

Choct M. Managing gut health through nutrition. British Poultry Science Volume 50, Number 1 (January 2009), pp. 9—15.

De Gussem M, “Coccidiosis in Poultry: Review on Diagnosis, Control, Prevention and Interaction with Overall Gut Health,” Proceedings of the 16th European Symposium on Poultry Nutrition, Strasbourg, 26-30 August, 2007, pp. 253-261.H.J. Dorman, S.G. Deans. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J Appl Microbiol, 88 (2000), pp. 308-316

Djeridane A., M. Yousfi M, Nadjemi B, Boutassouna D., Stocker P., Vidal N. Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem, 97 (2006), pp. 654-660

Farag R. S., Daw Z.Y., Hewedi F.M., El-Baroty G.S.A. Antimicrobial activity of some Egyptian spice essential oils. J Food Prot, 52 (1989), pp. 665-667

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.

Guo, F.C., Kwakkel, R.P., Williams, B.A., Li, W.K., Li, H.S., Luo, J.Y., Li, X.P., Wei, Y.X., Yan, Z.T. and Verstegen, M.W.A., 2004. Effects of mushroom and herb polysaccharides, as alternatives for an antibiotic, on growth performance of broilers. British Poultry Science, 45(5), pp.684-694.

Hafeez A., Männer K., Schieder C., Zentek J. Effect of supplementation of phytogenic feed additives (powdered vs. encapsulated) on performance and nutrient digestibility in broiler chickens. Poult. Sci. 2016;95:622–629.

Hammer K.A., Carson C.F., Riley T.V. Antimicrobial activity of essential oils and other plant extracts. J Appl Microbiol, 86 (1999), pp. 985-990

Hashemipour H, Kermanshahi H, Golian A, Veldkamp T. Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. Poultry Science. Volume 92. Issue 8. 2013, Pp 2059-2069,

Khattak F., Ronchi A., Castelli P., Sparks N. Effects of natural blend of essential oil on growth performance, blood biochemistry, cecal morphology, and carcass quality of broiler chickens. Poult. Sci. 2014;93:132–137

Kraehenbuhl, J.P. & Neutra, M.R. (1992) Molecular and cellular basis of immune protection of mucosal surfaces. Physiology Reviews, 72: 853–879.Krishan and Narang J. Adv. Vet. Anim. Res., 1(4): 156-162, December 2014

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Liu, S., Song, M., Yun, W., Lee, J., Kim, H. and Cho, J., 2020. Effect of carvacrol essential oils on growth performance and intestinal barrier function in broilers with lipopolysaccharide challenge. Animal Production Science, 60(4), pp.545-552.

Mitsch, P., Zitterl-Eglseer, K., Köhler, B., Gabler, C., Losa, R. and Zimpernik, I., 2004. The effect of two different blends of essential oil components on the proliferation of Clostridium perfringens in the intestines of broiler chickens. Poultry science, 83(4), pp.669-675.

Mohammadi Gheisar M., Kim I.H. Phytobiotics in poultry and swine nutrition—A review. Ital. J. Anim. Sci. 2018;17:92–99.

Oso A.O., Suganthi R.U., Reddy G.B.M., Malik P.K., Thirumalaisamy G., Awachat V.B., Selvaraju S., Arangasamy A., Bhatta R. Effect of dietary supplementation with phytogenic blend on growth performance, apparent ileal digestibility of nutrients, intestinal morphology, and cecal microflora of broiler chickens. Poult. Sci. 2019;98:4755–4766

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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.

Phase		Control	AGP	Activo
Nursery	0-7 days	—	Gentamycin 2.7kg/t	0.4kg/t
	8-42 days	—	Haloquinol 0.2kg/t	0.3kg/t
Growing	42-52 days	—	Tylosin 0.45kg/t	0.4kg/t
	53-87 days	—	Enramycin 0.125kg/t	0.2kg/t
Finishing	88-97 days	—	Tylosin 0.45kg/t	0.4kg/t
	98-126 days	—	Enramycin 0.063kg/t	0.2kg/t

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):

Feeding valid for all groups		Group / Product	Inclusion rate and period of application
3-phase feeding after weaning:		Mecadox	50 g/t of feed during the whole period
Phase I (days 0-7):	23 % CP, 5.4 % CF	Activo Liquid 3	375 ml/1000 L of water for 3 days post-weaning
Phase II (days 8-21):	21 % CP, 4.1 % CF	Activo Liquid 5	375 ml/1000 L of water for 5 days post-weaning
Phase III (days 22-42):	19 % CP, 4.4 % CF	Activo Liquid 7	375 ml/1000 L of water for 7 days post-weaning

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.

By Dr. Inge Heinzl, Editor, EW Nutrition

Since early 2020, COVID-19 has been keeping the world under a cloud of uncertainty. With all eyes focused on this pandemic, we nevertheless must not forget that another, silent pandemic is developing: antimicrobial resistance (AMR). Unfortunately, the COVID-19 could easily exacerbate the AMR pandemic.   

What is the relationship between COVID-19 and AMR? 

The COVID-19 pandemic, as well as AMR, have a direct health impact on people: they get ill, suffer from its short- and long-term effects, or even die. AMR, on the other hand, is not a disease in itself but makes various bacterial infections difficult to treat and is considered a pandemic due to its dramatic global scope (Cars et al., 2021). Both pandemics, the ‘loud’ COVID-19 and the ‘silent’ AMR pandemic, are monitored by official institutions. Still, for both, significant uncertainties around actual case figures exist, especially in low-income countries. 

Beginning in China in around December 2019, SARS-CoV-2 spread to the rest of the world within a few months. Figures collated by the WHO show over 250 million confirmed cases and over 5 million deaths to date, with excess mortality rates indicating this to be an underestimation. Quantifying the death toll due to AMR is far more challenging, as disease conditions vary, resistant bacteria go undetected, or the causative pathogens are not identified in the first place (Giattino et al., 2021).

O’Neill (2014) reported about 700,000 people dying from infections with resistant pathogens every year. He forecasted that, by 2050, 10 million people per year will die if we don’t change anything. This figure would represent twice the number of people who died from COVID-19 within the last two years.  In the US and the EU, according to CDC, antibiotic resistance causes 23,000 and 25,000 deaths per year, respectively. In Thailand, 38,000 deaths are attributable to ABR. And in India, 58,000+ babies died from infections with resistant bacteria, usually passed on from their mothers. 

Woerther et al. (2013) note a continuous increase of resistant strains globally. In 2010/11, ESBL carriage rates of 3 to 20 % were the “norm”, but some WHO regions already showed 60 to 70% carriage rates by 2011. In the US, 223,900 cases of Clostridium difficile occurred in 2017, and at least 12,800 people died (CDC, 2019). 

As in the case of SARS-CoV-2, the spread of AMR organisms can be prevented by hygiene measures. Except for hospital settings reported in developed countries, the spread of resistant bacteria is invisible. Regardless of how little we know about it from official reports, there are indications that bacteria resistance is ubiquitous, triggered to a large extent by the (over)use of antibiotics in community settings. Moreover, it is far more difficult to identify that a patient suffers from AMR infection than from SARS-CoV-2. The latter is easily detected with widespread testing systems, including self-testing.  

COVID and AMR have severe economic consequences 

Besides claiming many lives, both COVID and AMR increase the costs for healthcare. Additionally, due to high sickness ratios and lockdowns, economic losses are tremendous. For COVID as well as for AMR patients, the hospitals need specialized systems and procedures (ventilation apparatus, extraordinary hygiene measures) and specially qualified personnel to treat the infected persons. In addition to the cases of infection, mental illness increases due to these exceptional circumstances. 

US study extrapolates ten-figure costs due to AMR 

In a US cohort study based on records of 25,000 patients from 2007-2015, Nelson et al. (2021a) calculated the treatment costs for infections with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Acinetobacter to be $4.6 billion.  

Another study done by Nelson et al. (2021b) with 87,509 elderly patients suffering from infections with the same resistant pathogens showed estimated costs of $1.9 billion, with 11,852 deaths and 448,224 inpatient days. In these two studies, only two resistant bacteria species were considered – and they alone triggered costs of more than 4 billion US dollars. 

Estimation of COVID costs shows long-lasting negative economic impact 

In the case of COVID, an estimation done by Tan-Torres Edejer et al. (2020) yielded $52.45 billion in added healthcare costs worldwide over four weeks in a status quo scenario. The costs would increase/decrease if the transmission increases/decrease. More detailed consideration is provided by Cutler and Summers (2020).   

Category	Cost (billions) in USD
Lost GDP	7592
Health loss
Premature death	4375
Long-term health impairment	2572
Mental health impairment	1581
Total	16121
% of annual GDP	90

Estimated Projected health cost of the COVID-19 crisis (Cutler and Summers, 2020)  

Economic losses due to Corona are tremendous – What about losses due to AMR?  

Some of the costs arising during the corona pandemic are partially compensated. New jobs within the health system, industries providing healthcare materials or developing vaccines/medicine partially cover the damages caused to the economy.  

Additional to the healthcare costs, costs due to the impact on the economy arise. According to Maliszewska et al. (2020), financial losses because of the COVID-19 pandemic can be attributed to four categories: 

1. the direct impact of a reduction in employment (shutdowns of operations), but also labor shortage due to illness of the personnel 
2. the increase in costs of international transactions 
3. the sharp drop in travel (caused by travel bans in certain countries) 
4. the decline in demand for services that require proximity between people (e.g., down periods of restaurants). 

According to a UN (2020) early estimate, the “economic uncertainty it has sparked will likely cost the global economy $1 trillion in 2020”.  

Comparing the costs for both pandemics, AMR does not seem to be as scary as COVID. However, we are only at the beginning. AMR figures are constantly increasing. If O’Neill (2014)’s scenario occurs, we will witness more AMR-caused deaths than deaths from COVID-19, as well as higher costs.  

Antibiotic use promotes the development of resistances 

Antimicrobial resistance is natural; Alexander Fleming mentioned it as early as 1929, soon after discovering penicillin. Most of the antibiotics are derived from natural substances. Penicillin, for instance, is produced by a mold fungus. This is why completely isolated cultures such as the Yanomami in Venezuela, who have never taken antibiotics, can also show resistant bacteria in their gut flora (Lahrtz, 2015). Every contact with an antibiotic has the potential to promote resistance.

Bacteria develop resistance in different ways 

In a typical situation, an antibiotic has an impact on “good” and “bad” bacteria. One bacterium, due to a random mutation, can develop resistance to antibiotic treatment. Suddenly, that resistant bacterium has survived the battle, remains the “king of the castle”, and can use all the space and nutrients to proliferate. 

Different types of resistance are possible (Levy, 1998). The bacteria can  

• stimulate the production of enzymes, modifying or breaking down (and, therefore, inactivating) the antibiotic 
• eliminate access ways for antibiotics or develop pumps discharging the antibiotic before it takes effect 
• change or eliminate the targets of the antibiotics, the molecules they would bind. 

Bacteria spread their ability to resist 

The problem of antibiotic resistance is not only that one bacterium, due to mutation, can withstand an antibiotic treatment. The more dangerous possibility is that it can also transfer this ability to other, potentially more harmful bacteria. How is this transfer achieved? Bacteria can acquire these mutated “resistance genes” through 

• vertical transfer from mother to daughter cells 
• the intake of these genes from dead bacteria, which is also possible between different strains (including between “good” and “bad” ones) 
• plasmids transporting the genes from one bacterium to another (horizontal transfer), which is also possible between strains 
• viruses transporting the genes.   

Due to this exchange of resistance genes, harmful bacteria can become resistant because they acquire the mutated gene and, therefore, the ability to resist antibiotics from a harmless bacterium.  

Enhanced antibiotic resistance due to COVID-19? 

Just as influenza (Morris et al., 2017), the COVID-19 pandemic is reported to influence the transmission of bacterial infections and the development of antimicrobial resistance. Several reasons and facts argue for this statement. 

1. Bacterial co-infections are often identified on top of viral respiratory infections. These are then the main reasons for higher morbidity and mortality (Mahmoudi, 2020). Also, COVID-19 weakens the immune system of people and paves the way for secondary infections. This is the reason why, in some cases, COVID-19 patients are given antibiotics prophylactically. Langford and co-workers (2020) published a summary of different studies concerning this topic, and other authors confirm this tendency (Garcia-Vidal et al., 2021; Rawson et al., 2020; Rodríguez-Baños, 2021; Russel et al., 2021). They reported a relatively low incidence of bacterial co-infections of 3.5% (95% CI 0.4-6.7%) and secondary bacterial infections of 14.3% (95% CI 9.6-18.9%). However, high use of antibiotics (70%) could be observed, most of them broad-spectrum antibiotics such as third-generation cephalosporins and fluoroquinolones (Langford et al., 2020). 
2. Contrary to influenza patients, who get bacterial secondary infections or co-infections in the community, COVID patients are more likely to get these infections in the hospital. There, the risk of “catching” a resistant pathogen is higher.  
3. This risk increases during a pandemic such as COVID simply because more people spend more time in the hospital. The hospital staff is overloaded; often, hygiene compliance is less than perfect. 
4. Due to the high number of patients, the determination of bacteria strains is often delayed, and, therefore, doctors more often resort to broad-spectrum antibiotics.  

Antibiotics in animal production contribute to AMR development 

In animal production, antibiotics are not only used for the treatment of diseases but also prophylaxis of the whole herd or growth-promoting purposes. Data collected in the US in 2017 (human) and 2018 (animals) revealed that, in total, nearly 80% of the antibiotics were used in animals. 

Use of antibiotics in animals and humans in the US 2017/18 (according to Benning, 2021) 

Reduction of antibiotics leads to a decrease in resistances 

A report published by the CDDEP in 2015 showed an earlier example (Dutil, 2010).  When the 3rd generation extended-spectrum cefalosporin (Ceftiofur) was used at the egg stage of broiler chicken farming in Canada, the prevalence of E. coli and Salmonella strains resistant to this antibiotic increased in chicken, but also humans. After discontinuing the antibiotics, the resistance dropped by one-half to one-quarter of the previous year’s value within one year. 

This decrease makes perfect sense. An antibiotic-resistant gene is not worth the organism’s effort if the associated antibiotic is not used, converting the gene into a negative factor for “fitness”. It only costs energy and, in the end, disappearance from the microbiome. 

Antibiotic reduction in animals shows first benefits 

Besides antibiotic stewardship in human medicine (no broad-spectrum antibiotics, targeted use, and only against bacteria rather than viral diseases), reducing antibiotic use in animal production is vital. The European Union has already made strides and banned antibiotics as growth promoters in animal production in 2006. The Netherlands has been leading the way when it comes to a reduction in veterinary prescribed antibiotics. From 2009 to 2018, antibiotic sales decreased by 70% (de Greeff et al., MARAN Report, 2020). First decreases of resistance have already be documented, among which: 

• no carbapenemase-producing Salmonella in 2019 
• only 19 ESBL-producing Salmonella isolates were confirmed, mainly from humans 
• the resistance percentage in commensal E. coli (caecal samples) has halved for most antibiotics, converting into consistently low values during recent years 
• no E. coli isolates resistant to extended-spectrum cephalosporins were detected in fecal samples from farm animals.  

Preserving the effectiveness of antibiotics is key  

Various feed supplements can support the animals at different stages of their life in order to reduce antibiotic use in animal production. In the long run, this will be a game-changer in ensuring that animal products and the process of animal production itself are not part of the problem. 

Antibiotic reduction has become an increasingly stringent task. In the wake of the COVID-19 pandemic, the world has gained a renewed awareness of the importance of infectious diseases. We saw how fast progress in healthcare could suffer setbacks and we were forced to recognize the need for resilient health systems (Cars, 2021).  

The pandemic can teach us a valuable lesson in this respect. We must realize that it is essential to use antibiotics further as an effective tool to treat harmful diseases. To that end, we must do everything we can to keep this weapon sharp. The first step is to reduce antibiotic use in human health, as well as in livestock production. It will not be an easy way. It is, however, the only effective way in the long run. 

 

References

Benning, Reinhild, and By. “Antibiotics: Useless Medicines: Heinrich Böll Stiftung: Brussels Office – European Union.” Heinrich-Böll-Stiftung, September 7, 2021. https://eu.boell.org/en/2021/09/07/antibiotics-useless-medicines.

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By Dr. Inge Heinzl, Marisabel Caballero, Dr. Twan van Gerwe, and Dr. Ajay Bhoyar – EW Nutrition

Concerns about antibiotic resistance in humans and production animals have prompted a push across the board to reduce antibiotic use, including in livestock rearing. To meet these demands, the industry must keep the pathogenic pressure in production units as low as possible, enabling production with no antibiotics or minimum use of antibiotics.

The 3 essential steps for reducing antibiotics in broiler production

In the following, we discuss experience-based insights and practical advice concerning best practices for broiler meat production with reduced antibiotic use, focusing on the following points:

• Farm biosecurity
• Management of the broiler house, including cleaning & disinfection, and environment & litter management
• Management of the flock, including DOC quality, disease prevention, and nutrition

1. General farm biosecurity

Biosecurity is the foundation for all disease prevention programs (Dewulf et al., 2018). Thus, it is essential in antibiotic reduction scenarios. It includes all measures taken to reduce the risk of introducing and spreading diseases, preventing diseases, and protecting against infectious agents. Its fundament is the knowledge of disease transmission processes.

The application of consistently high biosecurity standards substantially reduces antimicrobial resistance by preventing the introduction of resistance genes into the farm and lowering the need to use antimicrobials (Davies & DWales, 2019).

First of all: everyone must act in concert!

Biosecurity is one of the preconditions for the success of an ABR program, and it is crucial to bring all workers/staff on track through regular training on the best practices and their subsequent rigorous implementation.  The biosecurity plan can only be effective if everyone on the operation follows it – all the time. Farm managers, poultry workers, and other persons entering the facility should adhere to the farm biosecurity measures, 24/24h – 7/7d.

Separation helps to prevent the spread of pathogens

One essential component for biosecurity is implementing a “line of separation” for the farm and each house. It is vital to have a good separation between high and low-risk animals and between areas on the farm that are dirty (general traffic) and clean (internal movements). In this way, it is not only possible to avoid the entrance but also the spread of disease, as potential sources of infection (e.g., wild birds) cannot reach the farm population.

The farm must be well isolated, not allowing the entry or passage of persons who do not work there and animals, including pets.

Inside the farm, the walls of the poultry house form the first line of separation, and the “Two-zone Danish Entry Protocol” constitutes a second line. This system utilizes a bench to divide the anteroom of a poultry house into two sides (outdoor / ‘dirty area’ and indoor / ‘clean area’). At a minimum, footwear should be changed, and hands washed or disinfected when passing over the bench; it is even better when workers have house-specific clothing and hairnets when entering the poultry area.

Figure 1: Safety procedures on the poultry farm – the Danish entry method

The room is divided into “dirty” and “clean” zones.

1. After the entrance from outside, workers/visitors step into a disinfectant boot tray.
2. They take off their street shoes and leave them on the dirty side of the entrance zone.
3. Then, they turn from the dirty to the clean side by swinging their legs without touching the floor.
4. They wash their hands and disinfect them by using the hand.
5. They must put on an overall, cap, mask, and boots of the poultry house.
6. Completely clothed, they can enter the poultry house.
7. When they leave the house, a reversed process must be followed.

Still more needs to be done to prevent the entrance and spread of disease.

Separate materials for each house

For each house, separate materials must be used, keeping a dedicated set of tools and equipment necessary for daily work.

Very important: no materials should be moved from one house to another unless thoroughly disinfected. Crates for bird transport in the case of thinning (partial depopulation of a broiler flock) are an important example.

Practice clean disposal of mortality

First, dead birds’ removal must be frequent (minimum twice a day) as carcasses are a source of infection. The next point is to make sure the route of birds’ disposal is strictly unidirectional, and the buckets or wheelbarrows for the transport of the dead birds do not reenter the poultry house. Finally, the carcasses should remain outside the farm or as far from the buildings as possible until collection, incineration, or composting.

2. Broiler house management

After the general organization on the farm, let’s move on to the poultry houses.

Cleaning and disinfection of the house are the first steps – and check their efficacy!

Cleaning and disinfection are essential components in preventing the persistence and spread of pathogens. Both together aim to decrease microbial numbers on surfaces (and in the air) to a level that will ensure that most -if not all- pathogens and zoonotic agents are eliminated.

Cleaning refers to the physical removal of organic matter and biofilms, so the microorganisms and pathogens are afterward exposed to the disinfectant.

For effective cleaning and disinfection, the all-out/all-in system has proven of value. When birds are collected, all organic material, including feed residues and litter/feces, is removed.

Effective detergents and hot water are used to remove any grease or organic material. Pay special attention to the floors! Also, all surfaces and equipment should be sufficiently cleaned and given final disinfection.

Cleaning is crucial

A study by Luyckx and collaborators (2015) revealed that the mean total aerobic bacterial count on swab samples taken in broiler houses decreases significantly already after cleaning (figure 2). Good cleaning not only strongly reduces microbiological contamination and organic material but also ensures that the subsequent disinfection has a stronger impact on the remaining microorganisms. Consider that all disinfectants, even in high concentrations, are barely effective in the presence of organic material.

Figure 2: % of reduction of bacteria on surfaces after cleaning and after cleaning and disinfection (adapted from Luyckx et al., 2015)

Keep an eye on cleaning & disinfection efficacy

After cleaning and disinfection are complete, it is good practice to check the floors for Total Viable Count (TVC), Salmonella, and E. coli to test the efficacy of the cleaning and disinfection process. Recommended levels of TVC should be less than ten colony forming units per square centimeter (CFU/cm²), and E. coli and Salmonella levels should be undetectable.

When high TVC are found, the cleaning and disinfection procedure must be evaluated, including the products (a rotation is recommended) and their application (e.g., dosage, dilution, water temperature, and exposure time). Also, possible reinfection by vermin or personnel during the downtime must be controlled.

Downtime: After cleaning and disinfection, a down-time time of 10 days allows disease-causing pathogens to die (UC Davis, 2019).

Cleaning and disinfection of the waterline against biofilm

In the waterlines, the build-up of biofilms can be an issue. Biofilm is a sticky film that can be found inside water lines, regulators, and nipple drinkers. It starts when bacteria attach to a surface and produce a matrix of extracellular polymeric substances (EPS), including proteins and sugars, giving the biofilm the stickiness that traps other bacteria and organic matter. It provides the bacteria with protection from the external environment, and thus they multiply and thrive.

Biofilms not only block the water flow, but they can also include pathogenic bacteria. Thus, the waterline must be regularly cleaned and disinfected, not only between flocks but also within each flock.

Between flocks, an effective waterline cleaning should include:

• Application of hydrogen peroxide at high concentration, leaving it in the system for 24-48 hours to remove the biofilm from the pipelines)
• Flush the line to remove the detached biofilm, also activate the nipples with a broom or stick to flush them
• Immediately before the placement of the new chicks, the water lines should be flushed to have fresh drinking water available to the chicks
• The water pressure must be adjusted so that a droplet of water is visible at the end of each nipple, and the drinkers are put to the correct height to stimulate water intake and avoid spilling

During the life of the birds, a water disinfectant should be used to prevent biofilm formation, e.g., hydrogen peroxide in weekly applications or the continuous use of chlorine. Also, flushing is a good practice during the whole cycle to make sure that biofilm is removed and the birds count with fresh drinking water.

To a certain extent, biofilm build-up can be prevented by using organic acidifiers in the water, which improves the sanitizers’ effectiveness and reduces bacterial growth in water lines.

Correct ventilation helps to prevent respiratory diseases

To keep broilers healthy, providing optimal ventilation in the poultry house is crucial. CO₂ and temperature are the most critical parameters. CO₂ should never exceed 2500 ppm and should be monitored continuously, most notably in the early morning before birds increase activity (e.g., eating). Ventilation rates should be adjusted to keep CO₂ below this limit. Draught or cold spots resulting in uneven distribution of birds in the house should be avoided, and causes should be investigated and repaired immediately.

Incorrect ventilation often is the reason for respiratory diseases and the need for antibiotic treatment. No matter if natural or power ventilation is used, proper monitoring of the system is indispensable to ensure the well-functioning of the equipment and, therefore, appropriate air quality (Neetzon et al., 2017).

Litter management to keep diseases in check

Effective litter management is another step on the road to keeping the birds healthy. Dryness of litter and ammonia level at bird’s level are two significant key success factors in raising broilers. Dry litter preserves the footpads, so litter material should have a good moisture-absorbing capacity (e.g., chopped straw, wood shaving, rice husks, sunflower husks). When using build-up litter, litter sanitation and treatments need more attention.

Litter treatment (with acidifying or binding substances) and adequate ventilation are the most practical measures to control ammonia and improve littler quality (Malone, 2005). Keep litter temperature at 28 – 30°C (82.4 – 86°F), and use only litter tested or certified to have a TVC <10 CFU/g.

3. Flock management

The basis: healthy, high-quality day-old chicks

To produce good-quality day-old chicks, the parent flocks (PS) must be of good health status. PS should be free from vertically transmitted diseases such as Mycoplasma and Salmonella and be vaccinated/protected against important diseases:

• Salmonella pullorum/Salmonella Gallinari should be assessed in PS by RPA serology in week 25-30, at least 60 samples per flock.
• Mycoplasma gallisepticum should be checked by RPA/ELISA serology on a regular basis, preferably at least monthly, with a minimum of 30 samples per flock.

Parent flock vaccination leads to the production of maternal antibodies that help prevent horizontal infection (from the broiler farm environment) in chicks at an early age. This type of prevention is the primary function of some vaccinations, such as against Gumboro disease.

An essential part of the broilers’ life occurs already in the hatchery. Single-stage incubation is recommended, and all floor eggs and dirty nest eggs should be excluded to assure the best day-old chick quality.

Comfortable conditions bring chicks to eat

The brooding phase needs special attention; it is about welcoming the chicks and making them comfortable in the house environment. For this, enough litter needs to be provided, the environment must be managed, and feed and water must be supplied.

At least 24 hours before chick placement, the house and floor temperature are increased to a minimum of 34°C and 28°C, respectively. Proper ventilation and lighting are also essential. These conditions need to be monitored and adjusted after the placement so the chicks feel comfortable and start feed and water consumption. Checking chick behavior is crucial during the first hours after placement.

Upon the placement of the chicks, it is recommended to have pre-starter crumble feed available on top of brooder paper underneath the drinking line. To stimulate early feed and water consumption, gently place the chicks onto that paper. The target is to have 100 % of chicks with crop filled within 48 hours of chick placement.

Reduce the stocking density

In general, high stocking density may restrict bird movement, interfere with airflow, and increase litter moisture and microbial growth, including pathogens, which potentially impairs broiler health, welfare, and performance.

When reducing antibiotics, increase the space per bird by 0.05 ft²/46 cm² per bird compared to your current conventional program. A lower stocking density helps keep litter moisture at a minimum, which reduces the shedding of cocci oocyst and pathogenic bacteria over the population.

Feed and water access must be granted to all animals at every moment. The number of chickens per feeder or drinker depends on the type of equipment used.

Consistent observation of the flock

To recognize emerging health issues, producers should critically observe the behavior of birds every day. On which points should they focus?

• First, when entering the house, birds’ behavior and response to the poultry worker should be observed with attention. Note the spread of birds throughout the house.
• Note birds’ drinking and eating behavior. Feed and water intake should be recorded daily, always at the same hour.
• The quality of the fresh fecal droppings should be judged. Any changes in the fecal droppings (loss of consistency) can help notice emerging disease and take measures against it.

Especially during and after feed change, attention to changes in the usual feces consistency is necessary.

Vaccination and judicious antibiotic use are crucial

Carefully consider vaccination programs for broilers. Unnecessary vaccinations impact the immune system, possibly resulting in reduced performance and, in some circumstances, make the birds more susceptible to other diseases. Hence, the vaccination program must be diligently attuned (Neetzon et al., 2017).

• The disease background of the parent farm as well as the broiler farm where the chicks will be placed are essential factors for the vaccination program
• If possible, vaccine strains that are the least immunosuppressive should be chosen
• If coccidiostats are not permitted, an effective vaccination against coccidiosis is required and must be done as early as possible
• All vaccinations must be given using a standard operating procedure that minimizes bird discomfort and optimizes the vaccine, and always administer vaccines following the advice from the manufacturer

After the vaccination, it is essential to monitor the effects of vaccination stress and take preventive measures to avoid any issues with broiler performance in terms of weight gain and mortality.

Use antibiotics with discernment

As we aim to reduce antibiotics, they should be limited to pure therapeutic use, only if other disease-prevention measures have not been successful, and mortality or disease symptoms make the treatment necessary. Before the treatment, the disease must be diagnosed by a qualified veterinarian. The diagnosis should be preferably followed up by isolation of the disease-causing bacteria, classification, and susceptibility testing before the antibiotics are applied.

Small-spectrum antibiotics that are less likely to cause antimicrobial resistance (AMR) should be preferred. Broad-spectrum antibiotics or antibiotics that are likely to cause AMR can only be used after susceptibility testing has demonstrated resistance to a first-choice antibiotic. The treatment effect must be evaluated by daily monitoring of disease symptoms, mortality, water, feed intake, and body weight gain.

Thinning – things to consider

If thinning (partial depopulation) is practiced, it should be done with the highest bio-security measures. Producers must ensure that the equipment used in the catching process is thoroughly cleaned before entering the house, and bird-catching personnel takes the same measures as farm personnel when entering the farm and the house. These policies will help to minimize the introduction of infectious agents.

Keep the feed withdrawal period for this process as short as possible to avoid flightiness, which can induce skin lesions (some regions catch birds in low light intensities to avoid flightiness). A short feed withdrawal period also prevents over-consumption of feed in a short amount of time, possibly disrupting feed passage in the gut and leading to bacterial imbalance and dysbacteriosis in the remaining birds. After thinning, feed and temperature must be adapted to the lower number of animals.

Provide your birds with high-quality water for drinking

Water is the most important nutrient for broilers. It plays an essential role in digestion and metabolism, thermoregulation, and waste elimination.

Several factors affect water quality: temperature, pH, bacteria, hardness, minerals, and total dissolved solids. These parameters should be analyzed at least twice per year. If necessary, corrective actions should be taken, e.g., a filtration to remove minerals, the addition of chlorine for disinfection, or the addition of organic acids to drop the pH.

Before each cycle, the water must be tested for total aerobic + enterobacteria, compared to reference values: Total plate count (TPC) should be < 1000 CFU/ml, and E.coli, Enterobacteriaceae, yeast, and molds at undetectable levels. The section about cleaning and disinfection of the waterline provides insights and practical advice about water sanitation and microbiological analysis.

Nutrition & feeding – a pillar for antibiotic reduction

Nutrition and feeding in ABR broiler production are not only about providing nutrients for growth but also about the effects of the feed on gut health. Gut health is essential for animals’ overall health, welfare, and productivity, even more so in antibiotic reduction scenarios.

Feed should be of the highest quality – in all respects

High feed quality is necessary to provide the animal with the required nutrients and achieve their optimal utilization. Also important is the absence, limitation, or management of harmful substances and pathogens. High quality, therefore, includes:

• Form and composition of the final feed
• Nutritional value of the raw materials
• Management of harmful substances.

From reception and storage of the raw materials to the dispatch of the finished feed, the feed mill management emphasizes their quality assurance system, which is decisive in this connection.

First measure: quality assurance at the feed mill level

The feed mills producing for operations with no or reduced use of antibiotics must have a quality assurance (QA) and/or a good manufacturing program (GMP) in place that guarantees the production of consistently good quality feeds.

Proper raw material management and processing of feeds are necessary to achieve the lowest possible microbial-pathogen load, including:

• An effective rodent and wild birds control
• Disinfection of all the vehicles entering the feed mill
• Proper storage and utilization of raw materials (e.g., first in-first out use, silo management)
• Periodic thorough cleaning of milling equipment, premises and storage areas, and the monitoring of these activities
• Standard operating procedure and quality assurance systems that guarantee feed safety and quality

Check the quality of the raw materials and the final feed

Digestion, absorption, and gut health depend on the quality of the feed ingredients. To provide the best preconditions for healthy growth, producers should avoid raw materials of a reduced and/or inconsistent quality. For this purpose, each raw material batch should be analyzed for its specific quality parameters. Quality parameters to consider are:

• Physical ones, such as color, odor, particle size, and general appearance
• Chemical ones, such as nutritional composition and specific parameters. For example, grains should be analyzed for mycotoxins and antinutritional factors; fats and oils need to be analyzed for free fatty acids (FFA), unsaturated/saturated (US) ratio, iodine value (IV), but also the peroxide value (PV) as oxidized fats have a lower energy value, and their intake is related to enteric diseases
• Biological ones, including yeasts, molds, and enterobacteria

Also, the finished feed should be monitored by analyzing every batch concerning composition compared to values in the feed formulation, as well as physical, chemical, and microbiological quality parameters.

Clean storage on the farm prevents feed spoilage

As in the feed mill, keeping the farm facilities clean is of the highest importance. Warehouses, silos, bins, feeders, etc., should be emptied, cleaned, and disinfected after each flock; this avoids the formation of feed aggregates that can lead to mold growth and mycotoxin contamination; also, insects, bacteria, and parasites can remain in those residues.

Adapt feed formulation and feeding to the feeding phase

The value of phase feeding

Having the correct number of dietary phases to meet animal demands and avoid excess nutrients provides better intestinal health and thus aids production animals in ABR scenarios. The feeding phases should be designed to prevent abrupt changes in nutrition and raw material inclusions, possibly leading to dysbacteriosis.

Feeding for gut health

When feeding broilers in antibiotic reduction scenarios, extra care should be taken when formulating diets. The challenge is to achieve the same performance as conventional management at an optimum cost.

• Don’t waste nutrients: Improve feed digestibility, and at the same time, reduce the dangers of antinutritional factors coming from different ingredients by using suitable exogenous enzymes.
• Keep an eye on fiber: Moderate levels of insoluble fibers with adequate structure and composition can be included to promote gizzard development and function. This measure leads to a better modulation of gut motility and feeds passage into the intestine. Additionally, it promotes gut health, resulting in higher nutrient digestibility.
• Be careful with protein: Excess of undigested protein in the hindgut may lead to the proliferation of Clostridium perfringens; then, subclinical challenges of necrotic enteritis may occur. Moreover, the excess of nitrogen may increase feces moisture content, leading to wet litter. The optimization of the diets based on digestible amino-acid profiles and the use of synthetic amino acids decrease or eliminate the minimum requirements of crude protein, avoiding its excess.

Which feed form?

The feed form depends on the age or feeding phase: starter feeds can be offered as coarse mash, but preferably as crumble or mini-pellets (< 2 mm diameter) and grower and finisher diets as 3 – 4 mm pellets.

When using pelleted diets, quality is also the most crucial criterion. Poor pellet quality and thus the excess of fine particles increase feed passage rate, resulting in poor gizzard development and compromised gut health.

A high-quality pelleted feed can withstand – without much breakage – the handling that occurs after processing, such as transportation, storage, and farm management. Pellet quality can be measured by the Pellet Durability Index (PDI) obtained by simulating the impact and shear forces in a known quantity of feed for a determined amount of time. After this time, the sample is sieved, and the fines are separated, weighed, and compared with the initial sample

The PDI should be measured in the feed mill and compared to a standard. Later, it is also recommended to measure the PDI on the farm, and the producer should take corrective actions if the pellets cannot maintain their quality.

Additionally, it should be known that coarse ground grains stimulate gizzard development and function. So, about 30 % of the feed should consist of particles between 1-1.5mm (post pelleting) in all feeding phases.

Broilers’ selection criteria for feed are form, color, size, and consistency

Broilers’ selection criteria for feed are form, color, size, and consistency. They prefer feed that is easy to pick, such as crumbles or pellets. 

Feed additives can support antibiotic reduction

The feed additive industry provides broiler farms and integrations with various solutions to make production more manageable and efficient.

A healthy start is half the battle

Let’s start with the chicks. The early introduction of beneficial bacteria into the intestinal tract has proven helpful for gut health optimization. This colonization can be achieved with the administration of suitable probiotics preparation at the hatchery. Multi-strain probiotic preparations effectively initiate healthy microbiome development for optimum gut health. For these challenges, support is offered through EW Nutrition’s VENTAR D and ACTIVO LIQUID, phytomolecule-based products for the feed and the waterline, respectively.

Maintain gut health

Gut health is one of the essential preconditions for efficient growth. Only a healthy gut guarantees efficient digestion and absorption of nutrients. Several approaches are recommended to maintain gut health:

• Promotion of beneficial and reduction of pathogenic gut flora: here, solutions can come in the shape of products based on phy­tomolecules that can be applied with the feed (VENTAR D) or the water (ACTIVO LIQUID)
• Management of bacterial toxins and mycotoxins: for this topic, products mitigating the toxins’ negative impact on the birds (Product range of MASTERSORB and SOLIS) are offered

Protect your feed

When feed is stored, there is always the risk of bacteria, mold, or yeast overgrowth. Oxidation of feed ingredients, such as fats and oils, reduces their nutritional value. These issues can be prevented by applying:

• Acidifiers that have antimicrobial effects due to their pH-decreasing effect, which, later on, improves the feed digestibility and stabilizes the GIT flora (ACIDOMIX, FORMYCINE, and PRO-STABIL)
• Antioxidants preserving ingredients susceptible to oxidation, such as fats and oils (AGRADO, SANTOQUIN, and STABILON)

Improve pellet quality

Moisture retention during the conditioning process influences pellet quality: higher moisture retention entails a higher starch gelatinization resulting in higher digestibility, pellet binding, fewer fines, and a higher PDI. Surfactants (for example, SURF•ACE) are compounds that can reduce the surface tension between the water and the feed, improving moisture absorption during the conditioning process.

Besides that, moist steam in the pelleting process penetrates better and has a higher antimicrobial effect leading to lower production of bacterial and mycotoxins. The possible reduction of the pelleting temperature protects the nutrients.

ABR in broiler production is practicable – by observing some rules

As shown above, antibiotic-reduced broiler production needs many aspects to be considered and a lot of measures to be taken. All of these measures seek to keep animals healthy and avoid antibiotic use. Maintaining gut health is crucial, as only a healthy gut performs well, achieves the optimal utilization of nutrients, and increases growth performance.

Maintaining a successful production unit with no or reduced antibiotic use requires a holistic approach in which best practices must be assured at all levels of the production chain. The feed additive industry provides a broad range of solutions to support animal production through this challenging task. The objective could not be more critical: lowering antibiotic resistance to assure the future of animal and human health.

 

References:

Davies, Robert, and Andrew Wales. “Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection.” Comprehensive Reviews in Food Science and Food Safety 18, no. 3 (2019): 753–74. doi.org/10.1111/1541-4337.12438

Dewulf, Jeroen, and Van Filip Immerseel. “General Principles of Biosecurity in Animal Production and Veterinary Medicine.” Essay. In Biosecurity in Animal Production and Veterinary Medicine: From Principles to Practice. Wallingford, Oxfordshire, UK: CABI, 2019. doi.org/10.1079/9781789245684.0063.

Luyckx, K.Y., S. Van Weyenberg, J. Dewulf, L. Herman, J. Zoons, E. Vervaet, M. Heyndrickx, and K. De Reu. “On-Farm Comparisons of Different Cleaning Protocols in Broiler Houses.” Poultry Science 94, no. 8 (2015): 1986–93. doi.org/10.3382/ps/pev143.

Kreis, Anna. “Broiler Feed Form, Particle Size Assists Performance.” Feed Strategy, September 20, 2019. https://www.feedstrategy.com/poultry-nutrition/broiler-feed-form-particle-size-assists-performance/.

Malone, B. “Litter Amendments: Their Role and Use.” University of Delaware – Agriculture & Natural Ressources – Fact Sheets and Publications. University of Delaware, November 2005. https://www.udel.edu/academics/colleges/canr/cooperative-extension/fact-sheets/litter-amendements/

Neetzon, A. M., Pearson, D., Dorko, N., Bailey, R., Shkarlat, P., Kretschmar-McCluskey, V., Van Lierde, E., Cerrate, S., Swalander, M., Vickery, R., Bruzual, J., Evans, B., Munsch, G., & Janssen, M. (2017, October). Aviagen Brief. Aviagen – Information Library. https://en.aviagen.com/assets/Tech_Center/Broiler_Breeder_Tech_Articles/English/AviagenBrief-ABF-Broiler-EN-17.pdf.

UC Davis Veterinary Medicine. “‘All out All in’ Poultry Management Approach to Disease Control. A Guide for Poultry Owners.” Poultry-UC ANR, March 2019. https://ucanr.edu/sites/poultry/files/301023.pdf

 

Water hygiene is essential for achieving antibiotic-free poultry production

Significant resources are spent on the correct nutrients in the diet and the correct additives for bird health. Water quality should be a priority, and a water quality monitoring program is essential for success in an ABF program. All things being equal, animals will perform better if they have access to high-quality water.

The variability of water quality in the grow-out region should determine how many water quality samples are taken. In highly variable areas, water quality should be measured at every season change on enough farms in every region to know if the solutes are changing. If the water quality is good and consistent, monitoring may be reduced significantly. Water quality should be a part of a “problem farm” work up or related to otherwise unexplained poor performance.

Water-soluble additives: Prevent biofilm

The use of water-soluble products is common in ABF production systems and their frequent use may provide a carbon source for bacteria. This, along with warm temperatures and slow water flow in enclosed water systems, makes the perfect environment for biofilm development.

It is important to frequently flush lines, give birds access to fresh water between additives, and sanitize water lines after using a product that can provide nutrients to bacteria in the line. The biofilm is a perfect location to harbor and protect pathogens from acids and mild or under-dosed disinfectants.

Designing a water quality program

Sample collection

The first step to building a water quality program is to understand the challenge on every farm. Correct sample collection is critical to achieving good results. Take a water sample from as close to the well as possible and submit for water quality analysis: pH, hardness, and minerals. This sample should also be submitted for bacterial load: total aerobic plate count (CFU) per mL and total coliforms per mL.

Monitor bacterial load

A drip sample should be collected from the end of the line for bacterial load analysis as well. This will help determine if the bacterial challenge begins at the source or is limited to the house. Additionally, a swab from the inside of the end of the water line should be taken to determine the level of biofilm. The total bacterial count should be less than 1,000 CFU/mL without fecal coliforms in a free-flowing sample, and total bacteria should be less than 10,000 CFU/mL on a biofilm swab.

Monitor water pH

Water should have a pH between 5 and 8. Water with a pH consistently lower than 5 can be damaging to equipment, while a pH over 8 reduces the efficacy of many disinfectants and can have a bitter taste to birds. Hard water can increase scaling of lines and equipment, leading to leaking seals. Scale also provides a matrix for biofilm formation, making cleaning and disinfection more difficult.

Clean and disinfect water lines

Cleaning water lines between flocks is the minimum program for ABF production. Stabilized hydrogen peroxide products are excellent for disinfecting water lines between flocks. The levels needed for proper disinfection of lines are generally too strong for birds, and the lines must be flushed prior to bird placement.

Water lines are often only cleaned in the house; it is important to periodically clean the lines that transport water from the well or water source to the poultry house as this may be a significant reservoir for bacteria. If the well is identified as a source of contamination, it is essential to seek the help of a qualified technician before adding any sanitizing product to a wellhead.

Continuous disinfection

Ideally, water should be continuously disinfected with a product that is approved for poultry consumption. One of the best products for continuous disinfection is chlorine dioxide, which is effective at reducing bacteria and also reducing the concentrations of some mineral components. High levels of iron in the water can create a favorable environment for E. coli and other bacteria such as C. perfringens.

In addition to disinfection, chlorine dioxide is an effective treatment to reduce soluble iron levels. High sodium and chloride levels can lead to flushing and promote the growth of some bacteria. If high levels of sodium and chloride are consistent across a grow-out region, it may be possible to decrease the levels in the feed to reduce flushing. If the levels of sodium and chloride are considerably high, reverse osmosis should be considered to improve water quality.

Bottom line: invest in high-quality water

Another effective product is stabilized hydrogen peroxide at an appropriate residual level for bird consumption. There are other options for water line sanitation that can be explored on a case-by-case basis.

There are excellent online resources [link] for poultry water quality. The important message remains, in any case, that investment in high-quality water is a critical step for success in ABF poultry production.

 

References

Austin, B.J., J. Payne, S.E. Watkins, M. Daniels, and B.E. Haggard. 2016. How to Collect Your Water Sample and Interpret the Results for the Poultry Analytical Package. Arkansas Water Resources Center, Fayetteville, AR, FS-2017-01: 8 pp.

Scantling, M. and Watkins, S. 2013. Identify Poultry Water System Contamination Challenges. FSA8011. University of Arkansas Division of Agriculture Research and Extension.

Watkins, S. 2008. Water: Identifying and correcting challenges. Avian Advice 10(3):10-15. University of Arkansas Cooperative Extension Service, Fayetteville, AR