By Rick Kleyn, SPESFEED (Pty) Ltd.

Anti-Biotic Growth Promoters (AGP’s) are widely used in the South African poultry industry. Their use has already been disallowed in Europe and the USA and South Africa may well follow suite. AGP’s are a cost effective way to ensure animal health and performance, but it is believed that their use leads to an increase in drug-resistant bacteria in human medicine and/or that our foods may contain drug residues. Political pressure is likely to be brought to bear on government, and South African producers may no longer have access to these drugs. This might result in a decline in bird performance with a concomitant increase in production costs. Farm management, especially with regards biosecurity, house environmental conditions and the management of stress will need to be addressed. Nutritionists will increasingly need to take the management of gut microflora into consideration in order to overcome the impact of AGP removal.

The Current Situation

Anti-biotics have been used in animal agriculture since shortly after their discovery. Anti-biotic Growth Promoters (AGP‟s) are commonly used in the South African poultry industry, principally in broiler diets but they may also be used in layer diets. As an industry, we have access to almost all of the AGP‟s ever developed. AGP‟s have characteristics that help explain their position as the additives of choice for growth promotion. In general, they are extremely effective at remarkably low doses and they are relatively cheap, thus yielding a significant return on investment.

The South African poultry industry does not stand in isolation, and it is imperative that we examine what is happening in other parts of the world in order to better understand our own position and how best to manage in future.

In Europe, the Scandinavian countries led the way in removing AGP‟s from their poultry diets. Sweden implemented a ban in 1986, and this was followed by Denmark where a ban came into effect in 1998. The remainder of Europe has followed suite, and in the European Union the use of all AGP’s in animal feed was banned last year (2006). Although, the U.S. Food and Drug Administration (FDA) has not taken action to prevent the use of AGP‟s in animal feed, large poultry producers (Perdue, Tyson, Gold Kist, and Foster Farms) say that they no longer use AGP‟s that may play a role in human medicine. In addition, companies such as McDonald’s and the Compass Group, a large contract food service company, have adopted policies that prohibit the purchase of certain meats if the animals were given anti-biotics important in human medicine to accelerate their growth.

The situation in the USA may soon change if proposed legislation is implemented. The Preservation of Anti-biotics for Medical Treatment Act, sponsored by incoming Senate Health Committee Chairman Edward Kennedy, will phase out the use of anti-biotics that are important in human medicine as animal feed additives within two years. The American Medical Association, the Infectious Diseases Society of America, and the American Academy of Paediatrics‟ are among the more than 350 health, agriculture and other groups nationwide that have endorsed this bill.

The situation in our southern neighbour, New Zealand is interesting. Although AGP‟s have not as yet been banned all drugs, including AGP‟s and coccidiostats require a veterinary prescription if they are to be used. Despite lobbying by the Green Party and retail chains to limit the use of AGP‟s in the poultry industry, the report of the Expert Panel on Anit-biotic Resistance, released in 2006, did not conclude that it was necessary. In Australia, AGP‟s are still allowed.

Against this background it would be worth looking into how AGP‟s work, what the objections to their use are, and what the implications are, should they no longer be available.

How AGP’s work

AGP‟s mode of action is through their effect on the intestinal microflora of the chicken. These microflora reduce animal efficiency through the following mechanisms (Bedford, 2000):

  • Competing with the host for nutrients in the intestinal tract;
  • In some circumstances eliciting an immune response which causes appetite depression and catabolism of muscle protein to fuel this response;
  • Disease, particularly necrotic enteritis (NE);
  • Lowering digestive efficiency by degrading the digestive enzymes and reducing the absorptive surface areas;

Increasing the size of the intestinal tract through the production of stimulatory compounds (e.g. volatile fatty acids); the net result is an increase in the energy required to maintain the gut, thereby leaving less energy available for productive processes.

Most AGP‟s target gram-positive organisms (Clostridium and Streptococcal bacteria), which are associated with poorer health and performance of the animal. AGP‟s lead to a reduction of the microbial destruction of essential nutrients and allow for a thinner intestinal wall, which enhances the absorption and utilisation of nutrients. In essence, AGP‟s not only help to restore a productive homeostatic state, but more importantly, they often prevent disturbances from taking place, thus negating the need for subsequent therapeutic treatments. They control such clinical diseases as NEs and cholaniohepatitis (caused by Clostridium perfringens).

The response of animals to AGP‟s is variable and this is probably dependent upon the environment in which they are raised and the diet that they are offered. As AGP’s exert little or no benefits on the performance of germ free animals, it is clear that their effect is related to their anti-microbial activity rather than being caused by direct interaction with the physiology of the animal.

Research using semi-synthetic diets has shown that the “energy cost” of the gut microflora in broilers was at least 10% of the total AME. A review of the literature by Rosen (1996) indicated that in 12,153 trials, the addition ofAGP‟s to animal diets increased productivity 72% of the time. Rosen‟s work would suggest that the average benefit of feeding AGP’s such as Zinc Bacitracin, to broilers, is an improvement of FCR of approximately 3%, with a range of 0 to 5%.

In some interesting work Graham (2007) and co-workers from the Johns Hopkins University, found that anti-biotics slightly accelerated chicken growth, but that the benefit was offset by the cost of purchasing anti- biotics, with the total cost rising by about one penny per chicken. The data used was supplied by Perdue farms.

Concerns about AGP Use

The first major concern over the use of AGP‟s in animal feed is that it is believed that their use leads to an increase the number of anti-biotic resistant organisms in existence. Under normal conditions, resistance arises as a result of single or multiple genetic mutations. This is a phenomenon to which all cells are susceptible, but which increases in the face of selection pressure. Selection pressure is largely determined by the number of individuals concerned and by the interval between generations, which means that micro-organisms are likely to mutate faster than other animals. More significantly, anti-biotic resistance can be transferred from one bacterium to another, or for that matter, between completely different species of micro-organisms. The ability of some bacteria to resist anti-biotics is carried in non-chromosomal pieces of genetic material called plasmids or R-factors. In addition, there is evidence that suggests that resistance for one class of compound may facilitate the acquisition of resistance of other compounds as well, such as Zinc Bacitracin and Vancomycin resistance in Enterococci.

The food animal population serves as a potential reservoir of resistance and there is a very real possibility of entrance of this resistance into the human population via the food supply. In the past, those of us involved in animal agriculture have argued that it is safe to use anti-biotics in animal production that are not directly used in human medicine. This thinking may well be flawed.

In animal production terms, the development of resistance to a specific compound comes about through normal mutation. The process involves changes in populations and ecology of intestinal microflora. Reduced efficacy of AGP‟s is usually temporary and takes place slowly over a period of months. The process involves changes in populations and ecology of intestinal microflora. Animal producers usually anticipate when bacterial populations are about to become resistant to a given AGP and switch products before efficacy is lost. Most producers change products two or three times per year. Some will also change products during the grow-out period to avoid resistance. In the absence of the old AGP, the bacteria revert to their original state and become sensitive to the new AGP.

The second major concern is that AGP‟s will result in drug residues in animal products. In reality, AGP‟s are absorbed minimally from the gut and do not have a systemic action. In higher animals, the toxicity of anti- biotics is low. There is therefore little risk of residues in the meat or eggs.

It would appear though, that everyone has an opinion on this issue. In December 2002, a report published jointly by the Sierra Club and the Institute for Agriculture and Trade Policy claimed that consumers could reduce their exposure to anti-biotic-resistant micro-organisms by purchasing poultry products that were raised without anti-biotics. This claim was made without doing any research, seriously weakening the assumption. Griggs (2006) and his co-workers were able to show that raising chickens without AGP‟s, especially when the birds are kept outdoors, could result in higher levels of Campylobacter and Salmonella contamination than in conventionally raised chickens. In addition, the removal of anti-biotics from chicken feed did not reduce the incidence of anti-biotic resistance. In the samples collected from chickens raised without anti-biotics, high levels of multiple anti-biotic resistances were noted. This finding is at odds with the work of Danish workers (Aarestrup, 2001) who were able to demonstrate that there was a dramatic reduction in the rates of resistance of specific microorganisms a few years after the withdrawal of AGP‟s. Perhaps it is unrealistic to expect a change in the microflora population in a single generation.

Agricultural and pharmaceutical interests have defended the use of AGP‟s by arguing that they are safe and are needed for efficient farm production. As recently as March this year, Lee of the University of Georgia, found that even birds raised in pristine laboratory conditions had levels of anti-biotic resistance levels comparable to what was seen on farms that used anti-biotics. This would suggest that poultry come to the farm harbouring resistant bacteria, possibly acquired as they were developing in their eggs. It was concluded that the resistances does not necessarily come from anti-biotic use in the birds that we eat and that banning anti-biotic use on the farm is not going to help.

As an industry we have failed to communicate our position to our customers. We need to be able to demonstrate that our products are safe and we need to communicate this in an unambiguous manner to the consumer.

Regardless of the fact that the evidence against the use of AGP‟s is inconclusive, they are perceived to be a risk by consumers and some regulators. The ultimate decision that is made is likely to based on risk management and politics rather than scientific fact. In many cases, influential people and organisations have already made up their minds regarding the dangers of using AGP‟s in animal feed, regardless of the available evidence.

What will happen if AGP’s are no longer available?

In South Africa, we use some of the highest broiler stocking densities in the world. We may not always get the best growth, but we probably achieve some of the highest yields per meter of floor space. This makes us reasonably competitive in global terms. By their very nature, high stocking densities lead to broilers being produced under conditions of high stress with a high bacterial challenge. These are exactly the types of situations where AGP‟s play the greatest role.

When AGP‟s were withdrawn in Sweden, no adverse effects were noted in layer or turkey production. However broiler production was negatively affected and it took approximately four years subsequent to the ban to develop alternative production strategies that could overcome this.

In some European countries, the ban on the use of AGP‟s was followed by an overall increase in total anti-biotic consumption. This fact is often upheld as a fallacy in banning AGP‟s in the first place. In reality, anti- biotics are used for therapeutic reasons at much higher rates, which may actually minimise the possibility of resistance developing. It is of interest that in Denmark, regulations were implemented, at the same time that AGP‟s were banned, to the effect that veterinarians could not profit from the sale of anti-biotics to animal producers.

The removal of AGP‟s from our broiler diets, particularly at high stocking densities will lead to a number of changes in technical efficiency:

  • Mortalities may increase
  • Feed conversion may become poorer.
  • Growth rates will probably decline.
  • It is likely that there will be an increase in conditions such as NE.The net result of these changes will be an increase in the cost of production. My calculations show that the profitability of a broiler operation drops by approximately 35% when stocking density is reduced from 20 to 10 birds per square meter, demonstrating how big an impact stocking density has on broiler profitability. Increased feeding costs and mortalities will probably account for another 10% increase in production costs. In reality, if AGP‟s are removed, producers would probably require a 20 to 30 % premium for their products to maintain their margins.How will we manage in the absence of AGP’s?When AGP‟s are no longer allowed to be used in poultry diets, South African producers will be hard pressed to maintain current performance, as measured by yield per meter, and profitability levels.The key management tool that needs to be used to avoid depression in performance is to avoid and/or prevent infection, through a reduction in the pathogen load the animals are exposed to. It is essential to monitor pathogen status, which is a task that is now routinely performed by the consultant veterinarians in our industry. Sentinel birds raised by SPF companies are available to monitor pathogen presence and causative organisms associated with specific disease.Good management will go a long way to preventing the occurrence and spread of disease. This process can broadly be covered by the term biosecurity, which is a thought process that must be instilled into all employees and strictly adhered to by management for limiting endemic pathogen spread on the farm and between farms.

Biosecurity begins with planning at a macro level (the big picture). The sighting of a poultry operation, its structure and the planning of individual sites always need to be the first consideration. Multi-age sites (and houses for that matter) will need to be eliminated. These should be replaced by “all in all out” systems. This can be taken a step further, as has been done in Brazil, where the biosecurity of whole regions are planned and controlled by a single integrator, who then apply a single health management program to that region.

At the house level a new urgency with regards sanitation, pest control, environmental quality and litter quality will be required. Producers will be forced to implement systems such as nipple as opposed to bell drinkers. Capital will need to be spent on improving the general environments in which we raise our birds. High stocking density levels impact on environmental quality as well as the prevailing pathogen burden in a house.

A second key area with regards the management of birds in and AGP free environment has to do with the level of physiological stress a flock experiences. Stressed birds are more likely to have compromised immune systems and are therefore less able to mount an effective challenge against the pathogens that occur in their environment. Much can be done to reduce stress through improving biosecurity and farm management. It needs to be borne in mind though that high stocking density levels have a direct impact on the levels of physiological stress that occur in a broiler house and these may well need to be reduced. Another aspect that needs to be considered when considering stress is the diet offered to the birds, which will be discussed below.

Nutritional management in the absence of AGP‟s will place a greater demand upon the nutritionist to design economical feeding programs to help nullify any health challenges experienced. These programs will focus on:

  • Reducing of stress
  • Feeding ingredients and nutrients that will maintain cellular integrity.
  • Enhancing the innate immune system
  • Establishing a beneficial microflora
  • Feeding nutrients and ingredients to promote the growth of the beneficial microbes
  • Feeding organic substances to block binding/adhesion of pathogenic bacteria

The nutritionist can play a role in stress management in the broiler flock. As the nutrient density of the diet increases, so too does the growth rate. Fast growing birds suffer far more from stress than slow growing birds, as is evidenced by the increase in metabolic disorders that they experience. Despite the fact that high density diets lead to improved technical and financial efficiencies under South African conditions (which is why they are widely used), it may well become necessary to reduce the nutrient densities of our diets under AGP free conditions.

The gastro intestinal tract (GIT) of the chicken is the largest lymphoid tissue in the body, which makes it an integral part of the immune system. It also means that the manner in which the GIT develops or not, as the case may be, directly affects the immune system. Nutritionists are becoming increasingly aware that nutrition and feeding can and do have an impact. Ensuring that birds have early access to feed and water has a dramatic impact on the development of the GIT, while ensuring adequate nutrient levels will also have a positive effect. Specialist additives such as nucleotides and betaine have been shown to have a direct impact on gut integrity.

Nutritional modulation of the remainder of the immune system, in the absence of AGP‟s, will require a re-evaluation of the nutrient requirements for all stages of growth, for protein and amino acid requirements, energy demands and sources, mineral and vitamin fortifications, and the value of dietary fibre. To date, these requirements have been determined in diets containing therapeutic or sub-therapeutic levels of antimicrobials and will probably need to be reassessed. Water quality will become even more important than it currently is.

Sound nutrition principles and feeding of diets with appropriate quantities and ratios of nutrients are essential for the maintenance of health and promotion of a strong immune system. Adequate nutritional supplementation will further allow the animal to take full advantage of the benefits afforded by alternative additives, of which there are a number on the market. However, there are few alternatives available today that can meet the benefits of the AGP‟s that they purport to replace (Revington, 2002).

Although beyond the scope of this article, there are a number of alternative additives that can be used as alternatives to AGP‟s. These would include:

Compounds that can enhance the structure of the digestive tract itself, such as nucleotides and betaine,

  • Compounds that would alter the form and structure of the gut microflora population such as prebiotics, probiotics and acidifiers
  • Enzymes, which improve the availability of nutrients for uptake by the animal, thereby reducing nutrient availability to the gut microflora.
  • Herbal extracts and other as yet undiscovered phytobiotic products which have an antibacterial or antioxidant activity.
  • Use of water treatments such as iodine or soluble organic acids which may have a residual effect in the birdMany of these products are brought to market on the basis of an hypothesis rather than scientific fact. It can only be suggested that they be properly screened and evaluated before use. Testing a “cocktail” of products is of little use as it is impossible to know which compound is responsible for the improvement or part thereof that was measured. Although few of the alternatives mentioned above will match the efficiency of growth promotion that we have come to expect, combinations of these strategies, applied in tandem, will serve to bring animal performance within reach of previous levels. Perhaps the most daunting impediment will be that of cost; most of these approaches are relatively expensive to implement on their own, let alone in combination (Revington, 2002).South Africa – the futureBefore starting on any discussion about the use of AGP‟s in South Africa, it would be a good idea to remember the market in which we operate. The vast majority of South African consumers simply want to buy cheap food and have little regard for how it was produced. There is a small section of the population, who live in some of the larger metropolitan areas, who are concerned that the meat they eat may contain drugs and hormones and the impact that this may have on their own health. Whether or not resistant human infections are a result of agricultural use or misuse on the part of the medical community is academic. The reality is that this sector of our population does not like the idea of routinely feeding anti-biotics to poultry. These consumers tend to be more vocal in their beliefs than the majority of our people and are thus more likely to be heard.They have already led to the creation of a „niche‟ market for drug-free and free range or „green‟ birds, for want of a better term. It is true that the supermarket chains want to offer their customers alternative products, but they may be driven by profit or image motives, rather than by altruism.

Despite the fact that most of our consumers only really want cheap food, the scientific evidence against the use of AGP‟s is mounting and so too is the perceived risk. It is likely that the future use of the drugs in South Africa will be a political issue rather than a scientific or economic one. Political pressures are likely to come from both local and international quarters. Internationally, the South African government will not want to be seen as being irresponsible and locally they may well listen to the more vocal minority. In short, there is a fair chance that AGP‟s will be excluded from our feeds in future. This will avoid any perceived risk, be it from a health or political perspective.

Producers, together with their nutritionists and veterinarians are urged to start thinking about how we are going to manage their farms without the aid of AGP‟s. We will need to start the learning process by examining what has already been done by other countries. Improved farm management will be required to reduce both the pathogen burden and the stress levels prevalent in our operations. Nutrition and feeding strategies and therapeutic medication must supplement, not be a substitute for, good farm management.

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