Introduction
Antimicrobials have been used in the poultry industry for growth promotion (sub-therapeutic doses), disease prevention (prophylactic doses), and treatment of infections (therapeutic doses; World Health Organization, Reference WORLD HEALTH ORGANIZATION1997). Phasing out of these substances from poultry diets is a change with many consequences (Bedford, Reference BEDFORD2000). Years of research and practical experience have shown that antimicrobial use has resulted in significant improvements in animal production performance and health status (Coates et al., Reference COATES, DAVIES and KON1955; Miles et al., Reference MILES, BUTCHER, HENRY and LITTELL2006). There is, however, increasing evidence concerning the economic feasibility of inclusion of antibiotic growth promoters (AGP) into poultry diets. A group of researchers at the Johns Hopkins University have recently investigated the economic effects of removing antibiotics used for growth promotion in commercial broiler chickens (Graham et al., Reference GRAHAM, BOLAND and SIRBERGELD2007). The use of AGP in poultry production may actually be associated with economic losses to producers. They concluded that the weight gains that resulted from these antibiotics were not sufficient to offset the cost of their incorporation into poultry diets.
Certain types of antimicrobials have also been used for disease control in human medicine. There is increasing microbiological and clinical evidence that resistant bacteria may pass from animals to humans, resulting in infections that are more difficult to treat (World Health Organization, Reference WORLD HEALTH ORGANIZATION1997; Gorbach, Reference GORBACH2001). Consumer and industry concerns regarding antibiotic-resistant bacteria and the need to treat diseases caused by pathogens that do not respond to antibiotics, has put tremendous pressure on the poultry industry to withdraw or limit use of AGP in poultry feed and to look for viable alternatives (Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004). It is unlikely that a single viable alternative to antimicrobials will be implemented successfully. An effective alternative to in-feed antibiotics should have a significant and sustainable beneficial impact on production performance and health, be safe for both poultry and humans, be easy to apply and store and provide a substantial return on investment (Collett, Reference COLLETT2004). Although several review papers have been published on egg yolk antibodies (Schade et al., Reference SCHADE, STAAK, HENDRIKSEN, ERHARS and HUGL1996; Carlander et al., Reference CARLANDER, STALBERG and LARSSON1999, Reference CARLANDER, KOLLBERG, WEJAKER and LARSSON2000; Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004), there is a need to focus on the roles that these antibodies may play in prevention and control of poultry diseases.
Characteristics of Egg Yolk Antibodies (EYA)
The presence of immunoglobulins in eggs is an example of passive immunity because these antibodies are derived from the dam and protect the offspring from various infectious diseases after hatch (Hatta et al., Reference HATTA, OZEKI and TSUDA1997). The acquisition of passive immunity in birds was first noted in 1893 when Klemperer showed the transfer of immunity to tetanus toxin from hen to chick (Rose and Orlans, Reference ROSE and ORLANS1981). Three immunoglobulin classes (IgA, IgM, and IgY) are present in chickens (Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004). Leslie and Clem (Reference LESLIE and CLEM1969) proposed that chicken IgG be designated as IgY, as it is different from mammalian IgG and forms the main immunoglobulin in chickens (Leslie and Clem Reference LESLIE and CLEM1969; Leslie et al., Reference LESLIE, WILSON and CLEM1971a;b). IgY is transported from the hen to the embryo via the egg yolk, which, as a result contains high concentrations of this antibody (Hamal et al., Reference HAMAL, BURGESS, PEVZNER and ERF2006). Other immunoglobulin classes are present in negligible amounts in the egg yolk (Carlander et al., Reference CARLANDER, STALBERG and LARSSON1999) and IgY is not present in the egg white (Rose et al., Reference ROSE, ORLANS and BUTTRESS1974). The amount of IgY deposited in the egg is directly influenced by the circulating levels in the dam (Hamal et al., Reference HAMAL, BURGESS, PEVZNER and ERF2006; Kitaguchi et al., Reference KITAGUCHI, MINOURA, NORITAKE, MIZUTANI, KINOSHITA, HORIO and MURAI2008). As stated earlier, higher levels of antibodies are usually found in egg yolk than serum, although published data in this area of research are not consistent (Rose et al., Reference ROSE, ORLANS and BUTTRESS1974; Kariyawasam et al., Reference KARIYAWASAM, WILKIE and GYLES2004; Malik et al., Reference MALIK, AYUB and QURESHI2006).
A laying hen can produce approximately 300 eggs annually, and each egg yolk volume is approximately 15 ml (Wilkie, Reference WILKIE2006). The amounts of IgY in yolk are 20-25 mg/ml (Rose and Orlans, Reference ROSE and ORLANS1981), which would supply over 100 g of antibody per hen per year. There are several reports in the literature indicating that IgY levels in the egg yolk are not always consistent and may vary within and between bird populations. Carlander et al. (Reference CARLANDER, WILHELMSON and LARSSON2001) demonstrated that there was day to day variation in concentration of IgY in eggs produced by individual laying hens although this variability was smaller than what was seen among hens. In another study, it was found that the IgY concentration varies significantly among different genetic lines. Great variations were also observed among individual hens within each strain (Carlander et al., Reference CARLANDER, WILHELMSON and LARSSON2003). Production parameters may play a role in this regard. Li et al. (Reference LI, NAKANO, SUNWOO, PAEK, CHAE and SIM1998) demonstrated that egg yolk weight and the percent hen-day production in laying hens may influence efficiency of IgY production. They compared two lines of laying hens and found that the total content of yolk IgY in the line with higher rate of egg production and larger egg size was greater, although there was no significant difference in the activity of IgY produced by two strains of laying hens. The above-mentioned information indicates that it is possible to increase IgY production by genetic selection within high-producing lines (Carlander et al., Reference CARLANDER, WILHELMSON and LARSSON2003). This could be an important step for large-scale production of egg yolk antibodies (EYA).
Egg yolk antibodies
Laying hens are efficient producers of antibodies compared to mammals as EYA can be obtained non-invasively (blood collection is not needed), are produced in high amounts, and isolation process of these antibodies from the yolk is efficient and economical (Schade et al., Reference SCHADE, STAAK, HENDRIKSEN, ERHARS and HUGL1996; Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004). Higher levels of antibodies are usually found in egg yolk than serum of hens following immunisation against a specific pathogen (Rose et al., Reference ROSE, ORLANS and BUTTRESS1974, Kariyawasam et al., Reference KARIYAWASAM, WILKIE and GYLES2004; Malik et al., Reference MALIK, AYUB and QURESHI2006). In order to produce EYA, hens are exposed (usually through intramuscular or subcutaneous injection) to an antigen which induces immune responses including production of specific antibodies to those antigens. These antibodies are then naturally transferred to the egg yolk (Loeken and Roth, Reference LOEKEN and ROTH1983; Sunwoo et al., Reference SUNWOO, NAKANO, DIXON and SIM1996). Booster immunisations are usually given at later time on a regular basis to ensure continued transfer of antibodies from hen to the egg yolk (Sunwoo et al., Reference SUNWOO, NAKANO, DIXON and SIM1996).
These antibodies are subsequently extracted from the egg yolk. The isolation process consists of separation of the yolk from the white and then antibodies (present in the yolk) are purified to remove all other materials. There are various methodologies for harvesting of IgY from the yolk, which generally have different rates of recovery (Akita and Nakai, Reference AKITA and NAKAI1992; Ko and Ahn, Reference KO and AHN2007; DeMeulenaer and Huyghebaert, Reference DEMEULENAER and HUYGHEBAERT2001). After extraction of antibodies from the yolk, they are purified and processed to be administered directly to the animal or incorporated into the feed.
Adding antibodies in the form of whole egg yolk powder to poultry feed is currently the most common method of application. Thermal destruction of IgY may occur at temperatures higher than 75°C, with antigen binding activity of IgY being decreased with increasing temperature and heating time (Chang et al., 1999). However, antibodies might be sprayed on the feed after processing in order to minimise denaturation of these compounds.
EYA can be administered in ovo but there are some concerns that injection of these antibodies may cause significant mortality and reduced hatchability. It may also affect absorption of yolk sac after hatch and subsequent growth rate of in-ovo injected chicks (Eterradossi et al., Reference ETERRADOSSI, TOQUIN, ABBASSI, RIVALLAN, COTTEE and GUITTET1997). These drawbacks may limit this type of application of EYA at commercial level.
Administering EYA has met with some degree of success in prevention or treatment of viral and bacterial infections in humans (Sarker et al., Reference SARKER, CASSWALL, JUNEJA, HOQ, HOSSAIN, FUCHS and HAMMARSTROM2001; Amaral et al., Reference AMARAL, TINO DE FRANCO, CARNEIRO-SAMPAIO and CARBONARE2002; Shin et al., Reference SHIN, YANG, NAM, KIM, MYUNG, BANG and Roe2002; Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004; Nilsson et al., Reference NILSSON, LARSSON, OLESEN, WEJAKER and KOLLBERG2008), pigs (Yokoyama et al., Reference YOKOYAMA, PERALTA, DIAZ, SENDO, IKEMORI and KODAMA1992; Yokoyama et al., Reference YOKOYAMA, HASHI, UMEDA, ICATLO, KUROKI, IKEMORI and KODAMA1997; Kweon et al., Reference KWEON, KWON, WOO, KIM, WOO, SON, HUR and LEE2000; Owusu-Asiedu et al., Reference OWUSU-ASIEDU, NYACHOTI, BAIDOO, MARQUARDT and YANG2003; Girard et al., Reference GIRARD, BATISSON, MARTINE, BRETON, HAREL and FAIRBROTHER2006), calves (Özpinar et al., Reference ÖZPINAR, ERHARD, AYTUG, ÖZPINAR and BAKLACI1996; Yokoyama et al., Reference YOKOYAMA, PERALTA, UMEDA, HASHI, ICATLO, KUROKI, IKEMORI and KODOMA1998), dairy cows ( Zhen et al., Reference ZHEN, JIN, GUO, LI, LU, CHEN and XU2008), fish (Lee et al., Reference LEE, MINE and STEVENSO2000) and rabbits (O'Farrely et al., 1992). EYA have also been used for diagnostic purposes in humans and animals through laboratory assays such as ELISA (Piela et al., Reference PIELA, GULKA, YATES and CHANG1984; Gottstein and Hemmeler, Reference GOTTSTEIN and HEMMELER1985; Gast et al., Reference GAST, PORTER and HOLT1997; Holt et al., Reference HOLT, STONE, GAST and GREENE2000; Hagan et al., Reference HAGAN, ASHTON, BRADBURY and MORGAN2004; Malmarugan et al., Reference MALMARUGAN, RAMAN, JAISREE and ELANTHALIR2005; Thomas et al., Reference THOMAS, BOUMA, VAN EERDEN, LANDMAN, VAN KNAPEN, STEGEMAN and BERGWERFF2006; Young et al., Reference YOUNG, SILVERSIDES and JONES2007; Cray and Villar; 2008).
EYA and poultry infectious diseases
salmonellosis
Lee et al. (Reference LEE, SUNWOO, MENNINEN and SIM2002) observed that the binding activity of IgY against Salmonella enteritidis or S. typhimurium resulted in inhibition of bacterial growth in vitro. This finding suggests that IgY can bind to Salmonella surface components and results in structural and functional changes of these molecules which may subsequently inhibit bacterial growth.
In a further study conducted by Wilkie (Reference WILKIE2006), anti-S. enteritidis EYA were administered to broilers through feed or oral gavage. These antibodies were able to inhibit pathogen attachment to rat epithelial cells and porcine mucin in vitro. In a follow-up study, EYA were orally administered to day-of-hatch broiler chicks which had been infected with S. enteritidis, however no significant reduction in intestinal colonisation was observed. It was concluded that more work is needed to understand the factors influencing antibody activity in broilers and the intestinal conditions that can antibody efficiency before EYA can be considered a prophylactic strategy to reduce salmonellosis.
The use of whole egg powder containing antibodies as a feed additive may be an alternative way to reduce the rate of Salmonella contamination of eggs. Gurtler et al. (Reference GURTLER, METHNER, KOBILKE and FEHLHABER2004) investigated the protective effect of orally-administered egg powder containing antibodies against S. enteritidis in laying hens. The rate of egg contamination was reduced from 29.4% to 13.3% by oral administration of whole egg powder containing S. enteritidis-specific antibodies.
A combination of probiotics and EYA might be more effective in reducing the colonisation of S. enteritidis in poultry (Fulton et al., Reference FULTON, NERSESSIAN and REED2002). These researchers found out that egg-derived anti-S. enteritidis antibody prevented infection of ducklings when given at least 5 d before experimental infection. It was observed that probiotics (Lactobacillus acidophilus, L. bulgaricum, L. reuteri, and Bifidobacterium bifidum) worked synergistically with orally-administered EYA to prevent infection. This synergism might be due to prevention of S. enteritidis from colonising the intestine through competitive exclusion or via the antimicrobial effect of bacteriocin secreted by probiotic bacteria (Fulton et al., Reference FULTON, NERSESSIAN and REED2002). A similar synergism between EYA and probiotics was reported by Tellez et al. (Reference TELLEZ, PETRONE, ESCORCIA, MORISHITA, COBB, VILLASENOR and PROMSOPONE2001).
Different feed additives including Lactobacillus spp., organic acids, multiple probiotics, or egg powder containing antibodies were evaluated for their efficacy in preventing gut colonisation and organ invasion in chicks infected with serotype S. enteritidis phage type 13a (Opitz et al., Reference OPITZ, El-BEGEARMI, FLEGG and BEANE1993). Gut colonisation and organ infection declined during the six-week experimental period in all treatments, but none of the feed additives proved to be effective as a single measure for preventing S. enteritidis infection in chickens.
campylobacteriosis
Anti-Campylobacter jejuni EYA were capable of significant reduction in colonisation by C. jejuni in rat epithelial cells and porcine mucin in vitro, there was no effect in day-of-hatch broiler chicks (Wilkie, Reference WILKIE2006). It was suggested that work is still needed to better identify prophylactic effects that these antibodies might have in vivo. Tsubokura et al. (Reference TSUBOKURA, BERNDTSON, BOGSTEDT, KAIJSER, KIM, OZEKI and L. HAMMARSTROM1997) used EYA obtained from immunised hens for prophylactic and therapeutic applications in chickens infected with C. jejuni. In a prophylaxis experiment, these antibodies caused a significant reduction (up to 99%) in the C. jejuni faecal count throughout the experiment. In a further trial, the therapeutic efficacy (antibodies given after establishment of the infection) was demonstrated, but at a lower rate of reduction (80-95%) compared to prophylactic trial. It was suggested that the main mechanism of action was prevention of attachment of bacteria to the intestinal wall which led to reduced colonisation.
necrotic enteritis
Laying hens hyperimmunised using Clostridium perfringens inoculation resulted in production of antibodies against C. perfringens, indicating possibility for EYA to be used to prevent clostridial diseases in poultry. However, more work is needed in this area. Feeding trials were performed to assess the efficacy of feed amended with the EYA in reducing the level of colonization of C. perfringens in challenged birds. It was observed that the oral administration of EYA did not reduce intestinal C. perfringens in experimentally-challenged birds. Surprisingly, intestinal lesion scores were higher in the birds that received the anti-C. perfringens EYA. This finding is an indication that the antibodies might in fact worsen necrotic enteritis although the reasons for this are unclear.
e.coli infections
EYA induced by immunising hens with selected Escherichia coli antigens were evaluated for their ability to protect broiler chickens against experimental respiratory tract infection and associated septicaemia caused by avian pathogenic E. coli (Kariyawasam et al., Reference KARIYAWASAM, WILKIE and GYLES2004). Seven groups of broiler breeder hens were each vaccinated with E. coli antigens and EYA were obtained from eggs produced by the vaccinated hens. This was injected intramuscularly into 11-day-old broiler chickens, which were challenged three days later with E. coli by the intra-air sac route. One-day-old chicks which received IgY intramuscularly developed protective antibodies in serum that were significantly higher compared to the control group for up to 21 days after administration of the IgY. These protective antibodies were still detectable at day 28 when the experiment was terminated.
Sunwoo et al. (Reference SUNWOO, LEE, MENNINEN, SURESH and SIM2002) investigated the activity of chicken EYA in vitro to determine the growth inhibitory effects of these antibodies on E. coli O157:H7. It was found that the growth inhibitory effect of IgY was high, dose-dependent and could be enhanced by higher concentrations of IgY. The mechanism of growth inhibition by antibodies is not fully understood but it appears to be related to interaction of these antibodies with surface components (i.e. outer membrane protein, lipopolysaccharide, flagella, and fimbriae) of E. coli O157:H7. This may impair biological functions of these essential surface components (Sunwoo et al., Reference SUNWOO, LEE, MENNINEN, SURESH and SIM2002).
Infectious Bursal Disease (IBD)
Malik et al. (Reference MALIK, AYUB and QURESHI2006) investigated the efficacy of EYA, obtained from laying hens immunized with IBD vaccines, in controlling of IBD in commercial laying hens. Antibody titres were significantly higher in yolk than serum of the hens. IBD-infected birds (commercial broilers, layers, broiler breeders, and indigenous birds) injected with these antibodies showed a 92% recovery rate, as compared to a 10% rate for saline-injected controls.
In-ovo inoculation of purified anti-IBD EYA may be a good experimental model for maternally transmitted anti-IBD immunity (Eterradossi et al., Reference ETERRADOSSI, TOQUIN, ABBASSI, RIVALLAN, COTTEE and GUITTET1997). Concentrated EYA were inoculated via the intra-vitelline route into 7-day-old embryonated specific pathogen-free (SPF) eggs. This resulted in hatching two series of SPF chicks with passive immunity against highly virulent IBD virus. The protective immunity produced as result of this method of application was comparable with those reported for non in-ovo injected chicks.
Newcastle Disease (NDV)
Wills and Lunginbuhl (1963) found that sub-cutaneous administration of egg yolk containing high levels of antibodies protected 80% of the birds against virulent NDV for the four week duration of the study. It was suggested that this approach can also be used for other poultry infectious diseases. Although there is a relative lack of recent studies in this area, other older studies reported similar results (Box et al., Reference BOX, STEDMAN and SINGLETON1969; Stedman et al., Reference STEDMAN, SINGLETON and BOX1969).
mixed infections
EYA obtained from hens immunised with a specific infectious agent can provide protection against the disease caused by that pathogen. Simultaneous immunisation of hens with a mixture of pathogens may result in production of EYA effective against each of these pathogens (Sugita-Konishi et al., Reference SUGITA-KONISHI, SHIBATA, YUN, HARA-KUDO, YAMAGUCHI and KUMAGAI1996). These researchers immunised hens with a mixture of twenty-six strains of bacteria and investigated the effects of antibodies collected from eggs on three infectious strains of bacteria (Pseudomonas aeruginosa, S. enteritidis and Staphylococcus aureus), representing opportunistic, invasive, and toxin-producing bacteria, respectively. The EYA produced by these hens prevented multiple bacterial diseases (produced by the above-mentioned strains) by inhibiting processes such as bacterial growth, toxin production or adhesion to cultured human intestinal epithelial cells (Caco 2).
Current challenges
Although beneficial effects of pathogen-specific EYA in animals have been known for about 20 years, results of experimental application of these antibodies to poultry have not always been consistent. Another interesting point is that the quantity of studies concerning possible beneficial effects of EYA in chickens is quite low compared to studies in human and other animal species. This may be a limiting factor in the application of this technology in the poultry industry. In addition, it has been suggested that technical difficulties including bird housing and problems associated with antibody extraction might have limited wider use of IgY in the industry (Schade et al., Reference SCHADE, STAAK, HENDRIKSEN, ERHARS and HUGL1996).
There are still many obstacles which make administration of EYA to commercial poultry a difficult goal to achieve. Like any other novel product, it may take a long time to get approval from regulatory authorities in order to use EYA on commercial poultry farms. Finding suitable alternatives to AGP is a high priority for the industry. This lack of immediate availability appears to have diverted attention from EYA to other more readily available alternatives such as organic acids, prebiotics and probiotics.
The dose of antigen in a given vaccine, route of vaccine administration (intramuscular vs. subcutaneous), frequency of vaccination (initial and boosters) and type of adjuvant present in the vaccine can all affect antibody production in the egg yolk. Adjuvants are different in efficacy and this difference can influence antibody titre in serum and subsequently in the egg yolk (Erhard et al., Reference ERHARD, SCHMIDT, ZINSMEISTER, HOFMANN and MÜNSTER. U. et al.2000; Levesque et al., Reference LEVESQUE, MARTINEZ and FAIRBROTHER2007). Chang et al. (1999) demonstrated that specificity of IgY of intramuscular treated hens was nearly ten times higher than those antibodies produced by subcutaneous route.
Another important consideration is the way that chickens generally respond to a treatment protocol in commercial operations. When a disease outbreak occurs, responses to treatment may vary within and between flocks. The same rule may apply when EYA are used for prophylactic or therapeutic purposes which may not be in agreement with what has been seen under experimental conditions. Variation in response to treatment is, to some extent, related to the virulence of disease-causing agent. The rate of transfer of antibodies against specific pathogens to the egg yolk is significantly different and some part of this variation might be due to genetic differences among chicken lines (Abdel-Moneim and Abdel-Gawad, Reference ABDEL-MONEIM and ABDEL-GAWAD2006; Hamal et al., Reference HAMAL, BURGESS, PEVZNER and ERF2006; Gharaibeh et al., Reference GHARAIBEH, MAHMOUD and AL-NATOUR2008).
Poultry are exposed a wide variety of infectious agents in commercial farms. The poultry industry could benefit more from EYA if they are produced against a variety of common disease-causing microorganisms (Sugita-Konishi et al., Reference SUGITA-KONISHI, SHIBATA, YUN, HARA-KUDO, YAMAGUCHI and KUMAGAI1996). If this approach works well, it may help, to some extent, to justify commercial application of these antibodies.
There is no consensus on what extraction method is most appropriate to use to obtain EYA (Schade et al., Reference SCHADE, STAAK, HENDRIKSEN, ERHARS and HUGL1996). Differences in methods can affect yield, purity, stability, and efficacy of EYA harvested from the egg yolk (Sunwoo et al., Reference SUNWOO, LEE, MENNINEN, SURESH and SIM2002; Karlsson et al., Reference KARLSSON, KOLLBERG and LARSSON2004; Ko and Ahn, Reference KO and AHN2007; Kitaguchi et al., Reference KITAGUCHI, MINOURA, NORITAKE, MIZUTANI, KINOSHITA, HORIO and MURAI2008).
Storage stability of EYA over time is a major concern, although literature in this area, including means of storage, is scattered and inconsistent. Larsson et al. (Reference LARSSON, BALOW, LINDAHL and FORSBERG1993) stored IgY for five to ten years at 4°C without any significant loss in antibody activity. These antibodies also retained their activity after six months at room temperature or one month at 37°C. In another study, purified antibodies stored at 24°C, 4°C, or -20°C lost their precipitating ability after seven days, 56 days, and 70 days, respectively. Lyophilised antibodies did not lose their precipitating ability until after 90 days, suggesting that lyophilisation may be the most effective mean of storage (Malik et al., Reference MALIK, AYUB and QURESHI2006). Nilsson and Larsson (Reference NILSSON and LARSSON2007) showed that IgY preparations are very stable when freeze-dried in the presence of disaccharides (which are used as a stabilising adjuvant). It was suggested that this may be an efficient way to simplify storage and transport requirements of antibodies for diagnostic and therapeutic applications. Shimizu et al. (Reference SHIMIZU, NAGASHIMA, HASHIMOTO and SUZUKI1994) reported that sugars, especially a non-reducing sugar such as sucrose had a stabilising effect on IgY under various physical and chemical conditions.
Orally-administered antibodies, like any other protein molecule, are susceptible to denaturation by the acidic pH of the proventriculus and gizzard and degradation by proteases, however a fraction of the administered dose retains some immunological activity against gastrointestinal tract infections (Reilly et al., Reference REILLY, DOMINGO and SANDHU1997). Activity of orally-administered antibodies decline from proximal to distal regions of the intestine but remained detectable in the caecum (Wilkie et al., Reference WILKIE, VAN KESSEL, DUMONNCEAUX and DREW2006), which may influence the ability of EYA to prevent colonisation of specific pathogens in the lower parts of the intestinal tract. It may be possible to develop a protease-resistant oral dosage form of IgY in order to increase the fraction of immunoreactive antibody delivered locally in the gastrointestinal tract (Reilly et al., Reference REILLY, DOMINGO and SANDHU1997). Viscosity and passage rate of the intestinal tract, in relation to dietary composition, can influence the stability of EYA.
Although there have been no studies conducted to provide estimates on the cost of EYA use in poultry production, it appears that production cost of high quality EYA in a large scale, commercial application is substantial and certainly higher than the cost of routine antibiotics (Casadevall and Scharff, Reference CASADEVALL and SCHARFF1994). Cost-effectiveness is a very important determinant in making a shift or implementing a new strategy in the poultry industry. It has been suggested that constant administration of EYA would be necessary for prophylaxis or therapy in viral or bacterial infections (Wilkie et al., Reference WILKIE, VAN KESSEL, DUMONNCEAUX and DREW2006). This could be a restrictive factor in terms of economical feasibility of their applications.
Conclusions
Specific EYA have beneficial effects in prevention or treatment of bacterial and viral infections in humans and animals. Available literature indicates that this technology has the potential to be used as a disease control strategy in the poultry industry. However, there are still many obstacles remaining, which make commercial production and administration of EYA a difficult goal to achieve.
