Nutritional modulation to enhance immunity in chickens

Prevention is better than cure, as they say. Many nutrients, energy, amino acids, vitamins and minerals - play different but significant roles in the immune response and so can contribute to keeping birds in good health, without the need for medication.

Presently, the aim of commercial poultry breeding is to achieve higher body weight and maximum egg production per unit of feed intake. However, there is a negative correlation between production and immunity in chickens as a result of the conflict between production and immunity, i.e. maturation and function oh the immune system. Accomodation of all the physiological demands within the limited resources, i.e. nutrients, available to birds may be the factor responsible for the negative relationship between performance traits and immunity. The genotypes with the maximum bodyweight exhibit lower immunity, as indicated by E. coli lesion score and cellular immunity antibody titres, compared to those having lower body weights. Therefore, the possibility of breakdown of the immune system in commercial chicken crosses is more evident nowadays than before.

In addition to genetic selection, certain non-genetic factors like dietary nutrient concentration also modulate the expression of the genes responsible for immuno-responsiveness by altering the maturity of the immune system and magnitude of antibody production.

Defence mechanism in chickens

Under intensive farming conditions, the poultry environtment contains ubiquitous micro-organisms that continuously challenge the bird;s immune system. Generally, the invading pathogen will be attacked by antibodies, whichs wil neyutralise, weaken and inactiveate the pathogen and finally, phagocytic cels will engulf the invader. The mechanism is quite effective in controlling extra-cellular phatogens, such as bacteria. For the intracellular pathogens-viruses-cell-medicated immunity (CMI) plays a key role. The CMI protects the host by destroying the cells that harbour the pathogen with the help of cytotoxic T-lymphocytes. Againts invading pathogens, the immune system produces a variety of compounds like acute phase protein (APP), proteolytic and hydrolytic enzymes, oxygen radicals and nitrogen derivatives, which destroy the invader or infective cells.

Nutrient recommendations are typically developed using indices of productivity such as growth, egg production and feed efficiency. The criteria for adequacy of immunocompetence are often ignored. Nutrients also influence the maturity of the immune system and magnitude of the antibody. During the acute phase of the immune response, the greatest nutritional need is for the synthesis and release of APP by the liver. The process requires more energy and amino acids than are normally needed for responding leucocytes. Interactions among various nutrients and imbalace or toxicity of nutrients lead to disturbances in normal physiology of the bird, with consequent immunosuppresiaon in chickens.

Energy

Variations on concentration of energy in the diet modulate the immune response in birds, probably due to the change in intake of nutrients, wich influence the immunity. Energy intake regulates the acitvity of the immune cells and activity of certain hormones, e.g. thyroxin, corticosteroids, growth hormones, glucagons, catecholamines, wich influence immunity. Variation in the level and composition of dietary fat also influence the immune response in chickens by altering the structure of the cell membrane and modulating the synthesis of prostaglandins. Mortality associated with E. coli and Mycobacterium tuberculosis was reduced by increasing the level of fat from 3% to 9% of the diet. Antibody titre against sheep red blood cells (SRBC) antigen was markedly increased with supplemental tallow at 6% in the chick diet. Higher levels of unsaturated fatty acids enhance immune function by stimulating macrophages.

Protein

The growth of bursa and thymus are relatively faster than the bird’s body growth. Therefore, it is important to supply the required quantity of protein, particularly during the early growth phase. Deficiency of protein at this stage leads to the improper development of lymphoid organs. Several research workers have suggested that there is a higher amino acid requirement for immunity than for growth. However, the influence of level of protein in diet on severity of disease depends on the type of infective organism. The lesion score to E. coli  inoculation dcreased with the increase in the protein level (18, 20.5 and 23%) in broiler diets. With coccidiosis, the mortality decreased from 32% to 8% in chickens fed protein-deficient diets compared to those fed a normal protein level.

High dietary protein increases the activity of trypsin in the chicken gut. A high level of trypsin in the gut leads to a faster release of coccidia from oocysts, which will aggravate the disease symptoms.

Dieatary methionine levels in exces of those required for maximum growth are essential for maximising immunity. Methionine is required by the thymus-derived- T-cell function. Methionine deficiency produces severe lymphocyte depletion and atrhopy of the bursa and an increased suspectibility to Newcastle disease coccidiosis.

Cystine supplementation also stimulates cellular and humoral immunity (70 to 84% as effective as methionine)

Deficiency (16 to 50%) of branched-chain amino acids, i.e. isoleucine, leucine, and valine, reduces the antibody titres againts SRBC in broilers.

Immunoglobulins contain a high concentration of valine and threonine. A deficiency of either of these amino acids reduces the immune response in chickens. A higher ratio between leucine to valine + isoleucine reduces immunity due to structural antagonism between the three amino acids. The absorption of valine and isoleucine are inhibited by a high leucine content din the diet.

Increasing the dietary concentration of lysine improved the haemagglutination and agglutinin titres, and IgG and IgM levels.

Arginine is a substrate in the synthesis of nitric oxide, a cytotoxic product that is helpfu in phagcytic activity of macrophages and kills bacteria and intracelluar parasites.

Vitamins

Vitamins act as co-factors in several metabolic functions in immune reactions and therefore, deficiencies  of vitamins cause impairmentt of immunity. Generally, higher levels of vitamins than the current recommendations will increase the immune response.

Retinal

This vitamins Is important for maintaining the cellularity of the lymphoid organs and epithelial tissues and for enhancing both cellular and humoral immunity. Vitamin A helps in maintaining the mucous membrane of natural orifices in healthy condition to prevent the invasion of microorganisms. Vitamin A directs differentiation and development of B-lymphocytes. The concentration of vitamin A in the diet modulates the expression of retinoic acid receptors on lymphocytes in chickens.

The production of immunosuppressive agents (hydrocortisones) is reduced with higher levels of vitamin A in the diet. Furthermore, deficiency of vitamin A causes keratinisation of basal cells of the bursa and impairment on the response of T-lymphocytes. Therefore, deficiency of vitamin A impairs immunity by producing defective T, B-lymphocytes, impaired phagocytosis and reduced resistance to infection. Increased morbidity due to Newcastle disease virus has been reported due to a deficiency of vitamin A in the diet. The requirement of vitamin A for maximum immunity, i.e. lymphoid organ weight, was higher than for the bodyweight gain in the chicken. An increase in vitamin A from 12850IU to 42850 or 74045IU/kg decreased mortality due to E. coli, and CRD in chickens and increased the rate of clearance of the pathogen from the blood. However, the benficial effect of higher levels of vitamin A depends on the concentration of other fat-soluble vitamins in the diet. An excessive level of vitamin A interferes with the utilisation of vitamins D and E.

The administration of 60IU of vitamin A per chick per day during a severe attack of coccidiosis reduced mortality from 100% to almost zero. However, practical chick and young layer diets should contain 4000 and 2000UI/kg, respectively. To minimize stress damage and also to prevent immune suppresion, dietary vitamin A levels shoul be increased to ten tomes the normal requirement. A combination of vitamin A (14000IU/kg) and zinc (65mg/kg) has been shown to enhance growth and both humoral and CMI immunity in chickens.

TO BE CONTINUE……

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Avian Influenza: Human Pandemic Concerns

Introduction

The likelihood that the next human influenza pandemic virus will emerge from the Asian strain of the H5N1 high pathogenic bird influenza virus that is causing widespread outbreaks in Eurasia remains unknown. (See Glossary for italicized terms.) Because these bird influenza outbreaks remain primarily an animal disease, there is hope that a human pandemic can be prevented. Eradication of the H5N1 high pathogenic bird influenza virus needs to occur at the farm level in the countries where it is currently circulating. Funding of prevention, surveillance, and eradication efforts in the countries where outbreaks are occurring or in at-risk countries will provide tools needed to facilitate the eradication process of this virus where it is detected and will prevent further spread and subsequent economic loss. Most importantly, stopping the spread of this virus

will decrease the opportunity for the virus to emerge as the next human pandemic influenza virus. Every new poultry infection, and subsequent human exposure, gives the virus an opportunity to adapt directly to humans or to exchange genetic material with other influenza viruses, including human influenza subtypes; either event increases the chances that the bird influenza will become a significant human disease.

Pandemics

A pandemic is an occurrence of a disease in excess of its anticipated frequency that is geographically widespread (perhaps globally). Essentially, a pandemic is an epidemic with a much broader geographic distribution. Pandemics occur when human populations are exposed to highly transmissible disease organisms to which they have little or no immunity. This exposure can result in infections, which result in disease. The organism then escapes the infected human and is transmitted to the next susceptible human. Because the human population is immunologically naïve, every person exposed to the organism is potentially susceptible and may become infected. This process can result in rapid spread of the disease within a population and subsequent spread to distant populations. Pandemics generally spread worldwide within 1 to 3 years. As long as susceptible humans continue to come into contact with the infectious organism, the disease continues to spread. This cycle stops only when large portions of the population become immune to the infection and are no longer shedding the organism in large numbers. Immunity occurs when people become infected, recover from the disease, and have circulating antibodies to protect them from future disease.

Influenza A Viruses

Influenza viruses are identified by proteins that are unique to their virus “type” and “subtype.” The type designation comes from two internal proteins, known as the nucleoprotein and matrix proteins and includes the type A, B, and C influenza viruses. Type A influenza viruses are the most common, and infections have been reported in mammals such as swine, horses, cats, dogs, marine mammals, mink, and humans, as well as in birds. Influenza A viruses have caused several pandemics in humans throughout history; type B and C influenza viruses also commonly cause human disease, but disease outbreaks generally are limited in size. Influenza A viruses are characterized further according to the antigenic characteristics of two surface proteins known as hemagglutinin (H) and neuraminidase (N), resulting in a subtype designation. There are 16 H subtypes and 9 N subtypes currently identified, resulting in 144 different possible combinations of H and N subtypes among the influenza A viruses. The unique segmented structure of the genetic material in influenza A viruses makes them inherently unstable and subject to genetic change (Swayne and Halvorson 2003). 

Humans are commonly infected with H1, H2, and H3 subtypes of influenza A viruses. Viruses of the H5 and H7 subtype are of the most concern to agriculture because some strains have historically caused severe disease in poultry. Because most influenza A viruses are relatively host specific, human influenza viruses generally do not infect birds and bird viruses generally do not infect humans. Certain influenza A viruses, however, have exhibited an unusual ability to infect more than one host species. When influenza A viruses from two host species co-infect the same animal, the viruses have the opportunity to exchange genetic  material that codes for the internal and surface proteins, a process known as antigenic shift. This exchange could result in an emerging virus with a new or expanded host range. As a result, the new virus could infect host species that have never been susceptible before and also could cause a change in the ability of the virus to cause severe illness (Perdue and Swayne 2005). This type of change in a virus capable of spreading among humans could produce a pandemic. Although some pathogenic organisms remain unchanged for many years and can be controlled with vaccines that protect the recipient for a lifetime, influenza A vaccines do not fit into this category. The influenza A viruses accumulate point mutations resulting in sequential minor changes in the dominant circulating strains. This process is known as antigenic drift. Therefore, the influenza vaccine is evaluated yearly and changed frequently to protect against new and emerging strains of influenza A viruses. This is why people in high-risk groups are encouraged to be vaccinated with updated influenza A vaccines every year. 

The subtle changes seen from year to year in influenza viruses generally do not lead to widespread severe disease, but they do make it unfeasible to stockpile large quantities of vaccine for periods longer than 1 to 2 years. Subtle changes in influenza viruses can render vaccines less effective with time. Sudden major changes can render vaccines totally ineffective. 

Historical Pandemics

There were three influenza A pandemics in the twentieth century. The influenza pandemic of 1918 was the deadliest. This pandemic may have began in the United States as an epidemic that was confined largely to military bases and prisons. Public health officials were not overly concerned with the disease because infections tend to spread rapidly among people living in crowded conditions. When American troops took the virus to Europe during World War I, it quickly became established in Europe and spread to Russia, North Africa, India, China, Japan, the Philippines, Brazil, and New Zealand. American troops returning home brought the virus back to the United States and it spread into the civilian population. Almost 700,000 people died from influenza in the United States alone, and 20 to 50 million people died worldwide. Two additional influenza A pandemics have occurred since 1918: the “Asian flu” that resulted in one to two million

deaths in 1957–58, and the “Hong Kong flu” that resulted in approximately one million deaths in 1968–69 (Carver 2005). Each pandemic introduced a new subtype of influenza A virus into the human population. Because people had no immunity to the new subtypes, infection rates were very high, resulting in the spread of the viruses around the world within 1 year of detection. All three pandemics were traced to viruses that originated in birds and could be considered to be zoonotic diseases, that is, diseases that originate as an animal disease, but also are capable of causing disease in humans.

Avian Influenza

All known subtypes of influenza A viruses have been recovered from birds living in an aquatic environment, and these birds are considered to be the natural reservoir. Avian influenza (AI) viruses are carried asymptomatically by ducks, geese, and shorebirds; they typically do not exhibit any signs of disease. These bird species are the perfect disseminators of influenza A viruses worldwide because they migrate for long distances, spreading viruses through contaminated feces. 

Pathogenicity is a measure of the degree of illness that AI viruses cause in chickens. By the current definition from the Office International des Epizooties (OIE) in France, highly pathogenic avian influenza (HPAI) viruses cause death in at least six of eight experimentally infected chickens. In addition, if the genetic sequence of the AI virus in question is similar to that observed for other HPAI strains, then the virus must be

considered to be highly pathogenic, whether or not it causes overt disease. All other AI viruses are considered to be of low pathogenicity (LPAI) (Swayne and Halvorson 2003). This definition of the ability of these viruses to make chickens sick does not apply to humans or human infections with AI viruses. The HPAI viruses are considered to be foreign animal diseases (FADs) in the United States, meaning that they do not normally occur here and they are required to be reported to the state veterinarian’s office and to the U.S. Department of Agriculture–Animal and Plant Health Inspection Service (USDA–APHIS) immediately after detection. To date, all recorded HPAI viruses have been of the H5 or H7 subtypes. The LPAI viruses are endemic to the United States, exist in wild waterfowl and live-bird market reservoirs, and occasionally infect commercial poultry flocks. The LPAI viruses of the H5 and H7 subtypes also are reportable to state authorities because of their historical ability to mutate to the highly pathogenic form.

High pathogenic AI infections cause severe economic losses to affected poultry producers and are, therefore, considered an emergency disease requiring immediate eradication efforts. 

Surveillance systems currently are in place in the United States that focus on detecting AI viruses in poultry. Detection and rapid response are key elements of the U.S. AI control program. The National Poultry Improvement Plan (NPIP), a program of USDA–APHIS in cooperation with the poultry industry, monitors breeder birds (parents) of commercial egg-type chickens, meat-type chickens, and meat-type turkeys for the

presence of antibody to AI viruses. The NPIP currently is establishing a monitoring program for table egg chickens, meat-type chickens, and meat-type turkeys. The NPIP program tested 390,000 AI samples from commercial poultry in 2003 to assure the U.S. poultry industry and their trading partners that poultry products in the United States are free of AI. In addition, many state diagnostic laboratories routinely test backyard and commercial birds presented with respiratory disease signs for the presence of AI. For example, the state of North Carolina tested almost 200,000 birds in 2004 and Georgia tested 100,000 birds in 2003. The USDA–APHIS is developing an AI monitoring program for the live-bird market system in the northeastern United States. 

This early detection must be complemented with rapid and complete containment plans. Avian influenza outbreaks involving low pathogenic strains of the H5 and H7 subtype generally are handled at the state level. Plans to eradicate H5 and H7 strains in poultry flocks have been developed in most poultry-producing states. These plans are widely disseminated and are activated immediately upon detection of one of these strains. These procedures allow poultry producers to protect their investments by quickly eradicating an influenza virus before it becomes highly pathogenic.

Human Cases of Avian Influenza

In recent years, there were fewer than 100 reported human deaths worldwide associated with AI. Most of these deaths were attributed to the Asian HPAI (H5N1) virus that is circulating in parts of (Eurasian) Asia. Most human deaths attributed to Asian HPAI (H5N1) have occurred in Asian countries (Sims et al. 2005). It seems that the virus has spread beyond Asia as migratory waterfowl move to winter nesting grounds or through the movement of infected domestic fowl, but only a small number of human cases have been reported outside of Asia. The farming practices and culinary customs unique to Asia are believed to be associated with the transmission of AI viruses from birds to humans. In most of the human cases of Asian HPAI (H5N1), there was close contact with infected live or recently dead birds. There have been no human cases of Asian HPAI (H5N1) associated with eating properly cooked poultry meat or eggs. The Asian HPAI (H5N1) virus strain infecting humans can cause severe disease and death partly because humans have little to no immunity to the H5 subtype viruses. There have been fewer than 200 documented human cases of Asian HPAI (H5N1) resulting in fewer than 100 deaths during an 8-year period despite the probable exposure of millions of people in these countries, making the transmission of the virus from birds to humans rare. Human-to-human transmission of Asian HPAI (H5N1) has been limited and sustained human-to-human transmission has not been documented; however, each additional human case increases the chance that the virus eventually will improve its transmissibility in humans. The emergence of an Asian HPAI (H5N1) virus strain that is transmitted readily among humans could result in the start of a new pandemic.

Pandemic Risk Assessment

Asian HPAI (H5N1) remains primarily an animal disease. It is not easily transmitted from birds to humans and human-to-human transmission has not been shown to be sustained. The relatively few confirmed human deaths that have occurred worldwide reflect how rare this virus infection is in humans. During the 8-year period cited previously, approximately 288,000 Americans died from human influenza. Currently, the risk of humans contracting Asian HPAI (H5N1) is extremely low. The spread of Asian HPAI (H5N1) to poultry in additional countries is likely during waterfowl migration, through trade in the live-bird markets, and through the movement of infected domestic fowl, especially ducks. Heightened surveillance for waterfowl die-offs and outbreaks in poultry flocks is needed to quickly identify virus spread and to initiate response programs. Because the Asian HPAI (H5N1) virus is highly pathogenic in most poultry species and some wild birds, disease detection should not be difficult in most cases, provided adequate diagnostic capability is available. Domestic ducks, however, have been shown to be asymptomatic carriers of the virus and may serve as a silent reservoir for the disease. Heightened efforts to detect influenza viruses in asymptomatic birds are important to ensure early detection and eradication. Rapid depopulation and destruction of infected flocks followed by thorough cleaning and disinfection are essential in ensuring that Asian HPAI (H5N1) remains an animal disease and is eventually eradicated altogether. Intensified testing of flocks in close proximity to known positive flocks could prevent asymptomatic flocks from moving to processing or to other markets. Unfortunately, many at-risk countries in Eurasia, the Middle East, and Africa lack the necessary diagnostic and animal health infrastructure to adequately carry out surveillance for the presence of Asian HPAI (H5N1) and will require significant financial help from the more developed countries. 

Introduction of Asian HPAI (H5N1) to the United States could occur via infected birds or infected humans. Because the United States does not import live birds or poultry products from countries where the Asian HPAI (H5N1) has been reported, the most likely bird source for Asian HPAI (H5N1) would be migratory waterfowl or illegally smuggled birds. Birds migrating into and out of the Asian HPAI (H5N1) endemic areas are not likely to be an issue in the United States until spring migration and the return of birds to summer nesting grounds. The eastern-most flyways for migratory birds in Asia do include the Arctic and Alaska, although no positive birds have been detected there to date. Increased surveillance along these flyways could facilitate early detection if Asian HPAI (H5N1) were to be introduced. No major poultry-producing regions exist in the Arctic or in Alaska, but the west coast of Canada and of the United States (Washington, Oregon, and California) are potentially at risk. 

Heightened human surveillance for signs of severe respiratory disease should be implemented, especially for those people traveling to or from endemic areas or those living there. Reporting of human cases of respiratory diseases and more intensive testing for influenza A viruses could provide early detection in the unlikely event that human infections occur. 

Different farming systems are associated with the differing risks of both bird infection and human infection. Birds grown in modern enclosed housing are at a much lower risk of contracting AI from wild birds than are birds raised outside. Modern U.S. farm production practices provide for more control over the movement of poultry and allow for the implementation of strict biosecurity procedures designed to prevent the introduction of disease agents to domestic flocks. In addition, commercial poultry raised in integrated agricultural systems typically are grown on farms dedicated to a specific processing plant and are not sold or commingled in livestock markets. Effective surveillance systems and veterinary oversight help decrease the risk of spreading AI viruses in commercial poultry in this country. This modern type of poultry production is more protective of birds and their health than traditional agricultural systems in which birds are raised in small flocks outside, a system that is commonly found in countries in the developing world. The spread of Asian HPAI (H5N1) in Southeast Asia is mostly occurring in small villages where poultry, especially domestic ducks, are raised in open air fields with exposure to wild migratory birds and then sold live in village markets (Sims et al. 2005). This practice promotes the maintenance of the virus reservoir in domestic ducks and leads to recurring infections.

Conclusions

The Asian HPAI (H5N1) remains primarily an animal agriculture disease today. Eradication of this disease needs to occur at the farm level in the countries where it is currently circulating. Adequate federal funding of prevention, surveillance, and eradication efforts in Asia and in the at-risk countries outside of Asia not only will facilitate the eradication process if this virus is detected but also will prevent further spread and subsequent economic loss to the affected country and decrease the opportunity for the virus to adapt to humans. Every new poultry infection, and subsequent human exposure, gives this virus an opportunity to exchange genetic material with other influenza viruses, including human influenza subtypes, and increases the chances that Asian HPAI (H5N1) will become a significant human disease. Education of U.S. citizens about the relatively low risk of becoming infected with Asian HPAI (H5N1) virus is needed to calm the fears of a pandemic created by the almost constant media publicity on this issue. 

GLOSSARY

Antigenic. Having the properties of a substance that induces a specific immune response; usually resulting in the production of antibodies that prevent future disease from specific organisms.

Antigenic drift. Small, gradual changes in the genetic make-up of the virus resulting from errors in copying the genetic material.

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