Immunosuppression due to Mycotoxicoses in Poultry: Control and Prevention
Mycotoxins, the secondary metabolites of fungi, are a global concern. At aerobic conditions, fungal growth in feed raw materials is inevitable. There are many species of fungi that produce mycotoxins, but the majority of the fungi that form mycotoxins belong to only three genuses: Aspergillus (aflatoxin & ochratoxin), Penicillium (ochratoxin) and Fusarium (fumonosins & trichothecenes). Although numerous mycotoxins produced by these fungi are present, only some of these mycotoxins exert pathogenic characteristics. The poisoning in animals caused by feeds contaminated with mycotoxins may range from a slight reaction to death. Fungal growth and mycotoxin production starts in the cropland, during transportation or storage, and are affected by environmental conditions like seasons, rainfall, drought and time of harvest. Poultry feed contain various raw materials that were produced under different climatic conditions and were transport and stored differently. For this reason, multiple types of mycotoxins might be found in a feed. Poultry feeds can contain one or more of the following toxins; aflatoxins, ochratoxin, fumonisins, trichothecenes (deoxynivalenol or DON and T‐2 toxin).
ABSTRACT
Immunosuppression is a status where the immunity is reduced. Humoral (antibodies) and/or cell immunity may be depressed. The causes of immunosuppression may be infectious agents or noninfectious agents. Each of these must be seriously worked out to prevent consequences of immunosuppression on profitability. Immunosupression may affect both health and performances. Increased mortality, uneven growth, decreased body weight, higher feed conversion, higher medication cost and higher rate of condemnations at slaughter are common findings in immunosuppressed birds. Mycotoxicosis is a disease condition caused by a natural toxin produced by a fungus. Mycotoxins on their own are directly immunosuppressive. The fungi that may contaminate the feed ingradients are typically represented by three genera – aspergillus, pencillium and fusarium. They produce mycotoxins that contaminating feed ingradients employed in the poultry industry. Maize, wheat, rice, peanut meal are most frequently implicated. In poultry, this usually results when toxin-producing fungi grow in grain and feed. Hundreds of mycotoxins have been identified, and many are pathogenic. Problems occur worldwide, but especially climates with high temperature and humidity and where grain is harvested with high water content.
INTRODUCTION
Mycotoxins are biologically active, toxic metabolites produced by toxigenic fungi mainly belonging to Aspergillus, Fusarium and Penicillium species, which invade crops in the field and may grow on foods during storage under favorable conditions of temperature and humidity. Mycotoxins may have additive or synergistic effects with other natural toxins, infectious agents and nutritional deficiencies. Mycotoxins cause a wide range of diseases due to immunosuppression, damage of vital organs and interferences with laying capacity is often greater than the impact caused clinical acute symptoms or mortality due to mycotoxin poisoning. Immunosuppression in chickens can be caused by several different factors. Consumption of mycotoxins, at rather low levels that do not cause clinical mycotoxicosis, suppresses immune functions and may decrease resistance to infectious disease. In India, the economy of poultry industry is heavily affected due to wide mycotoxin exposure or contamination of various agricultural commodities. The economic losses are primarily due to the decreased growth rate, feed conversion efficacy, carcass yield, carcass quality and increased susceptibility to other diseases caused due to their immunosuppressive effects among the affected birds. Out of more than 350 mycotoxins identified in nature, aflatoxins, citrinins, fumonisins, ochratoxins and tricothecenes are the most common and important in poultry. Toxicological spectrum of various mycotoxins is very wide encompassing different kind of toxicities viz. acute and chronic toxicities, carcinogenicity, genotoxicity, immunotoxicity, mutagenicity and teratogenicity in animals and poultry.
Mechanism of immunosuppression by various mycotoxins
1.Decreases T or B lymphocytes activity ii) Suppressed immunoglobulin and antibody production iii) Reduced antibody titers and serum concentration of antibodies iv) Impaired macrophage-effector cell function v) Reduced complement of interferon activity .
AFLATOXICOSIS (AFLATOXIN B1)
The aflatoxins are toxic and carcinogenic metabolites of Aspergillus flavus, A parasiticus and others. Aflatoxins B1 (AFB1) is the most common. Aflatoxin B1 (produced by aspergillus) has been shown to impair the immune cells function by reducing the amount of antibodies following infection or vaccination, and by reducing the activity of phagocytic cells. Aflatoxin is also responsible for lymphoid depletion and necrosis in the bursa of Fabricius, spleen and thymus. Aflatoxicosis in poultry primarily affects the liver but can involve immunologic, digestive and hematopoietic functions. Aflatoxin can adversely affect weight gain, feed intake, feed conversion efficiency, pigmentation, processing yield, egg production, male and female fertility and hatchability. Some effects are directly attributable to toxins, whereas others are indirect, such as reduced feed intake. Susceptibility to aflatoxins varies, but in general, ducklings, turkeys, and pheasants are susceptible, while chickens, Japanese quail, and guinea fowl are relatively resistant. Aflatoxins causing immunosuppression due to damage of thymus and bursa of Fabricius make the birds susceptible to other infection like colibacillosis, chronic respiratory disease and Ranikhet disease. Clinical signs vary from general unthriftiness to high morbidity and mortality. In layers, the aflatoxin cause drop in egg production and poor hatchability. At necropsy the lesions are found mainly in the liver. In chronic aflatoxicosis, the liver becomes yellow to gray due to lipid accumulation and atrophied. The aflatoxins are carcinogenic, but tumor formation is rare with the natural disease, probably because the birds do not live long enough for this to occur. The significant microscopic lesions include bile duct epithelium hyperplasia, degenerative and necrotic changes in hepatocytes, nodular hyperplasia of liver parenchyma with infiltration of polymorphonuclear lymphocyte cells in portal tracts, besides considerable changes in kidneys.
CITRININ TOXICOSIS
Citrinin, a nephrotoxic mycotoxin produced by Penicillium citrinum and has been implicated as a causal factor for endemic nephropathy in poultry species. This mycotoxin is a natural contaminant of corn, rice, and other cereal grains. Citrinin causes a diuresis that results in watery fecal droppings and reductions in weight gain. At necropsy, lesions are generally mild and involve the kidney. The kidney appears to be the primary site of action of CIT and produced degenerative and necrotic changes in the renal tubular epithelial cells. The enlargement in size and the increase in the relative weight of the liver during CIT toxicity in poultry might be due to hepatic degeneration and sinusoidal congestion.
OCHRATOXICOSIS
Ochratoxins are quite toxic to poultry. These nephrotoxins are produced chiefly by Penicillium viridicatum and Aspergillus ochraceus in grains and feed. Ochratoxicosis causes primarily renal disease but also affects the liver, immune system, and bone marrow. Severe intoxication causes reduced spontaneous activity, huddling, hypothermia, diarrhea, rapid weight loss, and death. Moderate intoxication impairs weight gain, feed conversion, pigmentation, carcass yield, egg production, fertility, and hatchability. OTA is a carcinogenic mycotoxin. Grossly, a dry and firm gizzard sometimes with mucosal erosions, catarrhal enteritis, dehydration, emaciated carcass, and proventricular mucosal haemorrhages have been observed. Kidneys become enlarged, pale and swollen and change in color from the normal mahogany to tan. Liver is enlarged, friable or haemorrhagic and pale. Extensive accumulation of urates occurs on the serosal surface of several organs. Swelling and color changes of the kidneys have been reported as one of the most consistent lesion of ochratoxicosis in chicken. Histopathologically in kidney, degenerative changes are most pronounced in proximal convoluted tubules (PCT) than in the distal tubules. Severe distension, enlargement and hypertrophy of the renal PCTs and thickening of the glomerular basement membrane are seen commonly. Liver revealed increased accumulation of cytoplasmic glycogen in the hepatocytes.
TRICHOTHECENES (T-2 toxin)
Trichothecens also called fusariotoxins (T-2 toxin), are produced by a number of species of the genus Fusarium. They are strong tissue irritants and alter mucosal membranes integrity. Secondly, they inhibit protein synthesis and consequently interfere with antibody production. The rapidly proliferating tissues such as skin and mucosa, as well as lymphocytic and hematopoietic tissues are primarily affected by these mycotoxins. The primary effect of T-2 toxicosis in young broiler chicks is buccal- oral ulcerations and affects body weight gain in growing chicks. It is generally regarded that the presence of oral lesions in poultry is the primary means of diagnosing trichothecenes toxicosis in the field. The main effects of trichothecenes on the immune system of poultry are: i) inhibition of lymphocyte proliferation ii) lymphopenia and lymphatic necrosis iii) increased mortality to pathogenic bacterial challenge iv) alteration in interleukin metabolism .
Control enviromental factors that influence fungal growth:
- Minimize moisture content of grain and feeds < 13%
- Minimize relative humidity of grain and feeds < 70%
- Minimize storage temperature of grain and feeds <20°C
- Minimize oxygen availability during storage < 0.5%
Diagnosis of mycotoxicoses
Mycotoxicosis should be suspected when the history, signs and lesions are suggestive of feed intoxication, and especially when moldy ingredients or feed are evident. Impaired production can be a clue to a mycotoxin problem, as can improvement because of correction of feed management deficiencies. Definitive diagnosis involves detection and quantitation of the specific toxin(s). Feed and also birds that are sick or recently dead should be submitted for testing. A necropsy and related diagnostic tests should accompany feed analysis if mycotoxicosis is suspected. Feed and ingredient samples should be properly collected and promptly submitted for analysis. Multiple samples taken from different sites increase the likelihood of confirming a mycotoxin formation zone. Samples of 500g should be collected and submitted in separate containers.
Processing of contaminated feeds for toxin inactivation: The physical and chemical treatments, found useful for inactivation of aflatoxins in contaminated feeds or ingredients includes:
- Raising the moisture levels up to 20% and autoclaving at 5 PSI for one hour followed by drying in an oven at 80°C with or without addition of sodium hydroxide (15 g per kg).
- Agitation of feed with Ca (OH)2@ 2% followed by addition of formaldehyde at 15% moisture followed by autoclaving at 15 PSI for half an hour and drying.
- Ensiling after addition of liquor ammonia (6%, v/w) at 20% moisture for 20 days followed by drying at 35°C in an oven.
However, the feasibility of such processing methods has not reached to the farmers’ door. Moreover, such processing methods may not be suitable for poultry feeds. Therefore, the best way of using contaminated feeds are accurate estimation of contents for different mycotoxins for the determination of the safe incorporation of such feeds in compounded feeds.
PREVENTION AND CONTROL
A continuous control of the immune suppression causes is of paramount importance to protect the integrity and the function of the immune system. This will, in turn, give better flock health, better performances and a better response to any vaccination or infection. Detoxification as well as routine analysis of feed ingredients and feed stuffs for mycotoxin contamination before the formulation of poultry ration is an important step in a control programme at field level. Monitoring and control of moisture is critical in the prevention of fungal growth and mycotoxin production. Bulk storage bins of grains must be well ventilated, and the materials must be protected from rain and wide fluctuations of temperatures. Ventilation of poultry houses to avoid high relative humidity also decreases the moisture available for fungal growth and toxin formation in the feed. Antifungal agents added to feeds to prevent fungal growth have no effect on toxin already formed but may be cost-effective in conjunction with other feed management practices. Organic acids (e.g. propionic acid @ 500–1,500 ppm) are effective inhibitors of mycotoxins, but the effectiveness may be reduced by the particle size of feed ingredients and the buffering effect of certain ingredients.
Precautions to be taken at the farm
- Feed troughs should be periodically emptied, and disinfected with a 5% sodium hypochlorite solution. Continuous topping up of feed through is a bad practice. Feeder system should be turned off weekly so that the animals will be forced to clean out all the feed in the troughs before it becomes excessively old and moldy
- Animal houses need to have adequate ventilation. The air inside these houses can be very humid due to respiration and defecation. The whole house including its facilities should be thoroughly cleaned before placing new animals into the houses.
- Leftover old feed should not be brought back to the mill after removing the flock as old feed can be a source of contamination
- Do not use recycled bags if they are wet or exhibit signs of mouldiness.
- Reduce stress to animals
- Reduce intake of suspected contaminated feed by 50% or replace completely
- Dietary manipulations. Because mycotoxins typically reduce nutrient absorption, one approach to alleviate these effects has been to increase levels of critical dietary nutrients
General recommendations to reduce the effects of mycotoxicosis
The following are general recommendations that can attenuate the effects of a mycotoxicosis in animals once these effects have already started.
(a) Increase the level of protein and energy in the diet, as well as the levels of some vitamins, especially riboflavin and D3, given that these vitamins help animals, especially poultry, to detoxify mycotoxin such as AFB1. On the contrary, a deficiency in thiamin has a protecting effect against aflatoxicosis since its deficiency mobilize the lipid reserves, interfering with the hepatic metabolism of aflatoxins.
(b) Provide the contaminated feed to adult animal, except breeding animals. The susceptibility to mycotoxins decreases with age.
(c) Use low level of broad spectrum antibiotics with vitamins and electrolytes in drinking water.
(d) Increase the levels of methionine and cystine in the diet. These amino acids are the precursors of glutathione, which forms conjugated complex with AFB1 inside the animal and especially in the liver. These complexes are then eliminated through feces and urine.
(e) Maintain animals at relatively low temperature. Poultry are more susceptible to aflatoxicosis at high temperatures.
(f) Reduce or eliminate factors that could produce stress in the animals such as sudden changes in temperature and moisture, vaccination, lack of water, inadequate ventilation or high levels of ammonia.
(g) Reformulate the feed using a lower concentration of contaminated ingredients.
(h) If the contaminated ingredients (s) cannot eliminated, give the feed containing the ingredient (s) to animals that are less sensitive, or not sensitive to the mycotoxin that is contaminating the feed.
Mycotoxins can produce a significant reduction in the performance of poultry even at low concentration i.e., 0.02 ppm for aflatoxin and 0.1 ppm for ochratoxin. Poultry is found to be less susceptible to the estrogenic effects of ZEN. At large concentrations in feed, the ill effects of ZEN in poultry may include vent enlargement and secondary sex characteristics. Relatively high concentration of fumonisins are required to produce negative effects in birds as chicken, duck and turkey appear to be fairly resistant to the toxic effects of fumonisins. TCT may impair performance of poultry even the birds receive balanced diet, so care should be taken while selecting the feed ingredients, as TCT mycotoxins are considered as the most potent amongst Fusarium mycotoxins affecting poultry production. Many chemical preservatives can also be used to prevent mould in stored grains. Organic acids such as propionic, acetic, butyric, fumaric, formic, benzoic, tartaric and citric acids can be effectively used. Mycotoxin detoxifying agents such as zeolite, sodium bentonite, mannan oligosaccharides, Saccharomyces cerevisiae, methionine and zinc can be effectively used in combating deleterious effects of aflatoxicosis in poultry.
CONCLUSION
The problem of mycotoxicosis is not so easy to solve and requires constant attention throughout the entire process of grain harvest, storage, feed manufacturing and its formulation. It is important to realize that the effects of mycotoxins on the immune system may severely affect the health status of the entire farm by not only increasing the susceptibility of the animals to disease, but also by lowering the efficacy of vaccination programs. The possible presence of toxic residues in the poultry products (egg, meat) which enters into the food chain may have potential risk by their detrimental effects on human health. There is an urgent need to implement effective mycotoxin counteracting strategy to protect animal health and increase economic growth of poultry industry.
Compiled & Shared by- This paper is a compilation of groupwork provided by the Team, LITD (Livestock Institute of Training & Development)
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