PIG

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Certain mycotoxins have been shown to cause significant, detrimental health and performance problems in pigs, including aflatoxin, deoxynivalenol, zearalenone, fumonisin, ochratoxin, ergot, and T-2 toxin. The fungi Aspergillus, Penicillium, Claviceps, and Fusarium spp. have been identified as producing the mycotoxins most detrimental to pigs. The symptoms exhibited and the degree with which pigs are affected by mycotoxin toxicity is largely affected by the kind of mycotoxin(s) involved and their respective concentration in feed, but also by the age and phase of production of the pig. Young pigs and breeding pigs are generally the most susceptible to mycotoxins. In addition, combinations of certain mycotoxins may produce elevated negative effects on performance above that normally expected for each of the mycotoxin levels evaluated individually, and therefore must be considered. Certain types of feeding and housing systems has increased the need for awareness and control of mycotoxicoses in pigs. For example, the use of straw bedding for welfare reasons throughout many developing countries means pigs are also exposed to toxins that may be present in bedding as well as in feed. Mycotoxins typically suppress immune function in pigs, which can decrease resistance to infectious diseases, re-activate chronic infections and/or reduce vaccine and therapeutic antibiotic efficiency. Liquid or wet feeding systems can introduce a significant mycotoxin challenge. It is important to employ strict hygiene procedures to minimise the presence of mycotoxins within the mixer tanks, feed lines and troughs. Even with regular cleaning, it should be noted that mycotoxins are extremely resilient and can survive in the bio-films of feed lines and equipment for significant periods. Do not recycle the waste water after the system is cleaned as this serves to re-introduce mycotoxins into the system.

Aflatoxins Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasitium, usually in warm and humid climates. Although aflatoxins are not considered to be a major problem in cold or more temperate regions, many feedstuffs are imported from warm and humid countries, and may be infected. There is a variety of aflatoxins (B 1, B 2, G 1, G 2, M 1, M 2) produced by Aspergillus flavus. This fungi can produce aflatoxins under temperatures of 10-25°C and grain moisture levels of 22% to 26% provide ideal conditions for producing aflatoxins in a variety of grains, including corn, wheat, barley, and oats. Aflatoxins have been shown to be carcinogenic, and there are concerns about the mycotoxin entering the human food chain via meat and other animal products. For pigs, they are the most acutely toxic of all mycotoxins, causing extensive liver pathology. Due to the carcinogenicity of aflatoxins, many countries have set upper limits for this. Grains containing aflatoxin levels in excess of 20 ppb cannot be used for human consumption and animal feeds, and should not be fed to young animals. At low levels (20 - 200 ppb), aflatoxin decreases performance and well-being. Feed intake is commonly reduced, resulting in depressed growth rate, while immune function is suppressed. At high levels (1000 ppb +), death may occur. Aflatoxins cause many symptoms, including reduced growth rate and feed efficiency and, at extreme levels, liver damage, (fatty liver, lobular necrosis, and an increase in basophilic cells at the periphery

of the lobule and bile duct). In extreme chronic cases, cirrhosis and death may occur. Indicators of liver damage include elevated serum activities of gamma-glutamyltransferase (GGT) and alkaline phosphatase, as well as elevated levels of serum albumin and total protein. Feeding diets contaminated with aflatoxin may exacerbate vitamin A and vitamin E deficiency in pigs, as well as reduce the immune function. This renders the animal more susceptible to any concurrent disease, such as PRRS, PMWS, viral influenza and mycoplasma pneumonia and secondary infections are common. Although low concentrations of aflatoxins may be tolerated by pigs, the combined adverse effects of aflatoxin on hepatic metabolism, protein synthesis and immune status typically reduces swine reproductive efficiency. Increasing the level of aflatoxin B2 to 800 microgram/kg of feed resulted in fewer piglets born alive and weaned (Smith et al., 2005). Indeed, the effects of different aflatoxins on swine reproduction seem to be cumulative.

Clinical signs of aflatoxin toxicosis include: 1. 2. 3. 4. 5. 6. 7.

Reduced feed intake Reduced growth rate Poor feed conversion efficiency Lower sow reproductive performance Reduced lipid digestion Altered kidney function Liver damage: 1. elevated y-glutamyltransferase 2. elevated serum alkaline phosphatase 3. reduced serum albumin and total protein concentration 8. Reduced serum retinol and tocophenol concentration 9. Vitamin A and E deficiency 10. Reduced immuno-competence = more susceptible to disease It has been proposed that 50 ppb should be the upper limit level to prevent the adverse effects of aflatoxins on pig performance. This limit takes account of the possible cumulative or synergistic effects of other mycotoxins that may affect immuno-competence and ensure minimal toxic residues in pork, which may affect the healthiness and safety of pork products. Research trials investigating aflatoxin B1 (Meissonnier et al., 2008) have proven that pigs exhibit reduced performance when exposed to high levels (1807 µg/kg feed) of this toxin. They also had liver lesions, impaired liver enzyme activity, and a reduced cellular-mediated immune response to vaccine antigens. Earlier research (Harvey et al., 1995) had already shown that pigs fed diets containing 2.5 mg aflatoxin/kg feed had reduced cell-mediated immune responses. Liu et al, (2002) showed that phagocytosis was reduced by 36% in an in vitro experiment using pig cells treated with 100 ng/ml B1 toxin. Other studies report that aflatoxin contamination interferes with other immune parameters, including antibody and interleukin production.

Ochratoxin Ochratoxin A is the most important of the ochratoxins which are produced by several species of Aspergillus and Penicillum. Citrinine and oxalic acid are also produced by those moulds. Ochratoxins are ubiquitous in both tropical and temperate climates and are commonly found on oats, barley, wheat and maize. These moulds are capable of producing ochratoxin A at levels up to 10 ppm. Such levels are rarely encountered, but ochratoxin is hazardous to pigs at levels as low as 0.2 ppm (Krogh, 1991). Ochratoxin from feed contaminates organs, fat, muscle tissue, and blood. If ingested over a long enough time period by pigs, this mycotoxin can enter most of the edible tissues, and can produce enough kidney damage to result in carcass condemnation. Acute ochratoxicosis (dietary concentrations exceeding 5 ppm) is characterised by nephropathy (impaired kidney function),

enteritis, fatty liver, necrosis of the lymph nodes, immunosuppression amongst other pathological conditions. In acute cases, death may occur due to acute renal failure. Interest in this mycotoxin has focused on the carcinogenic nature of the compound as it can accumulate in the meat of animals, leading to human health issues. In order to protect the food chain, in Europe in 1997 maximum tolerances of 5 parts-per-billion (ppb) for ochratoxin were set for all foods, and Germany currently enforces a 3 ppb limit. In Denmark, an entire swine carcass is considered contaminated and is condemned if 25 µg/ml ochratoxin is detected in the blood. Pigs are more susceptible to ochratoxin contamination compared to other animals owing to a rather long serum half-life of 72-120 hr. Recent surveys have detected ochratoxins as a natural contaminant of pig blood in Canada, and in many European countries, including Germany, Norway, Poland, Sweden, and former Yugoslavia. In addition, ochratoxin has been found in swine kidneys in the USA, Austria, Belgium, Denmark, Finland, Germany, Poland, Switzerland, Britain, and former Yugoslavia.

Clinical signs of ochratoxin poisoning include: 1. 2. 3. 4. 5. 6. 7. 8. 9.

Reduced performance (feed intake, growth rate, feed conversion efficiency) Pale and enlarged kidneys = tubular degeneration, interstitial fibrosis Impaired renal function = hyperproteinaemia, azotemia Kidney failure = mortality Increased water intake (polydypsia) and urinary output (polyuria) Suppression of cellular immunity = greater susceptibility to infection Reduced boar semen quality = reduced fertilisation rate = reproductive performance Oedema in piglets = stiff arched back, impaired gait Gastric ulcerations

Feeding trials have shown that ochratoxins are associated with loss of immune response in growing pigs (Harvey et al., 1992). Pathological reports indicate that pigs fed up to 2.5 mg/kg ochratoxin had pale, enlarged kidneys with thickened external membranes, and that changes in the kidney cells could be observed (Tapia and Seawright, 1985; Harvey et al., 1994). Corresponding damage with the toxin citrinine have been published (Braunberg et al., 1992).

Zearalenone Zearalenone (F2) is produced by a strain of Fusarium gramearum and proliferates under hot, humid conditions in a variety of feedstuffs, but especially maize. It is an oestrogenic toxin (i.e. mimics the action of hormones) and hence affects reproduction. Rectal and vaginal prolapses are also common symptoms in grow-finish animals. Pre-pubertal gilts are most susceptible to contamination. Gilts and sows exhibit vulval reddening and swelling, while vaginal and rectal prolapses may also occur with zearalenone consumption. Irregular oestrous cycles and reduced litter sizes are also commonly observed. When fed 60-90 ppm zearalenone for the first 15 days post-mating, embryo development is stopped . Not only is the litter lost, but females often won't return to oestrus for several months. This toxin is absorbed from the feed and is detected in the plasma for up to five days after the last administration. It is excreted in urine bound to glucuronic acid, as well as in faeces and influences reproductive function and reduces the activity of 3-alpha-hydroxy-steroid-dehydrogenase. Like DON, zearalenone has been found in masked forms, which complicates analysis. The proposed action/intervention level for Zearalenone is 200 ppb. Zearalenone contamination commonly occurs in combination with DON, as a result of Gibberella ear rot in corn or scabby wheat. However, it is more likely to occur during storage of the grain rather than in the field. The most striking clinical feature of zearalenone toxicosis is the swollen, red vulva of gilts and sows. Reproductive performance is affected as are the number of progeny per litter, increased numbers of stillborn, splay-legged and weak piglets. Piglet birth weight may be highly variable, as blood flow within the uterus can be impaired by the toxin. Semen quality in boars is affected, resulting in loss of fertility.

Clinical effects of Zearalenone: Pre-breeding gilt:

3-5 ppm

Sows

5-10 ppm

Boars:

30-60 ppm 30-60 ppm

All animals:

Swelling and reddening of vulva Enlargement of teats and mammary glands Ovarian and uterine swelling, uterine oedema Retention of corpa lutea (CL) and anoestrus Increased duration of oestrus cycle Additional to the above: Pseudo pregnancy (retention of CL) Reduced litter size; Abortions Reduction and variability in piglet birth weight Birth of weak, stillborn and spaylegged piglets Vulva/teat enlargement in female piglets Increased wean-mating interval Complete embryonic failure Reduction in semen quality; increase in abnormal sperm Reduced libido, loss of hair, oedema of prepuce Rectal and vaginal prolapses Reduced performance

Fumonisin Fumonisins are produced mainly by Fusarium moniliform. Their chemical structure enables them to inhibit lipid synthesis. Historically pigs have been considered not as sensitive to these toxins in comparison to other mammals, e.g. horses, but recently they have been identified as a mycotoxin of concern to pig production. Fumonisins can be found in corn-producing areas. Types B1, B2, and B3 are the most abundant forms, with B1 accounting for approximately 75 percent of total detectable content. Unacceptably high levels of fumonisins can cause excessive fluid to leak into lung tissue causing pulmonary oedema. They also affect the liver, resulting in jaundice and orange-yellow coloured lesions, which are evident at post-mortem. The presence of fumonisins can be easily detected by measuring the ratio of sphingamine to sphingosine in the liver, pancreas and adrenal glands (this biomarker may be used to indicate the presence of other mycotoxins). At toxic levels, pig performance is reduced and pulmonary oedema is evident. Foetal damage may occur and the immune system may be compromised

Clinical symptoms 1. 2. 3. 4. 5. 6. 7. 8.

Reduced performance Foetal damage Acute respiratory failure Pulmonary oedema Cyanosis (blue colour) of skin Jaundice Increased tissue sphingamine: sphingosine ratio (biomarker) Reduced immune competence = increased susceptibility to infection = reduced vaccination response

A threshold level of 200 ppb is proposed for fumonisin, as immune-suppression effects are observed at this level. Residues in pork products are not as hazardous as those of other mycotoxins.

Trichothecenes Trichothecenes: T-2 toxin, Diaceptoxyscirpenol (DAS), Deoxynivalenol (DON), HT-2 toxin Trichothecenes are a group of toxins produced by several Fusarium fungi, notably Fusarium graminearum and Fusarium sporotrichioides. The most important structural features causing the biological activities of the Trichothecenes are the 12, 13-epoxy ring, the presence of hydroxyl or acetyl groups and the structure and position of the side-chains. Trichothecenes are typical field toxins. They are found on harvested grain and enter the feed via contaminated feedstuffs. Trichothecenes are tissue irritants, and oral lesions, dermatitis and intestinal irritation are indicative of their ingestion in affected animals. The major physiological response to trichothecenes mycotoxins is loss of appetite, thus earning them the name, feed refusal toxin. Trichothecenes are strong immune suppressive mycotoxins affecting cellular immune response by directly affecting bone marrow, spleen, lymphoid tissues, thymus and intestinal mucosa, where actively dividing cells are damaged. The main toxins affecting pigs from this group are DON, otherwise known as vomintoxin and T-2 toxin.

Vomitoxin Vomitoxin (Deoxynivalenol or DON) Deoxynivalenol (DON) is commonly known as vomitoxin. This mycotoxin is produced by Fusarium graminearum that often occurs on corn (Gibberella ear rot), wheat and barley (grain Head Scab). The mould usually develops during cool damp weather, resulting in a white or reddish (‘rust’) fungus. Levels above 1 ppm may reduce feed intake and subsequent rate of weight gain. Concentrations above 5 ppm result in feed refusal and above 10 ppm may result in weight loss and vomiting. When contaminated feed is replaced with clean feed, pigs will generally resume normal intake patterns with no other visual apparent symptoms.

Symptoms of DON exposure include: 1. 2. 3. 4.

Gastro-intestinal tract lesions and irritation 3-5 ppm: reduction in feed intake and poor weight gain > 5 ppm: feed intake depression may become severe 10-20 ppm: vomiting and complete feed refusal, resulting in reduced body weight gain or body weight loss 5. Pigs will initially consume sufficient amounts of the ration to induce vomiting, but will voluntarily reduce intake to stop vomiting 6. Adult sows are more tolerant than young pigs 7. Immune suppression Research trials with DON alone and in combination with zearalenone contamination have shown that when these toxins are present in growing pig feeds, they cause reduced weight gain (Casteel et al., 2003).

T-2 toxin 1. 2. 3. 4.

More potent but less common than vomitoxin More likely to be produced during long periods of cool wet weather 1 ppm or greater causes vomiting and decreased feed intake and growth rates Levels of 16-20 ppm cause complete feed refusal

Because of the decline in appetite and performance, as well as the immuno-suppressive effects, it is recommended that action be taken if the concentration of DON in animal feed is >0.2 ppm.

Ergot toxins These are produced from the ergot fungus Claviceps purpurea which affects wheat, oats, ryegrass and other grains by entering the seed and developing into a dark elongated body called a sclerotum. This contains toxic alkaloids, one of which is ergometrine. This reduces the size of the blood vessels and restricts the blood supply, particularly to the mammary gland and body extremities. Levels above 1 g of sclerotum per kg of feed produce clinical signs of ergot poisoning. Typical symptoms include: poor growth rates, increased respiratory rate and general depression. Newborn piglets are small and weak, with a low survival rate. Blood flow to the mammary gland is restricted and this causes loss of milk production (agalactia) in lactating sows. Lameness may also be evident due to necrosis and sloughing of the hooves. Tail and ear necrosis is common, eventually leading to gangrene.

Symptoms Common symptoms associated with mycotoxicoses in pigs include: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

Reduced feed intake Poorer growth rate Decreased feed conversion efficiency Increased incidence of disease Reduced immunity Vomiting Rectal or vaginal prolapse Sudden death Pale or weak pigs Bloody faeces Reduced sow productivity Abortion Increased foetal re-absorption = return to oestrus Inconsistency of sow body condition Delayed puberty in gilts and boars Reduced libido Poorer semen quality = reduced fertility Higher incidence of liver and/or kidney disease

A summary of different fungi, the mycotoxins they produce and the effect of these in pigs, is summarised in the table below:

Individual mycotoxins and their effects on pigs Fungi Aspergillus flavus

Mycotoxin Tissue affected Aflatoxin B1, B2, G1, G2 Liver necrosis, fatty infiltration of the liver, immune-suppression Aspergillus ochraceus Ochratoxin A Renal nephropathy, catum immune-suppression Fusarium moniliforme Fumonisin Pulmonary oedema, Fusaric acid Immune-suppression Vomiting, lethargy, loss of muscle condition Fusarium graminearum Deoxynivalenol (DON, Vomiting, intestinal Vomitoxin etc.) lesions, immunesuppression

Fusarium roseum

Zearalenone

Claviceps purpurea

Ergotoxin

(Smith et al., 2005) Symptom: Lesions

Symptom: Rectal Vaginal prolapse

Symptom: Splay legs

Hyper-oestrogenism, abortion, infertility, prolapses, ulceration Reduced appetite, gangrene, agalactica, mammary gland failure

Symptom: Inflammation of vulva in piglet

Symptom: Skin lesions

Are there safe levels of mycotoxins for pigs? Pigs are extremely sensitive to mycotoxins and their presence, even at low levels, in feed reduces performance in growing and breeding animals, affects the immune and health status and can ultimately lead to death. Irreversible tissue damage can occur, impairing animal performance even when no mycotoxins are present, according to the analysis. The toxicity thresholds vary between classes of stock and health status. Seldom do mycotoxins occur in isolation and there are additive or synergistic interactions between different toxins which markedly decrease the thresholds for concern. Consequently there is really no safe level of mycotoxins. Maximum Tolerable Level of Mycotoxins Commonly Found in Pig Feeds

Mycotoxin

Maximum tolerable Comments level

Aflatoxins (B1, B2, G1, < 20 ppb for human Carcinogenic. G2) use, dairy feed, feed for Immunosuppressant. immature animals Acute signs: anorexia, depression, ataxia, < 100 ppb for breeding epistaxis. swine Chronic signs: reduced feed efficiency, reduced < 200 ppb for finishing milk production, icterus, swine (>120 lbs body decreased appetite. weight) Zearalenone < 1 ppm for young Oestrogenic effects. growing pigs Swollen vulvas, vaginal or rectal prolapses in

< 2 ppm for breeding herd < 3 ppm for finishing pigs and young and old boars.

Deoxynivalenol (vomitoxin)

< 5 ppm on grain and grain by-products. DON contaminated feedstuffs should not exceed 20% of the diet. (< 1 ppm in complete feeds)

T-2 toxin

< 1 ppm

Fumonisin

Not established < 5 ppm (extrapolated from horse data)

Ochratoxin

< 200 ppb has been associated with kidney damage in swine

Ergot

< 200 ppb

Adapted from Feedstuffs Reference Issue (1997)

pre-pubertal gilts. Enlarged uterus, swollen or twisted uterus, shrunken ovaries. In boars, testes atrophy, enlarged mammary glands, decreased fertility. Reduction in feed consumption and weight gain are inversely proportional to concentration of DON. High concentrations cause feed refusal and vomiting. Potent immunosuppressive agent that directly affects immune cells and modifies immune response as a consequence of other tissue damage. Frequent defecation, vomiting, weight loss and feed refusal. Carcinogenic in laboratory tests using rats. Associated with pulmonary oedema in pigs. Ochratoxin A is most common and potent. Reduction in growth, feed efficiency, increased mortality, liver and kidney damage. Vertigo, staggers, convulsions, temporary posterior paralysis, eventual death. Decreased peripheral blood supply. Reduced growth, tail loss, reduced reproductive efficiency of sows.

Permitted limits for mycotoxins in pig diets A summary of the threshold levels at which the different mycotoxins affect pig performance and immune function is presented below: Toxin Threshold level Aflatoxin 50 ppb Ochratoxin 50 ppb Zearalenone 200 ppb Fumonisin 200 ppb Trichothecenes 200 ppb Ergotoxin 0.1%