47 Mycotoxins and mycotoxicoses

Mycotoxins, secondary metabolites of certain fungal species, are produced when toxigenic strains of fungi grow under defined conditions on crops, pasture or stored feed. The acute or chronic intoxication following ingestion of contaminated plant material is termed mycotoxicosis. More than 100 fungal species, many of them belonging to the genera Penicillium, Aspergillus and Fusarium are known to elaborate mycotoxins. For fungal growth and toxin production, a suitable substrate must be available, along with moisture and optimal temperature and oxygen levels.

Mycotoxins are non-antigenic, low-molecular-weight compounds. Many are heat-stable, retaining toxicity following exposure to the processing temperatures used for pelleting and other procedures (Box 47.1). Some mycotoxins produce clinical signs relating to alterations in functioning of the CNS. Immunosuppression, mutagenesis, neoplasia or teratogenesis may also result from exposure. Epidemiological and clinical features of mycotoxicoses are summarized in Box 47.2.

Mycotoxicoses of defined veterinary importance are presented in Table 47.1. The severity of clinical signs is influenced by the duration of exposure to contaminated feed or pasture, the effect of the mycotoxin on palatability, the amount of mycotoxin ingested and the organs or tissues affected.

Table 47.1 Mycotoxicoses of domestic animals.

Disease / Mycotoxins	Fungus / Crop or substrate	Species affected / Geographical distribution	Functional or structural effects / Clinical findings
Aflatoxicosis / Aflatoxins B₁, B₂, G₁, G₂	Aspergillus flavus, A. parasiticus / Maize, stored grain groundnuts, soyabeans	Pigs, poultry, cattle, dogs, trout / Worldwide	Hepatotoxicity, immunosuppression, mutagenesis, teratogenesis, carcinogenesis / Ill-thrift, drop in milk yield, rarely death from acute toxicity
Citrinin toxicosis / Citrinin	Penicillium citrinum, P. expansum, Aspergillus terreus / Wheat, oats, maize, barley, rice	Pigs, cattle, poultry / Worldwide	Kidney lesions in pigs, haemorrhagic syndrome in cattle / Increased water consumption in pigs, dilute urine, haemorrhages in cattle
Cyclopiazonic acid toxicosis / Cyclopiazonic acid	Aspergillus species, some strains of Penicillium camembertii / Stored grain, meal	Pigs, poultry / Worldwide	Interference with ion transport across cell membranes / Weakness, food refusal
Diplodiosis / Unidentified neurotoxin	Diplodia maydis / Maize cobs	Sheep, cattle, goats, horses / South Africa, Argentina	Neurotoxicity / Ataxia, paresis and paralysis in adults, perinatal deaths in lambs and calves
Ergotism / Ergotamine, ergometrine, ergocristine	Claviceps purpurea / Seed-heads of ryegrass and other grasses, cereals	Cattle, sheep, deer, horses, pigs, poultry / Worldwide	Neurotoxicity and vasoconstriction / Convulsions, gangrene of extremities, agalactia, hyperthermia in hot climates
Facial eczema / Sporidesmin	Pithomyces chartarum / Pasture litter from ryegrass and white clover	Cattle, sheep, goats / New Zealand, Australia, South Africa, South America, occasionally USA and parts of Europe	Hepatotoxicity, biliary occlusion / Photosensitization, jaundice
Fescue toxicosis / Ergovaline	Neotyphodium coenophialum / Tall fescue grass	Cattle, sheep, horses / New Zealand, Australia, USA, Italy	Vasoconstriction / Dry gangrene in cold weather in cattle and sheep (fescue foot); hyperthermia and low milk yields (fescue summer toxicosis)
Fumonisin toxicosis / Fumonisins, especially B₁ and B₂	Fusarium verticillioides, other Fusarium species / Standing or stored maize	Horses, other Equidae, pigs / Egypt, South Africa, USA, Greece	Mycotoxic leukoencephalomalacia in horses, porcine pulmonary oedema / Neurological signs in horses include weakness, staggering, circling, depression
Mouldy sweet potato toxicosis / Derivative of 4-ipomeanol	Fusarium solani, F. semitectum / Sweet potatoes	Cattle / USA, Australia, New Zealand	Cytotoxicity producing interstitial pneumonia and pulmonary oedema / Respiratory distress, sudden death may occur
Mycotoxic lupinosis / Phomopsins A, B, C, D and E	Diaporthe toxica / Growing lupins with stem blight	Sheep, occasionally cattle, horses, pigs / Worldwide	Hepatotoxicity / Inappetence, stupor, jaundice, ruminal stasis, often fatal
Ochratoxicosis / Ochratoxins A, B, C and D	Aspergillus alutaceus, other Aspergillus species, Penicillium verrucosum, other Penicillium species / Stored barley, maize and wheat	Pigs, poultry / Worldwide	Degenerative renal changes / Polydipsia and polyuria in pigs, fall in egg production in birds
Oestrogenism / Zearalenone	Fusarium graminearum, other Fusarium species / Stored maize and barley, pelleted cereal feeds, maize silage	Pigs, cattle, occasionally sheep / Worldwide	Oestrogenic activity / Hyperaemia and oedema of vulva and precocious mammary development in young gilts; anoestrus and reduced litter size in mature sows; reduced fertility in cattle and sheep
Patulin toxicosis / Patulin	Penicillium expansum, Aspergillus species / Rotting fruit, especially apples, apple juice, mouldy bread	Cattle, sheep, pigs / Worldwide	Antibiotic-like effect on ruminal flora, acidosis, vomiting and anorexia in pigs / Poor feed utilization in ruminants, weight loss in pigs
Slaframine toxicosis / Slaframine	Rhizoctonia leguminicola / Legumes, especially red clover, in pasture or hay	Sheep, cattle, horses / USA, Canada, Japan, France, the Netherlands	Cholinergic activity / Salivation, lacrimation, bloating, diarrhoea, sometimes death
Sterigmatocystin toxicosis / Sterigmatocystin	Aspergillus versicolor, A. flavus, other Aspergillus species / Stored wheat flour, cereals, peanuts, dried beans	Cattle, poultry / Many countries	Hepatotoxicity, enteric lesions / Drop in milk yield, dysentery
Tremorgen intoxications
Perennial ryegrass staggers / Lolitrem B	Neotyphodium lolii / Perennial ryegrass	Cattle, pigs, poultry, sheep, horses, deer / USA, Australia, New Zealand, Europe	Neurotoxicity / Muscular tremors, incoordination, convulsive seizures, collapse
Paspalum staggers / Paspalinine, paspalitrems A, B, C	Claviceps paspali / Seed-heads of paspalum grasses	Cattle, sheep, horses / New Zealand, Australia, USA, South America	Neurotoxicity / Muscular tremors, incoordination, convulsive seizures, collapse
Penitrem staggers / Penitrem A, Verruculogen, other mycotoxins	Penicillium crustosum, some Aspergillus species / Stored feed and pasture	Ruminants, other domestic animals / Probably worldwide	Neurotoxicity / Muscular tremors, incoordination, convulsive seizures, collapse
Aspergillus clavatus-induced tremors / Unidentified neurotoxin	Aspergillus clavatus / Sprouted wheat, miller's malt culms	Cattle / China, South Africa, Europe	Neurotoxicity, degeneration of neurons / Frothing from mouth and knuckling of limbs when forced to move
Trichothecene toxicoses
Deoxynivalenol toxicosis / deoxynivalenol	Fusarium graminearum, Fusarium culmorum / Cereal crops	Pigs, rarely other species / Countries with temperate or cold climates	Neurotoxicity / Contaminated feed refused, vomition, poor growth
T-2 toxicosis / T-2 toxin	Fusarium sporotrichioides, F. poae, other Fusarium species / Mouldy wheat, other cereals	Cattle, pigs, poultry / USA	Cytotoxicity, immunosuppression / feed refusal in pigs, rumenitis in cattle, beak lesions in chicken
Diacetoxyscirpenol toxicosis / Diacetoxyscirpenol	Fusarium tricinctum, other Fusarium species / Cereals	Cattle, pigs, poultry / North America, some other regions	Necrotic lesions, mucosal haemorrhages, vomition / Necrotic lesions in alimentary tract, haemorrhages in skin
Stachybotryotoxicosis / Satratoxin, roridin, verrucarin	Stachybotrys chartarum / Stored cereals, straw, hay	Horses, cattle, sheep, pigs / Former USSR, Europe, South Africa	Cytotoxicity, coagulopathy, immunosuppression / Stomatitis, necrotic lesions in alimentary tract, haemorrhages
Myrotheciotoxicosis / Roridin	Myrothecium verrucaria, M. roridum / Ryegrass, rye stubble, straw	Sheep, cattle, horses / Former USSR, New Zealand, south-eastern Europe	Inflammation of many tissues, pulmonary congestion / Unthriftiness, sudden death

Aflatoxicosis

Ingestion of aflatoxins, a large group of difuranocoumarins produced by toxigenic strains of Aspergillus flavus, A. parasiticus and some other Aspergillus species, can cause aflatoxicosis. Aflatoxins B₁, B₂, G₁ and G₂ are particularly important in disease production. After absorption from the gastrointestinal tract, aflatoxins are metabolized in the liver to a range of toxic and non-toxic products. Toxicity relates to binding of metabolites to macromolecules, especially nucleic acid and nucleoproteins. Toxic effects include reduced protein synthesis, hepatotoxicity, carcinogenesis, teratogenesis and depressed cell-mediated immunity.

Clinical signs of disease are usually vague. Epidemiological features and postmortem findings may be of diagnostic value. Aflatoxin may be demonstrated in tissues obtained postmortem. Procedures for aflatoxin detection include thin-layer chromatography, high performance liquid chromatography, immunoassay techniques and biological assays.

Ergotism

Ingestion of toxic levels of certain ergopeptide alkaloids found in the sclerotia of Claviceps purpurea can cause ergotism. This disease occurs worldwide in many domestic animal species and in humans. The fungus colonizes the seed-heads of ryegrasses, rye and other cereals. The most important ergopeptide alkaloids in the sclerotia are ergotamine and ergometrine. These alkaloids have a number of pharmacological effects including direct stimulation of adrenergic nerves supplying arteriolar smooth muscle.

Convulsive ergotism, an acute form of the disease following ingestion of a large amount of mycotoxins, is occasionally observed in ruminants. Small amounts of mycotoxins absorbed over relatively long periods result in persistent arteriolar constriction and endothelial damage. Swelling and redness of body extremities accompanied by lameness is followed by terminal gangrene. Ergotism can often be diagnosed clinically and the presence of ergots in pasture grasses or grain provides supporting evidence. The presence of alkaloids can be confirmed by chromatography.

Facial eczema

This economically important disease of sheep and cattle occurs in Australia, New Zealand and South Africa. The skin lesions develop as a result of photosensitization following exposure to the hepatotoxin sporidesmin in the spores of the saprobic fungus Pithomyces chartarum.

During warm, humid conditions in late summer or early autumn, the fungus sporulates prolifically on pasture litter. Hepatobiliary lesions develop as a result of the accumulation and concentration of sporidesmin in the bile. Necrosis of biliary epithelium results in obstruction of intrahepatic ducts. The reduced capacity of the liver to excrete phylloerythrin, a potent photodynamic compound formed from chlorophyll by enteric organisms, results in photosensitization. In sheep, lesions develop in non-pigmented areas not covered by wool. Jaundice is usually present. In cattle, lesions are limited to areas of non-pigmented skin. Milk production may be seriously affected. In ruminants, photosensitization accompanied by jaundice is suggestive of the disease. Elevated liver enzymes are found in affected animals. Using competitive ELISA techniques, sporidesmin can be detected in many body fluids.

Mycotoxic oestrogenism

Zearalenone is a potent non-steroidal oestrogen produced by certain Fusarium species, particularly F. graminearum, when growing on stored maize and other cereals. Pasture levels of zearalenone in some countries may be sufficient to cause reproductive problems in cattle and sheep. Pigs, particularly prepubertal gilts, may be affected within weeks of ingesting contaminated food. Vulval oedema and hypertrophy of the mammary glands and uterus are features of the disease in gilts. In multiparous sows, anoestrus, pseudopregnancy and infertility may suggest oestrogenism. The mycotoxin can be detected by chromatography. Oestrogen activity in feed can be assayed by injection of extracts into sexually immature mice. An ELISA technique has been developed for detecting zearalenone in pasture samples and urine.

Tremorgen intoxications

Tremorgens, a heterogeneous group of mycotoxins, produce neurological effects including muscular tremors, ataxia, incoordination and convulsive seizures following ingestion.

Perennial ryegrass staggers is one of the most common mycotoxicoses of ruminants and horses in New Zealand, Australia, Europe and the USA. Acremonium lolii, growing on perennial ryegrass, produces lolitrems which are responsible for the clinical signs. Although morbidity may be high in affected herds or flocks, deaths are rare and recovery is rapid if animals are moved from contaminated pasture.

Paspalum staggers is caused by the ingestion of tremorgens present in the sclerotia of Claviceps paspali which are found in the seed-heads of paspalum grasses. The mycotoxins paspalinine and paspalitrems A and B produce typical tremorgen ataxia. Many Penicillium species and some Aspergillus species produce tremorgens when growing on pasture plants or stored feed. The clinical signs resemble those which occur with ryegrass staggers.