Toxicology 2 Course 9: Mycotoxins and Associated Pathologies in Animals

CONTENTS

MYCOTOXINS

• ERGOTISM
• FESCUE DISEASE
• MYCOTOXIC ESTROGENIC SYNDROME
• DEOXYNIVALENOL INTOXICATION
• FACIAL ECZEMA OF RUMINANTS
• MYCOTOXIC LUPINOSIS
• TREMORGEN INTOXICATION
• EQUINE LEUKOENCEPHALOMALACIA

Emanuela Badea assistant professor | DVM | PhD | MSc Faculty of Veterinary Medicine of Bucharest UASVMV.

MYCOTOXINS

Fungi are the largest group of microorganisms in the biological system including about 250,000 species, however only several tens of species are of real importance in pathology. The most important pathologies produced by fungi are mycoses, fungal allergies, and mycotoxicosis. Mycoses are diseases caused by fungi whose presence is mandatory in the affected body, such as candidiasis, dermatophytosis (Microsporum spp., Trichophyton spp.), etc. Fungal allergy is a syndrome most commonly caused by mould spores. Mycotoxicoses are diseases caused in animals and humans due to the entry into the body of toxic metabolites (mycotoxins) of some species of fungi, which usually enter the body with food / feed in which they have been synthetized by toxic fungi. Mycotoxicoses do not involve the presence of fungi in the body and sometimes not even in the substrate in which the mycotoxin was developed. Mycotoxins they are metabolism by-products developed by toxin-containing fungi through a series of enzyme-catalyzed reactions under specific conditions of humidity and temperature. The role of these metabolites for the organisms that produce them is not fully known. The name comes from the Greek language (mykes (gr) = fungus + toxikon (gr) = poison). Mycotoxins are produced by all fungi, including macroscopic ones (macromycetes, which produce macro-mycotoxins), but are usually used to describe the toxic metabolites of microscopic fungi (micromycetes, which produce micro-mycotoxins).

ERGOTISM

Ergotism is a mycotoxicosis that occurs from the consumption of parasitic plant products of the ergot fungus, Claviceps purpurea. The toxic part of the mould is the sclerotia (which are compact masses that serve as survival structures, contributing to long-term survival and spread of fungal pathogens). In case of the ergot fungus, the sclerotia are called ergot bodies or ergots. The ergots develop on the spikelets or inflorescences of grasses and cereals. The main plants affected are rye, wheat, barley, oats, ryegrass, orchard grass, Johnson grass, fescue, etc.

Toxic Principles of Ergotism

The toxic principles are classified into three main categories:

• Biogenic amines, are able on their own to cause a range of disorders
  • histamine
  • tyramine
  • isoamyl-amine
• alkaloids
  • peptide alkaloids
    • ergotamine group (ergotamine, ergosine)
    • ergotoxine group (ergocryptine, ergocristine, ergocornine)
  • lysergamides / lysergic acid amides (ergometrine)
  • clavines (clavine alkaloids)
• ergosterol, which is converted by UV irradiation into ergocalciferol (vitamin D2)

Ergotism Toxicodynamics

In general, these substances cause vasoconstriction, uterine contractions, adrenergic blockade and have antagonistic action against serotonin, thus producing central effects (vomiting, bradycardia, inhibition of the vasomotor centre, excitation syndrome, mydriasis, hyperthermia, hyperglycemia) and peripheral effects (stimulation of smooth muscles, which causes vasoconstriction and hypertension, but also oxytocic effect, manifested on the pregnant uterus). Ergotism in animals causes clinical manifestations with different evolutions and intensities depending on the species, the alkaloid content of ergots, and the amount consumed. Cattle and birds seem to have the greatest sensitivity, but the intoxication can also be found in pigs and horses.

Ergotism Clinical Signs

Symptomatology in ergotism is characterized by four types of categories of clinical signs. Gastrointestinal disorders are encountered in cattle, and sometimes in pigs, and include changes in the oral mucosa similar to those found in the foot-and-mouth disease, specifically vesicles (sized from a grain of lentil to a bean) and erosions. The same lesions are found on the rest of the digestive mucosa and in the interdigital space. Other signs include diarrhoea, colic, difficulty when getting up from decubitus, heavy, cautious movement. In pigs, vomiting constantly occurs. The second category of clinical signs, represented by the gangrene of the extremities ("ergotismus gangrenosus"), is found in cattle and pigs, being characterized by mummification of the extremities (phalanx, metacarpus, metatarsus, ears, tail, teats). Birds will present comb and wattle cyanosis, and the gangrene of the beak, tongue, and phalanges, stage after which the extremities they fall off. The third syndrome is characterized by uterine disorders, manifested by exaggerated uterine peristalsis, which leads to abortion, followed by prolonged infertility or sterility. The fourth category of clinical signs, represented by nervous disorders ("ergotismus convulsivus"), is found in cattle and sheep and is translated as hyperexcitability, mydriasis, amaurosis, amyotrophy, or muscle cramps. Despite the impressive symptoms, mortality is low. Sometimes the mentioned symptomatology can be found combined in different ways in the same herd, the diagnosis being, thus, difficult to make. The small amounts of alkaloids, insufficient to determine the mentioned symptomatology, can still cause progressive weight loss, up to cachexia.

Ergotism Diagnosis

The diagnosis is established based on the clinical sings, lesions, and the analysis of the feed from a chemical, macro- and microscopic point of view. The differential diagnosis includes foot-and-mouth disease and intoxication with butenolide (mycotoxin developed by Fusarium tricinctum).

Ergotism Treatment

Treatment is usually ineffective; however, symptomatic treatment can be performed, consisting of the evacuation of the digestive tract, administration of tannin, cardiotonics, vasodilators, and vitamin B3.

FESCUE DISEASE

Fescue disease is a cattle mycotoxicosis caused by butenolide (trichothecene mycotoxin), produced by Fusarium tricinctum and Fusarium nivale, which parasitize orchard fescue (Festuca arundinacea).

Fescue Disease Toxicodynamics

The mechanism of action of butenolide is similar to that of ergotamine, respectively peripheral vasoconstriction.

Fescue Disease Clinical Signs

Clinical signs appear 10-14 days after the cattle are taken out to pasture and continue to appear until one week after the animals are removed from the contaminated area. The symptoms and lesions are similar to those found in ergotism, with an emphasis on lameness, due to gangrene of the extremities of the limbs, but also of the tail and ears, signs accompanied by hypogalactia.

MYCOTOXIC ESTROGENIC SYNDROME

Mycotoxic estrogenic syndrome is produced by zearalenone (F2 toxin), a mycotoxin produced by Fusarium graminearum (Gibberella zeae) which parasitizes corn grains or cobs. The fungus also grows on barley, oats, and wheat when they are stored and preserved incorrectly. Mycotoxic estrogenic syndrome is a disease found worldwide especially in piglets, less often in cattle and birds. The condition for mould development implies a humidity of over 25%. The development of the toxigenic fungus is favored by the temperature of 24-27℃, while the synthesis of zearalenone is optimal at lower temperatures (12-14℃). This ecological particularity explains the higher incidence of intoxication in spring and autumn, when the humidity is high, and high and low temperatures alternate.

Mycotoxic Estrogenic Syndrome Toxicodynamics

The mechanism of action is due to the steroid structure of zearalenone, its main biological effects being estrogenic and anabolic.

Mycotoxic Estrogenic Syndrome Clinical Signs

In pigs, the syndrome begins 4-7 days after the ingestion of contaminated corn and can be easily recognized because it is a mass intoxication, occurring simultaneously in young females and males of 1-4 months old. In females, initially, there is oedema and congestion of the vulva, which progresses until vaginal prolapse occurs, and in males, rectal prolapse and edema of the foreskin are observed. Gestating sows abort or give birth to unviable piglets. In cattle, vulvovaginal congestion and prolonged heat are found. In birds, especially in turkeys, the swelling of the cloaca, cloacal prolapse, and the increase of the bursa of Fabricius can be observed, and in males, the decrease of the sperm fertilization capacity, especially in turkeys and drakes, the roosters being resistant.

Mycotoxic Estrogenic Syndrome Anatomopathological Changes

In pigs, anatomopathological changes include vulvar, vaginal, mammary, foreskin congestion and oedema, vaginal prolapse, hypertrophy of the myometrium, hyperplasia of the uterine mucosa. In birds, cystic degeneration of the oviduct and seminiferous epithelium can be found.

Mycotoxic Estrogenic Syndrome Treatment

Remission is spontaneous if the feed is replaced. After healing, the reproductive function is not affected. LH treatment is ineffective.

DEOXYNIVALENOL INTOXICATION

Deoxynivalenol intoxication is a benign mycotoxicosis in pigs, caused by deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin, produced by Fusarium spp., which parasitize corn or combined fodder. It is also called emetic and feed refusal factor intoxication.

Deoxynivalenol Intoxication Clinical Signs

The disease usually occurs along with mycotoxic estrogenic syndrome and whole populations of finishing pigs. The first clinical sign is the refusal to consume contaminated feed, even if the animals are hungry; individuals who still consume this feed will vomit. Sometimes, emesis is generalized throughout the population. This manifestation has a negative effect on growth performance.

FACIAL ECZEMA OF RUMINANTS

Facial eczema of ruminants is a mycotoxicosis caused by a mycotoxin named sporidesmine, produced by Pithomyces chartarum, which parasitizes pastures, especially plant debris on grasslands, in New Zealand and Australia. Facial eczema of ruminants affects sheep and cattle.

Facial Eczema Toxicodynamics

Sporidesmine has cytotoxic and photosensitizing action in mammals. Initially, sporidesmine causes degeneration of the bile duct epithelium; subsequently, the bile ducts are obliterated with cellular detritus and coagulated bile, and the proliferative connective tissue from the liver produces compression of the bile ducts. Photosensitization is a secondary manifestation, a consequence of the inability of the liver to process phylloerythrin from the blood. Phylloerythrin will accumulate in the peripheral circulation and will absorb solar energy through depigmented and exposed skin areas, thus skin lesion of varying degrees of severity will develop. The animals can be affected repeatedly, which proves that no immune reaction is triggered.

Facial Eczema Clinical Signs

The symptoms are initially represented by anorexia and diarrhoea. After 7-10 days, photodermatitis signs start to appear, with facial and vulvar oedema, and often septic complications (due to trauma occurring in those regions). Depigmented and exposed skin areas are targeted in this intoxication, where lesions can evolve from erythema, oedema, vesicles, to ulceration, crusting, bleeding, and necrosis.

Facial Eczema Anatomopathological Changes

The most frequently observed anatomopathological changes are represented by dermatosis and cutaneous suppuration, diffuse or spotted hepatosis, thickening of the bile ducts, biliary occlusion with coagulated bile, and perihepatitis (on the diaphragmatic side).

Facial Eczema Treatment

The recommended treatment is symptomatic and hygienic-dietary. The animals must be taken out of the action of the sunlight, and shade must be provided. Additionally, it is recommended to administer antihistamines, glucocorticoids, and antibiotics (in case of septic complications). Fluid therapy is also necessary, and, prophylactically, the pastures can be treated with CuSO4.