Mycotoxins in Animal Feed

• Contaminants found in animal feeds and livestock water include fungus, mycotoxins, environmental contaminants, and bacterial contaminants.
• This summary covers mycotoxins specifically, as well as other fungal-associated toxins and their effects on livestock health and production.

Mycotoxins

• Mycotoxins are metabolites produced by fungi.
• Mycotoxins are not essential for fungal growth but are produced periodically under fungal stress.
• Mycotoxins are low molecular weight, non-antigenic substances.
• These substances are produced on various substrates including animal feeds under suitable conditions of temperature and moisture.
• Over 300 mycotoxins have been identified from around 350 fungal species.
• In the field, mycotoxins are associated with conditions like facial eczema in New Zealand and lupinosis in Australia for sheep & cattle on lupin stubble.
• The three most reported mycotoxins in livestock production are Aflatoxin, Zearalenone (ZEN), and Deoxynivalenol (DON).
• Aflatoxins are produced by Aspergillus fungi and are acutely toxic, hepatotoxic, immunosuppressive, mutagenic, teratogenic, and carcinogenic.
• AFB₁ (produced by A. flavus) is the most dangerous aflatoxin.
• When AFB₁ is metabolized in mammalian livers, it becomes AFM₁.
• Around 2-6% of AFB₁ ingested by lactating animals is transmitted into their milk as AFM1.
• This means that dairy animals can secrete carcinogenic metabolites (aflatoxin M series) in their milk if they consume aflatoxin-contaminated feed.
• Aflatoxins can be a problem in rain-fed (non-irrigated) peanuts grown in parts of the Burnett region in Southeast Queensland, Australia.
• There have been reported cases of aflatoxicosis in poultry, sheep, pigs, cattle, and dogs.
• Peanut meals and by-products, moldy bread and other bakery waste, and grain sorghum and maize stored with high moisture contents are potential sources of aflatoxins.
• Order of animals most to least susceptible: ducks > turkeys > chicken > fish > pigs > cattle > sheep.
• Fetuses, young animals and fast-growing animals, and males are the most susceptible to Aflatoxins.
• No animal species is resistant to the acute toxic effects from Aflatoxins.
• Aflatoxins are passively absorbed from the gastrointestinal tract (GIT).
• Aflatoxins are absorbed from the intestinal tract into the hepatic portal system.
• Aflatoxin B1 can bind reversibly to albumin, with unbound aflatoxin B1 passing from circulation into tissues.
• Aflatoxins do not readily accumulate in tissues, but repeated exposures can generate toxic effects.
• Aflatoxins may cross the placenta and damage fetal tissue.
• Aflatoxins are eliminated through bile, feces, urine, milk, and eggs.
• Most species will eliminate the toxin within 24 hours after exposure.
• Heat-stable molecules cannot be eliminated using different heat treatments, so preventing formation is essential.
• Decontamination of feed by adding adsorbents to diet can bind aflatoxin such as: clinoptilolite, montmorillonite, bentonite and aluminosilicate.
• Microbial detoxification of contaminated feed has been investigated in chickens.
• Other additives like butylated hydroxytolouene, Urtica diocia seed extract, grape seed proanthocyanidin extract, poultry litter biochar have been used to counteract AFB1 in chickens.

Clinical Signs, Recognition and Treatment

• Mycotoxicosis may be suspected when outbreaks occur and the cause is not readily identifiable, the condition is not transmissible, syndromes may be associated with certain batches of feed, treatment with antibiotics or other drugs has little effect, and outbreaks may be seasonal as weather conditions may affect mold growth.
• Biological action of toxin in host is delayed.
• It is difficult to detect the toxin as it is not uniformly distributed.
• Some toxins only have a short period of existence in the animal, further hampering diagnosis.
• Diagnosis depends on recognition of specific clinical signs which may/may not be present in affected animals.
• General clinical signs of mycotoxins include GI dysfunction, decreased productivity (milk, eggs, weight gains, etc.), decreased feed utilization & efficiency, anaemia, and jaundice.
• Good agricultural, manufacturing, & hygienic practices can help prevent mycotoxins.
• Plant management and appropriate storage conditions are important.
• Chemical & physical decontamination can be used to remove toxins.

Other Mycotoxins

• Ochratoxins are secondary metabolites produced by several species of Penicillium & Aspergillus.
• Ochratoxins block protein synthesis.
• Ochratoxin A is the most toxic, causing neurotoxic, nephrotoxic, teratogenic, hepatotoxic & immunotoxic effects.
• Ochratoxin A can also cause mild liver damage, enteritis, and immunosuppression.
• Ochratoxin A is acutely toxic to poultry & pigs, but is not considered a significant risk to livestock in Australia.
• Ochratoxins also include Ochratoxin B, Ochratoxin C, and Ochratoxin a.
• Ochratoxins enter the circulatory system through GI adsorption and act through several mechanisms at the cellular level.
• Ochratoxin A is a competitor of phenylalanine-tRNA ligase, inhibiting protein synthesis.
• Other mechanisms include formation of DNA adducts, apoptosis, interference with cytoskeleton, lipid peroxidation & inhibition of mitochondrial respiration.
• Ochratoxins are rapidly absorbed & distributed but slowly eliminated & excreted, leading to potential accumulation in the body
• Absorption rate varies between species.
• Ochratoxins are low concentrations in cow milk because of efficient degradation in rumen.
• Non-toxic bacteria, yeasts & fungi isolated from natural microbiota of soil, fruits & vegetables have shown promising results in controlling ochratoxin-producing fungi.
• Fusarium Toxins are capable of inducing both acute & chronic effects depending on dose levels & duration of exposure.
• Fusarium Toxins include Trichothecenes (Type A: T-2 toxin & HT-2 toxin and Type B: DON), Zearalenone and Fumonisin B1.
• Trichothecenes affects actively dividing cells such as those lining the GIT, skin, lymphoid & erythroid cells
• It can cause Intoxication: irritation, haemorrhage, & necrosis throughout GIT but also lower regenerative processes in bone marrow & spleen.
• Type A is not found in Australia.
• T2-toxin inhibits protein synthesis followed by secondary disruption of DNA & RNA synthesis.
• T2-toxin can lower immunoglobulins & certain other humoral factors such as cytokines and causes impaired immune system function but May be changes in reproductive organs.
• T2 Toxin clinical signs: Weight loss, Poor feed utilisation, Inappetance, Vomiting, Bloody diarrhoea, Abortion and In acute cases, death.
• Deoxynivalenol in trichothecenes inhibits reproductive performance & immune function and cause vomiting and persistent feed refusal in pigs at 1mg/kg DM.
• Chickens are more tolerant than pigs to Deoxynivalenol.
• The guidance levels in Australia: Pig diets: 0.5 mg/kg DM, Broiler, layer & duck diets and Sheep & cattle diets: 2 mg/kg DM.
• Zearalenone is a Non-steroidal oestrogenic mycotoxin implicated with infertility in pigs, cattle & sheep.
• It affects the size of mammary glands & reproductive organs at low exposurebut interferes with conception, ovulation, implantation, foetal development & survival at higher doses or longer exposure.
• Young female pigs are susceptible to oestrogenic effects at 0.2 mg/kg in diet.
• Poultry quite resistant.
• Ewes have a lower ovulation rate and increased duration of oestrus and uterine weight from it.
• Fumonisin: FB₁ are fumonisins present in maize in all Australian growing regions and are not regulated in Australia.
• Fumonisin risks for livestock are low given maize rarely as main grain component of mixed diets.
• Major MOA is interference with sphingolipid metabolism leading to a wide range of illnesses such as Leucoencephalomalacia in horses and Pulmonary oedema in pigs

Ergot Alkaloids

• Alkaloids are the compounds produced by certain fungi, specifically Claviceps purpurea and Epichloë species.
• Alkaloids only produced pre-harvest
• Claviceps purpurea occurs predominantly on rye, wheat & barley.
• Different ergot alkaloids have different biological activities.
• Epichloë species (formerly Neotyphodium species) may infect perennial rye grass & tall fescue.
• The biological activity is largely due to the similarity of ergoline ring structure to serotonin, dopamine, noradrenaline, & adrenaline.
• Ergot alkaloids bind biogenic amine receptors & to elicit effects such as: ↓ serum [prolactin] and Vasoconstriction with Associated with D₁-dopaminergic receptor inhibition & partial agonism of a₁-adrenergic & serotonin receptors.
• Ruminants generally less affected than non-ruminants
• Rectal temperatures of affected cattle ~ 41-42°C, ↑ respiration rate.
• Susceptibility seems to vary with species, breed, age, gender, & physiologic state
• Ruminants: vasoconstrictive effects predominate & cause gangrenous & hyperthermic forms of ergot alkaloid intoxication
• Clinical signs in cattle include: loss of ear tips, Loss of tail, or hyperexcitability, loss of tail & recumbency, episcleral congestion, Severe meningeal congestion.

Other Fungal Metabolites & Treatment

• Fat necrosis affects Cattle, goats, deer, pigs, horses and are Hard masses of necrotic fat in mesentery of intestinal tract.
• Fat necrosis can interfere with normal passage of digesta, reproductive capacities & parturition.
• Decreased conception or ↑ early embryonic mortality, Abortions, and Prolonged gestation happens in the mare.
• Thickened (oedema) or retained placental membranes also happens in the mare and causes Agalactia and ↑ rates of newborn mortality.
• Treatment : Recovery unlikely in animals with clinical peripheral gangrene
• Do not handle or move affected animals if ambient temp > 30°C.

Facial Eczema/Lupinosis

• Photosensitisation in sheep, cattle, goats & deer caused by mycotoxin (sporidesmin A) which produced by Pithomyces chartarum that grows on the base of rye grass dominant pasture during warm moist conditions in late summer & Autumn.
• Biologically active center molecules has S-bridged dioxopiperazine ring whileROS responsible for initiating damage to biliary system which lead to cholestasis and photosensitisation.
• Modes of action: liver & biliary tract due to uptake of toxin by liver & excretion in bile and other organs affected include kidney, urinary bladder, & adrenal glands.
• Clinical signs in sheep includes a Photosensitisation 14-18 d after intake of the toxin which leads to Jaundice in severe & chronic cases. In addition, ↑ proportion of barren ewes , ↓ number of ewes with multiple births and ewe & lamb survival. Also ewe & lamb weights is affected.
• Typical Post Mortem signs are Characteristic spherical or “boxing-glove” shape to the liver in sheep.
• Lateral part typically atrophied & became firmer and Hypertrophy of medial part.
• Cattle get Oedema & inflammation of face, ears, lips, vulva, escutcheon & udders of cattle in addition to Diarrhoea& inappetance.
• Cattle can also become irritated in sunlight, seek shade & may suffer stress.
• Clinical signs & Before any clinical signs or elevations in y-glutamyltransferase activity or Bile duct lesions described in subacute cases.
• Affected animals should be kept in dark shed & allowed to graze at night.
• Other prevention of Facial Eczema includes treat pasture with benzimidazole fungicide, Zn prophylactic treatment, and zinc bolus administration to animals.
• Resistance can be achieved via Molecular studies in sheep & cattle to identify chromosomal regions with quantitative trait loci associated with FE resistance.
• Lupinosis is problems in Australia for sheep and cattle that’s caused by Mycotoxins Diaporthe toxica produced by fungi in lupine stubble.
• Clinical signs occurs after as toxicity increases in stump and conditions are wet.
• Clinical signs includes, sheep that is moving stifflegged
• Avoid grazing, and remove the affected cows from the area

Bacterial Contaminants

• Bacterial Contaminants in animal feeds include Clostridium botulinum, Listeriosis and Escherichia Coli.
• Types C & D botulism intoxication (cattle) are mostly related to animal protein derived from cadavers infected with C. botulinum.
• Intoxications is also associated with grazing of land on which poultry litter spread
• Clinical aspects & disease pattern of Type B are also associated with grazing of land on which poultry litter spread but are completely different from botulism caused by C or D type toxins.
• Type B botulism differs since it needs vegetable protein to grow & produce toxin
• Listeriosis is commonly found in silage that are pH levels are around 5.
• Mineral acids, SCFA, isopropyl alcohol, aldehydes, trisodium phosphate are added to feeds to control such bacterial pathogens

Cynaobacteria

• It blooms floating masses of a scums
• They cant be confirmed if it is toxic without examination
• Major hepatotoxic cyanotoxins associated with freshwater includes Microcystins and Cylindrospermopsin. While Neurotoxins Includes Saxitoxins, Anatoxin-A and Anatoxin-a(s)