Mycotoxicoses (Proceedings)

It has been my experience in an academic environment that mycotoxicoses are generally thought to be exclusively a large animal problem. It is true that equine and food animal practitioners do encounter mycotoxin-related issues more commonly than their small animal colleagues, because of the grain- and forage-based diets that livestock consume. However, there are certainly mycotoxicoses with which small animal practitioners should be familiar, especially if contaminated grain byproducts are inadvertently incorporated into a commercial diets, purchased pet food is improperly stored, homemade "vegetarian" diets are improperly prepared, or animals are allowed to roam free and come into contact with garbage and compost piles.

Mycotoxins

Mycotoxins are toxic secondary fungal metabolites, which are generally produced sporadically by certain species of fungi, growing on grains or other matrices of plant origin under specific environmental conditions. Moisture, temperature, pH, and plant stressors can all contribute to the production of mycotoxins. Acute exposures to high doses of fungal toxins can be associated with disease and or death. Chronic exposures to lower mycotoxin doses can be associated with the slower onset of clinical signs and/or ambiguous clinical signs, such as lethargy and failure to thrive.

It has been estimated that 200,000 to 3,000,000 secondary fungal metabolites are possible and that approximately 10% of those metabolites can be classified as toxic. At the present time, only 6,000 secondary fungal metabolites have been identified, and less than 500 of those are considered to be toxic. We are still seeing just the "tip of the iceberg" when it comes to mycotoxins. We probably have a fairly good grasp of the adverse health effects of high doses of the more common mycotoxins, but health problems associated with long-term exposures to lower doses of these fungal toxins have yet to be fully appreciated.

Mycotoxins of clinical relevance to small animals

Aflatoxins

     • Most common mycotoxins produced in raw agricultural commodities worldwide

     • Produced by Aspergillus flavus and Aspergillus parasiticus in CORN, peanuts, and cottonseed, as well almonds, pistachios, Brazil nuts, spices, figs, copra, pecans, walnuts, raisins, and, even, coconuts

     • Conditions of plant stress (drought) followed high moisture (>14%) and elevated temperature (>25° C) favor aflatoxin production.

     • Classified as Polycyclic Furans

     • Include Aflatoxin B1 (predominant and most toxic), Aflatoxin B2, Aflatoxin G1, and Aflatoxin G2 in grains and Aflatoxin M1 in milk urine and, potentially, tissue

     • Aflatoxin B1 is metabolized in the liver to at least 7 metabolites, with Aflatoxin B1-8,9-epoxide being highly electrophilic and capable of damaging macromolecules.

     • Aflatoxins are generally hepatotoxic, as well as carcinogenic, and cause reductions in feed intake weight gain, milk production, hemorrhage, fertility, and immune system function.

     • Dogs and cats appear to be susceptible to pet food concentrations >100 to 300 ppb.

     • FDA "action level" for Aflatoxins is 20 ppb for dogs and cats.

     • Diagnosis is based on evidence of liver damage and the detection of Aflatoxins in pet food and, possibly liver

     • Therapy involves removal from source, prevention of absorption, increased elimination, and supportive care, including administration of antioxidants.

     • Postmortem changes include pale, fatty liver, hepatocyte degeneration, biliary hyperplasia, interlobular fibrosis, and hepatic tumors.

Trichothecenes

     • Produced by Fusarium species and other genera growing on wheat, corn, barley, and oats

     • Cool, wet weather during the flowering and seed development stages favor trichothecene production.

     • Classified as Sesquiterpene Lactones and divided into Class A (T-2, HT-2, and DAS, Class B (Vomitoxin or DON), Class C (Satratoxin produced by Stachybotrys) and Class D (Crotocin)

     • Tricothecenes are extremely potent inhibitors of protein synthesis and interfere with the initiation, elongation, and termination phases of translation, as well as various stages of DNA and RNA synthesis.

     • Vomitoxin (Deoxynivalenol or DON) is produced by Fusarium graminearum (roseum) and is the most common but least toxic of trichothecenes (usually associated feed refusal, vomiting, diarrhea, and immunomodulation

     • Vomiting was initially induced in dogs and cats exposed to dietary levels of DON between 4 and 10 ppm.

     • In dogs, feed intake is reduced with dietary levels of DON >4.5 ppm, and similar reductions in feed intake are observed in cats with dietary levels of DON >7.7 ppm.

     • FDA "action level" for DON is 2 ppm for dogs and cats.

     • Diagnosis is based on the detection of DON in pet food, vomitus, or stomach contents.

     • Therapy involves removal from source, prevention of absorption, increased elimination, and supportive care.

Zearalenone

     • Zearalenone is produced by Fusarium graminearum (roseum) growing on corn, wheat, barley and oats

     • Moisture >23% (45% optimal) and temperatures between 20 and 25° C increase zearaleonone synthesis.

     • A Phenolic with estrogenic activity

     • Reports of dietary concentrations of 1-3 ppm of Zearalenone being associated with reproductive abnormalities in the ovaries and uteri of exposed bitches

     • Diagnosis is based on clinical signs and the detection of Zearalenone in pet food.

     • Therapy involves removal from source, prevention of absorption, increased elimination, and supportive care.

Ergot alkaloids

     • Produced by Claviceps purpurea (ergot) in cereal grains and characterized by the replacement of seed heads by ergot sclerotia (ergot bodies), under conditions of Cool, wet weather

     • Ergot Alkaloids are associated with hypoprolactinemia and vasoconstriction.

     • Prolactin is both luteotrophic and lactogenic in the bitch, especially during the second half of pregnancy, and Ergot Alkaloid exposure can be associated with canine abortion

     • Agalactia and/or dry gangrene of the extremities have also been observed in instances of Ergot Alkaloid exposure.

     • Diagnosis is based on clinical signs and the detection of ergot alkaloids in pet food.

     • Therapy involves removal from source, prevention of absorption, increased elimination, and supportive care, including the possible administration of D2 dopamine receptor antagonists.

Tremorgenic Mycotoxins

     • Penitrem A and Roquefortine are the primary Tremorgenic Mycotoxins, which are clinically relevant in small animals.

     • Produced by Penicillium crustosum and other fungal species growing on moldy cheeses and walnuts, as well as in garbage containers and compost piles

     • Tremorgenic mycotoxins can decrease the concentration or function of inhibitory neurotransmitters, such as GABA and glycine, and increase presynaptic neurotransmitter release.

     • Diagnosis is based on clinical signs of tremors and/or seizures, the detection of Tremorgenic Mycotoxins in pet food, garbage, composted material, vomitus, stomach contents, or urine.

     • Therapy involves removal from source, prevention of absorption, increased elimination, and supportive care, including control of tremors and seizures

Mycotoxins, including Aflatoxins, Trichothecene, Zearalenone, and Ergot Alkaloids, pose a risk to small animals, especially when pets are consuming lesser quality pet foods, products which have been improperly stored. Dogs are especially susceptible to exposure to Tremorgenic Mycotoxins because of their indiscriminant eating behavior and potential access to garbage containers and compost piles. The diagnosis of most mycotoxicoses is generally based on the observed clinical signs and the detection of mycotoxins in pet food, garbage, composted material, vomitus, and/or stomach contents. Therapy for most mycotoxicoses involves removal from the source, prevention of further absorption, increased elimination, and supportive care.