Trichothecene Toxicosis

The trichothecene mycotoxins are a group of closely related secondary metabolic products of several families of imperfect or plant pathogenic fungi. Those of most importance in much of the world are produced species of Fusarium, but also from genera of Trichothecium, Myrothecium, Cephalosporium, Stachybotrys, Trichodesma, Cylindrocarpon, and Verticimonosporium. Trichothecenes are classified as nonmacrocyclic (eg, deoxynivalenol [DON] or vomitoxin, T-2 toxin, diacetoxyscirpenol [DAS], and others) or macrocyclic (eg, satratoxin, roridin, verrucarin). For livestock, the most important trichothecene mycotoxin is DON, which is commonly a contaminant of corn, wheat, and other commodity grains. Lesser amounts of T-2 toxin and DAS are found sporadically in the same sources.

The trichothecene mycotoxins are highly toxic at the subcellular, cellular, and organic system level. Trichothecenes inhibit protein synthesis by affecting ribosomes to interfere with protein synthesis and covalently bond to sulfhydryl groups.

Toxicity of T-2 toxin and DAS is based on direct cytotoxicity and is often referred to as a radiomimetic effect (eg, bone marrow hypoplasia, gastroenteritis, diarrhea, hemorrhages). Direct contact with skin and oral cavity causes irritation and ulceration. Stomatitis, hyperkeratosis with ulceration of the esophageal portion of the gastric mucosa, and necrosis of the GI tract have been seen after ingestion of trichothecenes. Systemic effects of T-2 and DAS are often self-limiting because of oral irritation and feed refusal.

Given in sublethal toxic doses via any route, the trichothecenes are immunosuppressive in mammals; however, longterm feeding of high levels of T-2 toxin does not seem to activate latent viral or bacterial infections. The toxins may affect function of helper T cells, B cells, or macrophages, or the interaction among these cells.

Irritation of the skin and mucous membranes and gastroenteritis are another set of signs typical of trichothecene toxicosis. Hemorrhagic diathesis can occur, and the radiomimetic injury (damage to dividing cells) is expressed as lymphopenia or pancytopenia. Eventually, hypotension may lead to death. Many of the severe effects described for experimental trichothecene toxicosis are due to dosing by gavage. From a practical perspective, high concentrations of trichothecenes often cause feed refusal and therefore are often self-limiting as a toxic problem.

Because of the immunosuppressive action of trichothecenes, secondary bacterial, viral, or parasitic infections may mask the primary injury. The lymphatic organs are smaller than normal and may be difficult to find on necropsy.

Refusal to consume contaminated feedstuffs is the typical sign, which limits development of other signs. If no other food is offered, animals may eat reluctantly, but in some instances, excessive salivation and vomiting may occur. In the past, the ability to cause vomiting had been ascribed to DON only (hence the common name vomitoxin). However, other members of the trichothecene family also can induce vomiting.

In North America and many other parts of the world, DON is a substantial concern because of its common occurrence in feed grains and its well-known ability to cause feed refusal. Swine appear to be most sensitive to feed refusal, with greater tolerance by horses and dogs and even higher acceptance by ruminants.

In swine, reduced feed intake may occur at dietary concentrations as low as 1 ppm, and refusal may be complete at 10 ppm. Ruminants generally will readily consume as much as 10 ppm dietary vomitoxin, and beef cattle have tolerated 12–20 ppm in some circumstances. Poultry may tolerate as much as 100 ppm. Horses may accept as much as 35–45 ppm dietary DON without feed refusal or adverse clinical effects. Dogs also will refuse foods containing DON, usually at concentrations >5 ppm. Related effects of weight loss, hypoproteinemia, and weakness may follow prolonged feed refusal. There is little evidence that DON causes reproductive dysfunction in domestic animals. Experimental studies suggest that DON may cause variable effects of immunosuppression or immunostimulation, but research is continuing to define whether DON has a practical role in disease susceptibility in field conditions.

Feed refusal caused by DON is a learned response known as taste aversion. The major effect of DON is feed refusal; it is rarely if ever a cause of the trichothecene effects described above. It appears related to brain neurochemical changes in serotonin, dopamine, and 5-hydroxyindoleacetic acid. Feed refusal response to DON varies widely among species. DON in swine causes conditioned taste aversion, and swine appear to recognize new flavors (eg, flavoring agents) added to DON-containing feed and thus develop aversion to the new taste as well. Once uncontaminated feed is provided, animals usually resume eating within 1–2 days. A less well-known mycotoxin, fusaric acid, appears to interact with DON in the neurochemical response, leading to feed refusal.

Confirmation of increased levels of DON by analysis in a ration is often used to confirm DON-related feed refusal or to judge the fitness of a feed ingredient. However, some mycotoxins may be “masked” or undetected by routine assay methods. These conjugated mycotoxins may escape detection and not provide adequate warning of feed refusal levels. Use of binders for DON mycotoxin is currently an active area of research. Currently, the aluminosilicates effective for aflatoxins appear not to be useful against DON. Glucomannan yeast-derived adsorbents may have potential to improve some aspects of DON feed refusal in swine, but work is ongoing to clarify use of this category of detoxicants. DON has been removed from barley by an abrasive pearling procedure, which removed two-thirds of DON with loss of only 15% of the grain mass. This and other forms of cleaning grain may prove useful to decrease DON when alternative grain is not available. In addition, diverting grain from swine to the more tolerable ruminants is an alternative as well.

Macrocyclic trichothecene–related diseases have received a number of specific names. The best known is stachybotryotoxicosis of horses, cattle, sheep, pigs, and poultry, first diagnosed in the former USSR but occurring also in Europe and South Africa. Cutaneous and mucocutaneous lesions, panleukopenia, nervous signs, and abortions have been seen. Death may occur in 2–12 days.

Myrotheciotoxicosis and dendrodochiotoxicosis have been reported from the former USSR and New Zealand. The signs resemble those of stachybotryotoxicosis, but death may occur in 1–5 days.