The trichothecene mycotoxins are a group of closely related secondary metabolic products of several families of imperfect, saprophytic, or plant pathogenic fungi such as Fusarium, Trichothecium, Myrothecium, Cephalosporium, Stachybotrys, Trichodesma, Cylindrocarpon, and Verticimonosporium spp. On the basis of molecular structure, the trichothecenes are classed as nonmacrocyclic (eg, deoxynivalenol [DON] or vomitoxin, T-2 toxin, diacetoxyscirpenol, and others) or macrocyclic (satratoxin, roridin, verrucarin).
The trichothecene mycotoxins are highly toxic at the subcellular, cellular, and organic system level. They swiftly penetrate cell lipid bilayers, thus allowing access to DNA, RNA, and cellular organelles. Trichothecenes inhibit protein synthesis by affecting polyribosomes to interfere with the initiation phase of protein synthesis. At the subcellular level, these toxins inhibit protein synthesis and covalently bond to sulfhydryl groups.
Trichothecene mycotoxins are generally cytotoxic to most cells, including neoplastic cells; they are not mutagenic. Toxicity of the trichothecenes, except for DON, is based on direct cytotoxicity and is often referred to as a radiomimetic effect (eg, bone marrow hypoplasia, gastroenteritis, diarrhea, hemorrhages). The cutaneous cytotoxicity that follows administration of these compounds is a nonspecific, acute, necrotizing process with minimal inflammation of both the epidermis and dermis. 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.
Given in sublethal toxic doses via any route, the trichothecenes are highly immunosuppressive in mammals; however, longterm feeding of high levels of T-2 toxin does not seem to activate latent viral or bacterial infections. The main immunosuppressive effect of the trichothecenes is at the level of the T-suppressor cell, but the toxins may affect function of helper T cells, B cells, or macrophages, or the interaction among these cells.
Hemorrhagic diathesis may occur after thrombocytopenia or defective intrinsic or extrinsic coagulation pathways. It appears that hemorrhage results from depression of clotting factors, thrombocytopenia, inhibition of platelet function, or possibly a combination of these.
Refusal to consume contaminated feedstuff 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.
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 may be related to neurochemical changes in serotonin, dopamine, and 5-hydroxyindoleacetic acid. Feed refusal response to vomitoxin varies widely among species. DON in swine causes conditioned taste aversion, and swine would be expected to recognize new flavors (eg, flavoring agents) added to DON-containing feed and thus develop aversion to the new taste as well. Provision of uncontaminated feed usually leads to resumption of eating within 1–2 days.
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 up to 10 ppm dietary vomitoxin, and beef cattle have tolerated from 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. Related effects of weight loss, hypoproteinemia, and weakness may follow prolonged feed refusal. There is little credible evidence that vomitoxin causes reproductive dysfunction in domestic animals. Experimental studies suggest that DON may cause variable effects of immunosuppression or immunostimulation, but research is needed to define whether DON has a practical role in disease susceptibility under field conditions.
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. Paresis, seizures, and paralysis occur in almost all species. 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 self-limiting as a toxic problem.
Due to 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.
Although no specific name has been given to most nonmacrocyclic trichothecene-related diseases, the term fusariotoxicosis is often used. Some other names used are moldy corn poisoning in cattle, bean hull poisoning of horses, and feed refusal and emetic syndrome in pigs. A condition in chickens, referred to as “rickets in broilers,” is also thought to be caused by trichothecenes.
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.
Because the clinical signs are nonspecific, or masked by secondary infections and disease, diagnosis is difficult. Analysis of feed is often costly and time consuming but ideally should be attempted. Interim measures are carefully examining feedstuff for signs of mold growth or caking of feed particles and switching to an alternative feed supply. Change of feed supply often results in immediate improvement and thus may provide one more clue that the original feed was contaminated.
Symptomatic treatment and feeding of uncontaminated feed are recommended. Steroidal anti-shock and anti-inflammatory agents, such as methylprednisolone, prednisolone, and dexamethasone, have been used successfully in experimental trials. Poultry and cattle are more tolerant of trichothecenes than are pigs. Pigs exposed to DON often recover appetite promptly when uncontaminated feed is offered.
Last full review/revision March 2012 by Gary D. Osweiler, DVM, MS, PhD