Diagnosis is based on clinical signs, liver lesions, and laboratory detection of aflatoxins in the feed or milk. Treatment includes immediately ceasing the aflatoxin contaminated feed and providing livestock with a quality diet with an appropriate level of protein, vitamins, and trace minerals. If animals are immunosuppressed, antimicrobial therapy for infectious processes and improved biosecurity should be considered. No specific antidote is available. Control of aflatoxicosis during drought or widespread contamination in crops requires avoiding aflatoxin contaminated feed and using analytical testing for aflatoxins in feed batches. While the use of mycotoxin binders in feed are not approved by the US FDA, it is generally recognized that hydrated sodium calcium aluminosilicates (HSCAs) are effective in binding aflatoxin in the feed and reducing absorption in the gut. The use of HSCAs can reduce, but not eliminate, contamination of aflatoxin M1 in milk of dairy animals fed aflatoxin contaminated feed. Recovery time can be prolonged and return to production status delayed or diminished.
Aflatoxins are bisfuranocoumarin metabolites produced by toxigenic strains of Aspergillus flavus, A parasiticus, and A nomius on peanuts, nuts, corn (maize), rice, cottonseed and other cereals, either in the field or during storage when moisture content and temperatures are sufficiently high for mold growth. Usually, this means consistent day and night temperatures >21.1°C (70°F). Climatic conditions of drought or prolonged hot weather, corn variety, and insect damage to crops can influence aflatoxin production. The toxic response and disease in mammals and poultry varies in relation to species, sex, age, nutritional status, and the duration of intake and level of aflatoxins in the ration. Earlier recognized disease outbreaks called moldy corn toxicosis, poultry hemorrhagic syndrome, and Aspergillus toxicosis may have been caused by aflatoxins. The primary aflatoxins analyzed in crops include aflatoxins B1, B2, G1, and G2, with the letter indicating the fluorescence color under ultraviolet light (ie, blue for B1 and B2 and green for G1 and G2). Aflatoxin B1 is recognized as the predominant toxin found in crops, and the most toxic and carcinogenic metabolite. Under optimal conditions, high concentrations of aflatoxins can be produced quickly or within a few days in field corn.
Aflatoxicosis occurs in many parts of the world and affects growing poultry (especially ducklings and turkey poults), young pigs, pregnant sows, calves, and dogs. Adult cattle, sheep, and goats are relatively resistant to the acute form of the disease but are susceptible if toxic diets are fed over long periods. Experimentally, all species of animals tested have shown some degree of susceptibility. Dietary concentrations of aflatoxin generally tolerated are ≤50 ppb in young poultry, ≤100 ppb in adult poultry, ≤50 ppb in weaner pigs, ≤200 ppb in finishing pigs, <50 ppb in dogs, <100 ppb in calves, and <300 ppb in cattle. Approximately 2 times the tolerable levels stated is likely to cause clinical disease, including some mortality. Dietary levels as low as 10–20 ppb result in measurable metabolites of aflatoxin (aflatoxin M1 and M2) being excreted in milk of lactating animals; feedstuffs that contain aflatoxins should not be fed to dairy cows, goats, or sheep. Acceptable regulatory concentrations in milk may range from 0.05 ppb to 0.5 ppb in different countries; individual state or federal regulatory agencies should be consulted when contamination occurs.
Aflatoxins are metabolized in the liver to an epoxide that binds to macromolecules, especially nucleic acids and nucleoproteins. Their toxic effects include mutagenesis due to alkylation of nuclear DNA, carcinogenesis, teratogenesis, reduced protein synthesis, and immunosuppression. Reduced protein synthesis results in reduced production of essential metabolic enzymes and structural proteins for growth. The liver is the principal organ affected. High dosages of aflatoxins result in hepatocellular necrosis; prolonged low dosages result in reduced growth rate, immunosuppression, and liver enlargement.
Clinical Findings of Aflatoxicosis in Animals
In acute outbreaks, deaths occur after a short period of inappetence; other acute clinical signs include vomiting, depression, hemorrhage, and icterus. Subacute outbreaks are more usual, with unthriftiness, weakness, anorexia, reduced growth and feed efficiency, and occasional sudden deaths. Laboratory changes in most species are related to liver damage, coagulopathy, and impaired protein synthesis. Specific laboratory changes include increased AST, ALT, and alkaline phosphatase concentrations; hypothrombinemia, prolonged prothrombin and activated partial thromboplastin times, hyperbilirubinemia, hypocholesterolemia, hypoalbuminemia, and variable thrombocytopenia. Generally, aflatoxin concentrations in feed twice the tolerable levels given above Aflatoxicosis in Animals are associated with acute aflatoxicosis. Acute and fatal aflatoxicosis with many of these signs and laboratory changes has been documented in dogs. Frequently, there is a high incidence of concurrent infectious disease, often respiratory, that responds poorly to the usual drug treatment. Dairy cattle experience inappetence, and ruminants may have decreased ruminal contractions at high concentrations (>1,000 ppb) of aflatoxins. Liver damage can lead to reduced clotting factor synthesis with acute to chronic hemorrhage. Subclinical effects are reduced growth rate and feed efficiency, hypoproteinemia, and reduced resistance to some infectious diseases despite vaccination.
In acute cases, there are widespread hemorrhages and icterus. The liver is the major target organ. Microscopically, the liver is enlarged and shows marked fatty accumulations and massive centrilobular necrosis and hemorrhage. In subacute cases, the hepatic changes are not so pronounced; however, the liver is somewhat enlarged and firmer than usual. There may be edema of the gallbladder. Microscopically, the liver shows periportal inflammatory response and proliferation and fibrosis of the bile ductules; the hepatocytes and their nuclei (megalocytosis) are enlarged. The gastrointestinal mucosa may show glandular atrophy and associated inflammation. Rarely, there may be tubular degeneration and regeneration in the kidneys. Prolonged feeding of low concentrations of aflatoxins may result in diffuse liver fibrosis (cirrhosis) and, rarely, carcinoma of the bile ducts or liver.
Diagnosis of Aflatoxicosis in Animals
Animal clinical signs and signalment
Serum biochemical analysis, CBC, and coagulation testing
Feed should be chemically analyzed for aflatoxins
Animal clinical signs and signalment, laboratory data including the changes in the serum chemical analysis (hepatic enzyme activity), CBC, and clotting times, postmortem examination findings, and microscopic examination of the liver should indicate the nature of the hepatotoxin; however, hepatic changes are somewhat similar in Senecio toxicosis Pyrrolizidine Alkaloidosis in Animals Photograph of rattleweed (Crotalaria sp). Photograph of tansy ragwort (Senecio jacobaea [Jacobaea vulgaris]). Pyrrolizidine alkaloidosis is typically a chronic toxicosis... read more and in mycotoxicosis from several Penicillium mycotoxins, including luteoskyrin and cyclochlorotine (islanditoxin) noted in yellow rice poisoning of Japanese soldiers during World War II and recent infrequent occurrences in animal feeds. Acutely affected animals have increases in liver enzymes (alkaline phosphatase, AST, or ALT concentrations), bilirubin, serum bile acids, and prothrombin time. Chronic exposure can cause hypoproteinemia (including decrease in both albumin and globulin). Aflatoxin M1 (principal metabolite of aflatoxin B1) can be detected in urine, liver, kidney, or milk of lactating animals if toxin intakes are high; realistically, however, chemical analysis of aflatoxin M1 in milk and possibly aflatoxin B1 or M1 in liver are available. Aflatoxin residues in organs and dairy products generally are eliminated within 1–3 weeks after exposure ends.
Control, Prevention, and Treatment of Aflatoxicosis in Animals
Attention to weather patterns, especially drought and insect infestations in crops during growth, and chemical analysis of feeds for aflatoxins prior to use.
Avoidance of aflatoxin contaminated feed, particularly to young or lactating animals; testing to ensure aflatoxin contaminated feed is below regulatory limits for the animal species, age, and production status.
Support of adequate liver function and providing a quality diet.
Use of hydrated sodium calcium aluminosilicates (HSCAs) can reduce adverse effects in pigs and poultry and partially reduce aflatoxin M1 in milk; however, it does not eliminate the residue.
Contaminated feeds can be avoided by monitoring batches for aflatoxin content. Local crop conditions (drought, insect infestation) should be monitored as predictors of aflatoxin formation. Young, newly weaned, pregnant, and lactating animals require special protection from suspected toxic feeds. Cleaning to remove lightweight or broken grains will often substantially reduce mycotoxin concentration in remaining grain. Ammoniation reduces aflatoxin contamination in grain; however, it is not currently approved by the US FDA for use in food animals in the US because of uncertainty about byproducts produced.
No specific antidote for aflatoxins is available. Exposure to contaminated feed should be stopped immediately. Animals should be provided a quality diet with attention to the protein level (neither very low nor high protein in consideration of hepatic damage), vitamins, and trace minerals to aid recovery. Patients may need support of hepatic function, and antimicrobial therapy for infectious processes and improved biosecurity may be needed. Recovery may be prolonged. With severe hepatic damage, animals may never return to a normal production status.
Numerous products are marketed as anticaking agents to sequester or bind aflatoxins and reduce absorption from the GI tract. One effective binder for aflatoxins is HSCAs, which reduce the effects of aflatoxin when fed to pigs or poultry at 10 lb/ton (5 kg/tonne. and also provide substantial protection against dietary aflatoxin. These reduce aflatoxin M1 in milk by ~50% but do not eliminate residues of aflatoxin M1 in milk from dairy cows fed aflatoxin B1. Other adsorbents (sodium bentonites, polymeric glucomannans) have shown variable but partial efficacy in reducing low-level aflatoxin residues in poultry and dairy cattle. To date, the US FDA has not licensed any product for use as a mycotoxin binder in animal feeds.
Aflatoxicosis is a worldwide problem resulting from Aspergillus flavus and A parasiticus infestation of corn (maize), peanuts, nuts, rice, cottonseed, and other crops during drought and insect infestations in the field or storage under conditions of appropriate moisture (grain moisture > 15% and relative humidity > 75%) and warm temperatures.
Aflatoxins adversely affect birds, companion pets (dogs and cats), livestock, rodents, fish, and humans, with the young at particular risk. Aflatoxins are mutagenic, carcinogenic, teratogenic, immunosuppressive, and target the liver. Adverse effects are related to liver damage and can cause poor production, food residues, and death.
Most countries have regulatory limits of aflatoxins in animal feeds, human food, and milk; feed should be chemically analyzed prior to use and aflatoxin contaminated feed should be avoided in lactating animals because of aflatoxin M1 residue in milk.
Treatment is supportive and the hydrated sodium calcium aluminosilicates can act as aflatoxin binders in feed and mitigate adverse effects and milk aflatoxin M1 residue.
For More Information
Meerdink GL. Aflatoxins. In: Plumlee KH, ed. Clinical Veterinary Toxicology. St Louis: Mosby, 2004;231-235.
Raisbeck MF, Rottinghaus GE, Kendall JD. Effects of naturally occurring mycotoxins on ruminants. In: Smith JE, Henderson RS, eds. Mycotoxins and Animal Foods. Boca Raton, Fla: CRC Press, 1991;647-677.
CAST (Council for Agricultural Science and Technology). Mycotoxins: Risks in Plant, Animal and Human Systems, Task Force Report No. 139. Ames, Iowa: Council for Agricultural Science and Technology, 2003.
Mostrom MS, Jacobsen BJ. Ruminant mycotoxicosis. Vet Clin North Am Food Anim 2011;27:315-344 (updated version submitted for 2021).