Aspergillus flavus and Aspergillus parasiticus are the molds that produce Aflatoxin. These fungi can produce their toxic compounds on almost any food that will support growth. The metabolites produced by these fungi are named AFB1, AFB2, AFG1, and AFG2, all which occur naturally. Of the four, AFB1 is found in highest concentrations followed by AFG1, AFB2 and AFG2. Aspergillus flavus only produces AFB1 and AFB2 and Aspergillus parasiticus produces these same metabolites along with G1 and G2. Aflatoxins are secondary metabolites that are highly mutagenic and toxic for human and also animal health.
Effect on human health:
Humans are exposed to aflatoxins by consuming foods contaminated with products of fungal growth. Such exposure is difficult to avoid because fungal growth in foods is not easy to prevent. Even though heavily contaminated food supplies are not permitted in the market place in developed countries, concern still remains for the possible adverse effects resulting from long-term exposure to low levels of aflatoxins in the food supply . Evidence of acute aflatoxicosis in humans has been reported from many parts of the world , namely countries, like Taiwan, Ouganda, India, and many others. The syndrome is characterized by vomiting, abdominal pain, pulmonary edema, convulsions, coma, and death with cerebral edema and fatty involvement of the liver, kidney, and heart. Conditions increasing the likelihood of acute aflatoxicosis in humans include limited availability of food, environmental conditions that favour fungal development in crops and commodities, and lack of regulatory systems for aflatoxin monitoring and control.
The expression of aflatoxin related diseases in humans may be influenced by factors such as age, sex, nutritional status, and/or concurrent exposure to other causative agents such as viral hepatitis (HBV) or parasite infestation. Ingestion of aflatoxin, viral diseases, and hereditary factors have been suggested as possible aetiological agents of childhood cirrhosis. There are evidences to indicate that children exposed to aflatoxin breast milk and dietary items such as unrefined groundnut oil, may develop cirrhosis. Malnourished children are also prone to childhood cirrhosis on consumption of contaminated food. Several investigators have suggested aflatoxin as an aetiological agent of Reye’s syndrome in children in Thailand, New Zealand etc. Though there is no conclusive evidence as yet. Epidemiological studies have shown the involvement of aflatoxins in Kwashiorkor mainly in malnourished children. The diagnostic features of Kwashiorkor are edema, damage to liver etc. These out breaks of aflatoxicosis in man have been attributed to ingestion of contaminated food such as maize, groundnut etc. Hence it is very important to reduce the dietary intake of aflatoxins by following the procedures for monitoring levels of aflatoxins in foodstuffs.
Effects on animals:
There are differences in species with respect to their susceptibility to aflatoxins, but in general, most animals, including humans, are affected in the same maner.
Acute toxicity is less likely than chronic toxicity. Studies have shown that ducklings are the species most susceptible to acute poisoning by aflatoxins. The LD50 of a day old duckling is 0.3mg/kg bodyweight.
The principal target organ for aflatoxins is the liver. After the invasion of aflatoxins into the liver, lipids infiltrate hepatocytes and leads to necrosis or liver cell death. The main reason for this is that aflatoxin metabolites react negatively with different cell proteins, which leads to inhibition of carbohydrate and lipid metabolism and protein synthesis. In correlation with the decrease in liver function, there is a derangement of the blood clotting mechanism, icterus (jaundice), and a decrease in essential serum proteins synthesized by the liver. Other general signs of aflatoxicosis are edema of the lower extremities, abdominal pain, and vomiting.
Animals which consume sub-lethal quantities of aflatoxin for several days or weeks develop a sub acute toxicity syndrome which commonly includes moderate to severe liver damage. Even with low levels of aflatoxins in the diet, there will be a decrease in growth rate, lowered milk or egg production, and immunosuppression. There is some observed carcinogenicity, mainly related to aflatoxin B1. Liver damage is apparent due to the yellow color that is characteristic of jaundice, and the gall bladder will become swollen. Immunosuppression is due to the reactivity of aflatoxins with T-cells, decrease in Vitamin K activities, and a decrease in phagocytic activity in macrophages.
Aflatoxins are inhibitors of nucleic acid synthesis because they have a high affinity for nucleic acids and polynucleotides. They attach to guanine residues and for nucleic acid adducts. Aflatoxins also have been shown to decrease protein synthesis, lipid metabolism, and mitochondrial respiration. They also cause an accumulation of lipids in the liver, causing a fatty liver. This is due to impaired transport of lipids out of the liver after they are synthesized.This leads to high fecal fat content. Carcinogenisis has been observed in rats, ducks, mice, trout, and subhuman primates, and it is rarely seen in poultry or ruminants. Trout are the most susceptible. In fact, 1ppb of aflatoxin B1 will cause liver cancer in trout. Carcinogenisis occurs due to the formation of –8,9-epoxide, which binds to DNA and alters gene expression. There is a correlation with the presence of aflatoxins and increased liver cancer in individuals that are hepatitis B carriers.
Specific species affects:
PIG: Aflatoxicosis in swine is mainly due to the fact that corn is a large part of their diet Piglets are more susceptible than adults are and it has been shown that feeding sows AFM1, during lactation, can cause stunted growth in litter.The groundnut cake implicated in the suspected aflatoxicosis of pigs had aflatoxin levels estimated at over 20000 mg /kg.
Large doses of aflatoxins have been shown to produce hepatic necrosis. The effects of aflatoxicosis can be compounded with the addition of stress. This can lead to ataxia and induced hemorrhaging. The hemorrhaging is due to the prolonged blood clotting time caused by lack of Vitamin K utilization.
Poultry: Aflatoxicosis has the same toxic effects in poultry as it does in mammals. The aflatoxicosis problem was mainly noticed in 1960 in turkey poults in England with the outbreak of a disease known as Turkey X disease. The affected birds lost appetite, became lethargic, and died with in 7 days after onset of symptoms. Livers of diseased turkeys were severely damaged. A similar disease of ducklings and also chickens was reported in Kenya. Later it was discovered that it was the contaminated groundnut meal which was included in their diet was the main cause of the disease. The groundnut meal was contaminated with a mold called as Aspergillus flavus and the disease was caused by the toxin produced by the fungus while growing on the meal, the toxin is named as aflatoxin. A dose of 0.25ppm in turkey poults and ducklings impairs growth, and a dose of 1.5ppm in broilers and 4ppm in Japanese quail also has a negative affect on growth. An increase in blood clotting time increases the susceptibility of the carcass to bruising even at doses below that to have an affect on growth. In poultry, aflatoxins impair the availability of bile salts, which decreases Vitamin D3 production. This causes a decrease in the absorption of fat-soluble vitamins. Aflatoxins also decrease the production of Vitamin A in the liver, and it has secondary effects such as decreased blood calcium levels, bone strength, tissue and serum tocopherol levels. This decrease in tocopherol levels can lead to Vitamin A and E deficiencies.
Cattle: The effects of aflatoxicosis in ruminants are similar to those of non-ruminants. Calves are more sensitive than yearlings and adults. The first symptomatic effect of continuous ingestion of toxic groundnut meal in calves was a reduction in growth rate followed by unthriftiness, and loss of appetite, and the terminal symptoms were characterized by severe tenesmus. A dose of 0.2mg/kg body weight can cause a decrease in weight gains. This can be attributed to poor feed utilization and a dramatic increase in alkaline phosphate activity in the rumen. Chronic aflatoxicosis in adult ruminants can cause anorexia, drying and peeling of the skin on the muzzle, rectal prolapse, and abdominal edema. Aflatoxicosis has also been shown to cause decreased fertility, abortion, and lowered birth weights in sheep.