Aflatoxicosis is acute poisoning or chronic intoxication that develops due to the use of products containing mycotoxins of Aspergillus fungi. Large doses of aflatoxins cause acute liver failure, coagulopathy, seizures; prolonged use of mycotoxins in smaller doses can provoke developmental delay in children, congenital anomalies in offspring, cirrhosis and liver cancer. The etiological diagnosis is established with the help of back-sowing of food samples and biomaterial of the patient. Additionally, liver tests, hemostasiogram, ultrasound of the liver are carried out. Treatment – detoxification, hepatoprotectors, antimycotics, B vitamins.
T64 Toxic effect of aflatoxin and other mycotoxins polluting food products
Aflatoxicosis is mycotoxicosis caused by secondary metabolites of aflatoxigenic fungi. Aflatoxins (AFT) were first isolated in 1961 from peanut flour contaminated with the mold fungus Aspergillus flavus. Subsequently, the symptom complex associated with the use of contaminated products was called aspergilloflavotoxicosis, or aflatoxicosis. The last major outbreak of fatal aflatoxicosis was registered in Tanzania in 2016. Children demonstrate the greatest sensitivity to the pathogenic effects of aflatoxins.
Sources of infection
The sources of aflatoxins are Aspergillus mold fungi: A. Flavus, A. Parasiticus and some others. These fungi usually affect products of plant origin:
- cereals (corn, rice, wheat, sorghum);
- legumes (cocoa, soy, chickpeas);
- nuts (peanuts, almonds, hazelnuts, walnuts),
- spices (nutmeg, pepper);
- dried fruits (dried apricots, raisins, figs);
- the products of processing of these crops (flour, butter, paste).
Aspergillus Flavus produces aflatoxins B1 and B2, A. parasiticus ‒ B1, B2, G1, G2. In addition, both types of fungus can synthesize aflatoxins M1 and M2. The latter are also formed as a result of hydroxylation of mycotoxins B1 and B2 in the tissues of farm animals that have consumed fungus-contaminated feed, therefore they are often found in milk, dairy products, eggs, meat.
The permissible concentration of aflatoxin B1 in plant products is 5 micrograms/kg, aflatoxin M1 in animal products is 0.5 micrograms/kg. Acute aflatoxicosis develops with the daily intake of mycotoxin B1 in the amount of 20-120 mcg / kg of body weight per day for 1-3 weeks. AFT have thermal stability, i.e. they practically do not break down during thermal and culinary processing.
Ways of infection
Aflatoxicosis is considered mainly as an alimentary disease, since the main way of getting aflatoxins into the body is food (with food, mother’s milk). Transplacental transfer of mycotoxins from mother to fetus is possible. Employees of granaries, feed mills, flour mills, farms may be exposed to inhalation of aflatoxins or their transdermal penetration. Cases of aflatoxin contamination of heroin have been reported, so in some cases infection occurs with intravenous drug use.
The conditions contributing to a higher frequency of infection of food crops with aflatoxigenic fungi are:
- subtropical and tropical climate (high temperature and humidity);
- adverse weather conditions for plant growth;
- damage to plants by insect pests;
- violation of harvesting technology, grain transportation and storage conditions (lack of light and ventilation);
- lack of sanitary and epidemiological control over the storage of products.
Aflatoxins are absorbed in the small intestine, enter the liver with blood flow, where they undergo hydroxylation to form metabolites (AFQ1, AFM1, aflatoxicol, 8,9-epoxy-AFB1, etc.). Aflatoxins form compounds with liver proteins (albumin, thrombin), block the synthesis of many enzymes, polypeptides and nucleic acids. Their excretion occurs with bile, feces, urine. Aflatoxin B1 is the strongest hepatotropic poison and one of the most dangerous carcinogens for humans. Its secondary metabolites bind to the nitrogenous bases of DNA (in particular, guanine), activating mutations of the tumor suppressor gene TP53 in codon 249.
Under the influence of AFT, hepatocyte dystrophy occurs in the liver, the formation of foci of fatty and coagulation necrosis, cholangiolar proliferation, intrahepatic cholestasis. Necrotic changes are also found in the heart muscle, spleen, kidneys. With aflatoxicosis, vitamin D metabolism is disrupted, prothrombin formation occurs, cellular and humoral immunity is suppressed, oncogenes are activated. Aflatoxins also have mutagenic, embryotoxic and teratogenic effects.
Signs of acute aflatoxicosis manifest within half an hour after ingestion of contaminated food. There is general weakness, lethargy, dizziness, short-term fever. There is abdominal pain, vomiting, upset stool. The severity and pain in the liver area are bothering, the skin and sclera become jaundiced. Symptoms of neurointoxication include ataxia, seizures, and paresis.
Subcutaneous hemorrhages and spontaneous bleeding occur, with acute aflatoxicosis, hepatosplenomegaly, edema, ascites rapidly progresses. If emergency care is not provided, patients fall into a coma, death occurs within a few days from acute liver or kidney failure, cerebral edema.
The long-term cumulative effect of subtoxic doses of aflatoxins leads to chronic liver damage with the development of cirrhosis, portal hypertension, hepatocellular carcinoma. Against the background of dyspepsia, children have protein-energy deficiency, delayed physical development and growth, and adults have progressive loss of body weight.
Aflatoxicosis is associated with the development of several types of cancer, in particular, cholangiocarcinoma, primary cancer of the liver, lungs, intestines. The risk of developing hepatocellular carcinoma is 25-30 times higher when aflatoxicosis is combined with viral hepatitis B or C. It is believed that aflatoxins are involved in the pathogenesis of kwashiorkor and Reye’s syndrome in children.
The course of aflatoxicosis may be aggravated by the presence of other mycotoxins in one product (for example, fumonisins) with the simultaneous development of combined mycotoxicoses. Mortality from aflatoxicosis is high, especially in the children’s population.
Diagnosis of aflatoxicosis is based on establishing the connection of poisoning with the use of mycotoxin-contaminated products. This requires a detailed collection of nutritional history, a thorough study of clinical and laboratory data. It is necessary to withdraw food products that allegedly caused poisoning, their special study (organoleptic, mycological, luminescent, chromatographic analysis, bioassays) in a sanitary laboratory. The examination of the victim includes:
- Detection of aflatoxins in the body. The concentration of AFT metabolites is determined in urine, blood plasma, breast milk. For microbiological isolation of the mushroom-producer, food residues, feces, and vomit are used.
- Blood tests. BT, liver enzymes, coagulogram, vitamin D level, electrolytes are examined. Aflatoxicosis is characterized by an increase in the level of transaminases, bilirubin, and an increase in prothrombin time.
- Other studies. To assess the degree of damage to internal organs, ultrasound of the liver, spleen, kidneys, and ECG registration are performed. If necessary, a liver biopsy is performed with the morphology of the biopsy.
As part of the differential diagnosis, other mycotoxicoses (fusariotoxicoses) are excluded, as well as food toxicoses of other etiology:
- staphylococcal food poisoning;
- viral gastroenteritis;
- poisoning with organochlorine, organophosphate compounds, pesticides, etc.
Like any acute food poisoning, aspergilloflavotoxicosis requires emergency care. There are no specific antidotes. At the first stage, to remove the maximum amount of mycotoxins, gastric lavage is performed, a siphon enema is administered, saline laxatives and activated carbon suspensions are introduced through a probe. Enterosorbents are prescribed for detoxification of the body, forced diuresis is performed, according to indications – hemo- / plasmosorption, albumin dialysis.
Planned therapy for aflatoxicosis includes taking antimycotic drugs active against aspergillus, immunomodulators, hepatoprotectors, vitamin and mineral complexes, probiotic bacteria.
Prognosis and prevention
Aflatoxicosis is dangerous with severe irreversible damage to the liver and nervous system, a high risk of death, serious separated consequences. Outbreaks of acute aflatoxicosis are regularly recorded in Asian and African countries, their victims are both adults and children. In addition, a high percentage of mortality from liver cirrhosis and hepatic cell carcinoma is registered in these regions.
Measures to combat aflatoxicosis include the prevention of contamination of agricultural products with mold fungi at all stages of its cultivation, processing, storage. For this purpose, breeding is carried out, genetic engineering methods are introduced, temperature and humidity control is provided in warehouses, chemical decontamination is carried out. Before cooking and eating products, it is necessary to carefully inspect them for the presence of mold fungi, do not use products of questionable quality, expired shelf life, violation of the integrity of the packaging.