Aflatoxicosis is quite rare in the developed world. This disease may be underdiagnosed as well. This disease should be suspected when an illness outbreak of unknown etiology is linked to certain food and appears to be nontransmissible. Another clue is a seasonal association when weather is favorable for mold growth. Also, drug therapy does not improve the patient's condition.

The clinical presentation in animals and likely humans occurs acutely or chronically.

Acute

When there is moderate to high amount of aflatoxin intake, the patient can develop acute liver damage, hemorrhage, nausea, vomiting, high fever, progressive jaundice, lethargy, edema, a change in the mechanism of processing nutrients, and even death. While adult humans can tolerate higher levels of aflatoxin in acute cases, children have fatal outcomes [8].

Chronic

Prolonged consumption of lower concentrations of aflatoxins yields subclinical effects such as the decline in food conversion efficiency and the decreased growth rates seen in animals [9].

• Fever

  Dengue fever Leptospirosis Rift Valley fever Yellow fever Ricin poisoning Acute chemical intoxication (eg, hydrocarbons) Best Tests Subscription Required Management Pearls Subscription Required Therapy Subscription Required References Subscription Required [visualdx.com]

  They experience a sudden onset of the following signs and symptoms: Liver damage High fever Vomiting Jaundice Edema Bleeding Lethargy Death Chronic cases occur following long-term intake of aflatoxins. [symptoma.com]

  “Farmer’s lung” is a disease that often afflicts grain handlers and is frequently associated with skin irritation, fever, wheezing, breathlessness, cough, and ulcers. [web.archive.org]

• Pain

  Aflatoxins can cause: Nausea, vomiting, and abdominal pain Convulsions Pulmonary edema, which is fluid buildup (edema) in the lungs ('pulmon-') Cerebral edema, which is fluid buildup in the brain ('cerebro-') Blood abnormalities, such as an increased [study.com]

  Patients will appear ill with fever, jaundice, nausea, vomiting, abdominal pain, and hemorrhagic diathesis, hepatomegaly, and elevated liver function tests. Patients may also develop limb edema, pulmonary edema, seizures, coma, and death. [visualdx.com]

• Falling

  The common syndrome in animals is of hepatic insufficiency including jaundice, blindness, circling, falling and convulsions. Called also groundnut poisoning. [medical-dictionary.thefreedictionary.com]

  For example, in the fall of 1974, more than 150 villages in northwest India became afflicted with aflatoxicosis. Almost 400 individuals were affected and 108 died. [symptoma.com]

• Inflammation

  Only a slight hemocytic inflammation accompanies the degenerative changes in this latter organ. [arizona.pure.elsevier.com]

  Gastro-intestinal tract - Mucosal inflammation and haemorrhage - intestines may appear red-black along much of their length. May be food such as corn or peanuts in the oesophagus, proventriculus and/or gizzard. [wildpro.twycrosszoo.org]

• Malaise

  Symptoms include hepatomegaly, abdominal discomfo rt, anorexia, malaise, jaundice and oedema of legs, face and trunk. [aspergillus.org.uk]

• Nausea

  Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. [ncbi.nlm.nih.gov]

  Aflatoxins can cause: Nausea, vomiting, and abdominal pain Convulsions Pulmonary edema, which is fluid buildup (edema) in the lungs ('pulmon-') Cerebral edema, which is fluid buildup in the brain ('cerebro-') Blood abnormalities, such as an increased [study.com]

  Patients will appear ill with fever, jaundice, nausea, vomiting, abdominal pain, and hemorrhagic diathesis, hepatomegaly, and elevated liver function tests. Patients may also develop limb edema, pulmonary edema, seizures, coma, and death. [visualdx.com]

  Acute When there is moderate to high amount of aflatoxin intake, the patient can develop acute liver damage, hemorrhage, nausea, vomiting, high fever, progressive jaundice, lethargy, edema, a change in the mechanism of processing nutrients, and even death [symptoma.com]

• Vomiting

  The case was a 17-year-old schoolboy presenting with vomiting, features of infection and gastrointestinal tract symptoms. [ncbi.nlm.nih.gov]

  Aflatoxins can cause: Nausea, vomiting, and abdominal pain Convulsions Pulmonary edema, which is fluid buildup (edema) in the lungs ('pulmon-') Cerebral edema, which is fluid buildup in the brain ('cerebro-') Blood abnormalities, such as an increased [study.com]

  Patients will appear ill with fever, jaundice, nausea, vomiting, abdominal pain, and hemorrhagic diathesis, hepatomegaly, and elevated liver function tests. Patients may also develop limb edema, pulmonary edema, seizures, coma, and death. [visualdx.com]

  They experience a sudden onset of the following signs and symptoms: Liver damage High fever Vomiting Jaundice Edema Bleeding Lethargy Death Chronic cases occur following long-term intake of aflatoxins. [symptoma.com]

• Abdominal Pain

  Aflatoxins can cause: Nausea, vomiting, and abdominal pain Convulsions Pulmonary edema, which is fluid buildup (edema) in the lungs ('pulmon-') Cerebral edema, which is fluid buildup in the brain ('cerebro-') Blood abnormalities, such as an increased [study.com]

  Patients will appear ill with fever, jaundice, nausea, vomiting, abdominal pain, and hemorrhagic diathesis, hepatomegaly, and elevated liver function tests. Patients may also develop limb edema, pulmonary edema, seizures, coma, and death. [visualdx.com]

• Food Poisoning

  Signs, Symptoms, and Effects Unfortunately, unlike some of the temporary signs and symptoms of food poisoning that stem from a run-of-the-mill virus, aflatoxin is extremely poisonous in the short and long term, and the symptoms of aflatoxicosis can last [study.com]

• Diarrhea

  Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. [ncbi.nlm.nih.gov]

• Jaundice

  Symptoms include hepatomegaly, abdominal discomfo rt, anorexia, malaise, jaundice and oedema of legs, face and trunk. [aspergillus.org.uk]

  The common syndrome in animals is of hepatic insufficiency including jaundice, blindness, circling, falling and convulsions. Called also groundnut poisoning. [medical-dictionary.thefreedictionary.com]

  Abstract Parts of Western India have experienced an outbreak of hepatitis affecting man and dogs and characterised by jaundice, rapidly developing ascites, portal hypertension, and a high mortality-rate. [ncbi.nlm.nih.gov]

• Convulsions

  The common syndrome in animals is of hepatic insufficiency including jaundice, blindness, circling, falling and convulsions. Called also groundnut poisoning. [medical-dictionary.thefreedictionary.com]

  Aflatoxins can cause: Nausea, vomiting, and abdominal pain Convulsions Pulmonary edema, which is fluid buildup (edema) in the lungs ('pulmon-') Cerebral edema, which is fluid buildup in the brain ('cerebro-') Blood abnormalities, such as an increased [study.com]

  Ataxia, convulsions and opisthotonus or wing-flapping may precede death. Ducklings and goslings may show cyanosis (bill, legs and feet purple), inappetance, reduced growth, abnormal vocalization, feather-picking and lameness. [wildpro.twycrosszoo.org]

• Seizure

  Patients may also develop limb edema, pulmonary edema, seizures, coma, and death. Chronic aflatoxicosis results in impaired food conversion and stunted growth. Aflatoxicosis is not transmissible. [visualdx.com]

• Opisthotonus

  Ataxia, convulsions and opisthotonus or wing-flapping may precede death. Ducklings and goslings may show cyanosis (bill, legs and feet purple), inappetance, reduced growth, abnormal vocalization, feather-picking and lameness. [wildpro.twycrosszoo.org]

Aflatoxicosis should be suspected in illness outbreaks that appear to be connected to food batches in mold seasons. Other key considerations are the geographical location, staple diet, and exclusion of other differential diagnoses. Hence, clinical assessment includes ascertaining this information, performing a physical exam and the relevant studies.

Food studies

Since the outbreak is a public health concern, the associated batch of food should be investigated for infectious agents, which will be positive for fungi only. Samples of food can be evaluated by 1) the enzyme-linked immunosorbent assay (ELISA) test for monoclonal antibodies, 2) chromatography (cell layer, gas, or liquid), or 3) mass spectrophotometry.

Diagnostic studies

The test of choice to determine human exposure is the analysis of body fluids for aflatoxin derivatives [10]. Generally, the metabolites exhibit a characteristic half-life in the body. Therefore, this allows the clinician to estimate the length of exposure. Measurement of AFM1 in the urine is suggestive of exposure within the past 24 hours. However, since the levels of this substance are variable from day to day, this test is not as much accurate in diagnosing chronic exposure as the aflatoxin-albumin adduct study. The latter is obtained from peripheral blood samples and measures long-term exposure as its half-life is 30 to 60 days [10].

Note that AFM1 in human urine is present in almost a third of a sample population and aflatoxin-albumin adduct is observed in more than 90% of the sample group [10].

• Hepatic Necrosis

  A high initial exposure to aflatoxins will produce acute hepatic necrosis from days to weeks later, but with multiple exposures likely in a terrorist attack, many victims will present with acute hepatic necrosis within a short period of time. [visualdx.com]

  The toxic effects of AFB1 are mainly localized in liver as manifested by hepatic necrosis, bile duct proliferation, icterus and hemorrhage. [ncbi.nlm.nih.gov]

• Hepatocellular Carcinoma

  Indeed, long-term aflatoxin exposure is linked to the development of hepatocellular carcinoma (HCC). Aflatoxin causes aflatoxicosis, which can be affected by several factors and is prevalent in many developing Asian and African countries. [ncbi.nlm.nih.gov]

  There is a positive association between dietary aflatoxins and hepatocellular carcinoma. [visualdx.com]

There is no particular therapy for aflatoxicosis. Hence, the treatment approach is focused on supportive care for the liver disease and other manifestations. Examples of therapeutic interventions include administration of intravenous fluids (IVF) along with vitamins, protein, and antioxidants. Additionally, scheduled L-methionine (200 mg/kg) and sodium thiosulfate (50 mg/kg) has been shown to be effective. The elimination of the contaminated food products is of paramount importance to prevent further cases of poisoning.

Regulation of aflatoxin levels

The FDA strives to maintain levels of contamination at a minimum. Specifically, the regulations designate safe levels of AFB1 as below 20 parts per billion in feeds. Furthermore, there are strategies such as chemoprotection and enterosorption to keep the concentrations of aflatoxins at the lowest possible. In the first method, yeast extracts such as esterified glucomanoses are used to decrease or block hepatocarcinogenesis secondary to AFB1. With regards to enterosorption, certain food additives can bind to the toxins in the gastrointestinal tract [11], although they do not eliminate the aflatoxins.

The outcomes of aflatoxicosis are associated with the severity of liver damage. When severe symptoms manifest, the prognosis is typically poor.

In terms of mortality, a study from the Indian outbreak reports a death rate that ranged from 10 to 60% in the acute phase. At the 1 year follow-up, a majority of the survivors had recovered and cleared from jaundice [7].

The etiology of aflatoxicosis is the ingestion of food containing aflatoxins. These compounds were discovered 4 decades ago while investigating the cause of death in turkeys [1]. Aflatoxins are synthesized by the fungal strains of A. flavus and A. parasiticus under favorable environmental factors such temperature ranging from 24°C to 35°C.

Generally, aflatoxins are most prevalent in peanuts, tree nuts, cottonseed, cereal grains, and corn. The prominent aflatoxins that are mainly involved in the disease are the subtypes B1, B2, G1, and G2.

Based on the data regarding the contamination of food and market samples, it is highly likely that a majority of the global population has been exposed to aflatoxins although at nontoxic levels.

According to studies investigating the environmental conditions conducive for the synthesis of aflatoxins, chronic exposure to this substance is most likely in developing areas located between 40° N and S of the equator. Moreover, it is estimated that approximately 4.5 billion people reside in this region.

There have been no outbreaks in humans in the United States although a few cases have occurred in animals. Globally, there have been a small number of cases. For example, in the fall of 1974, more than 150 villages in northwest India became afflicted with aflatoxicosis. Almost 400 individuals were affected and 108 died. Another outbreak occurred in Kenya in 1982, in which there were 20 affected people with 12 deaths.

The most toxic aflatoxins in order of decreasing toxicity are B1, G1, B2, and G2 with B1 being most frequently found in studies in the laboratory and livestock animals. If poisoning occurs, the disease typically presents as acute or chronic. Studies have demonstrated that the outcomes of aflatoxicosis are influenced by the dose and duration of the exposure. For example, excessive quantities in a short length of time cause liver cirrhosis and even death whereas long-term nonlethal amounts lead to carcinogenic, nutritional and immunologic consequences. Additionally, the cumulative lifetime dose contributes to the risk of cancer.

Hepatotoxicity

The organ most frequently targeted is the liver as it induces hepatocellular necrosis, mitochondrial destruction, and bile duct proliferation. A serious complication of liver damage is the reduced synthesis of clotting factors and thereby hemorrhage [2].

Cancer

This agent is identified as a Class 1 carcinogen by the International Cancer Research Institute [3]. This substance mainly promotes the development of liver cancers and occasionally lung cancer. Its oncogenic potential is associated with its role in the mutation of the p53 tumor-suppressing gene. Therefore, the amount of aflatoxin in milk and other foods is dangerous and must be regulated [3].

Reproductive

There are numerous studies that have investigated the effects of these toxic substances on the follicular growth and maturation, hormone levels, fetal growth, and spermatogenesis.

In male mice, aflatoxins target the testes causing degeneration and affecting sperm production [4]. In female rats treated with various doses of AFB1, results showed a decline in the number of oocytes, changes in serum hormone levels, and decrease in the size of the uterus and ovaries [5].

Additionally, AFB1 can cross the placenta in both humans and animals. Moreover, elevated amounts of AFB1 in the umbilical cord is linked to serious outcomes such as low birth weight, kernicterus, and fetal mortality. Aflatoxins appear to be teratogenic in the majority of animal species.

Pathologic findings

Reports of animal autopsies from horse suggest findings such as firm and pale colored liver, yellow ascites and a collection of pleural fluid. Histopathology from equine tissues reveals brain edema and hemosiderin deposition in tubule cells among other features [6].

Currently, there are numerous implemented strategies in order to prevent aflatoxicosis in humans and animals. For example, food batches should not contain any level of the toxins above what is acceptable. Also, the feed storages must be well-ventilated and away from places of moisture such as the floor and the walls. Additionally, food should be freshly prepared and stored for no more than 14 days.

Farms, feed storages, grain mills, and feeding troughs need to be cleaned routinely with antifungals while feeds in storage bins should be treated regularly with antifungals such as organic acids, copper sulfate, ammonium hydroxide and others. Finally, routine and frequent inspection should be performed.

Aflatoxicosis refers to the poisoning that results from ingestion of aflatoxins, which are substances produced by ubiquitous fungi such as Aspergillus flavus and Aspergillus parasiticus. These toxins are mostly produced in the temperature range of 24-35°C or when the moisture content of the food products is more than 7%. Aflatoxins are found to have hepatotoxic and hepatocarcinogenic effects.

Following consumption of aflatoxins, the ensuing consequences manifest in either of these forms 1) acute severe intoxication or 2) chronic sub-symptomatic disease. The first type occurs with the ingestion of lethal doses, which leads to direct liver damage, illness, and death. Chronic disease is associated with the prolonged intake of aflatoxins and is often difficult to diagnose as it results in decreased physical growth and other nonspecific signs. Very importantly, the insidious carcinogenic role of these toxins is a concern for the western nations.

Aflatoxicosis should be suspected in cases where there are non-transmissible outbreaks of unknown etiology that can be traced to a specific food. The workup consists of the patient's history, investigation of staple foods and other similar geographical criteria, a physical exam, and laboratory studies. The latter is comprised of diagnostic tools such as the urine aflatoxin M1 (AFM1), which is reflective of recent exposure to aflatoxins, and the serum aflatoxin-albumin adduct tests, which are indicative of chronic consumption of the contaminants.

Since these carcinogens pose serious health hazards, the levels of aflatoxins are regulated by government. In order to deliver safe food with only minimal levels of aflatoxins, preventative strategies require the implementation of safe techniques during production, drying, and storage phases. Finally, strict standards have to be maintained in the food delivery process.

What is aflatoxicosis?

Aflatoxicosis is the poisoning that occurs after ingestion of aflatoxins, which are toxins produced by two fungi known as Aspergillus flavus and A. parasiticus. These toxins are commonly found in staple foods in developing countries. It is difficult to avoid the formation of these toxins since they can contaminate food at any stage: harvest, storage, and food processing. The production of these toxins is favored in particular conditions of temperature and humidity.

This fungus tends to grow on peanuts, corn, cottonseed, and cereal grains stored in wet conditions without sufficient ventilation and drying.

Where does this occur?

This disease is rare in developed countries since they have regulations that minimize the quantity of aflatoxins in food. However, the developing regions do not have the same level of control.

What are the signs and symptoms?

This disease can be acute or chronic. Acute cases occur following intake of large amounts of aflatoxins over a short period of time. They experience a sudden onset of the following signs and symptoms:

• Liver damage
• High fever
• Vomiting
• Jaundice
• Edema
• Bleeding
• Lethargy
• Death

Chronic cases occur following long-term intake of aflatoxins. The disease is difficult to recognize in these patients. Some features include:

• Decreased absorption of nutrients
• Decreased physical growth rates in affected people
• The long-term consequences associated with aflatoxins such as their role in developing liver cancers.

How is it diagnosed?

When there is a disease outbreak associated with a certain food batch, the clinician should suspect aflatoxicosis as the possible cause. Also suggestive of this poisoning is the fact that the weather is favorable, the disease is not contagious, and medical drugs do not improve the symptoms.

Laboratory studies include investigating body fluids for aflatoxins. The AFM1 product is found in urine and measures toxins consumed within the last 24 hours. The aflatoxin-albumin adduct product is found in blood samples and measures the amount of toxin consumed over long periods of time.

Note that contaminated foods and feeds should be tested as well with specific measurement tools.

How is it treated?

There is no specific drug for aflatoxicosis. However, the therapy should focus on treatment of the liver damage. Intravenous fluids, vitamins, and proteins are all very beneficial.

How is it prevented?

There are regulations on how to handle harvest, storage, and food processing with adequate drying and appropriate conditions that prevent the fungal growth. Also, food storages should be treated with antifungals and other products. They should also be routinely checked to ensure that the appropriate standards are maintained.

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2. Greene HJ, Oehme FW. A possible case of equine aflatoxicosis. Clinical Toxicology. 1976;9(2):251-4.
3. Henry SH, Bosch FX, Troxell TC, Bolger PM. Reducing liver cancer—global control of aflatoxin. Science. 1999; 286(5449):2453-4.
4. Agnes VF, Akbarsha MA. Spermatotoxic effect of aflatoxin B(1) in the albino mouse. Food and Chemical Toxicology. 2003;41(1):119-30.
5. Ibeh IN, Saxena DK. Aflatoxin B1 and reproduction. II. Gametoxicity in female rats. African Journal Reproductive Health. 1997; 1(2):79-89.
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7. Bhat RV, Krishnamachari KAVR. Follow-up study of aflatoxic hepatitis in parts of western India. Indian journal of medical research, 1977, 66(1): 55-58.
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9. Marin DE, Taranu I, Bunaciu RP, et al. Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin. Journal of Animal Science. 2002;80(5):1250-7.
10. Wild CP, Pisani P. Carcinogen DNA and protein adducts as biomarkers of human exposure in environmental cancer epidemiology. Cancer Detection and Prevention. 1998;22(4):273-83.
11. Huwig A, Freimund S, Käppeli O, Dutler H. Mycotoxin detoxication of animal feed by different adsorbents. Toxicology Letters. 2001; 20;122(2):179-88.