Tuesday, January 3, 2017

Aspergillus flavus and Aflatoxicosis

            In the 1960s, turkeys in England began to contract a disease that had previously not been characterized (Wannop, 1961). This disease became known as turkey “X” disease and was seen in at least 500 separate outbreaks across southeast England (Wannop, 1961). The disease had a very high mortality rate—up to 100% in many outbreaks (Wannop, 1961). As a result, more than 100,000 turkeys died(Cornell, 2015). The disease also affected other birds in England including ducks and pheasants (Cornell, 2015). Scientists began to investigate what could be causing this disease.
            Eventually it was discovered that many of the outbreaks were associated with the consumption of a specific feed, the Brazilian peanut meal(Cornell, 2015). Investigation of the questionable feed began, and the scientists found that it was toxic to the birds (Cornell, 2015). Upon further examination, they found that it was not the Brazilian peanut meal itself that was causing the disease (Cornell, 2015). They suggested that the toxin was actually produced by a fungus found within the feed (Cornell, 2015). Later, they identified this fungus as Aspergillus flavus (Cornell, 2015).
Figure 1. Depicts A. flavus hyphae forming the mycelium   
A. flavus is a filamentous fungus that produces hyphae (Center for Integrated Fungal Research, 2005). These branching hyphae form a network called the mycelium, which give the fungus a “fuzzy” appearance (Center for Integrated Fungal Research, 2005). The spores, also known as conidia, produced asexually at the tips of the hyphae appear yellow-green in color (Center for Integrated Fungal Research, 2005). As the fungus ages, the conidia become darker (Center for Integrated Fungal Research, 2005). A. flavus is most often found in warm temperate zones (Kilch, 2007). This fungus is characterized by its unique spore-bearing structure (Kilch, 2007).

Aspergillus flavus is an opportunistic pathogen of humans, animals, and plants (Kilch, 2007). It is commonly found in soil and therefore affects many crops (Kilch, 2007). In the field, A. flavus predominantly affects oilseed crops such as corn, peanuts, cottonseed, and treenuts (Kilch, 2007). However, A. flavus can grow in almost any crop seed that is stored improperly (Kilch, 2007). When A. flavus infects a crop it may cause ‘rot,’ which is when parts of the plant begin to decay, as seen in Figure 2 (Kilch, 2007). Additionally, A. flavus is the main species of Aspergillus causing superficial infection and the second leading species causing invasive infections in immunocompromised humans (Hedayati, MT, et al).
Figure 2. Shows rot occurring on corn as a result of A. flavus infection.    
In healthy organisms, it is not the A. flavus infection itself that causes the most harm.  The fungus produces a toxin, known as aflatoxin which is more damaging to sthe host organism than other symptoms of the infection. Aflatoxins are a secondary metabolite produced by A. flavus (Kilch, 2007). This means that aflatoxins are produced as biproducts of normal metabolic proceses within the fungus. There are about 20 different types of aflatoxins, but only four are naturally found within foods (Lawley, 2013). Aflatoxin B1 is the most common in foods and is also the most toxic (Lawley, 2013). Aflatoxins are stable compounds and can withstand harsh conditions (Lawley, 2013). This means that the toxins may still be present in processed foods such as, peanut butter that was derived from infected crops (Lawley, 2013).
Exposure to or ingestion of alfatoxins can cause poisoning of the organism known as either acute aflatoxicosis or chronic aflatoxicosis (Kilch, 2007). Organisms affected by acute aflatoxicosis generally die (Kilch, 2007). The turkeys killed by turkey “X” disease had acute aflatoxicosis. They died quickly even though they were otherwise in good condition (Wannop, 1961). On the other hand, chronic aflatoxicosis mainly targets the liver and can result in cancer and suppression of the immune system (Kilch, 2007). These negative effects can be seen after consumption of high levels of aflatoxin or long-term ingestion of low levels of the toxin found in food sources (Cornell, 2015).
The link between aflatoxins and liver cancer has been studied extensively. Because of the high positive correlation between exposure to aflatoxins and liver cancer, aflatoxins have been classified as a Group 1 carcinogen (Wild, et al, 2015). In one study, it was found that patients with liver cancer were exposed to 4.5 times more aflatoxin per day on average (Wild, et al, 2015). Simultaneous exposure to both aflatoxins and Hepatitis B further increases risk of developing liver cancer (Wild, et al, 2015). Another study showed that patients that had both Hepatitis B infection and exposure to high levels of aflatoxin had a 10-fold increase of liver cancer when compared to people exposed to only low levels of the toxin (Wild, et al, 2015).
Due to the harm aflatoxins can cause in humans and livestock, preventative measures must be taken. To ensure that crops are free of aflatoxins before they are harvested, growth of A. flavus must be limited. To do so, farmers must abide by Good Agricultural Practices (GAP) including: proper land preparation, cultivation of fungus-resistant plants, control of insect and fungal pests, prevention of drought stress on crops, and harvesting at optimal moisture and maturity levels (Lawley, 2013). After harvesting, crops must be stored under proper moisture and temperature conditions to limit A. flavus growth (Lawley, 2013).
Even when these practices are closely followed, aflatoxins can still contaminate food (Cornell, 2015). Aflatoxins are seen as an “unavoidable contaminant (Cornell, 2015).” However because aflatoxins are known to be carcinogenic, the FDA has created guidelines for acceptable levels (Cornell, 2015). They recommend that most food contains under 20 parts per billion of aflatoxins (Cornell, 2015). They recommend similar levels for agricultural feed (Cornell, 2015). Unfortunately, it is very difficult to accurately measure aflatoxin concentration, which means some foods on the market may have dangerous levels (Cornell, 2015).
It is important to identify and prevent future A. flavus outbreaks. This opportunistic pathogen has a great impact on humans and the agriculture industry. Not only does it negatively affect infected crops and livestock, but also subsequent exposure to the produced aflatoxins occurs frequently. This is mainly a problem in low and middle-income countries that have fewer regulations on agriculture (Wild, et al, 2015). The best way to prevent this issue is by following proper pre- and post-harvest practices such as moisture control during harvest. By reducing the incidence of A. flavus in crops, it is possible that associated liver cancer rates would also decrease.

1.     Center for Integrated Fungal Research (2005). Aspergillus flavus. From: aspergillusflavus.org [accessed Nov. 8, 2016].
2.     Cornell University (2015). Aflatoxins: Occurrence and Health Risks. Department of Animal Science-Plants Poisonous to Livestock, College of Agriculture and Life Sciences.
3.     Hedayati MT, Pasqualotto AC, Warn PA, Bowyer P, and Denning DW (2007). Aspergillus flavus: Human Pathogen, Allergen, and Mycotoxin Producer. Microbiology, Vol 153, pp 1677-1692.
4.     Kilch MA (2007). Aspergillus flavus: The Major Producer of Aflatoxin. Molecular Plant Pathology, Vol 8 no. 6, pp 713-722.
5.     Lawley R (2013). Aflatoxins. Food Safety Watch, The Science of Safe Food.
6.     Wannop CC (1961). The Histopathology of Turkey “X” Disease in Great Britain. Avian Diseases, Vol 5 no 4, pp 371-381.
7.     Wild CP, Miller JD, Groopman JD ed. (2015). Mycotoxin Control in Low- and Middle-Income Countries, Chapter 3: Effects of Aflatoxicosis and Liver Cancer. International Agency for Research on Cancer, no 9, pp. 13-16.

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