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Aflatoxins Hazardous and Strategy for remediation

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1 Aflatoxins Hazardous and Strategy for remediation
Ramadan Badran Environmental Health Dept. (Microbiology)

2 What are Aflatoxins? Toxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus Aflatoxins are secondary fungal metabolites. Aflatoxin types include B1, B2, G1, G2. B1 is most prevalent and toxic aflatoxin. Detection: Fluorescence can be used to detect presence of Aspergillus on crops Biomarkers are used to detect aflatoxin exposures in humans Aflatoxin is a mycotoxin produced by the soil fungi Aspergillus flavus (AF) and Aspergillus parasiticus. It exists in multiple types; the primary ones being B1, B2, G1, and G2.1 AFB1 is the most prevalent and most toxic.2 Aspergillus can be detected on commodities such as corn using fluorescence which differentiates between B1 and B2 (blue) or G1 and G2 (green). Biomarkers are used to measure the level of exposure of humans and animals.3, 4 Although large amounts of the fungus may be visible to the naked eye, aflatoxins are often toxic at such low levels that contamination may escape visual detection. Young conidia (asexually produced fungal spores) of A. flavus appear yellow-green in color and darken as the fungus ages.5 After ingestion, aflatoxins are metabolized by cytochrome p450 group enzymes in the liver. Of the metabolites produced, of greatest concern is aflatoxin 8,9-epoxide which can be incorporated into DNA.6 The amount of aflatoxin 8,9-epoxide formed determines species susceptibility. In most experimental animal models, susceptibility to aflatoxin is impacted by liver detoxification systems, genetic make-up, age, and nutritional factors.7 Aflatoxin metabolites are stable and not generally destroyed by heat.8 Microscopic view : spore formation of Aspergillus

3 The One Health Approach
“The concept of One Health is an evolving, interdisciplinary way of approaching complex health issues by recognizing the interconnectedness of human health, animal health and the environment.”† The goal of this presentation is to illustrate that aflatoxins are a worldwide health problem that could benefit from a One Health approach The goal of One Health is to improve the health and well-being of plants and animals through a better understanding of complex relationships and dependencies between humans, animals, and the environment . Aflatoxin management at a global level requires such an approach because aflatoxins occur world-wide and adversely effect both human and animal health in regions where they occur. †North Carolina One Health Collaborative background statement

4 Aflatoxins and One Health
Aflatoxins cause health problems around the world including areas as diverse as Africa, Southeast Asia, Western Pacific, East Mediterranean and Latin America where as many as 5 billion persons may be exposed Aflatoxins have a negative economic impact on agriculture through reduced marketing options for crops and adverse health effects on livestock9 A One Health solution to the aflatoxin problem must: Be collaborative across scientific disciplines and leverage shared knowledge Address cultural and societal issues related to plant agriculture, human and animal health. Utilize advances in biotechnology and medicine Aflatoxins are naturally occurring mycotoxins produced by fungi in the soil and on plants. They can cause significant crop loss by rejection of produce secondary to regulations against contamination in foods. These toxins have a global distribution with the greatest number of health problems occurring in developing countries where exposure is not adequately controlled. In addition to crop damage, inhalation of Aspergillus spores can cause lung damage 8 and ingestion of aflatoxins in contaminated foods can cause serious health consequences in both humans and animals. Control of aflatoxin production and food contamination can be considered a One Health issue because of the interaction of environmental conditions and human practices that determine impacts on human and animal health.

5 Examples of Aflatoxin-Related Events
United Kingdom 1960s: Turkey X disease and bird die-offs attributed to ‘syndrome X’ Both incidents were the result of acute aflatoxicosis United States 1998: Crop contamination Aflatoxin contamination of maize (corn) in the south-eastern U.S. led to rejection rates of corn of up to 50%. Aflatoxin contamination reached 1500 ppb (5 times the 300 ppb highest acceptable limit in animal feed set by the U.S. Food and Drug Administration) : Crop contamination Drought conditions and moisture stress led to aflatoxin on corn in Missouri which caused rejection of some harvested corn by buyers Kenya : Acute Aflatoxicosis and human mortality Aflatoxin contamination of maize caused over 150 human deaths Aflatoxin exposure is recognized as a global health problem for animals and humans. It was first identified in poultry in the 1960s, when acute aflatoxicosis caused “turkey X” disease resulting in numerous bird deaths.3 Since then, implications of aflatoxins for human health have been demonstrated numerous times in both field and experimental settings. Aflatoxin Outbreak in 1998: Corn harvested in 1998 in the southeastern United States, including Texas, Louisiana, Mississippi, Arkansas, Tennessee and Missouri was found to contain high levels of aflatoxin. Concentrations reached as high as 1500 ppb and at one point as much as 30% of corn presented was rejected by buyers. Aflatoxin Outbreak in : The growing seasons in Missouri were affected by drought conditions which favored Aspergillus flavus growth and aflatoxin production on; some loads of corn were rejected by buyers.13 These events created increased awareness of the health risks posed by aflatoxins and highlighted the importance of preventing crop contamination in conjunction with improved post-harvesting aflatoxin detection methods. 9 Kenya: saw outbreaks of acute aflatoxicosis in Kenya resulting from contaminated maize from family farms. The outbreak resulted in hundreds of cases and over 150 deaths.3

6 Aflatoxins: Human, Animal, and Environmental Interactions
Fungal growth / aflatoxin production Contamination of human & animal food Animal consumption Human consumption Environment: extreme drought, moisture, heat, compromised plants Environmental factors such as soil moisture and temperature create the conditions under which Aspergillus can grow and produce toxins on crops or food. Animals and humans are exposed to aflatoxins through consumption of contaminated products such as meat,14 dairy products (e.g. milk, cheese, and yogurt), 15 or eggs16 . Infants can be exposed to aflatoxins through breast milk or in utero.17 Agricultural practices may contribute to the growth of Aspergillus through poor land management and crop storage practices.11 Breast milk In utero Milk eggs Infants

7 Aflatoxins and Environmental Conditions
Conditions favoring aflatoxin formation include: High temperature High humidity Presence of external plant stressors: Periods of drought Insect infestation Soil conditions conducive to Aspergillus growth High organic content High moisture Aspergillus can grow on organic matter found in a wide range of soil types and thrives in a warm, moist environment. Aspergillus will grow on plants especially when they are stressed by insects or drought. 18 This type of plant stress, followed by increased rain provides excellent conditions for aflatoxin contamination of crops.19

8 Aflatoxins and Food Production
Major crops affected by aflatoxins include maize (corn) and groundnuts (peanuts). Agricultural practices can be modified to reduce aflatoxin production / contamination. Farming practices irrigation pesticide use time of harvest Storage practices drying techniques processing, such as shelling peanuts exposure to pests Certain crops are more susceptible to aflatoxin formation than others; maize (corn) and peanuts are two key staples that are prone to extensive contamination. Other staples such as rice and cassava may also be contaminated. Contamination can occur at all stages of crop production: harvest, storage and processing. Farming and storage practices which affect temperature, humidity, and insect damage to crops can significantly impact aflatoxin levels. Irrigation and pesticide use, timing of harvest, drying techniques, and storage environment are all important. Irrigation and pesticide use reduce stress on the plant thereby decreasing susceptibility to Aspergillus growth. However, irrigation can also provide moisture that the fungus needs to grow. Time of crop harvest, drying techniques, and storage conditions all affect moisture content; lower moisture content decreases continued Aspergillus growth. Processing techniques and insects can physically spread the toxin.18 Aspergillus on maize Drying maize

9 Aflatoxins and Acute Human Health Effects
Acute aflatoxicosis can be fatal. Presenting symptoms are determined by amount of toxin consumed. Clinical symptoms in humans include: Abdominal pain Vomiting Pulmonary edema Liver necrosis Aflatoxin causes both acute and chronic negative health outcomes. At high levels of exposure, aflatoxicosis causes acute onset of abdominal pain, vomiting, pulmonary edema, and liver necrosis. It can be fatal.3

10 Chronic Aflatoxin Exposure and Human Health
Carcinogenicity Liver cancer is a serious consequence of long-term exposure to aflatoxins. Hepatitis B infection may exacerbate the effects of aflatoxin exposure and vaccination against Hepatitis B can help reduce carcinogenicity of the toxin. Other consequences of chronic exposure include decreased immune and reproductive function. Children chronically exposed may experience growth failure. Infants may be exposed through breast milk. The fetus may be exposed during pregnancy if the mother consumes aflatoxins. No level of aflatoxin exposure is considered safe for humans. Long-term human exposure to aflatoxin increases the risk of liver cancer. This is particularly problematic in areas where hepatitis B is prevalent. Aflatoxins and hepatitis B have a synergistic effect on the development of liver cancer. Chronic aflatoxin exposure in humans also negatively impacts the immune and reproductive systems. Statistically significant correlations of maize consumption and HIV/AIDS transmission/mortality have been demonstrated. Although the role of aflatoxins have not been clearly elucidated, it is believed the immunosuppressive effects of aflatoxins could impact HIV progression.20 In children, aflatoxins can cause growth failure and delayed development. Stunting and low weight put children at increased risk of death. Maternal aflatoxin exposure during pregnancy has been correlated to decreased growth during the first year of an exposed infant’s life. Breast milk and weaning foods such as maize based porridge, may also contain aflatoxin.17 Aflatoxin M1 is a major carcinogenic metabolite found in the milk of lactating women and animals exposed to Aflatoxin B1. Additionally, because lipid-based supplements may contain peanuts, it is important that aflatoxin levels in crops be carefully controlled to prevent feeding aflatoxin contaminated supplemental foods to already vulnerable populations.21 No level of aflatoxin exposure is considered safe.

11 Aflatoxins in Wildlife
Migratory birds are often exposed. Birds are a highly sensitive species. Birds consume aflatoxins when they feed on contaminated crops. Contaminated crops such as corn, fed to hunting game as attractants, may result in wildlife population decline; this is a One Health issue since humans are responsible for this exposure. Wildlife are typically exposed to aflatoxin by consuming contaminated grains. Wild birds such as geese and ducks may feed on contaminated fields, resulting in extensive die-offs. Humans can inadvertently poison wildlife by feeding them aflatoxin contaminated crops.22 This may result in loss of life, population decline, and an accompanying negative economic impact.

12 Aflatoxins in Farmed Animals
Poultry Highly sensitive Aflatoxin toxicity impairs uptake of essential nutrients as well as causing tissue damage Ruminants Ruminants are relatively insensitive; however, aflatoxin exposure can cause growth impairment in young or lactating animals. Metabolites in milk and related dairy products Aflatoxin consumed by cows is excreted in milk as the M1 metabolite. The M1 metabolite can be absorbed by calves or humans causing growth failure. The M1 metabolite also remains present in milk-based products such as cheese and yogurt. Fish When farmed fish are accidentally fed contaminated grains, large die-offs may occur. Rainbow trout are highly sensitive Animal deaths and reduced productivity from aflatoxin exposure can have significant negative ‘economic’ impact in addition to the negative health outcomes for those who consume contaminated animal products. The most widespread human exposure to aflatoxins from animal sources has occurred when aflatoxin-contaminated feed was given to domestic animals. Among agricultural animals, poultry are generally more sensitive to aflatoxins than ruminants. In poultry, aflatoxin toxicity includes impairment of the uptake of essential nutrients. In ruminants, aflatoxin exposure can cause immunosuppression and impaired growth of young animals. 1 Humans can be exposed to aflatoxins by consuming contaminated animal products, including milk15 or eggs16 containing M1 and M2, the partially detoxified, hydroxylated metabolites of the potent carcinogens, Aflatoxins B1 and B2. .

13 Aflatoxins in Companion Animals
Aflatoxin has been found in pet foods in North and South America, Europe, and the Middle East. Examples of pet food recalls in the U.S. Diamond Pet Foods Company recalls dry dog food recalled in 2007 76 dogs died Cause: aflatoxin-contaminated corn O’Neals Feeder Supply, Inc.’s Arrow brand dry dog food recalled in 2011 Aflatoxin contamination found and food recalled before health effects were reported Aflatoxins can affect companion animals as well. Seventy-six dogs in the U.S. were believed to have died from Diamond Pet Food that was contaminated by aflatoxins at a plant in Gaston, SC. The food had been also shipped to 29 countries outside the U.S. when Diamond Pet Food issued a recall on the contaminated products and offered reimbursement to pet owners for veterinary costs In another similar case, O’Neals Feeder Supply, Inc., the supplier of Arrow brands, recalled dog food contaminated with aflatoxins as a precautionary measure before any adverse health effects were reported. 25

14 Aflatoxin Pathogenicity in Laboratory Animals
Experimental studies in animals are used to study the mechanism of acute and chronic human health effects of aflatoxins Species sensitivity varies Rodents Rats demonstrate malignant transformation of cysts in livers ( Rat studies were used to determine that there is ‘no safe level’ of aflatoxin exposure. Adult mice may be more resistant, but aflatoxins are highly pathogenic in young rats Primates Rhesus, Cynomolgus, and African Green monkeys given aflatoxin for at least 2 months have an overall liver tumor incidence of 50%; for those surviving more than 6 months the incidence was 19%3 Experimental studies in animals have been extensively used to study the acute and chronic health effects of aflatoxin exposure. Animal studies have shown that different species have very different sensitivities to aflatoxins. Studies with rats have shown malignant transformation of cysts in livers. Other rat studies have shown that there is no safe level of exposure for aflatoxins. 3 Even among rodents, certain rats are much more susceptible to aflatoxins than are mice. 1 Studies in primates have also shown the development of liver tumors. 3

15 Strategies for Reducing Aflatoxin Exposure
Regulations Agricultural production quality control Food processing and crop storage safety Early recognition and medical management of health effects Educational outreach Community Individual Because of the serious health consequences of aflatoxin exposure to humans and animals, it is important to prevent exposure when possible. Aflatoxin exposure can be prevented or decreased by improving and enforcing safety regulations, changes in farming and crop storage practices, detoxification and other preventive measures. Both pre- and post-harvest interventions can be used to mitigate the health impacts of aflatoxins in humans and animals.

16 Aspergillus on peanuts
Regulation Although no level of aflatoxin is considered “safe”, some exposure to aflatoxins is probably unavoidable at low levels At least 99 countries have aflatoxin regulations Even with regulations in place, lack of adequate testing in some countries may prevent enforcement Safety standards U.S. safety regulations include aflatoxin limits for human foods (maximum 20 µg/kg) and animal feeds (300 ppb) E.U limits are stricter than in the US (maximum 10 µg/kg for direct human consumption) Although there is no “safe” level of exposure, the U.S. government considers aflatoxins to be an unavoidable contaminant of food and acknowledges that low levels may be present. U.S. food safety regulations include a limit of 20 µg/kg for total aflatoxins (B1, B2, G1 and G2) in all foods except milk and a limit of 0.5 µg/kg for M1 in milk. Higher limits apply for animal feeds. 26 The European Union also regulates the amount of aflatoxin permitted in foodstuffs and sets even lower contamination levels. In the EU, the highest permissible concentration for food intended for direct human consumption is 10 µg/kg, but only 0.05 ppb for M1 in milk A 2006 international consensus review on aflatoxins noted that at least 99 countries had regulations, a 30% increase from However, there still in exists a lack of regulations in lesser-populated countries and no clear regulation in many other developing countries. Aspergillus on peanuts

17 Allowable Aflatoxin Levels in Human Foods26
Amount Food type 20 ppb Foods in general 0.5 ppb (aflatoxin M1) Milk Peanuts and peanut products Pistachio nuts Brazil nuts The United States Food and Drug Administration sets the maximum allowable levels of aflatoxin in food for direct human consumption at 20 ppb. 26 Food lots, either domestic or imported, found to contain 100 ppb on initial testing may be detained for further testing. Raw peanuts with levels exceeding 25 ppb may be shipped to processors “if facilities are available to remove moldy or otherwise defective nuts from the lot before incorporation into the finished product.“29 Aflatoxin concentrations in pistachio nuts are measured by grinding the shell and nut together for testing, while brazil nuts are first shelled, then ground before testing.

18 Allowable Aflatoxin Levels in Animal Feeds26
Amount Feed Type 20 ppb For corn and other grains intended for immature animals (including immature poultry) and for dairy animals, or when its destination is not known For animal feeds, other than corn or cottonseed meal; 100 ppb For corn and other grains intended for breeding beef cattle, breeding swine, or mature poultry 200 ppb For corn and other grains intended for finishing swine of 100 pounds or greater 300 ppb For corn and other grains intended for finishing (i.e., feedlot) beef cattle and for cottonseed meal intended for beef cattle, swine or poultry To protect human and animal health, the U.S. government regulates allowable aflatoxin levels in feeds for various agricultural animals. 26

19 Farming and Storage Practices that Prevent Aspergillus Growth
Pre-harvest Pest management for insects (particularly soil insects), weeds, and nematodes Planting date Irrigation Crop rotation or fertilization Use of drought tolerant and locally adapted varieties Harvest Prevent compromise to the crop by harvesting when mature For maize, harvest early to prevent completion of the Aspergillus life cycle Post-harvest Proper drying Storage in a dry place Farming and storage practices play an important role in the growth of aflatoxin-producing fungi. As mentioned, environmental conditions such as temperature, humidity and insect damage can affect fungal growth in the field and the level of aflatoxin contamination in the final commodity. Preventive strategies targeting safe pre-harvest, harvest, and post-harvest practices can reduce contamination. Farmers can begin preventive measures by monitoring weather patterns for conditions favoring aflatoxin production. Pre-harvest interventions incorporate planting at the appropriate time and managing pests, including insects (particularly soil insects), weeds, plant disease and nematodes. Testing soil samples for levels of nutrients and alternating fertilizers or rotating crops to improve conditions can help. Irrigation reduces the levels of Aspergillus infection when applied during pollination. 30 Harvesting when the crop is mature helps prevent fungus growth. Post-harvest prevention strategies include proper drying techniques, followed by appropriate storage which minimizes exposure to excess humidity. 32 Because Aspergillus prefers warm, moist conditions, significant fungal growth and aflatoxin production can occur during storage if crops are not kept properly dry. When harvested corn is ‘clean’ (Aspergillus free), temperatures can be kept at 16 to 17% moisture during the winter storage period. However, when corn is harvested with mold already present, the moisture percentage should be maintained at 15% after immediate drying. It is important to note that for long term storage of corn, it should be dried first to 14%. Moldy corn is not suitable for long-term storage.31

20 Post-Exposure Management and Prevention of Disease
Dietary interventions Increase dietary diversity Consume compounds that impair aflatoxin absorption NovaSil™: clay that binds aflatoxin in the gut Fermentation: Lactobacillus may bind aflatoxin Hepatitis B vaccination Hepatitis B and aflatoxin exposure interact to increase risk of liver cancer Vaccination against Hepatitis B reduces liver cancer rates by % Although it is preferable to avoid aflatoxin consumption all together, there are various ways to minimize the risk of negative health effects for those whose diets contain foods likely to be contaminated with aflatoxins. Certain compounds reduce absorption of aflatoxins when they are consumed simultaneously. One promising intervention is the use of NovaSil™ clay (sodium calcium aluminosilicate), which adsorbs aflatoxin in the intestine and prevents its uptake. It has been effective in animal models and has been shown to be safe in phase I and II clinical trials in humans.3, 33 However, while initial results are promising, further research is needed to ensure it is not also binding to and preventing absorption of important nutrients.34, 35 Hepatitis B vaccination does not affect aflatoxin exposure itself, but it can dramatically lower liver cancer rates in endemic areas.32 Finally, increased dietary diversity in areas where aflatoxin-prone foods such as corn and groundnuts are staples can improve outcomes. Research is ongoing to discover which particular substances protect against aflatoxin toxicity. Other proposed methods of aflatoxin mitigation include thermal inactivation , irradiation , microbial inactivation and fermentation. Fermentation may reduce aflatoxin absorption because Lactobacillus binds to aflatoxin B1.32

21 Prevention: Economic Challenges
Cost is a major challenge since many areas where aflatoxin contaminated crops are staples lack financial resources Losses due to aflatoxins cost $900 million annually in Indonesia, the Philippines and Thailand alone28 Stakeholders who benefit are not necessarily those who bear the costs Growers: carry the cost burden of many interventions Consumers: benefit most from interventions Government: mediate between growers and consumers, by regulation or funding of interventions, to improve public health Local markets provide very little financial incentive to reduce aflatoxin contamination A One Health approach will try to balance the needs of the growers to make a sustainable living with protecting consumers from aflatoxin contamination by managing environment. Most aflatoxin control measures will involve some degree of financial cost, a major challenge since many of the areas relying on commodities prone to aflatoxin contamination lack financial resources. Additionally, grain that is believed to be aflatoxin contaminated may become more locally affordable since it will no longer be marketable to an international market. Under these conditions, economics appear to favor eating and feeding grain to livestock through winter as an alternative to hay as a primary energy source. Some farming interventions, such as increased irrigation and pesticide use, can carry a significant cost burden to growers. Implementation of these as well as other techniques, such as proper drying of harvested crops, will also require increased knowledge on the part of growers on how to effectively combat aflatoxin contamination. The most effective types of intervention may depend on local conditions which are responsible for aflatoxin contamination. 36 One of the largest problems is that the costs of aflatoxin minimization are generally born by the growers while the primary beneficiaries of these interventions are the consumer. Government can play an important role in mediating this gap, both by providing some interventions itself (such as hepatitis vaccination) and by creating an environment that promotes aflatoxin prevention through regulations and subsidies. Advocacy to encourage governments to keep consumers informed while supporting growers who work to reduce aflatoxin is important. Educating subsistence farmers on the risks of aflatoxin consumption to their own families is also important.

22 The Benefits of an Interdisciplinary One Health Approach
Educating stakeholders on the interconnectedness of humans, animals and the environment is the first step in preventing aflatoxin-related health issues Human Animal Environment Aflatoxin contamination of foodstuffs and its affect on human and animal health is a complex issue. It is only by understanding its epidemiology that holistic solutions can be found. A One Health understanding of aflatoxicity considers how human behaviors influence the environment to promote or inhibit aflatoxin production. By understanding and educating stakeholders on the interconnectedness of humans, animals, and the environment, it becomes possible to find solutions that address each of the contributing factors. One Health

23 Innovative Solutions to the Aflatoxin Problem
Biocontrol Atoxigenic Aspergillus Atoxigenic strains of Aspergillus compete with toxigenic strains, preventing production of aflatoxin Aflasafe™ is one such strain Use in Nigeria resulted in an 80% reduction in aflatoxin levels May not need to be reapplied annually United Nations Industrial Development Organization is supporting the use of Aflasafe™ Bioengineering has been used as a mechanism to implement new, technologically-based solutions. Genetic modification to develop crop resistance to Aspergillus is being explored. Additionally, certain strains of Aspergillus are atoxigenic and are able to be introduced into the agricultural environment to prevent production of aflatoxin. The “biopesticide” Aflasafe™ is an example of one of these strains. Aflasafe is not a chemically derived pesticide, and trials in the US have shown successful reduction of contamination (in the context of integrated crop management programs). In a case study in Nigeria, provisional registration and use of Aflasafe™ in 2009 allowed farmers to reduce aflatoxin by 80%. Additionally, Aflasafe includes some long-term benefits, as it may not need to be applied every year (depending on the environment). In addressing the global Aflatoxin problem, the United Nations Industrial Development Organization (UNIDO) is taking action in Kenya and Nigeria to provide further case studies of prevention methods with Aflasafe™. Future goals include manufacturing, marketing, and distribution on a wide-scale. 16, 37 However, applying Aflasafe™ is an additional cost for farmers and it must be applied early before farmers even know if aflatoxin will be a problem during any growing season. Use of atoxigenic Aspergillus may be cost-prohibitive for farmers in many developing countries. Genetic modification to develop crop resistance to Aspergillus is also being explored. Toxigenic and atoxigenic strains of Aspergillus

24 Production Recommendations
Improved Farming Practices Irrigation reduces stress on plants Pest management prevents crop damage Crop rotation Harvest at the appropriate time Storage Proper drying pre-harvest and storage in a dry place Using proper farming and storage practices are simple interventions that can be gradually introduced A One Health approach recognizes that human impacts on the environment play an important role in Aspergillus growth and the production of aflatoxins. Irrigation and pest management help reduce stress on plants that can leave them more vulnerable to Aspergillus growth and aflatoxin contamination. Agricultural techniques like crop rotation and appropriate harvest timing are helpful in this regard. It is important to assure proper pre-harvest drying and post-harvest sorting in a controlled environment.18 These are basic, low-cost interventions. However, for subsistence farmers accustomed to existing cultural practices and with very little margin for error, adoption of some of these techniques represents a big change. Change should therefore be incremental, recognizing that even small steps to reduce aflatoxin exposure are important for public health.

25 Human Consumption Recommendations
Exposure reduction Dietary modification Diet diversity reduces aflatoxin exposure and improves overall human nutrition Dramatic dietary alterations may not be affordable or culturally acceptable in many areas Education on sources of aflatoxin can alert consumers to risks Dietary modification can also be a useful tool in prevention. For example, a shift that decreases maize consumption in favor of other grains could reduce aflatoxin exposure. Certain food preparation techniques such as fermentation may reduce the intestinal absorption of aflatoxins. While such changes are not always possible for large-scale application, they may be adopted on an individual level. Education regarding the sources of aflatoxin can help consumers avoid foods that are most likely to be contaminated.

26 Human Health Recommendations
Post-exposure management Hepatitis B vaccination Decreases rates of liver cancer Complementary to decreasing aflatoxin exposure This intervention can be funded and implemented by governments without burdening growers NovaSil™ clay Prevents intestinal uptake through adsorption of aflatoxins Prevention is the primary long-term goal In addition to preventing aflatoxin exposure, another public health strategy to minimize the adverse health effects is Hepatitis B vaccination. An advantage of this intervention is that it can be widely implemented by governments without increasing the costs for growers. Trapping agents, such as NovaSil™, may also provide protection from aflatoxin’s negative health effects. Primary prevention to reduce aflatoxin exposure however, is the best public health strategy.

27 Sources Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001;167(2): European Union. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs Accessed April 24, 2012. Kensler TW, Roebuck BD, Wogan GN, Groopman JD. Aflatoxin: a 50-year odyssey of mechanistic and translational toxicology. Toxicol Sci. 2011;120 Suppl 1:S Epub 2010 Sep 29. Shephard GS. Aflatoxin analysis at the beginning of the twenty-first century. Anal Bioanal Chem. 2009;395(5): Epub 2009 May 31. Aspergillus flavus. Accessed April 24, 2012. Wild CP, Turner PC. The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis. 2002;17(6): Bommakanti AS, Waliyar F. “Importance of Aflatoxins in human and livestock health."Aspergillus and Aflatoxin in Groundnut. International Crops Research Institute for the Semi-Arid Tropics Available at: Accessed April 1, 2012. Hollis PL. Preventing aflatoxin begins on the farm.  Southeast Farm Press   Accessed April 1, 2012. Brandenburg, RL. William Personal communication. April 27, 2012. Krenke R, Grabczak EM. Tracheobronchial manifestations of Aspergillus infections. ScientificWorldJournal. 2011;11: Epub 2011 Nov 20. Strosnider H, Azziz-Baumgartner E, Banziger M, et al. Workgroup report: public health strategies for reducing aflatoxin exposure in developing countries. Environ Health Perspect. 2006;114(12): Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118(6): Epub 2010 Feb 19. Sweets, Laura E., and J. Allen Wrather. "Aflatoxin in Corn." University of Missouri Delta Research Center. College of Agriculture, Food, and Natural Resources Accessed Mar. 9, 2012. Olufunmilayo GO, Oyefolu AB. Natural occurrence of aflatoxin residues in fresh and sun-dried meat in Nigeria. Pan Afr Med J. 2010;7:14. Epub 2010 Nov 19. Prandini A, Tansini G, Sigolo S, Filippi L, Laporta M, Piva G. On the occurrence of aflatoxin M1 in milk and dairy products. Food Chem Toxicol. 2009;47(5): Epub 2007 Oct 13. Pandey I, Chauhan SS. Studies on production performance and toxin residues in tissues and eggs of layer chickens fed on diets with various concentrations of aflatoxin AFB1. Br Poult Sci. 2007;48(6): Khlangwiset P, Shephard GS, Wu F. Aflatoxins and growth impairment: a review. Crit Rev Toxicol. 2011;41(9): Epub 2011 Jun 28. Wagacha JM, Muthomi JW. Mycotoxin problem in Africa: current status, implications to food safety and health and possible management strategies. Int J Food Microbiol. 2008;124(1):1-12. Epub 2008 Jan 24. Cotty PJ, Jaime-Garcia R. Influences of climate on aflatoxin producing fungi and aflatoxin contamination. Int J Food Microbiol. 2007;119(1-2): Epub 2007 Aug 14. William JH, Grubb JA, Davis JW, et al. HIV and hepatocellular and esophageal carcinomas related to consumption of mycotoxin-prone foods in sub-Saharan Africa carcinomas and mycotoxin prone foods. Am J Clin Nutr. 2010;92:  

28 Sources (cont.) Manary MJ. Local production and provision of ready-to-use therapeutic food (RUTF) spread for the treatment of severe childhood malnutrition. Food Nutr Bull. 2006;27(3 Suppl):S83-9. Perkins, JR. Supplemental feeding Texas Parks and Wildlife Department Fisheries & Wildlife Division. Accessed April 24, 2012. Leung MC, Díaz-Llano G, Smith TK. Mycotoxins in pet food: a review on worldwide prevalence and preventative strategies. J Agric Food Chem. 2006;54(26): "Toxic Pet food may have killed dozens of dogs." MSNBC News. 5 Oct Accessed Mar. 12, 2012. Sagman, Mike. "Arrow Brand Dog Food Recall." Dog Food Reviews. Dog Food Advisor, Accessed April 24, 2012. U.S. Food and Drug Administration. Guidance for Industry: Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed Accessed April 24, 2012. European Union. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs Accessed April 24, 2012. Takumi, Yoshizawa. "Mycotoxins and Food Safety Current Situation of Food Contamination, Regulations and Risk Assessment for Mycotoxins." Foods & Food Ingred J Jpn (2006): Web   Accessed April 12, 2012. United States. Federal Department of Agriculture. Inspections, Compliance, Enforcement, and Criminal Investigations Accessed April 24, 2012. Lawley, Richard. "Aflatoxins." Food Safety Watch. N.p., Nov Web.   Accessed March 9, 2012. Munkvold G, Hurburgh C. "Aflatoxin in Corn." Iowa State University Accessed May 7, 2012. Khlangwiset P, Wu F. Costs and efficacy of public health interventions to reduce aflatoxin-induced human disease. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010;27(7): Groopman JD, Kensler TW, Wild CP. (2008) Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health. 29: Review. PubMed PMID: Afriyie-Gyawu E, Wang Z, Ankrah NA, Xu L, Johnson NM, Tang L, Guan H, Huebner HJ, Jolly PE, Ellis WO, Taylor R, Brattin B, Ofori-Adjei D, Williams JH, Wang JS, Phillips TD. NovaSil clay does not affect the concentrations of vitamins A and E and nutrient minerals in serum samples from Ghanaians at high risk for aflatoxicosis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess Jul;25(7): Marroquín-Cardona A, Deng Y, Garcia-Mazcorro J, Johnson NM, Mitchell N, Tang L, Robinson A 2nd, Taylor J, Wang JS, Phillips TD. Characterization and Safety of Uniform Particle Size NovaSil Clay as a Potential Aflatoxin Enterosorbent. Appl Clay Sci Dec;54(3-4): Schmale III, David G, and Gary P Munkvold. "Mycotoxins in Crops: A Threat to Human and Domestic Animal Health: Economic Impact." Mycotoxins (2012). APSnet. Web. Available at: 21 Apr 2012.  Accessed April 24, 2012. Atherton, G. "New biopesticide Aflasafe™ may solve Kenya's ongoing maize contamination problem.” The Aspergillus Website blog. N.p., 12 Jul Web. Available at: Accessed Mar. 12, 2012. FAO and University of Nairobi. “Prevention and control of Aflatoxin contamination along the maize value chain” Web.

29 Review Slide Aflatoxins are mycotoxins , produced by the fungus, Aspergillus; they are toxic to humans and animals. Aflatoxin toxicity ranges from acute effects (death) to chronic effects (liver cancer). Exposure of children to aflatoxins can retard growth. Wildlife, agricultural animals, laboratory animals, and pets are all susceptible to the negative health effects of aflatoxin exposure Environmental conditions, such as moist soil and warm temperatures, promote Aspergillus growth and aflatoxin production.

30 Review Slide (continued)
Regulations for aflatoxin contamination in foods vary from country to country. Farming and storage practices that protect plants from stress help reduce aflatoxin production and crop contamination. Increased dietary diversity and Hepatitis B vaccination can help protect humans against the effects of aflatoxins. A challenge to aflatoxin regulation is the cost of rejected crops and mitigation efforts borne by food producers and other stakeholders Control of aflatoxin contamination and exposure is an opportunity to demonstrate the value of a One Health approach for solving a complex problem involving humans, animals, and the environment.

31 Image Credits Slide 1: “Broadcasting Aflasafe in maize field.” © 2008 International Institute of Tropical Agriculture Image Library. Used under a Creative Commons Attribution-NonCommercial license:  Slide 1: “Grain Sampling Program”  © 2010 Texas AgriLife Research photo by Blair Fannin. Used under a Creative Commons Attribution-NonCommercial-NoDerivs license:  Slide 1: “Aflatoxin-contaminated groundnut kernels” © 2008 International Institute of Tropical Agriculture Image Library. Used under a Creative Commons Attribution-NonCommercial license:  Slide 2: “B Aspergillus spore formation (conidia), phase contrast” ©2003 Wellcome. Used under a Creative Commons Attribution-NonCommercial-NoDerivs license:  Slide 2: Public domain: Slide 8: “Grain Sampling Program”  © 2010 Texas AgriLife Research photo by Blair Fannin. Used under a Creative Commons Attribution-NonCommercial-NoDerivs license:  Slide 8: “Aspergillus infected maize” © 2011 International Institute of Tropical Agriculture Image Library. Used under a Creative Commons Attribution-NonCommercial license:  Slide 13: Based on the work: “Dog food” 2008 photo by notto86. Used under a Creative Commons Attribution-ShareAlike license: Slide 16: “Aflatoxin-contaminated groundnut kernels” © 2008 International Institute of Tropical Agriculture Image Library. Used under a Creative Commons Attribution-NonCommercial license:  Slide 23: “Atoxigenic and toxigenic strains” © 2003 International Institute of Tropical Agriculture Image Library. Used under a Creative Commons Attribution-NonCommercial license: 


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