Aflatoxin: A One Health Issue - University of Pittsburgh
Aflatoxin s In Search of One Health Solutions Esther Giezendanner* Blair Budd* In collaboration with the North Carolina One Health Collaborative 2012 North Carolina One Health Collaborative 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. Microscopic view : spore formation of Aspergillus
Chemical structure of aflatoxin B1 Detection: Fluorescence can be used to detect presence of Aspergillus on crops Biomarkers are used to detect aflatoxin exposures in humans 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 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 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) 2006-2007: Crop contamination Drought conditions and moisture stress led to aflatoxin on corn in Missouri which caused rejection of some harvested corn by buyers Kenya 2004-2005: Acute Aflatoxicosis and human mortality Aflatoxin contamination of maize caused over 150 human deaths Aflatoxins: Human, Animal, and Environmental Interactions Breast milk In utero Infants
Milk eggs 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 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 Aspergillus on maize Storage practices drying techniques processing, such as shelling peanuts exposure to pests Drying maize 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 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. 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. 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. 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 ONeals Feeder Supply, Inc.s Arrow brand dry dog food recalled in 2011 Aflatoxin contamination found and food recalled before health effects were reported 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 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 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 g/kg) and animal feeds (300 ppb) E.U limits are stricter than in the US (maximum 10 g/kg for direct human consumption) Aspergillus on peanuts Allowable Aflatoxin Levels in Human Foods26 Amount
Food type 20 ppb Foods in general 0.5 ppb (aflatoxin M1) Milk 20 ppb Peanuts and peanut products 20 ppb Pistachio nuts 20 ppb
Brazil nuts 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 20 ppb 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 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 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 45-50% 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. 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
One Health Innovative Solutions to the Aflatoxin Problem Biocontrol Atoxigenic Aspergillus Atoxigenic strains of Aspergillus compete with toxigenic strains, preventing production of aflatoxin Toxigenic and atoxigenic strains of Aspergillus 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 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. 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
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 Sources 1. 2. 3. 4. 5. 6.
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concentrations of aflatoxin AFB1. Br Poult Sci. 2007;48(6):713-23. Khlangwiset P, Shephard GS, Wu F. Aflatoxins and growth impairment: a review. Crit Rev Toxicol. 2011;41(9):740-55. 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):109-15. 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 subSaharan Africa carcinomas and mycotoxin prone foods. Am J Clin Nutr. 2010;92:154-60. Sources (cont.) 21. 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. 22. Perkins, JR. Supplemental feeding. 1991. Texas Parks and Wildlife Department Fisheries & Wildlife Division. http://www.tpwd.state.tx.us/publications/pwdpubs/media/pwd_bk_w7000_0033.pdf Accessed April 24, 2012. 23. Leung MC, Daz-Llano G, Smith TK. Mycotoxins in pet food: a review on worldwide prevalence and preventative strategies. J Agric Food Chem. 2006;54(26):9623-35. 24. "Toxic Pet food may have killed dozens of dogs." MSNBC News. 5 Oct 2006. http://www.msnbc.msn.com/id/10771943/ns/health-pet_health/t/toxic-pet-food-may-havekilled-dozens-dogs/ Accessed Mar. 12, 2012. 25. Sagman, Mike. "Arrow Brand Dog Food Recall." Dog Food Reviews. Dog Food Advisor, 2012. http://www.dogfoodadvisor.com/dog-food-recall/arrow-brand-dog-food-recall/ Accessed April 24, 2012. 26. U.S. Food and Drug Administration. Guidance for Industry: Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed. 2000. http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/ChemicalContaminantsandPesticides/ucm077969.htm Accessed April 24, 2012.
27. European Union. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. 2006. http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:2006R1881:20100701:EN:HTML Accessed April 24, 2012. 28. Takumi, Yoshizawa. "Mycotoxins and Food Safety Current Situation of Food Contamination, Regulations and Risk Assessment for Mycotoxins." Foods & Food Ingred J Jpn. 211.12 (2006): 1018-1026. Web. 2012. http://www.ffcr.or.jp/zaidan/ffcrhome.nsf/7bd44c20b0dc562649256502001b65e9/b71bcd8b8ad963b54925725000229627/$ FILE/211(12)5.pdf Accessed April 12, 2012. 29. United States. Federal Department of Agriculture. Inspections, Compliance, Enforcement, and Criminal Investigations. 2005. http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074598.htm Accessed April 24, 2012. 30. Lawley, Richard. "Aflatoxins." Food Safety Watch. N.p., Nov 2007. Web. http://www.foodsafetywatch.com/public/482.cfm Accessed March 9, 2012. 31. Munkvold G, Hurburgh C. "Aflatoxin in Corn." Iowa State University. 2009. http://www.extension.iastate.edu/Publications/PM1800.pdf Accessed May 7, 2012. 32. 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):998-1014. 33. Groopman JD, Kensler TW, Wild CP. (2008) Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health. 29:187203. Review. PubMed PMID: 17914931. 34. 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. 2008 Jul;25(7):872-84. 35. Marroqun-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. 2011 Dec;54(3-4):248-257. 36. 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: http://www.apsnet.org/edcenter/intropp/topics/Mycotoxins/Pages/EconomicImpact.aspx 21 Apr 2012. Accessed April 24, 2012. 37. Atherton, G. "New biopesticide Aflasafe may solve Kenya's ongoing maize contamination problem. The Aspergillus Website blog. N.p., 12 Jul 2010. Web. Available at: http://aspergillusblog.blogspot.com/2010/07/new-biopesticide-aflasafe-may-solve.html Accessed Mar. 12, 2012.
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. 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. Image Credits
Slide 1: Broadcasting Aflasafe in maize field. 2008 International Institute of Tropical Agriculture Image Library. http://www.flickr.com/photos/iita-media-library/6846617887/ Used under a Creative Commons Attribution-NonCommercial license: http://creativecommons.org/licenses/by-nc/2.0/deed.en Slide 1: Grain Sampling Program 2010 Texas AgriLife Research photo by Blair Fannin. http://www.flickr.com/photos/agrilifetoday/6432128831/ Used under a Creative Commons Attribution-NonCommercialNoDerivs license: http://creativecommons.org/licenses/by-nc-nd/2.0/deed.en Slide 1: Aflatoxin-contaminated groundnut kernels 2008 International Institute of Tropical Agriculture Image Library. http://www.flickr.com/photos/iita-media-library/4684917072/ Used under a Creative Commons Attribution-NonCommercial license: http://creativecommons.org/licenses/by-nc/2.0/deed.en Slide 2: B0004539 Aspergillus spore formation (conidia), phase contrast 2003 Wellcome. http://www.flickr.com/photos/ wellcomeimages/5987578301/ Used under a Creative Commons Attribution-NonCommercial-NoDerivs license: http://creativecommons.org/licenses/by-nc-nd/2.0/deed.en
Slide 2: Public domain: http://commons.wikimedia.org/wiki/File:Aflatoxin_B1.png Slide 8: Grain Sampling Program 2010 Texas AgriLife Research photo by Blair Fannin. http://www.flickr.com/photos/agrilifetoday/6432128831/ Used under a Creative Commons Attribution-NonCommercialNoDerivs license: http://creativecommons.org/licenses/by-nc-nd/2.0/deed.en Slide 8: Aspergillus infected maize 2011 International Institute of Tropical Agriculture Image Library. http://www.flickr.com/photos/iita-media-library/5781888774/ Used under a Creative Commons Attribution-NonCommercial license: http://creativecommons.org/licenses/by-nc/2.0/deed.en Slide 13: Based on the work: Dog food 2008 photo by notto86. http://www.flickr.com/photos/nickotto/2164557362/ Used under a Creative Commons Attribution-ShareAlike license: http://creativecommons.org/licenses/by-sa/2.0/deed.en Slide 16: Aflatoxin-contaminated groundnut kernels 2008 International Institute of Tropical Agriculture Image Library. http://www.flickr.com/photos/iita-media-library/4684917072/ Used under a Creative Commons Attribution-NonCommercial license: http://creativecommons.org/licenses/by-nc/2.0/deed.en Slide 23: Atoxigenic and toxigenic strains 2003 International Institute of Tropical Agriculture Image Library. http://www.flickr.com/photos/iita-media-library/5761978714/ Used under a Creative Commons Attribution-NonCommercial license: http://creativecommons.org/licenses/by-nc/2.0/deed.en
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