Aflatoxins

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.

• Detection: • Fluorescence can be used to detect presence of Aspergillus on

crops • Biomarkers are used to detect aflatoxin exposures in humans

Chemical structure of aflatoxin B1Microscopic view : spore formation of Aspergillus

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

Milk eggs

Infants

Breast milk In utero

Aflatoxins: Human, Animal, and Environmental Interactions

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

Farming practices • irrigation • pesticide use• time of harvest

Storage practices• drying techniques• processing, such as

shelling peanuts• exposure to pests

Major crops affected by aflatoxins include maize (corn) and groundnuts (peanuts). Agricultural practices can be modified to reduce aflatoxin production / contamination.

Drying maizeAspergillus on 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• 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

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 µg/kg) and animal feeds (300 ppb)• E.U limits are stricter than in the US (maximum 10 µg/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 Type20 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

• 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™

Toxigenic and atoxigenic strains of Aspergillus

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

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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-NonCommercial-NoDerivs 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-NonCommercial-NoDerivs 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