Measuring the burden of aflatoxin induced human disease

International Food Policy Research Institute International Center for the Improvement of Maize

and Wheat International Crops Research Institute for the Semi-Arid Tropics Uniformed Services University of the Health Sciences

University of Pittsburgh ACDI/VOCA/Kenya Maize Development Program Kenya Agricultural Research Institute Institut d’Economie Rurale

Felicia Wu and Yan Liu

Department of Environmental & Occupational Health Graduate School of Public Health

University of Pittsburgh

And

Clare Narrod, Marites Tiongco, Rosemary Scott International Food Policy Research Institute

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Aflatoxin: background & health effects Influence diagram linking aflatoxin to sequelae Burden of disease caused by aflatoxin

Global liver cancer cases

Expected liver cancer cases in Kenya Results using Kenya Integrated Household Budget Survey (KIHBS, 2005-2006) data

to Limitations and future directions

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Produced by Aspergillus flavus, A. parasiticus Maize, peanuts, almonds, pistachios, hazelnuts Exposure highest in warm regions when these foods

are dietary staples Poor nations

(Postulated) Human health effects Liver cancer (fatal in 1-3 months)

▪ Synergizes with chronic hepatitis B virus (HBV) infection: >> higher risk than either exposure alone

Childhood stunting Acute aflatoxicosis Cirrhosis Immune suppression A. flavus invasive aspergillosis

Hepatitis B Hepatitis C Liver cancer Cirrhosis of the liver

WORLD 1.63 0.84 9.47 11.99

AFRICA 1.64 0.72 8.19 3.85

THE AMERICAS 0.57 0.92 4.16 12.87

EUROPE 0.83 0.52 7.33 20.94

SOUTH-EAST ASIA

2.21 0.82 3.50 12.57

WESTERN PACIFIC

1.60 0.88 21.68 9.53

KENYA 0.50 0.22 2.58 2.47

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Aflatoxin

consumption

Stunted

growth in

children

Immune

suppression

Acute

aflatoxicosis

Liver cancer Modulation of

cytokine expression

AF-8,9-

epoxide binds

to DNA

Chronic hepatitis B

infection

Liver

biotransformation to

aflatoxin-8,9-epoxide

Altered intestinal

integrity

Poor storage

conditions

Fungal growth and

aflatoxin accumulation

in food crops

Intermediate

dihydrodiol

binds to liver

proteins

Plant stress in

field

Source: Wu 2010

How many global liver cancer cases each year are caused by aflatoxin?

Dose-response assessment

Slope of curve = cancer “potency” ▪ Aflatoxin liver cancer: 0.01 cases /

100,000 / yr / ng/kg bw/day

▪ Aflatoxin + Hepatitis B virus liver cancer: 0.30 cases / 100,000 / yr / ng/kg bw/day

Exposure assessment

Find, for each nation: Daily consumption of maize / nuts

Aflatoxin levels in maize / nuts

Hepitits B virus prevalence

Population size

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Global population cancer risk = Σ(all nations) ([PopulationHBV+ /100,000 * PotencyHBV+ * Average aflatoxin intake] + [PopulationHBV- /100,000 * PotencyHBV- * Average aflatoxin intake])

PotencyHBV+ = 0.30 cases per 100,000/yr per ng/kg bw/day PotencyHBV- = 0.01 cases per 100,000/yr per ng/kg bw/day

Data Sources: • Hepitits B virus prevalence: WHO, multiple peer-reviewed

papers • Aflatoxin exposure & food consumption: WHO GEMS

database, multiple peer-reviewed papers

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13 DALYs per case 328,000-2,000,000 DALYs/yr

Liu Y, Wu F. (2010). “Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment.” Environmental Health Perspectives 118:818-824.

World Region # DALYs annually attributable to aflatoxin-induced HCC

Africa 147,940-778,700

North America 143-182

Latin America (inc. Central America) 8,749-65,520

Eastern Mediterranean 10,231-219,960

Southeast Asia 41,600-583,700

Western Pacific 117,260-360,230

Europe 2093-7,228

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Estimated daily maize and peanut consumption (KIHBS 2005): ▪ Maize: 357 g/day/person

▪ Peanuts: 44 g/day/person Hepatitis B Virus prevalence: 11-15% Lifetime average daily dose (LADD) of aflatoxin in Kenyan adults

5.2 to 200 ng/kg bw/day Estimated aflatoxin-induced Liver cases/yr: 82- 4,080 Estimated DALYs associated with aflatoxin-induced Liver

Cancer: 1066-53,040 per year

Note: These exposures do not take into account occasional excursions to very high aflatoxin levels (e.g., 2004, 2010), as acute toxicoses are not associated with subsequent HCC.

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Estimated daily maize consumption in urban vs rural areas:

Maize: urban areas 352 g/day/person, rural 624 g/d/ person

Currently no way to estimate aflatoxin exposure in urban vs. rural populations

What we do know: rural maize consumption 1.77 times higher than urban maize consumption

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Aflatoxin exposure (ng/kg bw/day)

HBV prevalence

AF-induced cases of HCC[1]

Africa

Lower 5th percentile

10 9 11,380

Geometric mean 42 13 26,100

Upper 95th percentile

180 20 59,900

Kenya

Lower 5th percentile

5.2 11 82

Geometric mean 32.2 12.8 578

Upper 95th percentile

200 15 4080

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Globally - 25,200-155,000 aflatoxin-induced liver cancer cases each year Translates to 328,000 to 2,000,000 DALYs per year

Most DALYs are suffered in 3 world regions: Africa, Southeast

Asia, and Western Pacific (China) Kenya 82- 4,080 aflatoxin-induced HCC cases/yr:

Translates to 1066-53,040 DALYs associated with aflatoxin-induced HCC

But secondary data of different quality – poor quality data leads to high variance

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