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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

International Food Policy Research Institute           University of Pittsburgh
International Center for the Improvement of Maize      ACDI/VOCA/Kenya Maize Development Program
and Wheat                                              Kenya Agricultural Research Institute
International Crops Research Institute for the Semi-   Institut d’Economie Rurale
Arid Tropics
Uniformed Services University of the Health Sciences
                                                                                               1
 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




                                                                               2
   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

                                                                3
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   2.21          0.82          3.50           12.57
ASIA
WESTERN      1.60          0.88          21.68          9.53
PACIFIC
KENYA        0.50          0.22          2.58           2.47




                                                                           4
Plant stress in        Poor storage
    field               conditions

         Fungal growth and
       aflatoxin accumulation
            in food crops

                                                   Intermediate
                                   Liver                                       Acute
    Aflatoxin                                       dihydrodiol
                           biotransformation to                            aflatoxicosis
  consumption                                      binds to liver
                           aflatoxin-8,9-epoxide
                                                      proteins

                                                      AF-8,9-
Altered intestinal           Modulation of
                                                   epoxide binds           Liver cancer
    integrity             cytokine expression
                                                      to DNA

                                                                                  Source:
      Stunted                                             Chronic hepatitis B
     growth in
                                  Immune                                          Wu 2010
                                suppression                   infection
     children                                                                              5
   How many global
    liver cancer cases
    each year are
    caused by
    aflatoxin?
   Dose-response assessment                              Exposure assessment




     Slope of curve = cancer “potency”                   Find, for each nation:
      ▪ Aflatoxin  liver cancer: 0.01 cases /                Daily consumption of maize / nuts
         100,000 / yr / ng/kg bw/day
                                                              Aflatoxin levels in maize / nuts
      ▪ Aflatoxin + Hepatitis B virus liver cancer:
         0.30 cases / 100,000 / yr / ng/kg bw/day             Hepitits B virus prevalence
                                                              Population size

                                                                                                   7
    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


                                                                            8
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.
                                                                                     9
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



                                                                          10
   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.
                                                                            11
 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



                                                            12
Aflatoxin exposure HBV          AF-induced    cases
                    (ng/kg bw/day)     prevalence   of HCC[1]
Africa
Lower         5th          10                  9         11,380
percentile
Geometric mean             42                 13         26,100
Upper        95th          180                20         59,900
percentile
Kenya
Lower         5th          5.2                11           82
percentile
Geometric mean            32.2               12.8          578
Upper        95th          200                15          4080
percentile
                                                                          13
   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


                                                                             14

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Measuring the burden of aflatoxin induced human disease

  • 1. 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 International Food Policy Research Institute University of Pittsburgh International Center for the Improvement of Maize ACDI/VOCA/Kenya Maize Development Program and Wheat Kenya Agricultural Research Institute International Crops Research Institute for the Semi- Institut d’Economie Rurale Arid Tropics Uniformed Services University of the Health Sciences 1
  • 2.  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 2
  • 3. 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 3
  • 4. 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 2.21 0.82 3.50 12.57 ASIA WESTERN 1.60 0.88 21.68 9.53 PACIFIC KENYA 0.50 0.22 2.58 2.47 4
  • 5. Plant stress in Poor storage field conditions Fungal growth and aflatoxin accumulation in food crops Intermediate Liver Acute Aflatoxin dihydrodiol biotransformation to aflatoxicosis consumption binds to liver aflatoxin-8,9-epoxide proteins AF-8,9- Altered intestinal Modulation of epoxide binds Liver cancer integrity cytokine expression to DNA Source: Stunted Chronic hepatitis B growth in Immune Wu 2010 suppression infection children 5
  • 6. How many global liver cancer cases each year are caused by aflatoxin?
  • 7. Dose-response assessment  Exposure assessment  Slope of curve = cancer “potency”  Find, for each nation: ▪ Aflatoxin  liver cancer: 0.01 cases /  Daily consumption of maize / nuts 100,000 / yr / ng/kg bw/day  Aflatoxin levels in maize / nuts ▪ Aflatoxin + Hepatitis B virus liver cancer: 0.30 cases / 100,000 / yr / ng/kg bw/day  Hepitits B virus prevalence  Population size 7
  • 8. 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 8
  • 9. 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. 9
  • 10. 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 10
  • 11. 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. 11
  • 12.  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 12
  • 13. Aflatoxin exposure HBV AF-induced cases (ng/kg bw/day) prevalence of HCC[1] Africa Lower 5th 10 9 11,380 percentile Geometric mean 42 13 26,100 Upper 95th 180 20 59,900 percentile Kenya Lower 5th 5.2 11 82 percentile Geometric mean 32.2 12.8 578 Upper 95th 200 15 4080 percentile 13
  • 14. 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 14