Impact of mycotoxins on child growth in sub-saharan Africa

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1 Impact of mycotoxins on child growth in sub-saharan Africa Michael N Routledge & Yunyun Gong School of Medicine/School of Food Science & Nutrition University of Leeds 10/23/2017 University of Leeds 1

Mycotoxin Fungi Crops Health impact Aflatoxin Aspergillus flavus A.

Acute toxicity Liver carcinogen Stunting Fumonisin Fusarium verticillioides etc

2 Mycotoxin Fungi Crops Health impact Aflatoxin Aspergillus flavus A. parasiticus Maize, peanuts etc Warm, humid climate Increases during storage Acute toxicity Liver carcinogen Stunting Fumonisin Fusarium verticillioides etc Maize Mainly field contamination Neural tube defects Animal carcinogen Animal growth loss Stunting? Deoxynivalenol Fusarium graminearum Maize, wheat etc Warm or temperate climates Non-fatal GI disease Animal growth loss 10/23/2017 University of Leeds 2

3 Biomarkers to measure exposure Aflatoxin albumin adducts in blood (ELISA) Urinary fumonisin B1 (stable isotope dilution assay by LC/MS) ln(af-alb)(pg/mg) ln(afb1intake)(ng/kg bw/day) lnfbintake lnufbcr Fitted values AF-alb versus dietary aflatoxin intake Urinary FB1 versus dietary intake Routledge et al (2014) Biomarkers 19, Shirima et al (2013) Mol. Nutr. Food Res. 57,

4 Our recent studies have focused on The Gambia in West Africa and Tanzania in East Africa with exposure also measured in some neighbouring countries (Senegal & Guinea/Kenya & Uganda) 10/23/2017 University of Leeds 4

20 0 Exposure may vary geographically within a

5 Our data give a snapshot in time for exposure in each study AF-alb overview pg/mg albumin Exposure may vary geographically within a country or in different years 10/23/2017 University of Leeds 5

600 500 pg/mg albumin 400 300 200 100 0 In 2004 there was

6 pg/mg albumin In 2004 there was an outbreak of high aflatoxin contamination in Kenya. In this region in 2004 there was an outbreak of aflatoxicosis that involved many deaths. 10/23/2017 University of Leeds 6

It is common to see variation in different regions of the same country K T I 80 60 pg/mg albumin 70 60 50 40 30 20 10 pg/mg albumin 50 40 30 20 10 0 North west Senegal

7 It is common to see variation in different regions of the same country K T I pg/mg albumin pg/mg albumin North west Senegal West Senegal South Senegal 0 Tabora Kilimanjaro Iringa This could be due to socio-economic conditions, farming practice or local climate 10/23/2017 University of Leeds 7

Variation in exposure of 3 mycotoxins in Tanzanian children 60 AF-alb Geometric mean (pg/mg alb) K 50 40 30 20 T I 10 0 Nyabula Kikelelwa Kigwa baseline 6 months 12 months Urinary FB1 Geometric mean

8 Variation in exposure of 3 mycotoxins in Tanzanian children 60 AF-alb Geometric mean (pg/mg alb) K T I 10 0 Nyabula Kikelelwa Kigwa baseline 6 months 12 months Urinary FB1 Geometric mean (pg/ml) Urinary DON Geometric mean (ng/ml) Nyabula Kikelelwa Kigwa 0 Nyabula Kikelelwa Kigwa baseline 6 months 12 months baseline 6 months 12 months 23 October 2017 School of Food Science and Nutrition

9 Exposure to Aflatoxin Associated with Impaired Growth 80 Z >0 Z 0 to-2 Z -2 to -3 Z <=-3 AF-alb (pg/mg) Height for Age Growth Status (Z score) Weight for Age Gong et al (2002) British Medical Journal 325, 20-21

10 Reduced height increase in Beninese children with higher aflatoxin exposure Aflatoxin Exposure Group a Mean AF-alb over 8 months Height increase (cm) Unadjusted Adjusted b lower quartile 4.9 (4.5,5.3) *,c 5.9 (5.2,6.6) mid-lower quartile 4.4 (4.1,4.7) ** 5.3 (4.8,5.9) mid-upper quartile 4.1 (3.8,4.5) ** 4.8 (4.4,5.2) upper quartile 4.1 (3.8,4.5) ** 4.2 (3.9,4.6) a The quartiles are <23.3, , , >101.5 pg/mg. b Adjusted for age, height, weaning status, mothers SES and village. c Data labelled * are significantly different to **. Gong et al (2004) Environmental Health Perspectives 112,

Tanzania study There were non-significant negative associations between AF-alb and LAZ scores at 12 months There were significant negative associations between urinary fumonisin and LAZ

11 Tanzania study There were non-significant negative associations between AF-alb and LAZ scores at 12 months There were significant negative associations between urinary fumonisin and LAZ scores There was a mean difference of 1.8 cm less growth in children in the highest UFB1 quartile compared to the lowest Shirima et al (2015) Environmental Health Perspectives 123,

12 Possible mechanisms for aflatoxin impaired growth Intestinal epithelium damage contributes to environmental enteropathy Immune suppression increases number of infections (eg diarrhoea that reduces nutrient uptake) Liver toxicity reduces IGF protein levels in circulation DNA methylation changes in genes affecting growth

13 Community hand sorting of peanuts to reduce aflatoxin in food Recruitment 25 women recruited from 5 villages (5 from each village) Nuts supplied by us Procured from market Provided with shells on weight decreases once shells removed Questionnaires Teaching With the aid of pictures Sorting Hand-sorting by participants Weigh the shelled nuts and dispatch 0.5 Kg to each participant Sample Collection baseline N=5 clean, N=25 mouldy, N=25 roasted, N=5 Sorted Mouldy Nuts Roasting included Lab Analysis

Calculation of aflatoxin B 1 reduction based on

and clean groundnuts Weight of baseline shelled

amount in mouldy nuts (µg) AFB 1 in remaining

14 Calculation of aflatoxin B 1 reduction based on measured AFB 1 levels after sorting into mouldy and clean groundnuts Weight of baseline shelled nuts (g) Weight of mouldy nuts removed (g) AFB 1 amount in mouldy nuts (µg) AFB 1 in remaining clean nuts (µg) Reduction in AFB 1 79,388 1, %

15 Evaluation of intervention effectiveness Study protocol: handsorting method to reduce maize fumonisins contamination, evaluating the intervention effectiveness with the urinary FB1 biomarker Finding: the intervention reduced FB1 intake and urinary FB1 biomarker level

16 Research gaps to address Evaluation of excretion of fumonisin and DON biomarkers in different age groups Understand contribution of aflatoxin to endemic enteropathy Explore the effects of dual or multiple exposures on growth Assess effectiveness of community interventions 10/23/2017 University of Leeds 16

Keneba, Gambia, September 2015 Acknowledgements (too many to

Africa Gordon Shephard Liana van der Westhuizen Gambia (MRC

17 Keneba, Gambia, September 2015 Acknowledgements (too many to mention!) Tanzania Martin Kimanya Candida Shirima Senegal IARC DM Diedhiou Chris Wild A Dem Ranajit Bandyopadhyay (IITA) South Africa Gordon Shephard Liana van der Westhuizen Gambia (MRC International Nutrition Group) Andrew Prentice (LSHTM) Sophie Moore (KCL) Momodou Darboe (Keneba) Leeds & Belfast Sinead Watson Ya Xu Gaoyun Chen

Food Chemical Contaminants and Environment Pollutants. What Roles Do They Play in the Double Burden of Malnutrition?

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