MYCO-GLOBE MEETING. Stanhope Hotel, Brussels, Belgium October 21 22, 2004

Transcription

1 MYCO-GLOBE MEETING Stanhope Hotel, Brussels, Belgium October 21 22, 2004

2 MYCOTOXINS: A GLOBAL PROBLEM WFO MARASAS PROMEC UNIT, MEDICAL RESEARCH COUNCIL TYGERBERG, SOUTH AFRICA wally.marasas@mrc.ac.za

3 MOST IMPORTANT MYCOTOXIN-PRODUCING FUNGI Aspergillus flavus Aspergillus ochraceus Penicillium verrucosum Fusarium graminearum Fusarium verticillioides

4 MOST IMPORTANT NATURALLY OCCURRING MYCOTOXINS Aflatoxin Ochratoxin Deoxynivalenol Zearalenone Fumonisin

5 MYCOTOXICOSES OF ANIMALS CAUSED BY MYCOTOXINS IN FEEDS Aflatoxicosis Aflatoxin Nephropathy Ochratoxin Feed Refusal Syndrome Deoxynivalenol Hyperoestrogenism Zearalenone Pulmonary Oedema Syndrome Fumonisin Leukoencephalomalacia Fumonisin

6 HUMAN DISEASES ASSOCIATED WITH MYCOTOXINS IN FOOD Aflatoxin Acute Toxic Hepatitis Liver Cancer Fumonisin Esophageal Cancer Neural Tube Defects

7 AFLATOXIN B 1 O O H O O O OCH 3 H

8 LIVER CANCER IN MOZAMBIQUE

9 MTL S OF AFLATOXIN IN SOME COUNTRIES Country Foods MTL (ppb) Total Afla AFB 1 China Groundnuts and Maize 20 - Rice 10 Wheat 5 - Germany All Foods 4 2 Japan All Foods - 10 South Africa All Foods 10 5 USA All Foods 20 - Data from FAO (1997)

10 STEREOCHEMISTRY OF B SERIES FUMONISINS CH 3 OR CH 3 Y NH 2 H 3 C CH 3 OR X OH O COOH Fumonisin B 1 : X = OH, Y = OH Fumonisin B 2 : X = OH, Y = H Fumonisin B 3 : X = H, Y = OH R = tricarballylic acid (TCA) COOH

11 MOLDY CORN EARS INFECTED BY FUSARIUM

12 EQUINE LEUKOENCEPHALOMALACIA

13 PORCINE PULMONARY EDEMA

14 LIVER CANCER IN A RAT

15 ESOPHAGEAL CANCER Fumonisin in home-grown corn is associated with human esophageal cancer in Transkei, South Africa and LinXian, China

16 TRANSKEI REGION, SOUTH AFRICA

17 CORN STORAGE CRIBS IN TRANSKEI

18 MOLDY CORN EARS INFECTED BY FUSARIUM

19 NEURAL TUBE DEFECTS Fumonisin inhibits folate uptake and causes neural tube defects in mice and possibly in humans

20 FDA GUIDANCE FOR INDUSTRY FUMONISIN LEVELS IN HUMAN FOODS Corn Products MTL (ppm) Total Fumonisins Dry milled corn products < 2.25% fat 2 > 2.25% fat 4 Cleaned corn - popcorn 3 Data from FDA (2001)

21 FDA GUIDANCE FOR INDUSTRY FUMONISIN LEVELS IN ANIMAL FEEDS Feeds MTL (ppm) Total Fumonisins Horses and Rabbits 1 Pigs and Catfish 10 Breeding Ruminants and Poultry 15 Ruminants for slaughter 30 Poultry for slaughter 50 Data from FDA (2001)

22 CORN INTAKE PROFILES g/70 kg bw/day South Africa - Rural 460 South Africa - Urban 270 Europe 7

23 PDI AND TDI (µg/kg/day) OF FUMONISINS IN CORN PDI TDI NOEL/1000 JECFA South Africa - Rural South Africa - Urban Europe

24 CORN INTAKE [g/person (60kg)/day] PMTDI = 2 µg/kg bw/day (nephrotoxicity) PMTDI = 0.8 µg/kg bw/day (carcinogenicity) FB (ppm) FB INTAKE (µg/kg bw/day)

25 IMPACT OF LOWER EU AFLATOXIN STANDARDS ON AFRICAN EXPORTS Number of cancer deaths saved ~2 per billion people Loss in African exports of groundnuts and cereals US $ 670 million Data from Otsuki et al (2001)

26 COMMENT BY KOFI ANNAN Secretary-General, United Nations A World Bank study has calculated that the European Union regulation on aflatoxin costs Africa $670 million each year in exports of cereals, dried fruit and nuts. And what does it achieve? It may possibly save the life of one citizen of the European Union every two years... Surely a more reasonable balance can be found

27 CORN INTAKE [g/person (60kg)/day] PMTDI = 2 µg/kg bw/day (nephrotoxicity) PMTDI = 0.8 µg/kg bw/day (carcinogenicity) FB (ppm) FB INTAKE (µg/kg bw/day)

28 BIOTECHNOLOGY SOLUTIONS Genetic engineering approaches are the most attractive methods now under development, and the future of fumonisin reduction may very well lie in the hands of these researchers Munkvold & Desjardins (1997) The 21 st Century will be biological and diverse, with biotechnology being the kingpin of the process Olusegun Obasanjo - President of Nigeria

29 TRANSGENIC STRATEGIES TO REDUCE MYCOTOXINS IN CROPS Reducing infection by the fungus Degrading the mycotoxin in planta Disrupting mycotoxin biosynthesis Inducing insect resistance

30 Bt CORN HYBRIDS Transgenic corn with the Bt gene for insect resistance is a promising solution to the fumonisin problem because of the close association between European corn borer infestation and Fusarium verticillioides infection in corn

31 Significantly lower levels of fumonisin have been found in Bt compared to conventional corn hybrids

32 REDUCTION OF FUMONISINS IN Bt CORN 25 TOTAL FUMONISINS (ppm) Natural ECB infestation Manual ECB infestation * * * * * CBH351 BT11 MON810 CBH351 BT11 MON810 MAIZE LINES Standard maize Bt-maize * = P<0.05 Data from Munkvold et al., 1997

33 CONCLUSIONS The ultimate solution to the global mycotoxin problem is not regulation, but reduction of fungal infection and mycotoxin levels in crop plants in the field and in storage contd..

34 CONCLUSIONS Implementation of the Code of Practice of the Codex Alimentarius Commission for the reduction of mycotoxins in cereal grains should reduce the risk of people who are not protected by traditional risk assessment Novel strategies need to be developed such as the eduction of fumonisin levels in genetically modified Bt corn and improved risk communication to inform rural communities about the health hazard of mycotoxins

35 ACKNOWLEDGEMENTS All my colleagues, past and present, at the PROMEC Unit of the South African Medical Research Council (MRC) for their invaluable contributions to the global knowledge about mycotoxins The MRC for continuous funding from 1975 to the present