Prof. David Miller (Carleton University, Canada) Workshop on “Engaging the Health and Nutrition Sectors in Aflatoxin Control in Africa” March 23 – 24, 2016

1. For our children
J. David Miller
Department of Chemistry
Carleton University
Canada

2. • Focus on the health of children
• Where corn is a staple crop,
exposure is usually to both
fumonisin & aflatoxin: the
combination increases hazard.
• Public health lens applied to
available data on interventions to
reduce exposure.
• Research on gender and
mycotoxin management needed
to ensure equitable access to
information by both men and
women.

3. 1. Epidemiology of stunting and wasting and interventions for
prevention or treatment
2. Prevalence, regulatory status for mycotoxin control and mycotoxin
exposure
3. Human studies of acute (aflatoxicosis) and chronic disease
4. Studies in children and impact of aflatoxin/fumonisin on growth
and development
5. Aflatoxin-related immune modulation
6. Experimental studies of acute and chronic toxicity
7. In utero exposure to fumonisins and child health

4. Cameroon
Analytica Chimica Acta 741:58
↓ ↓
In 2011, JECFA concluded that co-exposure to aflatoxin and fumonisin
results in additive effects beyond exposures to the individual toxins.

5. A
Cameroon
Cote d’Ivoire
Guinea
Uganda
50:50
I
Benin
Ghana
Kenya
Mozambique
Tanzania
Zimbabwe
70:30
J
DR Congo
Congo
Gambia
Nigeria
20:80
maize:groundnuts

6. Focus on biomonitoring
• Population exposure assessments are straightforward
in fully developed market economies. There is no
immediate prospect of enabling uniform information
collection in many developing countries.
• Increasing the availability of mycotoxin
biomonitoring including an improved biomarker for
fumonisin exposure seems to be the sensible course.
• Availability of reagents, analytical costs and absence
of high throughput technology remains a restriction.

7. Proc Nutrition Soc 2000 59:149

8. “It may be that the
enteropathy arises and is
maintained by frequent
exposure to a combination
of faecally-derived
organisms. Other possible
initiation factors include
food toxins, e.g. aflatoxin,
which can be a problem in
The Gambia (Wild et al.
1992), or much less likely,
a so far unidentified
nutrient deficiency.”
Proc Nutrition Soc 2000 59:149Am J Trop Med Hygiene 86:756

9. An estimated 162 million children
aged less than 5 years worldwide
were stunted. Poor quality diets
and high rates of infection, both
in pregnancy and in the first years
of life, are known to result in poor
child growth.
While the relative contribution of
these factors to stunting are
unknown, provision of all of these
established nutrition-specific
interventions in the most affected
regions had reduced stunting by
less than 20%.

10. Environ Health Perspect 112:1334
Environ Health Perspect 111:217

11. Child growth
• Six studies were deemed to be of high quality, with
well-defined sample sizes, exposure or dose
assessments, outcome measures, and appropriate
multivariate analyses.
• Taken together, these studies suggest that mycotoxin
exposure contributes to child growth impairment,
independent of and together with other risk factors
that may cause stunting.
• What is the attributable risk?

12. Possible mechanisms
• Enteropathy may be partly attributable to aflatoxin
related toxic damage on the intestine epithelium,
resulting in poor uptake of nutrients;
• aflatoxin associated immune suppression could
increase children’s susceptibility to infections such as
diarrhea;
• liver toxicity of aflatoxin may damage the production
of insulin like growth factor pathway proteins in the
liver and an adverse impact on child growth.

13. A recent study of aflatoxin adducts was conducted in populations
participating in randomized community trials of antenatal
micronutrient supplementation in southern Nepal and
northwestern Bangladesh.
Findings from the Nepal samples demonstrated exposure to
aflatoxin, with 94% detectable samples ranging from 0.45 to
2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In
the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin
B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg
aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to
76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to
81.44 pg aflatoxin B1-lysine/mg albumin at age two years
Food Chem Toxicol 74:184

14. 1. Epidemiology of stunting and wasting and interventions for
prevention or treatment
2. Prevalence, regulatory status for mycotoxin control and mycotoxin
exposure globally
3. Human studies of acute (aflatoxicosis) and chronic disease
4. Studies in children and impact of aflatoxin/fumonisin on growth
and development
5. Aflatoxin-related immune modulation
6. Experimental studies of acute and chronic toxicity
7. In utero exposure to fumonisins and child health

15. “It thus becomes the plain duty of health officers, as a
body, to determine the actual and relative importance
[of interventions]….and to use their efforts to build
up the more useful and employ along the lines of
greatest public benefit those facilities placed at their
disposal.”
Am J Public Health (N Y) 1912 2:7

16. Public health evidence
• The “best quality” evidence (i.e. indicating that
an intervention is ready for implementation) is
for an approach that has reached a mature
stage of development, results in significant
intervention effects, and addresses the needs
of important stakeholders.

17. 1.Sufficient evidence for implementation as evidenced
with multiple studies with health metrics and/or
biomarker data.
2. needs more field evaluation
3. needs formative research
4. no evidence/ineffective

18. As currently envisaged, the
recommendations would be
relevant for investment of public,
nongovernmental organization, and
private funds at the scale of the
subsistence farmer, the smallholder,
and through to a more advanced
value chain.

19. Table 7.1. Summary of the Working Group’s evaluation of interventions associated with the reduction of aflatoxin and/or fumonisin exposure
Intervention
Category
of
evidencea
Context Gap (research/translation) Combination/issues/comments
Dietary diversity —b
Dose effect reduction of
HCC
• Investment in appropriate crops for the target region
both suitable for the climate and culturally acceptable
Difficult in food-insecure situations or in food-, arable land-, or water-insecure
countries.
Genetic resistance Contamination
Aflatoxin in maize 3
• Movement of resistance in agronomic lines
• Identification of resistance genes
Combination: Biocontrol; agronomic and post-harvest practices
Issues: Small research community; large environmental effect on phenotype
expression; resistance is polygenic
Fumonisin in maize 2
Combination: Agronomic and post-harvest practices
Issues: Small research community; large environmental effect on phenotype
expression; resistance is polygenic
Aflatoxin in peanuts 4
• Identification of sources of resistance
• Movement into agronomic lines
Combination: Biocontrol; agronomic and post-harvest practices
Issues: Large environmental effect on phenotype expression limits resistance
expression over large areas; small research community; resistance is polygenic;
resistance is not well described

20. Table 7.1. Summary of the Working Group’s evaluation of interventions associated with the reduction of aflatoxin and/or fumonisin exposure
Intervention
Category
of
evidencea
Context Gap (research/translation) Combination/issues/comments
Biological control Contamination
Atoxigenic strains 2
• Frequency and outcomes of genetic recombination
• Consistency of efficacy evaluated across geography
and users
Combination: Agronomic and post-harvest practices
Comment: Ongoing translational research in the USA and Africa

22. Table 7.1. Summary of the Working Group’s evaluation of interventions associated with the reduction of aflatoxin and/or fumonisin exposure
Intervention
Category
of
evidencea
Context Gap (research/translation) Combination/issues/comments
Primary prevention Dose effect
Dioctahedral smectite
clay
2
• Dose and duration on efficacy and safety
• Effects on infants, children, and pregnant women
Combination: Clay amended with chlorophyllin and other trapping agents
Issue: Formulation strategies
Comments: Possible enhanced efficacy during outbreaks; potential to mitigate
aflatoxins and fumonisins
Chlorophyllin 2
Lactobacillus 3
Yeast glucan 4
Chemoprevention Dose effect
Broccoli sprout
extract
2
• To date, phase II clinical trials for efficacy; need for
scaling to longer-term interventions
• Translation to local, culturally acceptable foods with
these enzyme inducers
• Biomarker studies to date; no health end-point studies
yet
Comment: Opportunity for use in acute-exposure situations; native plants; dietary
diversification

23. Intervention
Category of
evidence
Context Gap (research/translation) Combination/issues/comments
Postharvest
Dose effect/
contamination
Package 1
• Knowledge translation is cultural
• Modules need to be developed in partnership with
farmers, area agricultural extension workers,
traditional leaders, church groups, health workers, and
civil society
Comments: Ready to be implemented; use in chronic-exposure situation as an
ongoing intervention package; needs to be applied as a multifactorial intervention
package
Sorting 1
• Done in all cultures for all crops; however, best
practices need to be formally taught at the village level Comment: Important for complementary food
Issue: Fate of the rejected food
Nixtamalization 1
• Requires adequate water for washing
• Has not been adapted in Africa or Asia

24. Ready for implementation
• Increasing dietary diversity
• Package of storage practices and
sorting
• Sorting
• Nixtamalization (in Latin America)

25. I
In 1630, Dr. Thuillier observed that the intensity of the malady was in
proportion to the amount of ergoty grain consumed and that those with
more diverse diets suffered less or not at all. He fed sclerotia to chickens,
geese and pigs & they all died. More than a century later, L'Abbé Tessier
proposed cultivation of potatoes instead of rye, improved drainage and
the enforced cleaning of grains.
Sorting contaminated grains is the primary tool used to reduce mycotoxin
contamination in grains and nuts after harvest. This has proven benefits
for health
Eur J Obstetrics Gyn & Repro Biol 60:109; Botany, Patronage, and Community at the 17th Parisian Royal Academy of Sciences, 1990

26. Sorting
Sorting emerged soon after the discovery of aflatoxin in 1961. The need
for efficient ways to remove aflatoxin contaminated nuts prompted
experiments on the concentrations of aflatoxin in kernels from shells
that were not visibly moldy. This revealed that visual sorting was an
efficient way to segregate more versus less contaminated kernels in the
laboratory.
Whitaker et al. (1998) demonstrated that visual sorting of groundnuts
provided a practical first action regulatory method. They found that
sound mature kernels and sound half kernels contained ca. 7% of the
aflatoxin with the damaged kernels containing the rest.

27. These strategies work best where there is on-going training. A study in the Philippines
found that manual sorting reduced aflatoxin concentration in a lot from 300 ng/g to
<15 ng/g. Recent research conducted in Kenya (and Haiti) demonstrated that manual
sorting of groundnuts purchased at local markets could reduce lot aflatoxin
concentrations by ~98%
In the case of maize in Africa, manual sorting is moderately effective at the village
level for segregating kernel lots for decreased concentrations of aflatoxin. Removing
visibly mouldy, insect-damaged and broken grains by hand reduced aflatoxin
concentrations by 40% based on reports from a study in Benin. Studies in South
Africa and Tanzania have demonstrated that hand-sorting of maize kernels by
removing the visibly infected/damaged kernels by local farmers reduced fumonisin by
20%.
In South Africa, the effectiveness of hand sorting to reduce fumonisin exposure was
documented by biomarkers

28. A recent study from Malawi found that most people recognized that
molds were dangerous to human health but about half thought that the
toxins were destroyed during cooking . This might explain why about a
third reported that they bought moldy maize. Women were less
informed on issues related to molds in foods (Mycotoxin Res 32:27).

29. We found that the education of women should be considered critical
because of their roles as mothers, educators, and businesswomen
managing household nutrition, farming, and the selling of smallholder
crops. More research on gender and mycotoxin management is needed
to properly develop education campaigns and ensure equitable access to
information by both men and women. Culturally-sensitive modules
need to be developed in partnership with farmers, area agricultural
extension workers, traditional leaders, church groups, health workers,
and civil society
What would be a productive approach to creating capacity to do this
work?

30. Table 7.1. Summary of the Working Group’s evaluation of interventions associated with the reduction of aflatoxin and/or fumonisin exposure
Intervention
Category
of
evidencea
Context Gap (research/translation) Combination/issues/comments
Dietary diversity —b
Dose effect reduction of
HCC
• Investment in appropriate crops for the target region
both suitable for the climate and culturally acceptable
Difficult in food-insecure situations or in food-, arable land-, or water-insecure
countries.
Genetic resistance Contamination
Aflatoxin in maize 3
• Movement of resistance in agronomic lines
• Identification of resistance genes
Combination: Biocontrol; agronomic and post-harvest practices
Issues: Small research community; large environmental effect on phenotype
expression; resistance is polygenic
Fumonisin in maize 2
Combination: Agronomic and post-harvest practices
Issues: Small research community; large environmental effect on phenotype
expression; resistance is polygenic
Aflatoxin in peanuts 4
• Identification of sources of resistance
• Movement into agronomic lines
Combination: Biocontrol; agronomic and post-harvest practices
Issues: Large environmental effect on phenotype expression limits resistance
expression over large areas; small research community; resistance is polygenic;
resistance is not well described

31. Proc Natl Acad Sci U S A. 2014 111:4001

32. Miracle 1966

33. Miracle 1966

34. Proc Natl Acad Sci U S A. 2014 111:4001

35. For our children
• There are some things that we know reduce
exposure to aflatoxin.
• More effort to develop and apply these ‘known
knowns’ will have important child health and
economic benefits.
• Strategies that make sense for urban and rural
areas are likely to be different.
• In all countries, reducing exposures has been a
tough challenge requiring engagement from
government, civil society and the private sector.

36. Cost of mycotoxins in Canada and the
USA, $ 0.5 to 2 billion/year depending
on the year. Cost of testing alone is $200
million. Effect on trade is very large.
For each of the three toxins aflatoxin
(1964), dexoynivalenol (1975) and
fumonisin (1990), it took upwards of 10
years to bring them under control.
Risk Analysis 10:561

37. In 2001, Dr. Jerry Rice was
contacted by a country in
Africa that had a lot of the
groundnut crop was highly
contaminated by aflatoxin.
He was upset that he had
no information that would
be immediately useful and
began work on such a
publication in 2003.
The project was restarted
in 2008 by Prof. Wild and
brought to completion.

38. Aflatoxin and fumonisin where there are important co-exposures.
ca. 100 pages of text accessible to policy makers