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Azole fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment) IATP webinar 5 March 2015 Erna van der Wal (CLM) Wouter van der Weijden (CLM) en Paul Verweij (Radboud UMC)

Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 1: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Azole fungicides, aspergillosis and preliminary ‘hot spots’

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Peter Leendertse CLM (Centre for Agriculture and Environment)

IATP webinar 5 March 2015

Erna van der Wal (CLM) Wouter van der Weijden (CLM) en Paul Verweij (Radboud UMC)

Page 2: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Resistant fungi: new risk for humans

•  In NL lots of attention on human health and antibiotic resistance, including measures

•  Little attention on human health and fungicide

resistance

Verweij: Doden door agressieve infecties met resistente schimmels, NOS, 17-06-2010

Van der Wal: Resistente schimmels zijn tijdbom, Nieuwe Oogst 7 maart 2012

Aspergillus fumigatus

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Page 3: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 4: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 5: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 6: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 7: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Human problem

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Page 8: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Where do these azole-resistant strains originate?

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Page 9: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 10: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

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Page 11: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Where do these azole-resistant strains originate?

1.   Where do we find Aspergillus?

2.   Where are azoles used?

3.   What azole amounts are used?

4.   Where are optimal conditions for development of restistance in Aspergillus?

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Page 12: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

1. Where do we find Aspergillus?

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Everywhere! •  Air •  Animals •  Compost •  Farms •  Humans •  Houses •  Hospitals •  Nursery •  Plants •  Soil •  Water

Page 13: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

2.Where are azoles used?

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Everywhere!

•  Human and animal protection (medicines) •  Animal protection (biocides) •  Crop protection (pesticides) •  Fruit conservation (pesticides) •  Wood conservation (biocides) •  House protection (wall paper paste, sealants) •  Film conservation (biocides) •  Many other protection or conservation

Page 14: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

3. What azole amounts are used?

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Total Agriculture NL: >130.000 kg yearly in > 50 crops

Fungicides Use (kg) Area(ha) Crops with highest use

Prothioconazool 40.000 152.000 Winter wheat, tulip, lily, onion

Epoxiconazool 25.000 100.000 Winter wheat, sugar beet

Tebuconazool 35.000 125.000 Winter wheat, tulip, lily, grass seed

Cyproconazool 3.600 26.000 Sugar beet, winter wheat,

Difenoconazool 8.500 40.000 sugar beet, cabbage, apple & pear

Metconazool 800 14.000 Winter wheat

Propiconazool 1.700 3.200 Pot plants, trees, flowers

(CLM estimates based on CBS 2012 and expert judgement), Official numbers still secret

Page 15: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

3. What azole amounts are used?

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Total other uses NL:

•  In Dutch healthcare: 400 kg of azoles annually

•  Other uses: unknown

Page 16: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Remarkable observations

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Promotion of azoles in maize

Quilt® Xcel (propiconazole/azoxystrobin) effectief tegen schimmelziekten Maïs langer groen en gezond Het nieuwe fungicide Quilt Xcel houdt maïs langer gezond en vitaal. Quilt Xcel biedt telers daarom meer zekerheid en rust. !promotion for azole even without fungus problems in maize

Page 17: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

4. Where are optimal conditions for resistance development?

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•  Presence of Aspergillus •  Azole pressure •  High moisture •  High temperature •  Presence of oxygen

Let’s search for “Hot spots”

Not everywhere!

Page 18: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Preliminary results in search of ‘hot spots’

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Composting material

sexual

a-sexual resistant a-sexual

resistant sexual

Compost 1. No azole resistant strains left after composting process 2. Sexual strain not reproducible

Page 19: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Preliminary results in search of ‘hot spots’

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Ecological farming (no fungicides)

Conventional farming (prothioconazool 10mg/kg)

Resistant sexual sexual

a-sexual resistant a-sexual

Peel waste of bulbs

Page 20: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Indications of the preliminary exploration

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•  Aspergillus in different predicted locations (compost, peel waste of bulbs)

•  Both sensitive and resistant strains

•  Sometimes only resistant strains

•  Sometimes hardly Aspergillus (dry straw of wheat, ecological farming)

Few samples & few replications!

Page 21: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

How to reduce the risk of fungicide resistance?

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Focus in four steps!

1.  Identify “hot spots” 2.  Analyse mechanisms 3.  Eliminate “hot spots”

-change methods for plant waste material -reduce azole use -stimulate alternatives, preferably methods with less or no induction of resistance.

4.  Cooperate internationally and advise registration authorities

Page 22: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Findings conference KNAW (Royal Dutch Academy of Sciences) 2-4 March 2015

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Page 23: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Findings conference KNAW

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Page 24: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Findings conference KNAW

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Page 25: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Findings conference KNAW

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Page 26: Azole fungicides, aspergillosis and preliminary ‘hot spots’ fungicides, aspergillosis and preliminary ‘hot spots’ 1 Peter Leendertse CLM (Centre for Agriculture and Environment)

Sustainable farming –

Healthy food – A living countryside

Thank you very much for your attention!

Any questions?