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DTU Food, Technical University of Denmark
Global threat of antimicrobial resistance genesThe One Health Approach
Frank M. Aarestrup ([email protected])
19-11-2015
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DTU Food, Technical University of Denmark
Importance of the food animal reservoir for human health
• Different estimates ranging from
– Almost zero (AHI and IFAH)
– 1,518 extra deaths and an associated increase of 67,236 days of hospital admissions in Europe as a result of cephalosporin use in chickens alone (Collignon et al. 2013)
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2015
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DTU Food, Technical University of Denmark
Treatment ofinfection in Lung
Selection ofResistancein gut
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DTU Food, Technical University of Denmark
Food products
Animal waste
Environment
Spread
Hospital
Veterinarian
TravelAdoption
Turist
Farmer
Population
Abbatoirs
Production animals
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DTU Food, Technical University of Denmark
Significant increase
But cephalosporins have not been usedfor danish broilers in 10 years
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DTU Food, Technical University of Denmark
The Danish broiler production
ESBL ESBL
ESBL
Day-old Grand Parant
ESBL
Grandparant flocks
Day-old Parant Parant flock and broiler flocks
Cephalosporin usage No Cephalosporin usage No Cephalosporin usage
Usage in one country can affect resistance in another country
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• The old zoonosis:
– Antimicrobial resistant Salmonella (DT104)
– Campylobacter (FQ and macrolide resistant)
• The new zoonosis (antimicrobial resistant):
– Enterococci
– E. coli
– S. aureus
– C. difficile
– Resistance genes
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Phylogeny of clones
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Phylogeny of plasmids
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De Been et al. conclusions
• Recent clone transfer between farmers and
pigs
• No evidence for recent clonal transfer
between chickens and humans
• Recent dissemination of plasmids between E.
coli from chickens and humans
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DTU Food, Technical University of Denmark
R Strep. pneumoniae
R Haem. influenzae
R Pseudomonas aeruginosaR Acinetobacter baumannii
R Salm.
R Camp.R E. coli
VRE
R E. coli
MRSA
RS. aureus
RS. aureus
R E. coliVRE
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DTU Food, Technical University of Denmark
R Strep. pneumoniae
R Haem. influenzae
R Pseudomonas aeruginosaR Acinetobacter baumannii
R Salm.
R Camp.
R E. coliVRE
C. diff.
R E. coli
MRSA
R E. coliVRE
C. diff.
Horizonta
l tr
ansfe
r of
resis
tance g
enes
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Antimicrobial consumption and millions of heads of pigs produced in Denmark from 1994 to 2013.
Frank M. Aarestrup Phil. Trans. R. Soc. B 2015;370:20140085
©2015 by The Royal Society
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Targeted controlCanberra and Copenhagen Expert Reports
http://www.who.int/foodborne_disease/resistance/FBD_CanberraAntibacterial_FEB2005.pdf
http://www.who.int/foodborne_disease/resistance/antimicrobials_human.pdf
Most critical :- Quinolones- 3rd gen. cephalosporins- Macrolides
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Effect on sales of antibiotics for animals - NL
• 56% reduction from 2007 to
2012
• Fluoroquinolones and
3rd/4th-gen cefalosporines
usage reduced to a
minimum
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Prevalence of ceftiofur resistance (moving average of the current quarter and the previous 2 quarters) among retail chicken Escherichia coli, and retail chicken and human clinical Salmonella enterica serovar Heidelberg isolates during 2003–2008 in Québec, Canada.
Emerg Infect Dis.2010 Jan;16(1):48-54
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DTU Food, Technical University of Denmark
Data on production characteristics for piglet mortality (per cent; grey triangles) and mean number of pigs produced per sow per year (black diamonds) (a), average daily gain (ADG,
grey triangles) and mortality rate (black squares) in weaning pigs (b), and a...
Frank M. Aarestrup Phil. Trans. R. Soc. B 2015;370:20140085
©2015 by The Royal Society
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20 19 November 2015
Berge et al. 2009, J. dairy sci.
Two times more diarrhea in calves routinely treated with antibiotics
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Treatment-Direct effect – saves life-Easy to show-Easy to quantify-Anima welfare
Production-Direct economy-Easy management tool-Me, me me
Restriction and human health- In-direct- Difficult to quantify- No direct economical interest- Low term effects- Perhaps effects- Others (not me)
Why is it so difficult to reduce consumption
Pharmaceutical lobby
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DTU Food, Technical University of Denmark
Conclusions – part I
• Total antimicrobial consumption can be reduced without compromising productivity
• Specific drugs can be almost or entirely removed
• This will led to reduction in resistance
• Use in one country affects other countries
• Still a lack of data quantifying the livestock contribution
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DTU Food, Technical University of Denmark
Despite 20 years of asking we still need
• Integrated, long-term surveillance with optimal sampling in settings where interventions occur
• Harmonised characterisation
• (real-time) Exchange of data and strains to allow comparisons and identification of transmission
• Data on associations between antimicrobial use, animal health, productivity and economy
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DTU Food, Technical University of Denmark
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DTU Food, Technical University of Denmark
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DTU Food, Technical University of Denmark
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Strategy to win a war
Putting up the right defense
Knowing:
Where
What
When
How Communicate & Prioritise
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NGS advantages• Laboratory diagnostics increasingly rely on (pathogen) genomic
information
• RNA / DNA are common across pathogens, therefore, methods to
analyse pathogen genomes potentially are universal
• Next generation sequencing capacity is developing fast, and costs
are becoming competitive
� Capturing NGS developments may provide a universal language
that can be harnessed for early detection of outbreaks across
disciplines and domains
� If the technology keeps developing, less equipped labs may
leapfrog
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Our vision: to build one system that serves all
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COllaborative Management Platform for detection and Analyses of (Re-) emerging and foodborne outbreaks in Europe
COMPARE is funded by the European Commission under H2020
A global platform for the sequence-based rapid identification of pathogens- Start date December 1st 2014
Coordinated byFrank M. Aarestrup (Technical University of Denmark)Marion Koopmans (Erasmus Medical Center, the Netherlands)
But managed by all participants
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The goal
An open web-based system for improving rapid identification, containment and mitigation of emerging infectious diseases and foodborne outbreaks
• Real-time data on occurrences of all infectious agents available for all
• Tools for automatic detections of related clusters in time and space, as well as novel pathogens
• Possibilities to observe trends in clones and species as well as virulence and resistance
• Specific sequence data available to all for the development of diagnostic tests and vaccines
• There can be no real-time surveillance without real-time data-sharing
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Stakeholder Consultations
Cost Effectiveness studies
Dissemination and Training
Su
pp
ort
ing
act
ivit
ies
Studies into Barriers to open data sharing
for sample processing and sequencing
Analytical workflows
for generating actionable information
Harmonized standards
for sample and data collection
RA Models & risk-based strategies
Data and information platform
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Data comparison problem
Global repositories
> 1-1000 Tb data
Client
~1-100 Gb dataInternet
~1Gb/hour
Bring the tools to the data
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Bacterial Analytic
Pipeline
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User Statistics
Until now: >175,000 submissions
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Pilot projects in 2016
• Escherichia coli and ESBL
• Influenza
• Meta-genomics (clinical, environmental, AMR)
• Ad hoc
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DTU Food, Technical University of Denmark
The future?
• What if people will not share?
• How do we then get a global surveillance?
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2015
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DTU Food, Technical University of Denmark
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DTU Food, Technical University of Denmark
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DTU Food, Technical University of Denmark
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DTU Food, Technical University of Denmark
Farm surveillance based on manure
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0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
Aerobic bacteria (TET)
P-value: 4.24e-04
Individual
Pen
flo
or
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
E. coli (TET)
P-value: 1.827e-04
Individual
Pen
flo
or
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
E. coli (AMP)
P-value: 1.411e-02
Individual
Pen
flo
or
CFU determination
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Meta-genomic
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Conclusions• WGS/NGS is rapidly entering diagnostic and public health arena,
with near real time data generation
• Meta-genomic sequencing is superior to conventional and other genomic methods for quantification of AMR
• Bottleneck at level of bioinformatics, particularly for intergroup comparison, national, international
• We aims to develop infrastructure and ICT to meet the coming demand
• In the coming years, we will be seeking global partners for pilot projects
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Global sewage surveillance - 2016
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Next logical step
Platform