global threat of antimicrobial resistance genes the one ......global threat of antimicrobial...

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DTU Food, Technical University of Denmark

Global threat of antimicrobial resistance genesThe One Health Approach

Frank M. Aarestrup ([email protected])

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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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Treatment ofinfection in Lung

Selection ofResistancein gut

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Food products

Animal waste

Environment

Spread

Hospital

Veterinarian

TravelAdoption

Turist

Farmer

Population

Abbatoirs

Production animals

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Significant increase

But cephalosporins have not been usedfor danish broilers in 10 years

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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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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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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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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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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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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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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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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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The future?

• What if people will not share?

• How do we then get a global surveillance?

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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

global threat of antimicrobial resistance genes the one ......global threat of antimicrobial...

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