EUU, Alm.del - 2017-18 - Bilag 62: Brev fra forhenværende belgisk premierminister til Folketingets formand vedr. antimikrobiel resistens

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INSIGHTS

P OLICY FORUM

GLOBAL HEALTH

Thomas P. Van Boeckel,

Emma E.

Glennon,

2,3

Dora Chen,

2,4

Marius Gilbert,

5,6

Timothy P. Robinson,

7,8

Bryan T Grenfell,

4,9

Simon A. Levin,

4,10

Sebastian Bonhoeffer,

Ramanan Laxminarayan

2,10

Compact quantum

memory

p. 1354

Mutations that increase

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p. 1358

Reducing antimicrobial use in food animals

Consider user fees and regulatory caps on veterinary use

tin (3), is an important challenge for human

medicine because it can lead to untreatable

infections. Evidence linking AMR between

animals and humans is particularly strong

for common foodborne pathogens resis-

tant to quinolones, such as

Campylobacter

spp. and

Salmonella

spp. (4). AMR is also a

threat to the livestock sector and thus to the

livelihoods of millions who raise animals

for subsistence (5).

The primary driver for the accumulation of

harmful resistance genes in the animal res-

ervoir is the large quantity of antimicrobials

used in animal production (6). Antimicrobial

use in livestock, which in many countries out-

weighs human consumption (7), is primarily

associated with the routine use of antimicro-

bials as growth promoters or their inappro-

priate use as low-cost substitutes for hygiene

measures that could otherwise prevent infec-

tions in livestock.

In Europe, regulations have been the prin-

cipal instrument to limit antimicrobial use

in animal production. In the United States,

consumer preferences have driven compa-

nies to reduce antimicrobial use in animals,

although the impact on livestock rearing

practices is still nascent (8). Some European

countries maintain highly productive live-

stock sectors while using less than half the

current global average amount of antimi-

crobial per kilogram of animal (50 mg/kg).

Therefore, this threshold has been proposed

as a potential target for global regulations on

veterinary antimicrobial use (9). However,

the impact that such policies would have on

the global consumption of antimicrobials has

yet to be quantified.

A second solution to reduce antimicrobial

consumption in animal production may be

to promote low-animal-protein diets: China

has recently revised downward its nutritional

guidelines for meat intake to 40 to 70 g/day

(10), which is approximately half the current

consumption level in the country. If followed,

this measure could have an indirect but sub-

stantial impact on the global consumption of

veterinary antimicrobials. A third solution

to cut antimicrobial use would be to charge

a user fee, paid by veterinary drug users, on

sales of antimicrobials for nonhuman use

(11). This approach has recently received sup-

port from the World Bank (12) on the basis

that the associated revenues could be in-

jected into a global fund to stimulate discov-

ery of new antimicrobials and support efforts

to preserve existing drugs (13). Without fur-

ther analysis, however, it is unclear whether

a user fee policy could achieve a meaningful

reduction in the global consumption of veter-

inary antimicrobials, let alone generate suffi-

cient revenues to support improved livestock

rearing practices or the development of new

drugs, vaccines, and diagnostics.

GLOBAL TRENDS

Veterinary antimicrobial sales volumes were

obtained via public records for 38 countries

and self-governing dependencies and esti-

mated for 190 more (supplementary materi-

als). In 2013, the global consumption of all

antimicrobials in food animals was estimated

at 131,109 tons [95% confidence interval (CI)

(100,812 to 190,492 tons)] and is projected

to reach 200,235 tons [95% CI (150,848 to

297,034 tons)] by 2030. Consumption lev-

els varied considerably between countries,

ranging from 8 mg/population correction

unit (PCU) (a kilogram of animal product)

in Norway to 318 mg/PCU in China (see fig.

S1). As the largest consumer of veterinary an-

timicrobials, both in relative (per PCU) and

in absolute terms, China has an important

leadership role with regard to its response to

AMR and has already set precedents in phas-

ing out drugs that are last resorts for human

infections but are still in use in Europe in ani-

mal husbandry.

In relative terms, humans and animals

use comparable amounts of antimicrobials

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he large and expanding use of antimi-

crobials in livestock, a consequence

of growing global demand for animal

protein, is of considerable concern in

light of the threat of antimicrobial re-

sistance (AMR). Use of antimicrobials

in animals has been linked to drug-resistant

infections in animals (1) and humans (2). In

September 2016, the United Nations (UN)

General Assembly recognized the inappropri-

ate use of antimicrobials in animals as a lead-

ing cause of rising AMR. In September 2018,

the interagency group established by the UN

Secretary General will report on progress in

the global response to AMR, including anti-

microbial consumption in animals. We pro-

vide a baseline to monitor efforts to reduce

antimicrobial use and assess how three global

policies might curb antimicrobial consump-

tion in food animal production: (i) enforcing

global regulations to cap antimicrobial use,

(ii) adherence to nutritional guidelines lead-

ing to reduced meat consumption, and (iii)

imposing a global user fee on veterinary an-

timicrobial use.

The rise of AMR in zoonotic pathogens,

including to last-resort drugs such as colis-

Institute of Integrative Biology, ETH Zurich, Zurich 8006,

Switzerland.

Center for Disease Dynamics, Economics and

Policy, Washington, DC

20005,

USA.

Department of Veterinary

Medicine, University of Cambridge, Cambridge

CB3 0ES,

UK.

Department of Ecology and Evolutionary Biology, Princeton

University, Princeton, NJ 08544, USA.

Université Libre de

Bruxelles, Brussels 1050, Belgium.

Fonds National de la

Recherche Scientifique, Brussels 1050, Belgium.

International

Livestock Research Institute, Nairobi 00100, Kenya.

Food and

Agriculture Organization of the United Nations, Rome

00153,

Italy.

Fogarty International Center, National Institutes of Health,

Bethesda, MD

20892,

USA.

Princeton Environmental Institute,

Princeton University, Princeton, NJ 08544, USA.

Email: [email protected]

1350

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EUU, Alm.del - 2017-18 - Bilag 62: Brev fra forhenværende belgisk premierminister til Folketingets formand vedr. antimikrobiel resistens

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Pigs in cages, Quanzhou, China. As the largest consumer of vererinary antimicrobials, China’s leadership is critical for combating antimicrobial resistance (AMR).

[118 mg/PCU and 133 mg/kg, respectively

(14)], but given that the biomass of animals

raised for food exceeds by far the biomass of

humans, new resistant mutations are more

likely to arise in animals. Furthermore, a

central distinction between animals and hu-

mans is the purpose of antimicrobial use. Un-

like in humans, antimicrobial use in animals

is primarily intended for growth promotion

and mass prophylaxis. These uses are often

administered both through feed, directly

targeting the gut, and in low-dose patterns

that promote the evolution of resistance (15).

These factors suggest that the food animal

reservoir is a greater source of resistance

genes than humans. However, the subse-

quent spread of those genes to humans fol-

lows complex pathways, and recent work has

highlighted that curtailing antimicrobial use

in animals alone will not suffice to contain

AMR in humans (16).

GLOBAL SOLUTIONS

The use of antimicrobials in food animals

could be reduced by 2030 between 9 and

80% with effective policies compared with a

business-as-usual target (BAU) of continued

growth of the livestock sector with current

levels of antimicrobial use (see the graph).

This could be achieved either by reducing the

quantity of antimicrobial used per animal

(targets 1 and 3) or the number of animals

that we raise for food (target 2).

Regulations.

A global regulation putting a

cap of 50 mg of antimicrobials per PCU per

year, the current global average amount,

could reduce total consumption by 64% (tar-

get 1A). If only countries of the Organization

SCIENCE

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for Economic Cooperation and Development

(OECD) and China were to adopt this regula-

tion, the global consumption in 2030 would

already be reduced by 60% (target 1B). In

the short term, target 1B may be preferred

because it would have substantial impact on

global consumption without targeting vul-

nerable farmers in low- and middle-income

countries (LMICs) who rely on the abil-

ity to treat livestock for subsistence (17). In

some high-income countries, regulatory ap-

proaches have achieved substantial reduc-

tion in antimicrobial use within a few years

and at moderate costs. However, in LMICs,

the cost of setting up surveillance systems is a

barrier to enforcement, and our findings are

contingent on enforceability.

Meat consumption.

Limiting meat intake

worldwide to 40 g/day—the equivalent

of one standard fast-food burger per per-

son—could reduce global consumption of

antimicrobials in food animals by 66% (tar-

get 2A). This reduction is comparable with

what could be achieved through regulations

targeting antimicrobial use (targets 1A and

1B). In comparison, meat consumption in

the United States currently averages 260 g/

day (OECD 2015). In this context, and given

increasing appetites for meat in emerging

economies, it seems unlikely that antimicro-

bial use in food animals could be reduced

substantially through voluntary adherence

to such drastic changes in dietary habits.

Under a more realistic global cap of 165 g

meat/day (projected EU average in 2030),

global consumption of antimicrobials could

be reduced by 22% (target 2B). Reduced

meat consumption could thus have substan-

tial benefits on AMR as well as other envi-

ronmental and human health issues.

User fees.

Imposing a user fee of 50% of the

current price on veterinary antimicrobials

could reduce global consumption by 31%

(target 3C). More important, such a policy

would also generate yearly revenues between

US$ 1.7 billion and 4.6 billion (Protocol

S4). In comparison, the level of investment

necessary for the development of one new

antimicrobial compound is typically US$ 1

billion (18). Alternative rates of 10 or 100%

for the user fee would reduce the global

consumption by 9 and 46%, generating rev-

enues of US$ 0.4 billion to 1.2 billion and

US$ 2.8 billion to 7.5 billion, respectively.

Concretely, the fee could be applied at the

point of manufacture or wholesale purchase

for imported products. The advantages of

this implementation are twofold. First, given

the limited number of drug manufacturers,

enforcement would require only limited re-

sources. Second, manufacturers are more

likely than veterinarians to keep records

of volumes traded, especially in countries

where drugs are used without prescription.

However, because user fees could be passed

on to individual farmers, these could also

have adverse effects if not accompanied by

other measures to reduce the need for an-

timicrobials in food production. Here, we

identify that demand for veterinary antimi-

crobials is on average more elastic in LMICs

(Protocol S4), with the notable exception of

China, where demand was inelastic because

of increased reliance on antimicrobials for

food production. LMICs could therefore be

disproportionally affected by a user fee.

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EUU, Alm.del - 2017-18 - Bilag 62: Brev fra forhenværende belgisk premierminister til Folketingets formand vedr. antimikrobiel resistens

INSIGHTS

P O L I C Y F O RU M

COMPARISON AND LIMITATIONS

The solutions presented in this analysis are

not mutually exclusive; if considered in com-

binations, regulatory caps, user fees, and

reductions in meat intake could potentially

reduce global consumption of antimicrobials

in animals by up to 80%. However, implemen-

tation of those policies should account for

differences across income groups. We show

that a global user fee policy could circumvent

the limitations inherent to regulatory ap-

proaches while still achieving a meaningful

reduction in antimicrobial use (31%).

Unlike regulations that may be virtually

impossible to enforce in LMICs, a user fee

policy could be applied immediately, without

waiting for costly surveillance networks to

put in place. In LMICs, large livestock pro-

ducers could follow the example from Eu-

ropean countries, where drastic reductions

in antimicrobial consumption could have

potential long-term benefits. In compensa-

tion for the reduction in antimicrobial use

in LMICs, major investments will be needed

to improve farm hygiene and expand veteri-

nary services. We show that these could be

partly financed with the revenues of the user

fee policy through a global fund. In parallel,

national programs should also ensure that

antimicrobials used for treatment by small-

holders remain affordable so that a global

user fee doesn’t become an obstacle for live-

stock-driven economic development.

In the long run, this transition to low an-

timicrobial use could benefit all countries:

Phasing out growth that promotes antimicro-

bials will likely have limited impact on food

production (19) but would reduce the risk

of emergence of pathogens resistant to last-

resort drugs (3). Reducing antimicrobial use

may also benefit LMICs to secure export mar-

kets where customers express preferences for

products obtained without antimicrobials (8)

and restriction on antimicrobial use may ap-

ply as part of trade agreements.

Our findings are subject to limitations. For

example, although more countries (including

LMICs) have reported sales of antimicrobials

for this estimate compared with 2010 (20),

information on sales broken down by species

and by classes of compounds is still limited.

As a result, consumption in nonreporting

countries can only be estimated through ex-

trapolations. In addition, available informa-

tion on antimicrobial prices prevents a more

advanced economic analysis on the impact

of user fees than presented in this study. Un-

like for human medicine, there is currently

no global database (public or private) on vet-

erinary antimicrobial sales accessible to the

public health community. Although present

data are limited, outlining current knowl-

edge allows inferences to be made about the

relative impact of different policies to curb

antimicrobial use. Our findings suggest that

imposing a user fee on veterinary antimicro-

bials is a plausible policy option to achieve

meaningful reductions in antimicrobial use

in the short term while simultaneously rais-

ing funds to improve farming practices that

will benefit the long-term viability of the live-

stock industry.

REFERENCES AND NOTES

Antimicrobial consumption in food animals by 2030

Business as usual and intervention policies are shown. Revenue ranges are estimated for different fee rates

(TR) and price elasticities of demand (PED). For 3C, 3D, and 3E, PEDs are derived from time series of imports of

veterinary antimicrobials in each country (Protocol S4); the global average PED was -0.95. See supplementary

materials for discussions of uncertainty in all estimates shown in figures. PCU, population correction unit.

Business

as usual

2030

Target 1:

Regulations

Target 2:

Meat reduction

2A 2B

Target 3:

User fee

3A 3B 3C 3D 3E

−9%

150

2013

100

−60%

−64%

−66%

−46%

−22%

−18%

−31%

−46%

−47%

−66%

−80%

Revenues from user fee

(10 US$ Billion)

Solutions

1A:

Cap 50mg/PCU

1B:

OECD+China cap

50mg/PCU

2A:

Cap 40g/day

2B:

Meat growth mitigation

and Cap 165 g/day

3A:

PED = −1.5, TR = 50%

3B:

PED = −0.5, TR = 50%

3C:

PED = −0.95, TR = 50%

3D:

PED = −0.95, TR = 100%

3E:

PED = −0.95, TR = 10%

Target 1, 2 and 3:

Combinations

2B+3C 2B+1B 2B+1B+3C

1. F. M. Aarestrup, H. Kruse, E. Tast, A. M. Hammerum, L. B.

Jensen,

Microb. Drug Resist.

63 (2000).

2. J. O’Neill, Antimicrobials in agriculture and the environ-

ment: reducing unnecessary use and waste (Review on

Antimicrobial Resistance, 2015); http://bit.ly/2d36sEH.

3. Y.-Y. Liu

et al., Lancet Infect. Dis.

16,

161 (2016).

4. J. Engberg, F. M. Aarestrup, D. E. Taylor, P. Gerner-Smidt,

I. Nachamkin,

Emerg. Infect. Dis.

24 (2001).

5. S. K. Lowder, J. Skoet, T. Raney,

World Dev.

87,

16 (2016).

6. F. M. Aarestrup,

Philos. Trans. R. Soc. B.

370,

20140085

(2015).

7. Center for Veterinary Medicine (CVM), CVM Updates—

FDA Annual Summary Report on Antimicrobials Sold or

Distributed in 2013 for Use in Food-Producing Animals

(U.S. Food and Drug Administration, 2013); www.fda.gov/

AnimalVeterinary/NewsEvents/CVMUpdates/ucm440585.

htm.

8. M. Bowman, K. K. Marshall, F. Kuchler, L. Lynch,

Am. J. Agric.

Econ.

98,

622 (2016).

9. J. O’Neill, Tackling drug-resistant infections globally: Final

report and recommendations (Review on Antimicrobial

Resistance, 2016); https://amr-review.org/Publications.

html.

10. S. Wang, S. Lay, H. Yu, S. Shen,

J. Zhejiang Univ.-Sci. B.

17,

649

(2016).

11. A. Hollis, Z. Ahmed,

N. Engl. J. Med.

369,

2474 (2013).

12. The World Bank, Drug-resistant infections: A threat to

our economic future (World Bank Group, 2016); http://

pubdocs.worldbank.org/en/527731474225046104/AMR-

Discussion-Draft-Sept18updated.pdf.

13. K. Outterson, T. Pogge, A. Hollis,“Combating Antibiotic

Resistance Through the Health Impact Fund,”

SSRN Scholarly Paper ID 1866768 (Social Science

Research Network, 2011); https://papers.ssrn.com/

abstract=1866768.

14. S. C. Walpole

et al., BMC Pub. Health.

12,

439 (2012).

15. Y. You, E. K. Silbergeld,

Front. Microbiol.

284 (2014).

16. B. van Bunnik, M. Woolhouse, Modelling the impact of curtail-

ing antibiotic usage in food animals on antibiotic resistance

in humans.

R. Soc. Open. Sci.

161067 (2017).

17. J. J. Carrique-Mas

et al., Zoonoses Pub. Health

62,

70 (2014).

18. R. Laxminarayan,

Science

345,

1299 (2014).

19. R. Laxminarayan, T. Van Boeckel, A. Teillant,“The Economic

Costs of Withdrawing Antimicrobial Growth Promoters

from the Livestock Sector,” OECD Food, Agriculture and

Fisheries Papers (Organisation for Economic Co-operation

and Development, 2015); www.oecd-ilibrary.org/content/

workingpaper/5js64kst5wvl-en.

20. T. P. Van Boeckel

et al., Proc. Natl. Acad. Sci.

112,

5649 (2015).

ACKNOWLEDGMENTS

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200

Global antimicrobial consumption

in food animals (1000 tons)

SUPPLEMENTARY MATERIALS

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The authors thank Veterinarians Without Borders for price

estimates of veterinary antimicrobials. The authors thank A.

Champetier de Ribes and B. Aragosta for discussions on user

fees. T.P.V.B. is supported by an ETH postdoctoral fellowship

and the program for Adaptation to a Changing Environment

from ETH Zurich. S.B. is supported by the European Research

Council (PBDR 268540). B.T.G. and S.A.L. were supported by the

Science and Technology Directorate, Department of Homeland

Security contract (HSHQDC-12-C-00058). B.T.G. and R.L. were

supported by the Bill & Melinda Gates Foundation (OP1091919).

E.E.G. was supported by the Fulbright program of the U.S.

Department of State. T.R. was supported by the Biotechnology

and Biological Sciences Research Council (BB/L019019/1).

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EUU, Alm.del - 2017-18 - Bilag 62: Brev fra forhenværende belgisk premierminister til Folketingets formand vedr. antimikrobiel resistens

Reducing antimicrobial use in food animals

Thomas P. Van Boeckel, Emma E. Glennon, Dora Chen, Marius Gilbert, Timothy P. Robinson, Bryan T Grenfell, Simon A.

Levin, Sebastian Bonhoeffer and Ramanan Laxminarayan

Science

357

(6358), 1350-1352.

DOI: 10.1126/science.aao1495

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