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15 Nov 2016

#DRIVERS, #DYNAMICS AND #EPIDEMIOLOGY OF #ANTIMICROBIAL #RESISTANCE IN #ANIMAL #PRODUCTION (#FAO, Summary)

 

Title: #DRIVERS, #DYNAMICS AND #EPIDEMIOLOGY OF #ANTIMICROBIAL #RESISTANCE IN #ANIMAL #PRODUCTION.

Subject: Antimicrobial Resistance, antibiotics use in animal production.

Source: Food and Agriculture Organization (FAO), full PDF file: (LINK). Summary and introduction.

Code: [     ]

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DRIVERS, DYNAMICS AND EPIDEMIOLOGY OF ANTIMICROBIAL RESISTANCE IN ANIMAL PRODUCTION

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Authors: B.A. Wall, A. Mateus, L. Marshall and D.U. Pfeiffer

Co-authors: J. Lubroth, H.J. Ormel, P. Otto and A. Patriarchi

Food and Agriculture Organization of the United Nations, Rome, 2016

Recommended Citation: FAO. 2016. Drivers, dynamics and epidemiology of antimicrobial resistance in animal production

Authors: B.A. Wall, A. Mateus, L. Marshall and D.U. Pfeiffer Veterinary Epidemiology, Economics and Public Health Group, Department of Production and Population Health, The Royal Veterinary College, North Mymms, London, UK

Co-authors: J. Lubroth, H.J. Ormel, P. Otto and A. Patriarchi Food and Agriculture Organization of the United Nations, Rome, Italy

The designations employed and the presentation of material in this  information product do not imply the expression of any opinion whatsoever  on the part of the Food and Agriculture Organization of the United Nations (FAO) concerning the legal or development status of any country, territory, city or area or  of its authorities, or concerning the delimitation of its frontiers or boundaries.  The mention of specific companies or products of manufacturers, whether or not  these have been patented, does not imply that these have been endorsed or recommended by FAO in preference to others of a similar nature that are not mentioned.

The views expressed in this information product are those of the author(s) and  do not necessarily reflect the views or policies of FAO.

ISBN 978-92-5-109441-9

© FAO, 2016

FAO encourages the use, reproduction and dissemination of material in this  information product. Except where otherwise indicated, material may be copied, downloaded and printed for private study, research and teaching purposes, or  for use in non-commercial products or services, provided that appropriate acknowledgement of FAO as the source and copyright holder is given and that  FAO’s endorsement of users’ views, products or services is not implied in any way.

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EXECUTIVE SUMMARY

It is now accepted that increased antimicrobial resistance (AMR) in bacteria affecting humans and animals in recent decades is primarily influenced by an increase in usage of antimicrobials for a variety of purposes, including therapeutic and non-therapeutic uses in animal production. Antimicrobial resistance is an ancient and naturally occurring phenomenon in bacteria.

But the use of antimicrobial drugs – in health care, agriculture or industrial settings – exerts a selection pressure which can favour the survival of resistant strains (or genes) over susceptible ones, leading to a relative increase in resistant bacteria within microbial communities.

It has been observed that, in countries where use of particular substances (e.g. fluoroquinolones) is banned in animal production, there are low levels of resistance to these antimicrobials in livestock populations.

The rate of AMR emergence in ecosystems such as the human or animal gut is likely to be highly dependent on the quantity of antimicrobials used, along with the duration and frequency of exposure.

In animal production, the prolonged use of antimicrobial growth promoters (AGPs) at subtherapeutic levels in large groups of livestock is known to encourage resistance emergence, and is still common practice in many countries today.

Due to the interdependence and interconnectedness of epidemiological pathways between humans, animals and the environment, determining the relative importance of factors influencing AMR emergence and spread in animal production is a significant challenge, and is likely to remain one for some time.

In intensive livestock production systems, resistant bacteria can spread easily between animals and this can be exacerbated if biosecurity is inadequate.

While some studies have shown reduced levels of AMR on organic farms, a high prevalence of multidrug-resistant (MDR) Campylobacter strains has been detected in organic pig farms in the United States even in the absence of antimicrobial usage (AMU).

In aquaculture, AMR can develop in aquatic and fish gut bacteria as a result of antimicrobial therapy or contamination of the aquatic environment with human or animal waste.

The extent and persistence of antimicrobial residues in aquatic systems is unknown and current evidence is conflicting.

Furthermore, no international guidelines currently exist for maximum antimicrobial residue limits in water. Water is an important vehicle for the spread of both antimicrobial residues and resistance determinants, since contaminated water can be consumed directly by humans and livestock and used to irrigate crops.

Food is likely to be quantitatively the most important potential transmission pathway from livestock to humans, although direct evidence linking AMR emergence in humans to food consumption is lacking. There is a theoretical risk of widespread dissemination of AMR due to the increasingly global nature of food trade and human travel. This would mean that strains of resistant bacteria could now very quickly reach parts of the world where they had previously not been present.

Agricultural systems in emerging economies such as China and India have changed radically in recent years, becoming increasingly intensive in order to meet growing domestic and global demands for animal protein. This is likely to heighten the occurrence and spread of infectious diseases in these systems, thereby leading to increased AMU and therefore resistance.

If the selection pressure resulting from AMU in animals and humans were to be removed, this would still not completely halt the emergence and global spread of AMR due to the ability of AMR genes to move between bacteria, hosts and environments, and the occurrence of spontaneous mutations.

However, the release of large quantities of antimicrobials or resistant bacteria into the environment is still thought to be an important point for control, and therefore measures which encourage the prudent use of antimicrobials are likely to be extremely useful in reducing the emergence and spread of AMR.

Future development of quickly biodegradable antimicrobials could help to reduce environmental contamination, and pharmacodynamic studies in livestock can be used to inform the optimization of AMU.

Improved hygiene and biosecurity should be a major focus for all types of animal production systems so that the risks of introducing pathogens and resistance genes – and the spread of these within animal populations – can be reduced.

Detailed, specific recommendations for countries to move towards more prudent AMU in different agricultural settings are, however, beyond the scope of this paper.

An improved understanding of the epidemiology of AMR emergence and spread in animal production will provide an essential foundation for successful mitigation strategies. There are still considerable gaps in our understanding of the complex mechanisms that lead to the emergence of AMR in bacteria, and the interactions that take place within microbial ecosystems enabling the transfer of resistance between bacteria.

There are insufficient data at present to determine quantitatively how important the selection pressure of AMU is for the emergence of AMR in bacteria. Evidence regarding AMR transmission pathways between food animals and humans is lacking, especially from low- and middle-income countries (LMICs).

Such pathways are likely to be highly complex and multi-directional, especially in LMICs, but are still largely unknown. There remains little doubt, however, that the most significant factor in AMR emergence in humans is AMU for human treatment and prevention.

It is clear that both human and animal AMU can contribute to environmental contamination, although collection of meaningful data is challenging. The relationships between different types of farming systems and both AMU and the emergence and spread of AMR are discussed in this paper, including extensive and organic systems, but there is still a notable lack of knowledge on the role that sustainable agriculture systems can play in combatting AMR.

Most importantly, future research needs to involve an interdisciplinary (e.g. One Health) approach, integrating agricultural, medical, environmental and social sciences, and especially recognizing the importance of human behaviour. A set of specific recommendations to fill current knowledge gaps is presented in the final section of this technical paper.

 

INTRODUCTION

Antimicrobial resistance (AMR)1 both in human and veterinary medicine has reached alarming levels in most parts of the world and has now been recognized as a significant emerging threat to global public health and food security. In June 2015, the Food and Agriculture Organization of the United Nations (FAO) passed a resolution on AMR at its governing Conference. This followed the adoption of counterpart resolutions on AMR by The World Organisation for Animal Health (OIE) and the World Health Organization (WHO) in May 20152, and marked the beginning of a joint effort by the three organizations to combat AMR globally.

The present technical paper was commissioned by FAO and is intended to inform a technical audience comprising scientists, policy-makers and stakeholders (including veterinarians and medics) in FAO Member States. A review was undertaken of the available scientific literature, grey literature, reports, and other sources of evidence, to examine the current state of knowledge on the relationship between animal production and AMR emergence and spread.

The review methodology is described in detail in Appendix 1.

Overuse of antimicrobials and improper use in many parts of the world are recognized as key drivers of the emergence and spread of AMR (Aminov and Mackie, 2007, APUA, 2008, Aarestrup et al., 2008, Acar and Moulin, 2012). Antimicrobials are used in food animals for treatment and for non-therapeutic purposes, and play a critical role in saving lives in both humans and animals.

Over the last decade, global livestock production has been growing rapidly and has moved increasingly towards industrialized systems where antimicrobial use (AMU) is an integral part of production. It is projected that two thirds of the future growth of AMU will be for animal production (Van Boeckel et al., 2015).

Although AMU in animals for growth promotion, prophylaxis and metaphylaxis (i.e. medicating mixed groups of healthy and infected animals in order to control outbreaks of disease) has been substantially reduced in high-income countries in recent years, data available indicate that livestock AMU will continue to increase in low- and middle-income countries during the next decades due to the growing demand in LMICs for animal protein (Van Boeckel et al., 2015).

Consequently, there is likely to be a commensurate increase in resistance to commonly used antimicrobials in these countries and regions, which does not bode well for treatment and management of infections in both humans and animals. This is especially important for zoonotic pathogens but also for commensal bacteria as these can act as reservoirs for resistance genes within the gut microbiota and the environment (the “resistome”) (APUA, 2008). Indeed, resistance to colistin, an antimicrobial used as a last resort for treating multidrug-resistant (MDR) infections in humans, was recently detected in animals, retail meat and humans in China and subsequently has been discovered in most world regions (Skov and Monnet, 2016).

Despite the public health significance of, and global attention to, AMR, a number of important questions are still surrounded by significant uncertainty, especially concerning the epidemiological relationships between AMU and food animals, the occurrence of AMR in food animals and the exposure of humans to AMR via food products.

This technical paper deals with the epidemiology of the emergence of AMR as a consequence of AMU in animal production, and the risk of its spread via food distribution and the environment. While this paper aims to take a global perspective, there are data gaps in certain regions of the world which means that some of the information presented has a European bias.

The discussion begins with a technical description of the current state of knowledge regarding the acquisition of AMR by bacteria, and types and mechanisms of resistance in bacteria. Subsequently, the influence of animal production on the emergence of AMR in animals and humans is discussed. This is followed by an overview of local and global pathways of AMR transmission, and how these may be influenced by different livestock production systems.

(…)

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{1} The term antimicrobial resistance (AMR) is used to refer to the ability of any microorganism (bacteria, viruses, parasites and fungi) to withstand the effect of one or more antimicrobial agents at clinically attainable concentrations, usually resulting in therapeutic failure. Throughout this document, AMR will be used to include resistance to antibacterial, antiviral and antiparasitic agents, although the focus will primarily be on bacterial resistance to antibacterial agents.

{2} Details of all three resolutions on AMR are now available in the public domain:  FAO resolution: http://www.fao.org/3/a-mm736rev1e.pdf  - OIE resolution: http://www.oie.int/en/about-us/key-texts/resolutions-and-recommendations/resolutions-adopted-by-the-oieinternational-committee/ 2015 - WHO resolution: http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_ACONF1Rev1-en.pdf

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Keywords: FAO; Updates; Antibiotics; Drugs Resistance; Food Safety.

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