Review of evidence on antimicrobial resistance and animal agriculture in development countries Jonathan Rushton

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Review of evidence on antimicrobial resistance and animal agriculture in development countries Jonathan Rushton Professor of Animal Health Economics Norbrook endowed chair in Veterinary Business Management Adjunct Professor, Institute of Rural Futures, UNE, Armidale, Australia jrushton@rvc.ac.uk Regional Seminar for OIE National Focal Points for Veterinary Products Entebbe, Uganda 1 st 3 rd December 2015 1

Acknowledgements OECD: GregoireTallard, Michael Ryan, Jonathan Brooks SAFOSO: Jorge Pinto Ferreira, Katharina Staerk VMD: Peter Boriello, Katherine Grace OIE: Bernard Vallet, Monique Eloit, Elisabeth Erlacher- Vindel, Patrick Bastiaensen Liz Redmond I want to recognise the support of Norbrook Pharmaceuticals and LCIRAH in the work I carry out 2

Introduction Antimicrobialshave become an integralpart of human and animal medicine In humans they are critical as a frontline defence for a wide range of pathogens They are used as a measure to manage and reduce infections caused by surgery It is believed that their importance to surgical proceduresis where there would be the most problems with a growth in antimicrobial resistance 3

Introduction - antimicrobial use in animals In animals there is widespread antimicrobial use in companion animals in a similarway to humans The situation in food animals is complicatedby the use of antimicrobials for: Growth promotion Prophylaxsis Metaphylaxsis And treatments for disease in general 4

Introduction - the range of antimicrobials There is a range of antimicrobials that have different actions on pathogens and also the hosts In countries with good regulation and enforcement the antimicrobial use is managed by species with guarded use of antimicrobialscritical for human medicine In poor regulatory environmentsthe management of use cannot be guaranteed Likely that use will be driven by private interests and ignorance 5

Introduction - the actual use of antimicrobials The recordingof the use of antimicrobials by species and production system is not common OECD countries rely on data from pharmaceutical companies and veterinarians It is rarethat data are generated at farm-level, albeit it is becoming an industry standard in the poultry sector and pig sectors are increasingly receptive 6

Introduction -The core issue The range of antimicrobials, different regulatory environments and different levels of use in animals creates difficultyand complexityin data collection The recording of these data hampersthe ability to look at causalityof useto AMR emergence Some argue that there are weak links in use in animals and AMR and that the problem lies elsewhere, yet it is important to address this issue scientifically 7

Introduction -The core issue There needs to be data collection systems that allow the proper investigationof the link between antimicrobial use in animals and AMR Does AMR emerge? At what usage rates is AMR emergence more likely? Where does AMR emerge? For which antimicrobials is AMR important? Only through such processes will it be possible to define what use is viable and useful to humanity as a whole 8

Summary I will examine this problem through: Looking at the contextin which animals are kept, raised and used Determining what is known about antimicrobial use in the main animal systems Determining what is known about resistance and residues in these systems Some reflections 9

The Context 10

Human world population projection (Gerland et al, 2014) Currently 7 billion 2050 8-11 billion

10 9 8 7 6 5 4 3 2 1 0 Where are these people? Where will they be? (FAOSTAT population 1961 to 2050 in billions) 1961 1965 Much of the increase will take place in Asia and Africa 1969 1973 1977 1981 1985 1989 1993 1997 2001 2005 2009 2013 2017 2021 2025 2029 Africa Americas Asia Europe Oceania 2033 2037 2041 2045 2049 12

1961 1965 1969 1973 1977 1981 1985 1989 1993 1997 2001 2005 2009 2013 2017 2021 2025 2029 2033 2037 2041 2045 2049 10 9 8 7 6 5 4 3 2 1 0 Global population rural and urban estimates 1961 to 2050 (FAOSTAT, 2015) The increase will be in the urban areas Rural Urban 13

People and the food system Geographical dimension Food system Local Rural Population Rate of change National Urban Population Food system National Time Dimension Rate of change Urbanised Population National International

Our grazing species 15

Simple food chain Family or household Purchased Inputs Inputs $ Product Residues Processing Production Processed Product Labour Fresh Produce Labour Consumption Fresh product Processed Product $ Products sold to consumers with low demands on quality certification and who process the food in their homes

Our scavenging species 17

The context Human populations are increasing The increases are predicted to be in: Africa and Asia Urban areas This will have an impact on the types of livestock food systems we can anticipate And the types of production systems we are increasingly reliant on 18

Food Systems From simple to complex in a generation in the OECD countries From simple to complex in a decade in Asia From simple to complex in five years in Africa? 19

Complex food chain Providers of inputs and services Input or Service $ Middlemen, transport, traders Fresh Product $ Processed Product Producer Processor Marketers Middlemen, financial services $ Processed Product $ Products sold to consumers with sophisticated demands who do very little home processing

Duck breeding flock -Egypt Chicken broiler flock -Tanzania Beef cattle Northern Ireland Dairy system Nairobi, Kenya Sheep NSW, Australia Outdoor pigs East Anglia, UK 21

Consumer Food Retailing Food Processing Catering There are only 339,000 people who work on agricultural holdings in the UK (0.6% of the population) yet they can affect the wellbeing of 60 million people Animal health contributions to the food chain Veterinary public health National Production Overseas Production Clinical treatments Epidemiology & Disease Control Diagnostics Immunology Inputs Vaccines Genetic Resistance

Summary of the animal role changes These changesin the role of animals have been dramatic in the last two decades Leading to changes in resource use to look after animals The role of animals is constantly evolving Pets and sporting animals have individual attention with: Some Increasingly of these sophisticated changes healthcare are demand driven Specialised diets Others relate to supply process changes Clothes, toys, treats While livestockare increasingly confined, raised,slaughtered and processed in large groups 23

Antimicrobial use in animals 24

What to measure? Level of use Type of product used Use versus number of animals Or use versus product produced 25

Where to measure At pharmaceutical production and sale At the import/export level With veterinary prescriptions In the feedmills Through farm-level data collection 26

What do we know on use? Globally more antimicrobials are used to treat healthy animals than unhealthy humans Country level use will vary with the systems in which animals are kept In the US it is estimatdthat of the antimicrobials sold for both humans and animals, almost 80% were reserved for livestock and poultry In 2012 Denmark used 103 tonnes of antibiotics in animals and 50 tons in humans, reflecting that this country has a large livestock population relative to the human population 27

What do we know on use? Interpretation of antimicrobial use in humans and animals should recognise that for every person in the world there are two to three times the numbers of animals when measured in biomass terms. For true comparisons the use per population correction unit between humans and animals would be needed. In Sweden(2012) it was reported that in humans there was a use of 104mg/kg versus 15 mg/kg to animals. The relatively low use in animals relates to investments in animal health systems that reduce the need for antibiotics in animals. 28

Production systems and antimicrobial use The need for the use of antimicrobials is heavily influenced by husbandry practices and its direct link to animal health. UK use of antimicrobials in the intensively farmed pig sector in the UK was 115 times higher than in sheep farming In the USA: 16% of all lactating dairy cows receive antibiotic therapy for clinical mastitis each year 15% of beef calves that enter feedlots receive antimicrobials for the treatment of respiratory clinical problems 10% of apparently healthy calves receive the same dose of antimicrobials as a prophylactic measure 42% of beef calves in feedlots are fed tylosin(a veterinary macrolide drug), to prevent liver abscesses that have negative impact on growth; 88% of fattening pigs are treated with growth promoters in their feed (tetracyclinesand tylosin). 29

Estimated antimicrobial use to produce one kilogram of meat in 25 European countries in 2011 (from ESVAC, 2013) 450,0 400,0 350,0 300,0 mg/pcu 250,0 200,0 150,0 100,0 50,0 0,0 Premix Oral Powder Oral Solution Injection Oral Paste Bolus Intramammary prep Intrauterine prep 30

And use in the developing countries? Otteet al.(2012) reported estimates that suggest the Asia and Pacific region to be much more important regarding the use of antimicrobials in livestock production than other regions, but they do not make a specific estimate. This region has well over half the world s pig population and a very high proportion of its poultry and the majority of the ducks. Many of these animals are reared in intensive or semi-intensive systems where the use of concentrate feed and high population densities require health management that involves antibiotic usage. Otteet al.estimate that this region has nearly half of the global antimicrobial market, with total 2011 sales in the region of about US$ 1.8billion 31

Antimicrobial use in Kenya in kg (Mitemaet al, 2001) 20000 18000 16000 14000 12000 10000 8000 6000 4000 2000-1995 1996 1997 1998 1999 Aminoglycosides β-lactams Tetracyclines Nitrofurans Quinolones Sulfonamides Macrolides Others (tiamulin) 32

Kenya livestock population 1995-1999 and 2009-2013 livestock units (FAOSTAT) LSU Millions 25 20 15 LSU Millions 25 20 15 10 10 5 5-1995 1996 1997 1998 1999-2009 2010 2011 2012 2013 Chickens Camels Cattle Goats Horses Pigs Sheep Chickens Camels Cattle Goats Horses Pigs Sheep 33

Projections of antimicrobial use (van Boeckel et al, 2015) 34

And the use in the developing countries? However, only very limited information is available from most of the developing countries, with Kenya being a notable exception, where both the total amounts and the classes of antimicrobials are monitored There are not enough data collection mechanisms to capture use of antimicrobials globally and this problem is greatest in the This key source of information to assess animal exposure developing and therefore public countries health risk is currently inadequately recorded and represents a key obstacle to risk assessment 35

Antimicrobial resistance 36

Resistance what and how to measure? Where do we need to measure AMR? Resistance in the environment Resistance in species Do we have a baseline How do we measure resistance? Plating Gene detection Whole genome sequencing What is the overall importance of AMR to human health? 37

Antimicrobial suspectabilitypatterns in beef carcasses in Nairobi, Kenya (Kariuki& Dougan, 2014) 38

Antimicrobial suspectability patterns in poultry in smallscale farms in Thika, Kenya (Kariuki& Dougan, 2014) 39

What do we really understand of the flows through these systems? Environment Wild Animals Household Food System Food & People People Human Pet Animals Animals & Feed Food Animals Animals & Food

Reflections 41

Set a baseline Data can be gathered relatively quickly Pharmaceutical companies Companies involved in feed production Companies involved in the intensive livestock industries An initial assessment of these data will provide information of the weaknesses of the regulatory environment 42

Strengthening the system The animal health system will have weaknesses They are likely to be at the level of interactions between animal owners and their animals The application of medicines and a poor understanding of withholding times could well influence the presence of antimicrobial residues in livestock products This may have impacts on the emergence of resistance and where this takes place 43

Rational & Proportionate Disease Control Measures Develop & Assess Vaccines & Diagnostics Analysis Pathogen Banks Surveillance System Data Disease Agent Active Disease Search Socio- Economic Livestock Sector Pets Wildlife Disease Improved Diagnostics Passive Surveillance Network Producers & Hunters Collectors Susceptible Animal Population

Key messages We know that livestock food systems are changing and in the process the use of antimicrobials is increasing and is altered Animal health decision making could be Our data capture and analysis systems need to improve improved by better use of data capture and analysis of antimicrobial use Only with better data can will it be possible to understand links between usage and AMR And to refine the use of antimicrobials in animals 45

Further information For more information on NEAT please look at www.neat-network.eu For information on NEOH please look at http://neoh.onehealthglobal.net For information on the work we are involved in with agriculture and health please look at http://www.lcirah.ac.uk/home For courses offered at RVC please look at http://www.rvc.ac.uk/postgraduate/distance/index.cfm http://www.atp-ilhp.org 46

References FAOSTAT (2015) http://faostat3.fao.org/home/e accessed 1 December 2015 Kariuki, S. & Dougan, G. (2014) Antibacterial resistance in sub-saharan Africa: an underestimated emergency. Ann N.Y. AcadSci1323 pp43-55 MitemaES, KikuviGM, Wegener HC, StohrK. An assessment of antimicrobial consumption in food producing animals in Kenya. J Vet PharmacolTher. 2001;24(6):385-90. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11903868. Accessed May 5, 2014. Rushton, J., J. Pinto Ferreira and K. D. Stärk(2014), Antimicrobial Resistance: The Use of Antimicrobials in the Livestock Sector, OECD Food, Agriculture and Fisheries Papers, No. 68, OECD Publishing. http://dx.doi.org/10.1787/5jxvl3dwk3f0-en Van Boekel et al (2015) Global trends in antimicrobial use in food animals. PNAS Early Edition 47