Antibiotic Stewardship in East and South East Asia: The Trials and Tribulations of a Field Veterinarian

I. INTRODUCTION

To introduce myself, I am a veterinarian by profession, a poultry veterinarian by accident and I am a field veterinarian by choice. My role as a field veterinarian (along with other professionals and the management team) is to turn expensive feed into profitable meat as efficiently as possible. Thus, my focus on-farm is on bird health and flock management to achieve the best biological performance we can. But along with that brief is the ‘social contract’ that comes as a result of my profession, my training and my responsibility to the wider community, to the environment and to the animal.

I do not think there is any more doubt or argument that we in the animal food supply chain have contributed to issues around antibiotic resistance through our use and misuse of antibiotics; the question remains though as to how much of the resistance problem we are responsible for and the wider and long-term impact of that use. Whilst this of course is a legitimate question to ask, it is not the subject of this paper and the fact remains that antibiotic stewardship in animal agriculture is both prudent and necessary. Efficient flock health and biological performance can be achieved, side by side with the principles of Antibiotic Stewardship and even (ultimately) with antibiotic freedom. Antibiotic Stewardship in my definition is:

“Use as little as possible but as much as necessary”

“Reduce Refine Replace”

My paper today is probably somewhat different to what you have been used to here at APSS. I am not going to give you a paper on how we achieve antibiotic stewardship or freedom; there are many such papers available on the internet and elsewhere. I will be discussing the how and why of antibiotic use in East and South East Asia, relying in a greater part on what I see and what I have to deal with every day when I am out in the field. I will look at the difficulties a field veterinarian faces in advocating and implementing the principles of antibiotic stewardship. There will be a lot of personal anecdotes and opinions in my paper because this is what I face every day. Some will amuse you, some will shock you but they are all real and we have to understand what is behind them before we can change them. I will also give you a glimpse of what is being done in the region to address the situation of antimicrobial resistance in the poultry industry, both at regional and national levels, and also some of the incredible work being done locally. My observations and comments on the how and why apply to all countries within this region to some extent or another.

Some countries (and within countries some companies) are only starting the journey of antibiotic stewardship and some are well on the way. Some observations are more relevant, at this point in time, in some countries than others. But, in reality, what we see happening in this region with regards to antibiotic use and misuse is not that different from what is happening, and of course what has already happened, in all other poultry growing regions and countries around the world. In some countries the process of change happened much more quickly and quite some time ago due to a variety of reasons we cannot go into here, but we all went through it at some stage or are going through it. Whilst my comments are specifically about the poultry industry, there is no doubt at all that my colleagues in the other livestock areas are going through much the same process.

II. INDUSTRY STRUCTURE

The structure of the industry in the East and South East Asian region does in some way contribute to the lack of antibiotic stewardship. The market has been rapidly developing and large integrations are seen as the way ahead for the poultry industry, as the market and consumer base becomes more sophisticated and as the movement away from wet markets builds momentum.

In Vietnam, the most recent agricultural census (2018) showed only 26.1% of chickens were raised in what we could class as intensive farms. The rest were raised in both backyard and semi-intensive commercial farms. To some degree or other this figure is repeated around the region with estimated figures of 60-80% of production being in the semi-intensive and backyard systems. Integrators can generally afford the luxury of employing in-house technical people who are more likely to understand the principle of good management health and nutrition and they generally have the resources, the necessary ‘hardware and software’ required to implement and maintain the principles that lead to good antibiotic stewardship. As well as the true integrators, there are a number of larger independent farms who buy in day-old chicks and then sell finished broilers to a range of processors or intermediaries. These independents sometimes have good resources available to them, similar to the integrators, but in most cases do not or have limited resources.

In many countries, local or indigenous chicken breeds of both egg and meat varieties have some significant importance and can make up a considerable portion of the local chicken supply. The market supplied by these birds is primarily the wet bird market for broilers; however, their appeal to the local populations is such that up to 10% of the supermarket shelving in some regions is given over to these birds. They are viewed as having some health benefits that the ‘commercial white broiler’ does not have or that the ‘commercial layer breeds’ do not have. The meat and egg supplied by these breeds commands a premium and so there is significant interest in rural areas to supply the market with farm sizes being small (less than 2000 birds). One problem that results from this is that farms go in and out of production due to the prevailing market. On many farms, the income from this type of poultry production is a secondary or supplemental income. Management expertise on these farms therefore is not as good as it could be. Biosecurity is poorly understood and poorly implemented and vaccination and disease prevention can be haphazard. Also, these birds (broilers) are slow growing compared to the commercial white broilers and can be up to 2-5 months before processing. These reasons can result in these birds having more disease problems than in the commercial white broiler market with a subsequent increased reliance on antibiotics.

III. ANTIBIOTIC USE IN THE REGION

a) Overview

There is little good published work on how much antibiotics are used to raise poultry around the world. Van Boeckel in 2015 estimated that 148 mg of antibiotics were used to raise 1 kg of chicken meat as a worldwide average (Van Boeckel et al., 2015). In the Mekong Delta of Vietnam, in semi commercial poultry production, an estimate of 260 mg/kg of poultry meat production was made (excluding in-feed antibiotics) (Carrique-Mas et al., 2014). Another study showed that, for 1000 chickens produced, 690.4 g of antimicrobial preparations were used (Carrique-Mas et al., 2014). Antibiotics are generally used prophylactically. Again, in a study in the Mekong delta of Vietnam, 84% of antimicrobial products were used for prophylactic reasons (Carrique-Mas et al., 2014). They are administered routinely at set times because there is a belief that “if we don’t use them we will have a problem”. I have often asked the question on farms ‘Why do you routinely use antibiotics?’ The answer reliably comes back as “If we don’t use them we will see a problem with mortality.” “Well when was the last time you didn’t medicate with antibiotics, and what sort of mortality did you get?”. “Oh we have never removed them, we have always used them”.

Some farmers managers and even veterinarians believe that using the same medication at the same age without any presenting mortality, but used to prevent expected mortality, is actually a therapeutic use. The reason given is that if they do not use the medication they will get mortality. In some cases, though a minority in my opinion, the statement that if antibiotics are not used, is entirely justified and antibiotics are used to prevent mortality due to vaccine reactions and poor management, particularly poor ventilation practices.

Many of the countries I work in have hot humid climates but one of the major problems I see is a vaccine reaction due to chilling of the birds - a result of the lack of understanding of the principles of ventilation and of wind chill and its effect in young birds. In a number of the countries I work in, commercial white broilers receive antibiotics continuously in feed and water for the first 2 - 3 weeks, the water use being made up of five or so different antibiotics. They also get in-feed antibiotics. I have also seen the use of two different antibiotics used in the same day. On questioning as to why this occurs, I have been told that the morning antibiotic is for the clinical infections and the afternoon antibiotic is for subclinical infections.

‘Native’ chickens can also receive antibiotic at intervals throughout their life. As their life is generally much longer and can be up to five months, they are also more valuable on an individual bird basis. Breeder birds and layer commercial birds also can have continual antibiotic use for the first week or two and then at routine intervals or following vaccinations or periods of known or perceived stress or for mortality episodes. In two countries in the region, the supply hatchery takes responsibility for mortality up to four days of age. It is common therefore for the hatchery to supply antimicrobial medications with the chicks to avoid any potential compensation issues.

b) What Antibiotics are Used?

Twenty-eight types of anti-microbials belonging to 10 classes were reported being used in semi commercial flocks in the Mekong Delta of Vietnam. Sixty-three per cent of all commercial formulations contained at least two antimicrobials. Polypeptides, tetracyclines, penicillins and aminoglycosides were the antimicrobials used by most farms, whereas penicillins, lincosamides, quinolones, and sulphonamides/ trimethoprim were quantitatively the most used compounds Carrique-Mas et al., 2014).

A study by Nguyen Van Trung et al looked at antimicrobial usage in chicken production in the Mekong Delta of Vietnam in 2012-2013 (Carrique-Mas et al., 2014). They found that 28 different types of anti microbial substances belonging to 10 classes were used. On one farm I was taking through the process of global food saftey accreditation, I was given a list of 59 different antimicrobial preparations that they wanted in their list of antimicrobial products that they could use. I have personally seen up to 12 different antimicrobial preparations in one farm’s medication store belonging to 5 different antibiotic classes.

The most common types of antibiotics used as water medication include penicillins, nitrofurans, tetracyclines, macrolides, flouroquinalones, polypeptides, sulphonamides and polymyxins. In-feed medication is usually either bacitracin tetracyclines or enramycin (Van Guong et al., 2016). As you can see, antibiotics classified by the WHO as critical for human use are used in the poultry industry in this region.

IV. WHY IS THERE MISUSE OF ANTIBIOTICS?

There are many reasons why the situation with misuse of antibiotics exists in the Asian poultry industry. I have listed here what I consider to be the main reasons as I see them in my farm visits.

a) Easy availability of antibiotics and their cost.

Generally throughout the region, antibiotics for use in agriculture are readily available. Many are sold ‘over the counter’ and do not require veterinary intervention or authorisation. Many are sold by travelling salespeople who visit farms. Many of these salespeople are pseudo technical and pseudo veterinarians who make diagnoses and then recommend medications. In a lot of circumstances these travelling technical people are the only technical advice some of these farms actually have, but of course their allegiance is to the company that employs them. Too often their income is also supplemented by commission on sales. On one large independent farm we were tasking through global food safety accreditation we had to give the owner an ultimatum - either he keeps these travelling technical sales people off the farm or we would stop the process of accreditation.

In rural Vietnam, the animal agricultural industries are serviced by veterinary pharmacies who advise farmers and supply medication. Rarely is a farm visit made or a postmortem done and if it is done it is done by a poorly trained staff member. Supply of medications is done on the symptoms described by the farm manager. The sale of medications is a significant part of the income of these pharmacies. In most countries, the cost of antibiotics is rather cheap and this, combined with their ready availability, makes overuse problematical. In most countries, the farm gate sale of antibiotics is poorly regulated. Some larger farms also have no problems getting around import restrictions and import directly from China. I have seen medication stores on farms filled with pallets of antibiotics imported directly.

In Vietnam, the low cost of antimicrobial products has been given as one reason for the excessive antimicrobial usage (Carrique-Mas et al., 2019). It is my experience also that this is the case throughout the region. The cost of the antimicrobial preparations could also be leading to the misuse of these antimicrobial agents as in many cases the label includes guidelines for both prophylactic and therapeutic use, with the cost of prophylactic use significantly less than the cost of the therapeutic use (Carrique-Mas et al., 2019)). In my experience again most people charged with using the medication do not understand the difference between therapeutic and prophylactic use and will use the lower recommended dose rate as it is cheaper.

b) Regulations: implementation and monitoring

Most countries have inadequate and weak systems for controlling antibiotic use. In a recent publication. Coyne et al. (2019) identified weak or non-existent regulatory framework, suboptimal framework and compliance with existing guidelines as reasons for AMR in Asian countries. In-feed use is probably the exception. Feed sales figures are available from the feed companies and these have been used to estimate the in-feed use. Data on imports of antibiotics is not centrally collected and examined.

In some countries, good regulations are in place; however, it is the implementation of these regulations that is lacking. Whose responsibility is it to monitor the use/misuse of antibiotics? There is a lack of resources to investigate and prosecute breaches of the law and there is a significant lack of understanding of the appropriate regulations. This is not just a problem with agricultural use.

In Vietnam, I once went to a pharmacy for an inner ear infection. I asked for a course of treatment and was given two tablets. My comment was an obvious “No I am after a course of treatment”, I was told that it was a course. People come to the pharmacy when they are sick and may buy antibiotics for one day’s treatment. If they feel sick the next day, they will get a second lot but of course if they feel better they will not. As ‘research’ for this paper I went to three separate pharmacies and was able to purchase augmentin, ciprofloxacin and doxycycline. This is despite there being a requirement for a medical prescription and despite the fact that all purchases require documentation in a centralised register. I have been able to purchase what we would consider prescription antibiotics freely in other countries in this region and in one country I saw antibiotics available for sale ‘over the counter’ at a kiosk in a regional airport.

c) Limited technical and diagnostic understanding and capabilities

Veterinary training varies considerably between countries. In one of the countries I service in this region veterinarians have never heard of histology. There are also a lot of pseudo technical and pseudo veterinarians employed by the vaccine and medication supply companies. These technical people can be the only technical contact a farmer has. There is also a lack of good diagnostic testing in some countries or the diagnostic testing available is quite expensive and is not therefore used. It is a common belief throughout the region that antibiotics can treat viral conditions.

The lack of good diagnostics is not the only problem. In many regions good diagnostic tests are available; however, it is the interpretation of the test results that leads to problems. On one farm, the technical manager took faecal samples from a layer flock because of what he considered to be a change in faecal colour and tested them for clostridia. Clostridia were found (obviously) and necrotic enteritis was ‘diagnosed’. Medication was given and was subsequently used for all flocks to treat this necrotic enteritis. Necrotic enteritis is the most over diagnosed condition I find here in East and South East Asia. In may cases, any condition resulting in a change in colour consistency or character of droppings, in litter quality or in gut health is diagnosed as necrotic enteritis and is treated as such. Lack of appropriate diagnostics mean that all mortality conditions can be treated with antibiotics.

On a number of occasions, I have been to look at problems on farms and before I have even entered a shed I have been asked what antibiotic they should be using. Understanding the problem is not important. I have asked then on those occasions what they have been using and have usually been given a list of antibiotics they have tried. I have made the comment that maybe it is the way the antibiotics are being used or that the condition is not even treatable with antibiotics; invariably the answer I have been given has been “Well what else can I use?”. Proprietary feed always comes with antibiotic added. If you do not want an in-feed antibiotic then you need to specifically order feed without it. In most cases, however, the feed companies will not allow changes to proprietary feed because of the issues this creates with production runs at the feedmill. The feed-milling industry is very competitive and to keep costs down, feed mills want long production runs and do not allow any changes to the feed they sell. Many farm managers and even the technical people do not actually know that the feed even contains antibiotic. On many occasions when I have asked what antibiotic is in the feed I have been told that there is not any in the feed. I have had to point out to them the list of ingredients on the feed bag and the antibiotic inclusion. Therefore, the concept of growth promotion using antibiotics is poorly understood. Some published surveys done in the region have reported that no antibiotic is used for growth promotion (WHO, 2018). Whilst that may truly have been the case, in my experience if the feed bags themselves were not actually checked by the authors then the use of antibiotics could have been missed.

Low levels of antibiotic awareness (Coyne et al., 2019) and the lack of understand of how antibiotic resistance occurs also contribute to the difficulty in getting antibiotic stewardship. I have on many occasions, when I have talked about antibiotic resistance, been told that antibiotic resistance is not a problem because farmers follow withholding periods. Most farm managers and staff have not even heard about antibiotic resistance or, if they have, they believe it is a foreign issue. The lack of understanding of how resistance occurs contributes to the misuse of antibiotics. Lack of appropriate awareness and input on how antibiotics should be used results in the use patterns we see. Not many of the farm staff actually charged with administering the antibiotics, know how they should be administered correctly and what happens if they do not administer correctly. Label use recommendations and instructions are rarely used and in my experience are not even consulted. In fact, with a lot of direct imported antibiotics the labels are in a foreign language unfamiliar to the farm manager and staff. I have often been told that antibiotic resistance should not be a problem on this farm because we adhere strictly to withholding periods. On most farms in the region, I find that there is a significant lack of understanding of how antibiotics actually work, even with veterinarians and technical people. Antibiotics are often given for maybe only 2-3 hours a day. Why? Because of other medications that the birds are given during the day or it is just too inconvenient.

The use of flouroquinolones, predominantly enrofloxacin, is common across the region. In Indonesia, it is common that they are used at 2-3 times the usual and published dose rate because ‘they do not work at the recommended dose rate’. When I discuss how antibiotics actually work, and that in most circumstances “more is not better”, I get agreement that the increased really does rate does nothing but no real commitment to change.

d) Lack Of understanding Of Products Used.

I have been onto farms and have asked for a list of the antibiotics used. As part of my farm visits, I always look in the medication store. On a number of occasions, I have seen antibiotic products that have not been included in the list I have been given. On questioning why they were not on the list I have been told they are not antibiotics. In good faith they have purchased various ‘tonics’ without understanding or enquiring about the composition. These tonics often contain low dose antibiotics.

The same thing applies as I have already mentioned with in-feed antibiotics. I find a significant number of farm managers and technical people, whose farms use proprietary feeds, have no or limited understanding of any antibiotics in feed and what they are in there for. In another country an integrator could not get their cholera vaccine on time. I recommended to the veterinarian that he gets some oxytetracycline to have on hand in case we get a break. I recommended an appropriate dose rate to use. On my next visit I saw that the product the veterinarian had bought was an anti stress product which had oxytetracycline at a very low level and which included various vitamins electrolytes and some amino acids. It was labelled as oxytetracycline anti stress pack. To actually treat a flock with cholera at an appropriate dose rate would have required over 80 kg of the product per day.

e) Counterfeit products, inadequate labelling and quality.

Counterfeit antibiotics are also common. It is estimated that close to 80% of counterfeit drugs available in the world are made in South East and East Asia and that 45% of these medications are consumed here (Delve-Pierre et al., 2012). Recent studies in the Mekong Delta of Vietnam have shown in aquaculture only 8 and 29% of aquaculture antimicrobial products and 28.8% of poultry antimicrobial products had antibiotic active ingredient levels within 10% of the label claim. (Phu et al., 2015; Yen et al., 2019). One study also showed that 65% of antimicrobial preparations for poultry had label recommendations for both therapeutic and prophylactic use, and 5% had no use indications at all; 40% of products had a withdrawal time specified for both egg and meat products, 55% had only a meat withholding period and one product had no recommended withholding period at all (Phu et al., 2015). I personally have seen on farms products with labels totally in Chinese writing.

V. WHAT IS HAPPENING TO ADRESS THE ISSUE OF ANTIBIOTIC USE AND MISUSE AND WHAT SHOULD HAPPEN.

There is much being done in the region through organisations such as WHO, OIE, FAO Asia Pacific Foundation for Infectious Disease (APFID), etc. Most of the recommendations and actions around the programs under the initiatives of these organisations have five main elements (WHO, 2014; Hong-Soong, 2015; WHO, 2015)

1. Improve awareness and understanding of antimicrobial resistance

2. To strengthen knowledge through surveillance and research

3. To reduce the incidence of infection

4. To optimise and promote appropriate use of antibiotics

5. Strengthen national infrastructure.

I am not going to spend any time discussing these regional and national initiatives in any more detail. Their effectiveness varies considerably from country to country. Rather, I will again put my perspective on things and also give some details as to a project of great significance that is happening in the South of Vietnam.

One of the most significant drivers I have seen in the region to address overall issues of food safety and to a lesser extent antibiotic use in animal agriculture is the rise of the middle class. The rise of Asian economies since the end of the Second World War, but more so in the last 20 years, has been spectacular. As an example of how the region has performed, let’s quickly look at Vietnam. After 19 years of war, this country was devastated both politically socially and economically. Since the reforms in the mid 1980’s, Vietnam has risen from one of the poorest countries in the world to now rank 36th in the world in terms of GDP. 45 million people were lifted out of poverty and now it is estimated that over 25% of the population can be defined as middle class.

Currently, it is estimated that two billion Asians can be defined as middle class which is set to increase to three and a half billion over the next ten years. As has been seen in other countries when there is an increase in prosperity and purchasing power, then there is a subsequent increase in consumer driven activism regarding food safety which includes the issues surrounding antibiotic use in agriculture. I am a member of a number of food blogs in Asia and it is here that I see active discussion (though not necessarily well informed) concerning agricultural practices. The middle class in Asia tends to not trust Asian produce and its purchasing practices are geared more towards imported foods wherever possible. This is making a difference in agriculture albeit slowly. Food safety auditing programs like Global GAP are becoming more common as a result of consumer pressure, an increase in export orientation as well as the rise in organic produce. The export sector is a significant driver of food safety accreditation and most of these programs have serious relation to antimicrobial stewardship and the prevention of antimicrobial resistance. Dramatic reduction in the use of antimicrobial products is a must in the region. I have already mentioned antibiotic stewardship and antibiotic stewardship is a key driver. We need to use, in my opinion, terminology like antibiotic stewardship, because we still do need antibiotics in animal agriculture in this region. It will be slow process and in the meantime antibiotics are essential. To achieve antibiotic stewardship there are three steps and principles we implement over time:

1. No use of banned or unregistered products e.g. Chloramphenicol, nitrofurans etc

2. Remove any antibiotic deemed by the WHO (and other bodies) as being of critical importance e.g. Cephaloproins, Quinolones, Polymixins etc

3. Remove all prophylactic antibiotics firstly in the water and then (possibly and if considered necessary) in feed ensuring firstly that:

They are replaced with proven alternative strategies and products (combinations are more effective in the field)

We have rigid principles of biosecurity in place.

We have a robust and proven vaccination programme.

We have a robust structure for diagnosis of mortality and poor performance events.

We have a pre-approved and pre-planned procedures and products for therapeutic use only when and if necessary.

Many things are needed to be implemented at both regional national local and farm level to drive the concepts of antibiotic stewardship. The following I see as priorities. Sơme may be controversial and some may disagree with what other have discussed but they are what I see at the ground level.

1. Better educate veterinarians as to the how and why of antimicrobial resistance and the necessity to play a part in antibiotic stewardship. Teach them how to make better choices and give them the sole authority and responsibility to use and prescribe antibiotics. We need to also teach them how to investigate both performance and health issues on farm in a way that identifies root causes.

2. Educate farmers and farm owners to enable them to carry out good husbandry practices that have been proven to result in better performance and flock health.

3. Reduce the availability of antimicrobial products and their cost.

4. Provide the resources to adequately administer and enforce legislation and regulations.

5. Empower consumers with sound knowledge and science regarding how and why antibiotics are used and give them more choice, like audited standards etc.

One of the most exciting projects in the region looking at antimicrobial product use and control is the ViParc project in the Mekong Delta of Vietnam. ViParc stands for Vietnamese Platform for Antimicrobial Reduction in Chicken Production. (www.ViParc.org). It is a collaboration of researchers from the Oxford University Clinical Research Unit and is funded by the Welcome Trust. It specifically targets smaller village type commercial and semi commercial poultry farms in the Mekong Delta and aims at providing scientifically sound interventions to deal with the problem of high antibiotic use. An important component of the project is that it integrates socio-economic analyses of the use of antibiotics to provide insights as to why antibiotics are used and the cost-effectiveness of any proposed interventions (Carriique-Mas 2017).

Presented at the 32th Annual Australian Poultry Science Symposium 2021. For information on the next edition, click here.

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