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Reducing use of antimicrobial drugs in livestock in low-income countries: Two scientists reflect on options


Graphic by Peter Hermes Furian / Shutterstock.

Delia Grace Randolph, a veterinary epidemiologist and food safety expert who co-leads the Animal and Human Health program at the International Livestock Research Institute (ILRI), in Kenya, was interviewed recently by Wilton Park, a non-profit discussion centre in the UK, which organizes many events each year debating global issues.

The Wilton Park event at which Randolph spoke was a workshop held 11–13 Apr 2018 in West Sussex on Innovations to reduce the use of antimicrobials in food-producing animals in low- and middle-income countries.

Participants in the workshop discussed ways to limit the emergence and spread of resistant bacteria throughout the world, the main drivers of antimicrobial resistance in food-producing animals and research gaps in possible vaccines and alternatives to antibiotics.

Interviewed along with Randolph was Dirk Werling, professor of molecular immunology at the Royal Veterinary College, in London.

A podcast of their interview was published by Wilton Park on 19 Jun 2018. Highlights of the remarks made by Randolph and Werling in their 20-minute interview follow, edited for brevity and sense.

Dirk Werling
We’ve reached a stalemate between our ability to combat certain diseases with antimicrobial drugs and the ability of the disease-causing microbes to develop tolerance to the drugs. So we’re no longer able to fight some specific infectious diseases.

This is a problem for veterinary, medical and environmental health alike. We’re not going to reduce the antimicrobial resistance problem in any one of these areas without reducing the problem in the other two areas as well.

In low- and middle-income countries, where people find it hard to pay to have their animals treated with antimicrobial drugs, farmers may use only half a dose of a drug to save money. In high-income countries, treatments are sometimes stopped before all the bacteria are killed, which enables the bacteria to develop resistance to the drugs.

Randolph
Overuse of penicillin and other antimicrobial drugs presents us with two issues. One is that the eggs, milk and meat products of animals treated with antimicrobials may contain some drug residues, leading to their consumption by humans. While such consumption is not terribly dangerous for people, most countries have regulations prohibiting such residues in foodstuffs.

A much more serious problem is that of drug resistance. When antimicrobial drugs are given to animals, thereby exposing the parasites in the animals to these drugs, the parasites will tend to evolve resistance to those drugs. In this way, with our drug use, we are actively selecting for populations of bacteria and other microbes that can grow quite well in the presence of antimicrobial drugs.

There was a time not so long ago, some 100 to 200 years past, that families typically had two or three children die of infections that are now easily cured with drugs such as penicillin.

If these drugs stop working, we may once again see large numbers of people dying from diseases that are now very curable. And if things don’t improve, we may see more deaths from bacteria and other microbes in 2030 than from cancer. The great majority of this new disease burden will fall on low- and middle-income countries, where I and my institute focus our animal health work.

But the rise of antimicrobial resistance is a global problem. If antimicrobial resistance is generated in China or Vietnam or India, say, those bacteria will not ‘stay at home’ but will travel with people, with food, with trade all around the globe. Antimicrobial resistance may be less of a problem in high-income countries, where there is good sanitation and the population is well nourished, but in lower income countries, where sanitation, diets and vaccination programs are inadequate, people, and children in particular, will be especially vulnerable to bacterial infections.

In addition, while demand for meat, milk, eggs and fish is relatively stable in high-income countries, a huge increase in such demand is occurring in low- and middle-income countries. In response to a projected doubling in demand for livestock-derived foods in the coming decades, we’re likely to see further intensification of livestock production and further numbers of animals.

Some models suggest that more antimicrobials are already used in agriculture in lower income countries than in higher income countries. Furthermore, nearly all the growth in antimicrobial use is going to occur in the lower income countries. So as well as being the greater victims of the problem of antimicrobial resistance, lower income countries will also increasingly be the greater creators of the problem. (This is in contrast to the greenhouse gas emissions causing climate change, where we see that while most of the victims of climate change live in poor countries, most of the people creating the problem live in rich countries.)

A lot of the effort to tackle antimicrobial resistance has focused until now on regulations—on getting appropriate regulatory frameworks in place. That’s good. We need that.

But regulation by itself will never succeed. If we want to change the behaviour of more than a billion people keeping livestock in developing countries, we need other levers in place.

These include not only education and awareness but also incentives. People must see immediate, direct benefits from changing their use of antimicrobials.

Some of the things with potential to do that are vaccines. It’s more attractive for farmers to have their animals never get sick, due to their vaccination, than to have their animals get sick and need treatment with antimicrobials to get better. But we need innovation in vaccine research to produce more vaccines (we’re much better at viral vaccines than at bacterial vaccines) and to develop vaccines appropriate for developing countries (e.g., those that require no cold chain or are cheap or come in small doses). There’s a whole range of possible alternatives to antibacterials, but further developing these and getting them to end users are our big challenges.

Werling
These problems are similar in so-called first-world countries. It’s very hard to convince farmers in England, for example, to use vaccines rather than drugs. They think vaccination is a waste of money if their animals don’t get sick; they would rather just treat the animals that do get sick. But that doesn’t help to reduce antimicrobial resistance and residues.

As Delia said, we do not have good vaccines against bacterial diseases. That’s an opportunity for us—an opportunity not only to develop new livestock vaccines but also to conduct socio-economic investigations of what prevents vaccines from reaching farmers or being taken up by them.

Randolph
Our research opportunities can be divided into two categories—fire fighting and fire prevention. Fire fighting is what we can do here and now to make a difference in how antimicrobials are used. Key to this is simply a better understanding of the alternatives to antimicrobials—what they are, their costs and effectiveness and how to improve their uptake. Taxpayers can clearly see why we should be doing fire fighting when there is a fire!

But for society there may be more benefits to prevention. That requires longer term research—research that, while not leading to immediate products, underpins the whole future of our ability to control infections. This longer term research would include not only development of completely new vaccines but also building better understanding of immunology, disease dynamics and transmission. There’s much that we still do not understand about how resistance to drugs is created, how it moves around, how it is dissipated, and the roles animals and environments play in that resistance. Without this basic understanding, we’re likely, even if we get over the immediate crisis, to run into big problems further down the line.

Werling
It recently became more difficult to obtain funding for basic animal research. Funders wanted to know why we needed to replicate vaccine research work done in mice or humans in fish, or pigs or chickens. But in the last ten years or so we have understood that the immune systems, the physiological systems, of these animals are so different from humans and mice that we cannot simply extrapolate from the data we generate in mice to livestock species. I think funding for such basic livestock research is improving at the moment, with organizations like the Bill & Melinda Gates Foundation ambitious to tackle so-called ‘grand challenges’ in the years to come.

Randolph
The problem of rising antimicrobial resistance is a very soluble problem. We work in other areas, such as preventing a new infectious disease—a new Spanish flu, say—from becoming a pandemic and killing 50 million or so people. Such problems are intrinsically much more difficult to solve.

In contrast, the problem of antimicrobial overuse is basically one of making appropriate technologies available and providing people with incentives to use them. We know what needs to be done. It’s just a question of obtaining the needed resources and commitment and ensuring that our products reach their end users.

Review of evidence on antimicrobial resistance and animal agriculture in developing countries, by Delia Grace, ILRI and UK Evidence on Demand, 2015.

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