From pig to pork

FROM PIG

FROM PIG TO PORK

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MA Communication Design

Marisa Espinheira

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Andrew Howard

April 2020

FROM PIG TO PORK Composed of three articles to make known and understand the use of antibiotics in the animal industry.

In particular focus on pig production, and its consequences on human health.

INDEX

9

Drug resistance: Does antibiotic use in animals affect human health?

17

Get pigs off antibiotics

25

WHO calls for an end to antibiotic use in healthy animals

31

Extra information

33

Bibliography

Drug resistance: Does antibiotic use in animals affect human health?

Antibiotic resistance is a global public health crisis. In this Spotlight feature, we look at the use of antibiotics in animals and its consequences for human health, covering research presented recently at the London Microbiome Meeting.

Antibiotic resistance poses a serious threat to public health, both in the United States and globally.

According to the Centers for Disease Control and Prevention (CDC), antibiotic resistance is responsible for 25,000 annual deaths in the European Union and 23,000 annual deaths in the U.S. As many as 2 million U.S. individuals develop a drug-resistant infection each year.

By the year 2050, some researchers predict that antibiotic resistance will cause 10 million deaths every year, surpassing cancer as the leading cause of mortality worldwide.

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Some of the factors that have led to this crisis include the overprescription of antibiotics, poor sanitation and hygiene practices in hospitals, and insufficient laboratory tests that can detect an infection quickly and accurately.

An additional factor that may contribute to drug resistance in humans is the overuse of antibiotics in farming and agriculture. Using antibiotics in animals may raise the risk of transmitting drug-resistant bacteria to humans either by direct infection or by transferring “resistance genes from agriculture into human pathogens,” researchers caution.

So, how are antibiotics currently being used in animals, and what might be the implications for human health? At the London Microbiome Meeting, which took place in the United Kingdom, Nicola Evans — a doctoral researcher in structural biology at King’s College London — shared some of her insights on these issues.

Global use of antibiotics in animals

On a global scale, the U.S. and China are the largest users of antibiotics for food production. According to the Food and Drug Administration (FDA), 80 percent of the total antibiotic use in the U.S. is in agriculture, with pigs and poultry receiving five to 10 times more antibiotics than cows and sheep.

Why are antibiotics used so widely in these animals, however? One answer comes from the demands of the meat industry, which place a strain on the animals’ health.

Farming animals for meat is a particularly intense process, with pig sows, for instance, not being given enough time to recover in-between births. This compromises their immune system.

Also, pigs and chickens live in confined, crowded spaces, which increases their stress and the risk of disease transmission.

Additionally, antibiotics are sometimes used to make the animals grow faster. In humans, 10 Drug resistance

GROW

FASTER

studies have shown that antibiotics raise the risk of weight gain and obesity, as they wipe out beneficial gut bacteria that help regulate weight.

In animals, however, this phenomenon has been seen as a positive, with several countries still using antibiotics as growth promoters.

Until a year ago, U.S. farmers used antibiotics as growth promoters, but the practice has since been banned. China and the E.U. have also outlawed this practice, but many other countries continue to use antibiotics to promote growth in animals, Evans explained.

Finally, the prophylactic, or preventive, use of antibiotics also adds to the problem. Many farms give chicks antibiotics as soon as they are born, regardless of whether they are ill or not.

11 Drug resistance

TAKEN AWAY

FROM THEIR MOTHERS

Antibiotics and the animal microbiome

The weaning practices that take place in farms influence the animals’ microbiome and create a false need for antibiotics. As Evans explained in her talk, piglets are taken away from their mothers too early — that is, before they’ve had a chance to develop a strong immune system or a healthy, fully matured gastrointestinal tract.

For example, piglets would naturally wean when they are around 3–4 months of age.

In the U.S., however, piglets are weaned when they are 17–28 days old.

Evans explained that not having access to the natural antibodies present in the mothers’ milk impacts the animals’ immune system. “Abrupt” weaning has also been found to raise the risk of gastrointestinal disease in calves and lambs.

In turn, these diseases call for the use of antibiotics, sometimes prophylactically. For instance, piglets, calves, and lambs can have post-weaning diarrhea and associated infections, so farmers give them antibiotics to prevent such infections.

Also, Evans explained in her talk, a pig’s microbiome “is colonized at birth and subsequently modified during the suckling period” and the weaning period.

During this time, the gut microbiome diversifies.

However, research has shown that abrupt weaning, which involves a drastic change in diet and environment, can cause a loss of microbial diversity and an imbalance between beneficial and harmful bacteria in the gut.

Furthermore, genomic studies cited by Evans have found a dramatic increase in Escherichia coli in the pigs’ small intestines after receiving antibiotics. E. coli is responsible for half of all piglet deaths worldwide.

An animal’s environment also plays a critical role in developing a diverse and healthy microbiome. Past studies, for example, found that a pig’s microbiome

13 Drug resistance

can be influenced by something as simple as the presence of straw.

Having straw in the environment led to a different ratio of gut bacteria in pigs, and straw has been associated with a lower risk of developing porcine reproductive and respiratory syndrome.

Separated from their mother and with no outdoor access, chicks cannot develop a healthy immune system and microbiome.

As Evans noted in her talk, the poultry microbiome is even more affected by intensive farming practices than that of the pig.

The main reason for this is that in birds, the early gut colonization occurs during the development of the egg in the mother’s oviduct. The chicks absorb microorganisms from the mother at this stage, as well as through the pores of the eggs during brooding.

Once the chicks have hatched, they continue to enrich their microbiome by exposure to feces. However, in modern farming systems, the eggs are taken away from the mother and cleaned on the surface, which removes the beneficial bacteria.

Also, when the eggs hatch, the chicks do not get access to an outdoor space where they would have access to feces and other sources of beneficial bacteria. They also do not interact with adult chickens.

Finally, the crowded conditions that chickens often live in can cause heat stress. This, in turn, is a fertile ground for the development of E.coli and Salmonella infections. This is yet another example of how the environment can affect the birds’ microbiome.

Implications for human health

So, what does this use of antibiotics in animals mean for human health? We spoke to Evans about the potential implications for antibiotic resistance in humans.

“The most important thing to consider,” she said, “is that any single time antibiotics are used, whether in animals or humans, you risk selecting for drug-resistant 14 Drug resistance

bacteria. We need to safeguard [antibiotics] for the use in both animals and humans, to ensure they can be used for the treatment of infection in the future.”

There are a few main ways in which antibiotics in animals can affect humans, Evans explained. Firstly, direct contact between animals and humans can cause disease. “For example,” said the researcher, “farmers are at risk of being colonized by the Livestock-Associated MRSA (LA-MRSA).”

“LA-MRSA isn’t as dangerous as [Hospital-Associated]-MRSA,” she explained, “as it is adapted for animals and does not spread as easily from person to person.

However, there is a risk that bacteria could change and adapt to humans,” Evans cautioned.

She went on to quote a Danish study that found that 40 percent of commercially sold pork meat contained methicillin-resistant Staphylococcus aureus (MRSA).

15 Drug resistance

A review of existing studies on the pork production chain found that “the slaughter process plays a decisive role in MRSA transmission from farm to fork.”

A second way in which animal antibiotic use can affect humans is through the consumption of antibiotic residues in meat, which then “provide a selection pressure in favor of [antibiotic-resistant] bugs in humans,” Evans explained.

However, “the risk [of] this is considered to be very low in the E.U. and America,” she continued.

“In these areas, there is something called a withdrawal period, [in which] antibiotic treatment of an animal is stopped so that antibiotics can clear the system before the animal is culled for meat or milked.”

The use of antibiotics in animals may affect the human gut bacteria.

This applies to both organic and nonorganic farming practices, Evans noted. After the withdrawal period, she said, “[t]he levels of antibiotic in the food are considered to be several hundred times below the levels [that] should affect bacteria in any way.”

Finally, the antibiotic-resistant bacteria present in meat may transfer antimicrobial resistance into human bacteria. However, the risk of this occurring is very low due to high cooking temperatures.

Also, “because of the withdrawal period,” Evans said, “it is very unlikely that antibiotic residues in meat would affect the [human] microbiome.”

Overall, the researcher told Medical News Today, “I think that all use of antibiotics poses a risk to human health, and that reducing unnecessary antibiotic use in animals should be part of the overall solution. “ “Antibiotics are needed […] to safeguard animal health and welfare, but should only be used when the animals are sick and not used for growth promoters or to prevent animals getting sick in the first place.

However, animal use shouldn’t detract from the fact that the vast majority of antibiotic resistance in humans is caused by overuse in humans.”

16 Drug resistance

Get pigs off antibiotics Frank Aarestrup explains how he helped Denmark to cut the use of antibiotics in its livestock by 60%, and calls on the rest of the world to follow suit.

The amount of antibiotics consumed by livestock worldwide is almost double that used by humans, according to some estimates. In the United States, for instance, about 300 milligrams of antibiotics are used to produce every kilogram of meat and eggs. These drugs are administered not just to treat or to prevent infections. In many countries, they are used to help the animals to grow faster. This is an unsustainable situation. Since many farmers began giving antibiotics to livestock in the late 1940s, people have been infected with strains of bacteria that are resistant to those antibiotics.

To try to combat this dangerous trend, the European Union banned the use of antibiotics for growth in livestock in 2006. The practice continues unabated in the United States, despite a statement from the Food and Drug Administration in April suggesting that farmers should stop voluntarily.

Some argue that, without antibiotics, the agricultural industry will collapse. My experience in Denmark proves otherwise. The country is the world’s largest exporter of pork, exporting 90% of all it produces, and it did much more than ban the use of antibiotics for growth. It reduced their usage overall and built a comprehensive surveillance system to track and target overuse. It also prohibited veterinarians

from profiting from the sale of drugs to farmers — a practice that continues in the United States and in much of Europe.

Pork production has risen steadily in Denmark, despite a voluntary halt to using antibiotics to boost growth.

Since the mid-1990s in Denmark, the use of antimicrobial agents per kilogram of livestock produced has dropped by 60%. And pork production has actually increased by 50% since 1994, before any interventions began.

Any country trying to limit the use of antibiotics in livestock can learn from what my colleagues and I did in Denmark, adjusting what worked there to local needs. Given how difficult it is to control how resistant bacteria behave and spread worldwide, reducing antibiotic use is something we must do for the future health of all — animals and people.

A growing problem

I got involved in helping Denmark to reduce its overuse of antibiotics almost by accident. In September 1994, I was a recently graduated vet, doing my PhD in bovine mastitis and one of its main causes, the bacterium Staphylococcus aureus, when I saw some data that worried me. At the annual meeting of the Danish Veterinary Association in Askov, researchers showed an increase in prescriptions for and usage of cheap tetracycline in animals — and a concurrent rise in resistance to the antibiotic among bacteria cultured from animals. These data prompted a heated debate and revealed that many vets were making a huge profit from selling antibiotics to farmers.

At that point, scientists were already concerned about the overuse of antibiotics in livestock. Farmers have been using antibiotics to boost growth since just after the Second World War, when there was a lack of good-quality feed. Experiments at the time showed that animals grew faster when fed low levels of the drugs — although researchers have never fully explained why. The practice spread quickly. As early as the 1960s, scientists began to 18 Get pigs off antibiotics

FARMERS HAVE BEEN USING ANTIBIOTICS TO BOOST GROWTH SINCE JUST AFTER THE SECOND WORLD WAR

19 Get pigs off antibiotics

see the same resistant bacteria in food animals and humans. This was no surprise. Bacteria linger in skin and faeces and can easily make their way into meat and onto the hands and kitchen counters of people preparing it. So, starting in the 1970s, countries in Europe began banning the use of antibiotics for growth, particularly those drugs that were being used therapeutically in humans.

After some prompting from my collaborator, the German microbiologist Wolfgang Witte, I decided to investigate whether farmers in Denmark prescribed antibiotics to animals purely for growth. I found, to my surprise, that this was common practice. In pig production, two-thirds of all antibiotics given were for growth; in poultry, it was around 90%.

Curious, my colleagues and I began to screen faecal samples from healthy chickens and pigs. On 25 January 1995, we isolated for the first time a bacterium that was resistant to one of the growth-promoting antibiotics. Subsequent studies showed a clear relationship between the use of a growth promoter called avoparcin and the widespread occurrence of resistant bacteria. This prompted the Danish government to ban the use of avoparcin to promote growth in livestock. Soon after, in 1997, the EU banned all use of avoparcin.

This became a major story in Denmark, and I began travelling to meetings and taking phone calls from the media and government agencies, all while trying to finish my PhD. Eventually, the director of the institute I was working at, the National Veterinary Laboratory in Copenhagen, asked me to focus on antibiotic resistance full time, including monitoring the ban on avoparcin. This became the foundation of the first comprehensive surveillance system to monitor the use and health effects of antibiotics in livestock.

In 1995, we established DANMAP, the Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (www.danmap.org). This 20 Get pigs off antibiotics

collaboration between vets and human-disease epidemiologists monitors antimicrobial usage and resistance in animals, food products and humans in Denmark. It collects and analyses samples from slaughterhouses, vets and hospitals to track the effects of policy intervention on antibiotic usage and to detect new problems. The United States, Canada, Japan and several countries in Europe now have surveillance programmes that are modelled on DANMAP. Meanwhile, as scientists found more instances of antibiotic resistance, the Danish government banned another growth promoter, virginiamycin, in 1998. That year, following much media interest and political pressure, and out of concerns for human health, the Danish poultry industry voluntarily stopped all use of antibiotics for growth. The country's pig industry followed in 2000.

Farmers were able to continue to use antibiotics to prevent and treat infections, which provided a back-door route for some of them to obtain inappropriate prescriptions. In 2010, the Danish agriculture ministry began issuing warning letters — dubbed yellow cards — to the pig farmers who had the highest consumption of antibiotics per pig produced. This has led to a reduction in antibiotic use for therapy of almost 25% during the past two years.

Even before Danish farmers cut back on antibiotics, many predicted that the cessation would have a disastrous effect on productivity and the economy.

However, in poultry production, it had no negative effects on either the total kilograms of chickens produced per square metre, or the amount of feed used. In pigs, reducing antibiotics had no negative effects on productivity, number of pigs produced per sow, average daily weight gain or the amount of feed needed to produce a kilogram of meat. In fact, pork production has increased steadily in Denmark as farmers have continued to modernize (see 'Bacon boost').

21 Get pigs off antibiotics

IN PIGS, REDUCING ANTIBIOTICS HAD NO NEGATIVE EFFECTS ON PRODUCTIVITY What worked

There were three secrets to our success in Denmark.

We had data showing that antibiotics were becoming a problem; there was political will to enforce regulations; and there was cross-sector collaboration between farmers, researchers and authorities.

One of the most important steps was the ban. But legal action means nothing without a way to monitor compliance. For example, Danish authorities use DANMAP to target the farms that are using the most antibiotics, or the most dangerous classes of drugs. Some countries' surveillance systems are not comprehensive enough. Data are not available from all animal species, and the systems do not integrate 22 Get pigs off antibiotics

data from humans and animals sufficiently. Some do record antibiotic resistance, but not all of them track usage.

Denmark took another key step that most countries have not yet taken. The government issued legislation in 1995 preventing vets from profiting from selling antibiotics to farmers. The conflict of interest is clear. The more antibiotics farmers use, the more money these vets make. I believe that this decision had a huge impact on the overuse of antibiotics in livestock. Vets in the United States and most of the EU continue to profit from prescribing these drugs.

In my view, it also helped that my scientific colleagues and I were very open about our findings of bacterial resistance. We communicated results in our annual meeting and through regular DANMAP reports, among other methods, even to people who we knew would take issue with what we had to say.

Reducing Denmark's reliance on antibiotics was far from easy. My lab was visited by pharmaceutical executives who did not like what we were finding, and I would be cornered at meetings by people who disagreed with our conclusions. I have even been publicly accused of being paid to produce biased results. Despite such challenges, it has been satisfying to see that Danish farmers and their livestock can thrive without the heavy use of antibiotics. With a little effort, I believe that other countries can and must help their farmers to do the same.

23 Get pigs off antibiotics

WE NEED TO TAKE ACTION IN ANIMAL PRODUCTION TO PROTECT PUBLIC HEALTH

WHO calls for an end to antibiotic use in healthy animals Citing the benefits to public health, the World Health Organization (WHO) today called for an overall reduction in the use of antibiotics in food-producing animals, recommending that farmers stop using antibiotics for growth promotion and disease prevention in healthy animals.

The formal guidelines issued by the WHO further recommended that when animals are diagnosed with a bacterial infection, antibiotics that are considered critically important for human medicine should not be used for treatment or to prevent the spread of the infection within a herd or flock, unless tests indicate those drugs are the only treatment option. Instead, antibiotics used for the treatment of sick animals should be chosen from those the WHO considers least important to human health.

WHO officials said the guidelines were driven by the need to preserve the effectiveness of medically important antibiotics, many of which are also used by farmers to promote growth and prevent disease in livestock and poultry. The widespread use of these drugs in animal agriculture is widely seen as contributing to the emergence of antibiotic-resistant pathogens that are transmitted to humans via food and the environment.

“We need to take action in animal production to protect public health,” Kazuaki Miyagishima, MD, PhD, director of the WHO Department of Food Safety and Zoonoses, said at a press conference in Geneva. He added that while the guidelines could have a negative impact on animal production and other sectors, the need to preserve antibiotics for human use “by far” outweighs that impact.

What worked

The agency said the guidelines are based on decades of expert reports and evaluations of how antibiotic use in food-animal production is contributing to antibiotic resistance in both humans and animals. That includes a systematic review of 179 studies, commissioned by the WHO and published today in The Lancet Planetary Health, that found that interventions to reduce antibiotic use in food-producing animals decreased drug-resistant bacteria in animals by approximately 15% and multidrug-resistant bacteria by 24% to 32%.

Although evidence that using fewer antibiotics in livestock and poultry has had an impact on human health was more limited, a meta-analysis of 13 studies showed that such interventions were associated with a 24% absolute reduction in the prevalence of antibiotic-resistant bacteria in humans.

The WHO said the evidence also indicates that broad restrictions on all antibiotic classes is more effective in reducing antibiotic resistance than narrow restrictions on particular drugs.

The WHO estimates that antibiotics purchased for use in food-producing animals account for up to 80% of all antibiotics sold in some countries. In the United States, that number is estimated to be between 70% and 80%. While the United States and the European Union have banned the use of medically important antibiotics for growth promotion in food animals, many low- and middle-income countries do not regulate the use of antibiotics in the animal production sector. The concern is that antibiotic use in food animals is going to soar in these nations as living standards rise and demand for meat grows.

A recent study estimated that global consumption of antibiotics in livestock and poultry will climb to 200,235 tons by 2030, up from 131,109 tons in 2013, without restrictions. The WHO said today that implementation of the guidelines in low- and middle-income countries may require assistance with animal health management and husbandry practices.

26 WHO calls for an end to antibiotic use in healthy animals

Officials at today’s press conference cited Denmark, the Netherlands, Norway, and the United Kingdom as countries that have adopted stricter restrictions on antibiotic use in food animals with minimal impact on livestock and poultry production. Denmark, which ended the use of antibiotics for growth promotion in 1999 and uses the drugs only for treating sick animals, has seen overall consumption of animal antibiotics drop by 49% since 1994, while meat production has increased by 15%.

“The good news is that these recommendations, including the ban on antimicrobials as growth promoters, have been successfully implemented in many parts of the world, in Europe in particular,” Aiwa Aidara-Kane, PhD, coordinator of the WHOs Department of Food Safety and Zoonoses, told reporters.

Addressing concerns about maintaining food safety, Miyagishima said there are several ways to prevent infectious disease in food animals without using antibiotics, including improving hygiene, raising animals in less crowded conditions, using better biosecurity methods, and vaccinating animals.

Recommendations receive praise, criticism

Tara Smith, PhD, an epidemiology professor at Kent State University who's done extensive research on the spread of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in humans, says she welcomes the recommendations. "I think it's commendable that the WHO has put this out, to provide aspirational goals for countries already starting work on controlling antibiotic use in livestock and to perhaps give an extra push for those who are a bit behind, like the United States," she told CIDRAP News.

While a ban on antibiotics for growth promotion went into effect in the United States this year, US farmers are still allowed to use antibiotics for disease prevention, under the guidance of a licensed veterinarian.

Smith and other experts contend that using antibiotics for disease prevention—a practice that continues in many countries besides the United States— 27 WHO calls for an end to antibiotic use in healthy animals

IMPROVING HYGIENE, RAISING ANIMALS IN LESS CROWDED CONDITIONS, USING BETTER BIOSECURITY METHODS, AND VACCINATING ANIMALS constitutes a much larger portion of antibiotic use in animals than growth promotion. "We won't know if the changes put in place this year restricting growth promotion use in the US will actually move the needle on antibiotic use for a while yet, but targeting prophylactic [preventive] use as a next step makes sense," she said.

Public health and animal medicine consultant Gail Hansen, DVM, agreed that calling for an end to the use of antibiotics for disease prevention in animals is a significant step for the WHO to take. "The WHO is saying we really need to mitigate antibiotic resistance, and the way to do that is not using antibiotics for growth promotion and not using them for prevention when there's no disease," she said.

28 WHO calls for an end to antibiotic use in healthy animals

Although the WHO recommendations are not binding, Hansen said they set a bar and send a strong message to countries that world bodies recognize antibiotic misuse in animal production as an important public health issue that needs to be addressed. She also thinks that the lessons learned in countries that have implemented antibiotic restrictions in the animal sector can be shared with low- and middle-income countries.

"I think the higher income countries can certainly give some ideas and give some help to those countries that are just starting to look at this issue," she said.

But not everyone agrees with the new guidelines. “The WHO guidelines are not in alignment with U.S. policy and are not supported by sound science," Chavonda Jacobs-Young, PhD, chief acting scientist with the US Department of Agriculture, said in a statement.

"The recommendations erroneously conflate disease prevention with growth promotion in animals."

The Animal Health Institute (AHI), a group that represents veterinary pharmaceutical companies, also challenged the recommendations, saying in an emailed statement that focusing only on the amount of antibiotic use, rather than judicious use, fails on two counts.

"First, both studies and experience show that programs aimed only at reducing use in animals has not been effective at reducing resistance rates in humans," AHI said. "Second, such programs lead to more animal disease and death, which undermines good animal welfare and can reduce food safety."

The WHO recommendations also included two "best practice" statements aimed at further protecting the effectiveness of antibiotics. The first calls for any new class of antibiotic developed to be considered critically important for human medicine. The second suggests that medically important antibiotics not currently used in food-animal production, such as carbapenems, should not be used in food-producing animals in the future.

29 WHO calls for an end to antibiotic use in healthy animals

EXTRA INFORMATION

Farms not Factories #TurnYourNoseUp https://farmsnotfactories.org/articles/turn-your-nose-up-at-pig-factories/ CBS News https://www.youtube.com/watch?time_continue=81&v=9BeFBMzyCDI&feature=emb_logo World Health Organization The evolving threat of antimicrobial resistance: options for action. https://apps.who.int/iris/bitstream/handle/10665/44812/9789241503181_eng.pdf?sequence=1&isAllowed=y

31 Extra information

BIBLIOGRAPHY

Sandoiu, Ana. “Drug resistance: Does antibiotic use in animals affect human health?” Medical News Today, Healthline Media, 9 November 2018, https://www. medicalnewstoday.com/articles/323639.

Aarestrup, Frank. “Get pigs off antibiotics.” Nature, Holtzbrinck Publishing Group, 27 June 2012, https:// www.nature.com/articles/486465a.

Dall, Chris. “WHO calls for an end to antibiotic use in healthy animals.” CIDRAP, 7 November 2017, https:// www.cidrap.umn.edu/news-perspective/2017/11/ who-calls-end-antibiotic-use-healthy-animals

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TO PORK