When the drugs don’t work

7th October 2016 Adam Pitt

With the UN taking the unusual step of hosting a high-level meeting on antibiotic resistance at this year’s General Assembly, Adam Pitt reveals why resistance could have a bigger impact on the world economy than the 2008 financial crisis

According to the Review on Antimicrobial Resistance, an independent body commissioned by the UK government that works with biomedical research charity the Wellcome Trust, the number of deaths from drug-resistant infections could hit 10 million annually by 2050, with economic losses of around US$100 trillion. 700,000 people are estimated to die every year because of drug resistance to illnesses such as bacterial infection, malaria, HIV/Aids or Tuberculosis.

In contrast, it is estimated that US$5 billion annually would be sufficient to develop new vaccines that would reduce the need for antibiotics and at the same time, provide diagnostic tools to determine the nature of an infection and alternatives to antibiotics. That is, according to a group of health experts led by Ramanan Laxminarayan, director of the Centre for Disease Dynamics, Economics and Policy in Washington DC.

“This is a period of time when [antimicrobial] resistance has grown dramatically across both developed and developing countries when we need to conserve the antibiotics we have, while looking for alternatives and better diagnostics,” says Laxminarayan.

Laxminarayan, who has studied antibiotic and antimicrobial resistance for 20 years, has urged the United Nations to set global targets for reduced antibiotic consumption, and alludes to the fact that encouraging doctors to be better stewards of antibiotics will be crucial in the future.

He also emphasises the economic case for using fewer drugs in agriculture.
“Antibiotics are used in animals to promote growth and are a substitute for hygiene, infection control, and nutrition. Many farmers simply say it’s cheaper to use antibiotics – and this lack of incentive to use drugs appropriately is seen in developed and developing countries,” he says.

The use of antibiotics in livestock is growing, and is particularly acute in China, which used 15,000 tons of antibiotics in farming in 2010. It is projected to double its consumption by 2030, and part of Laxminarayan’s work has been to find out what it would cost farmers to withdraw antibiotics.

“It turns out the figure is not very high – it’s about US$3 billion in China,” he explains.

However, while he recognises the long-term transition costs may be higher, the continued use of antibiotics in a sector where food is predominantly produced for human consumption adds further to the risk of resistance.

“Since the livestock sector produces food, the danger is that antimicrobial resistant pathogens are transmitted in food chains, contributing to resistance and resulting in food safety issues,” says Daniela Battaglia, Livestock production officer at the Food and Agriculture Organization (FAO).

Ramanan Laxminarayan, director of the Centre for Disease Dynamics, Economics and Policy
Ramanan Laxminarayan, director of the Centre for Disease Dynamics, Economics and Policy

Such is the international and multidisciplinary concern over antibiotic resistance, the United Nations devoted a full day to the subject at the General Assembly on September 21, representing only the fourth time in its history that the organisation has met at this level to hold talks on a global health crisis.

In the build-up to the September gathering of world leaders, the World Bank shed further light on the significance of the need for a solution in a report entitled Drug Resistant Infections: A Threat to Our Economic Future. Alarmingly, the report suggests resistance to antibiotic and other drugs in humans and animals could cause economic damage comparable to the financial crisis in 2008.

The financial implications include a 3.8 percent drop in global economic output and a dip of the same level in international exports, by 2050. Global increases in healthcare costs could range from US$300 billion to more than US$1 trillion per year in the next 30 years. And the decline in global livestock production could also move from a low of 2.6 percent to a high of 7.5 percent a year.

With so much at stake, one of the big questions the international community must answer is how to reduce antibiotic use without compromising universal access to healthcare for the 400 million people worldwide that are unable to benefit from even the most routine treatments.

The need for performance indicators
A further challenge will be cleaning up pharmaceutical supply chains that are feared to have contaminated water systems, without increasing manufacturing costs that ultimately price live-saving drugs out of reach of some of the world’s poorest and most vulnerable populations.

One way to achieve this would be tying investment in pharmaceuticals to a set of environmental performance indicators, a process that Battaglia believes is already underway.

“Financial institutions are aware of issues of global interest when it comes to environmental pollution, climate change, and animal welfare and are asking enterprises in which they invest to comply with certain guidelines,” she says.

“I think having specific guidelines on antimicrobial resistance from the World Bank or regional development banks would also be interesting.”

Sacha Marschang, policy coordinator for health systems, European Public Health Alliance
Sacha Marschang, policy coordinator for health systems, European Public Health Alliance

Battaglia’s views are shared by Sacha Marschang, policy coordinator for health systems at the European Public Health Alliance, an association comprised of non-governmental organisations and not-for-profit entities working in public health in Europe.

“If global pooling of funds for the development of new antibiotics becomes a reality, this should as a matter of principle exclude companies that cannot demonstrate ‘clean’ supply chains,” says Marschang.

Such comments are driven by the findings of a recent paper published by the alliance, in which the pharmaceutical industry is said to be contributing to the rise of superbugs through pollution in its supply chains. The new paper focuses on how new research has identified environmental pollution from the production of antibiotics as an additional cause of antimicrobial resistance.

Improving manufacturing standards
Factories in China and India, which produce the lion’s share of the world’s antibiotics supply, are among those where the dumping of manufacturing waste into surrounding areas is resulting in the contamination of rivers and lakes and fuelling the proliferation of drug-resistant bugs.

Marschang adds that stricter manufacturing practices are one of the ways to create pressure for industries not to work with such producers anymore.

Even then, both he and Laxminarayan share the view that new antibiotics cannot be a long-term solution to antimicrobial resistance because resistance will develop quickly to those drugs too.

“The answer is to invest in prevention – vaccination, infection control, maintaining good physical and mental health, animal welfare – to avoid the need for antibiotics at all,” explains Marschang.

In echoing calls for more prudent use of antibiotics, Laxminarayan argues that countries should aim to consume no more than the current median global level of antibiotics (8.54 defined daily doses per capita per year), an amount he says would cut global antibiotic use by 17.5 percent.

“When you think about it, resistance is not a problem for any other kind of drugs,” observes Laxminarayan. “Antibiotics are very unique in having this problem, but we don’t really have an alternative. For better or worse, at the moment we don’t really have the option of a life without antibiotics.”

Dependence is high, says Laxminarayan, because we use them for fighting common infections as well as secondary infections after the flu and in preventing infections after surgeries and transplants but we must adopt a new approach to using the drugs.
“If we don’t, the problem is only going to get worse, to the point where we run out of road.”

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