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Global Trends by Martin Khor

Monday 9 May 2016

Super drug-resistant gene raises new health alarm

A recently discovered gene that is resistant to an antibiotic used as a last resort and which can spread easily among bacteria has raised fresh concerns about the coming end of the use of antibiotics – if action is not taken immediately.

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Antibiotic resistance – a process by which antibiotics no longer work because bacteria have become resistant to them – has climbed up the global agenda because of growing awareness of the immense threat this poses to human health and survival.

However, there is still not enough action to tackle this crisis.  Health Ministers meeting at the World Health Assembly in Geneva later this month have an opportunity to review the extent to which a Global Action Plan adopted last year has been implemented.

In the background is the recent disturbing news of the discovery by scientists of a gene, MCR-1, which creates resistance to colistin, a powerful antibiotic used as a last resort to treat infections when other medicines do not work. 

Even more worrying is that the gene has the characteristic of being able to move easily from one strain of bacteria to other species of bacteria. This raises the spectre of many infections eventually becoming untreatable, bringing us closer to the nightmare of a post-antibiotics era.

Malaysia is one of the first countries in which scientists found the MCR-1 gene.  Thus there is an even more serious need for our policy makers to deal with this issue, including to consider banning the use of colistin in animal feed.

The gene was discovered during a study undertaken in China.  Last November, Yi-Yun Liu and colleagues published a paper in The Lancet Infectious Diseases journal revealing they found the MCR-1 gene in 166 out of 804 pigs at slaughter that they tested, 78 of 523 samples of chicken and pork being retailed and in 16 of 1,322 hospital patients.

The study indicates there is a chain in the spread of resistance from the use of colistin in livestock feed, to colistin resistance in slaughtered animals, in food and human beings.      

One of the authors, Prof. Jian-Hua Liu from South China Agricultural University, was quoted by the Guardian  as saying these are extremely worrying results, which reveal the emergence of the first polymyxin resistance gene that is readily passed between common bacteria such as E. coli and K. pneumonia. 

This suggests that “the progession from extensive drug resistance to pandrug resistance is inevitable”, added Liu.   Extensive resistance is when a bacterium is resistant to many drugs while pandrug resistance indicates resistance to all drugs. 

Colistin is part of a category of antibiotics known as polymyxins.  In the past they had not been widely used as they are known to have toxic effects, but they have been recently more used as a last resort when other antibiotics don’t work because of resistance.

“All key players are now in place to make the post-antibiotic world a reality,” another of the paper’s co-authors, Prof. Timothy Walsh from University of Cardiff, told the BBC News website. 

“If MCR-1 becomes global, which is a case of when and not if, and the gene aligns itself with other antibiotic resistance genes, which is inevitable, then we will have very likely reached the start of the post-antibiotic era.   At that point, if a patient is seriously ill, say with E. coli, then there is virtually nothing you can do.” 

A major reason for the emergence and spread of the gene is suspected to be the heavy use of colistin to feed livestock to promote their growth.  Much of the worldwide annual use of 12,000 tonnes of colistin in animal feed takes place in China, according to the paper by Lui and colleagues.

The paper mentions that besides China, the MCR-1 gene has also been found in Malaysia and Denmark.  It revealed that Malaysian scientists had found bacterial DNA sequences in December 2014 with genes that look like MCR-1.  The possibility that E.coli with the MCR-1 gene had spread into other South-east Asian countries is “deeply concerning”, said the authors.

After the paper was published, new papers and information have shown that the MCR-1 gene has been found in bacterial samples in many other countries, including Thailand, Laos, Brazil, Egypt, Italy, Spain, England and Wales, the Netherlands, Algeria, Portugal and Canada.

The most frightening thing about MCR-1 is the ease with which it can spread resistance to other species of bacteria through a process known as horizontal gene transfer.  

A few years ago, there was a similar scare about NDM-1, a gene with the ability to jump from one bacteria to other species, making them highly resistant to all known drugs, except two, including colistin. 

If the colistin-resistant MCR-1 were to combine with NDM-1, then the bacteria having the combined gene would be resistant to virtually all drugs.

In 2010, only two types of bacteria were found to be hosting the NDM-1 gene – E Coli and Klebsiella pneumonia.  Within a few years, NDM-1 had been found in more than 20 different species of bacteria. 

The discoveries of NDM-1 and now of MCR-1 add urgency to the task of addressing anti-microbial resistance.

In 2012, World Health Organisation Director General Dr Margaret Chan warned that every anitibiotic ever developed was at risk of becoming useless.  “A post-antibiotic era means in effect an end to modern medicine as we know it.  Things as common as strep throat or a child’s scratched knee could once again kill.”

The World Health Assembly is an opportunity to take stock of the Global Action Plan on antimicrobial resistance. 

An immediate action needed is to ban the use of colistin in livestock production.  The well-respected Lancet journal published a Comment in February that we must take the call to curtail the use of polymyxins (including colistin) in agriculture to the highest levels of government or face more patients for whom we need to say, “Sorry there is nothing I can do to cure your infection.” 

Other antibiotics that are used by human beings should also be prohibited or heavily restricted in the livestock sector, especially if they are used as growth promoters. The Global Action Plan has five objectives: to use medicines properly in human and animal health; reduce infection by sanitation, hygiene and infection prevention measures; strengthen surveillance and research; educate the public as well as doctors, veterinarians and farmers on proper use of antibiotics;  and increase investment in developing new medicines, diagnostic tools and vaccines.

 


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