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Fungal resistance to drugs emanating from agriculture products


By Maneka Gandhi

Candida auris is a dangerous fungal infection that emerged
in 2009 in Japan and, in just a few years, has spread round the world, especially in hospitals. It is a superbug: a germ that has evolved defences against common medicines and cannot be treated by the fungal medications now available. These include antifungals such as fluconazole, the standard antifungal drug in many countries, and echinocandins.
Once the germ is present, it is hard to eradicate it from a facility. Some hospitals have had to bring in special cleaning equipment, and even rip out floor and ceiling tiles, to get rid of it.
It is a life threatening fungus with a high death rate. It has been identified in Japan, South Korea, India, Pakistan, South Africa, Kenya, Kuwait, Israel, Venezuela, Colombia, the United Kingdom, Canada, and the United States. Other countries have it, but probably cannot identify the fungi because the specialised laboratory methods needed to do so are not available.
People with weakened immune systems are the most vulnerable – newborns, the elderly, people who are sick with other infections, diabetics, people who have undergone broad-spectrum antibiotic or antifungal therapy. The rise of C. auris has been little publicised because it is relatively new. Outbreaks have been played down, or kept confidential, by hospitals and even governments, as publicising an outbreak would scare people into not going to hospitals. In America, even the Centre for Disease Control is not allowed to make public the location, or name of hospitals involved in outbreaks.
The symptoms of C. auris — fever, aches, fatigue — are not unusual, so it is hard to recognise the infection without testing. The next step is blood poisoning/sepsis, coma, organ failure and death. The fungus can colonise on human skin, or surfaces, and live for a long period of time, allowing it to spread to new patients.
One reason is the indiscriminate doling out of antifungals by the medical community. But even more harmful is the use of antifungals in modern agriculture/animal husbandry.
It is clear that Candida auris’ resistance can be traced to industrial agriculture’s mass application of fungicides which are similar in molecular structure to human antifungal drugs.
Wheat, banana, barley, apple, potatoes, soya bean, grapes, corn, stone fruit, are some of the varied crops that fungicides are used on.
Before 2007, six main classes of fungicides were rarely used. Azoles, morpholines, benzimidazoles, strobilurins, succinate dehydrogenase inhibitors and anilinopyrimidines. Now they are common – with azoles leading the pack. Azoles, used in both crop protection and medicine, are broad-spectrum fungicides, annihilating a wide range of fungi.
It cannot be a coincidence that Candida auris has developed resistance to the azole antifungals, including fluconazole, amphotericin B, and echinocandins.
C. auris has probably been fought off for centuries by the human system. It is only now that it has become immune to human intervention, and can enter the bloodstream.
In an effort to identify the source of the infection, an international team collected fungal germs from hospitals across Pakistan, India, South Africa, and Venezuela in 2012–2015.
They found azole resistance in all – but the strains were varied and related to the fungicide that was used in that country. In response to wide exposure to fungicides in the field, each strain evolved its own unique solution to the problem. This fungus spread and diversified, because patients and crops, through agricultural trade, migrate.
In 2015, scientists discovered that the Candida auris genome had several genes of a superfamily (MFS). MFS effectively destroys broad classes of drugs. It permits C. auris to survive an onslaught of antifungal drugs. They also found that the C. auris genome also had many genes that increased its virulence.
Candida auris is not the only fungus on the cusp of multidrug resistance. There are many more which plants and humans are becoming resistant to.
One fungus, Aspergillus fumigates, causes infection in the lungs and is a major cause of mortality. Azole antifungals, itraconazole, voriconazole, and posaconazole, have long been used to treat pulmonary asperillogosis. In the last decade, it has developed a resistance to these drugs, causing the deaths of lakhs of people each year.
Studies comparing long-term azole users and patients just beginning to take the drug have shown that drug-resistant A. fumigatus was prevalent in both groups, suggesting that resistance came from the food they ate and the antifungals used in fields, rather than in the medicine they took. Agricultural, rather than medical reasons.
In many field studies scientists have found fungicide resistant A. fumigatus in the soil /crops across the world. In simple terms, due to agricultural practices, Aspergillus is entering hospitals already adapted to the slew of antifungal cocktails designed to check its spread. By using azoles to control fungi on fruit and grain, conditions have been created to accelerate drug resistance in human patients.
Aspergillusfumigatus and Candida auris share similar geographical distributions.
One would have thought that both these funguses would have been enough for governments to realise the acute danger its people were in and to phase out all fungicide.
But, instead, government policy has actively promoted the expansion of fungicide use.
Agricultural azole fungicides comprise a third of the total fungicide market. Twenty-five different forms of agricultural azole fungicides are being used in millions of tonnes, compared to just three forms of medical azoles. Fungicides use to control soyabean rust have quadrupled between 2002 to 2006; 30% of corn and wheat had fungicides applied in 2009 and now it is more than 50%. Boscalid fungicide is now commonly used in fruit and vegetables. As many as 33 different fungicides are used on potatoes.
Global sales have tripled since 2005, from $8 billion to $21 billion in 2017, expanding not only in sales but also in geographic distribution.
And, of course, all the fungicide leaches into the water, and you drink it.
Climate change brings heavy unseasonal rains and drought and higher temperatures. This means more funguses. And more fungicides. Unless the government finds a better organic way now.
Instead of blaming hospitals and hospital workers for contamination, we should be looking at agricultural bans of antibiotics and fungicides. Various Indian agriculture ministers, and prime ministers, have promised in Parliament to do so – but have done the exact opposite. As time goes on, companies will propose more genetically modified crops to, supposedly, combat funguses, and these will prove to be as deadly as GM Cotton and require even more deadly fungicides in time. As I see it, large chemical companies run governments and the world. And you and I are the victims.
There is so much empirical evidence that simply rotating crops and putting different crops together, like soya bean and flax, can greatly remove funguses. In California, strawberry producers have found that planting broccoli, between rotations of strawberry crops, removes fungus.
Scientists have discovered that instead of azole fungicides to control blight in potatoes, silica works much better.
Organic farming supports good fungi, which crowd out pathogenic fungi. Reducing chemical fertilizers and limiting tillage creates beneficial strains of fungi that form beneficial relationships with plant roots .Crop rotations, the incorporation of legumes, and the cultivation of soil aggregates, instead of burning, create good conditions for soil microbiota.
Leaving small wild areas also removes fungal depredation. For instance, a study done by University of Michigan and Vandemeer, on agroecological fungal control in coffee, found Mycodiplosis fly larvae, from nearby wild areas, feed on the coffee rust in Mexico and Puerto Rico.
What we are doing to our farmers is giving them absolutely the wrong information and tools – of which fungicides are one. Monocultures need fungicides and both cause disease. Agribusiness, and their governments, views nature as their enemy. So wiping out local ecologies and the benefits these offer in helping farmers enrich their soils, clean their water, pollinate their plants, feed their livestock, and control pests—pathogenic fungi among them—means the largest companies can now sell their poisons to a captive market. There must be some reason that our Indian governments refuse to train agricultural scientists, and are happy to have totally ignorant people working in Krishi Vigyan Kendras. Could it be a business plan? Financed not just by pesticide companies but by hospitals and the medical industry? Is there any difference between the rich and poor if both don’t have food safety?
Long before climate change finally does us in, it is catastrophic superbug outbreaks that are now killing millions. While data is available, it is rarely taken seriously by politicians. In the US, alone, 2 million illnesses and thousands of deaths are caused by drug resistant infections. In India it would be at least a crore, because we indiscriminately use medicines on animals grown for food and on crops. We need an intelligent far sighted humane government.
(To join the animal welfare movement contact gandhim@nic.in, www.peoplefor animalsindia.org)