A deadly and potentially incurable disease that strikes at people with weakened immune systems has quietly emerged. The culprit is a fungus called Candida auris (C. auris), which has been added to the Center for Disease Control and Prevention’s list of organisms deemed “urgent threats”—and its appearance may be linked to agricultural fungicides.
Some of these fungicides are used in viticulture. Experts are divided on how easily they can be replaced.
What’s the problem?
According to The New York Times, which broke the story, C. auris is a drug-resistant infection so persistent that once it’s present, hospitals must use special cleaning equipment, and even rip out ceiling and floor tiles to get rid of it. Many of those infected with the fungus—typically those already vulnerable due to compromised immune systems or other issues—have died.
The parallel problem of antibiotic resistant ‘superbugs’ is already well known. “The global problem of antibiotic resistance is fast becoming one of the major scientific issues of modern times,” says the introduction to the Longitude Prize, an award that challenges scientists to develop ways of tackling antibiotic (or antimicrobial) resistance. “The development of new antibiotics is slow and difficult work, but bacterial resistance is ... posing a catastrophic threat as ordinary infections become untreatable.”
The emergence of drug-resistant fungal infections such as C. auris is more recent and not well recognized. This adds “a new and frightening dimension to a phenomenon that is undermining a pillar of modern medicine,” according to the Times report.
“Some scientists cite evidence that rampant use of fungicides on crops is contributing to the surge in drug-resistant fungi infecting humans,” the article continued. Disturbingly, the drug-resistant strain of C. auris didn’t emerge in one place, but in several, with outbreaks in Japan, the UK, Spain, the USA, Venezuela, India, Pakistan and South Africa. These outbreaks have happened within the last five years.
The role of fungicides
One of the earliest encounters with C. auris, said the Times, was its appearance in the lab of Dr Jacques Meis, in the Netherlands. “Dr Meis, the Dutch researcher, said he believed that drug-resistant fungi were developing thanks to heavy use of fungicides on crops.” The drug normally used to treat some fungal infections in humans is itraconazole, “a virtual copy of the azole pesticides that are used to dust crops the world over.”
In other words, as the article’s authors said, “Azoles have created an environment so hostile that the fungi are evolving, with resistant strains surviving.”
These fungicides are used across many agricultural crops, such as wheat. Meininger’s asked a range of experts whether azole fungicides are used in viticulture and, if so, what possible substitutes exist.
“There are eight triazole fungicides approved by the Australian regulator (the APVMA) for use in viticulture,” said Marcel Essling, senior viticulturist at the Australian Wine Research Institute in Australia, via email. “They are primarily used against powdery mildew; however, one is also part of a mixture registered to control both botrytis bunch rot and downy mildew. It is the AWRI’s understanding that triazole fungicides are also used in other wine-producing countries.”
Researchers in France, one of the world’s leading wine producers, meanwhile confirmed that azoles are used in vineyards there.
Research director at INRA, the country’s national agricultural research body, Marie-France Corio-Costet, said they are mainly used against oidium and black rot. But applications appear to have peaked in the years 1978 to 2000. The drop-off since then, she said, is mainly due to developing resistance in the oidium fungus.
Many members of the azole family of treatments are now banned in France, including flusilazole. More face the same fate in the next European and national reviews, according to Corio-Costet, mainly because they are potential endocrine disrupters. This means they may risk causing cancers, birth defects and other developmental disorders by affecting the body’s hormonal system.
In terms of possible replacements, said Laurent Deliere, INRA agricultural engineer, they already exist, mainly because of resistance that has developed in the last 30 to 40 years. This meant other treatment options had to be developed both to treat attacks, and to reduce further resistance risks, by alternating active molecules. Substitutes, he said, include strobilurin, SDHI, and other fungicides. Sulphur can also be used, “so it would not be impossible to replace,” he said. Alternatives for black rot include mancozeb and strobilurin, while organic winegrowers use a mix of sulphur and copper – although that will not, of course, fix the underlying problem of resistance, Deliere said.
Chemical producer BASF France, which does not currently supply any azoles to European wine producers, was less sanguine about replacements. In an email a spokesperson described azoles as “antifungal agents of high importance” in the medical, veterinary and agricultural sectors.
Azoles, they warned, “are the backbone of disease control in food and feed production and an essential part of fungicide-resistance management.” They went on to describe the agents as “a powerful and unique class of chemistry with strong efficacy against powdery mildew and black rot in grapes” for which they see “no easy replacement”. BASF’s current approach is to take “the issue of resistance development of fungi towards azoles very seriously” and to work on mitigating it via management programmes and research.
Asked his view, the director of French anti-pesticide lobby, Générations Futures, François Veillerette, said in an email they had already seen the Dutch studies on this subject. “The hypothesis that the apparition of medical resistance to the azole family of fungicides is connected to the very high use of agricultural fungicides of the same family seems solid...and worrying!”
Veillerette also named some examples of authorized French viticulture products that contain azoles: cyproconazole (found in a product called Phytopast); fenbuconazole (found in Ecrin Pro); penconazole ( Topaze); tetraconazole (Antene); tebuconazole (Abilis).
The implications of the Times report, both for agriculture and for human health, are disturbing. Wine producers who want to know more are advised to contact advisors from their local chamber of agriculture or wine council.
Sophie Kevany and Felicity Carter