£250m antifungal drug at risk from US crop spraying, experts warn

Crop spraying in the United States could make a £250 million antifungal drug ineffective before it even reaches the market, experts have warned.

Researchers at the University of Manchester have raised the alarm over the future of Olorofim, a novel treatment for fungal infections that took 20 years to develop.

Scientists hope it can be used to treat drug-resistant infections which kill millions of people around the world each year, but say its effectiveness is being undermined by US agricultural practices.

In particular, research in Nature Microbiology found efforts to tackle the Aspergillus fungus – a common mould which causes aspergillosis, a lung condition – are at risk.

There are a limited number of treatments for Aspergillus, and drug-resistant strains of the fungi are twice as likely to kill you.

When the fungus is exposed to a new agricultural fungicide, ipflufenoquin, it can also become resistant to Olorofim.

This is because Olorofim kills Aspergillus fungus in the same way as ipflufenoquib. It targets an enzyme that the fungus uses to create new DNA, which is essential for making new cells.

“Olorofim was identified in the early 2000s but it wasn’t until about three years ago that we became aware that ipflufenoquin was being developed,” said Professor Micheal Bromley, Lecturer in Drug Discovery at the Manchester Fungal Infection Group.

“I​t’s being sprayed, as we speak, in the US to treat fungal infections of pome fruits [apples and pears] and almonds,” he told The Telegraph.

“The worry is that we’re going to see a lot more resistance, more people are going to die.”

The World Health Organization (WHO) warned last week that the world remains vulnerable to fungal infections, with a lack of effective treatments partly to blame.

Creating new drugs to kill fungi is also difficult because their cells are biologically so similar to ours, making it hard to find treatments which are not also toxic for humans.

Currently, doctors treating aspergillosis mostly use a family of antifungal drugs called azoles, but resistance to them has grown because they are also used extensively in agriculture.

“The use of azole fungicides has driven the emergence of resistance to antifungals we use in clinics,” said Prof Bromley.

Professor David Denning, fungal disease researcher at the University of Manchester, added: “[Resistance] was first described in Holland in 1995 and has been found in almost all parts of the world since then.”

Experts hope that Olorofim could soon be used to treat fungi which are resistant to azole drugs but there are concerns that the same resistance pattern could be repeated.

As with antibiotics, controlling the use of fungicides in agriculture is seen as key to fending off the rising threat of antimicrobial resistance (AMR).

And just as antibiotics are used to keep animals healthy, fungicides are an important tool in maintaining crops and food production.

“The farmers don’t use fungicides just for fun,” said Prof Bromley. “They’re doing it to prevent damage to crops. And that damage to crops can actually reduce yields very, very significantly.”

Experts are now calling for a better balance to how fungicides are used in order to preserve the benefits in advancements of antifungal treatments while allowing agriculture to keep up with demand.

“There needs to be a much more nuanced approach than just saying food or medicine: It’s which foods and which crops,” said Prof Denning.

“ We do need rice, we do need potatoes, we need wheat. Those are very important crops,” he added. “The others are economic issues. Are we better off having more and nicer strawberries or, are we better off not having that and maintaining a drug that’s useful for human health?”

Prof Bromley said: “What we’re calling for is that before any new fungicides are approved, there has to be a proper risk assessment carried out to see what the potential is.”

Prof Bromley doesn’t think that Aspergillus fumigatus will evolve to become a risk to healthy people – the fungus is likely to remain a problem for only a limited number of patients who are immunocompromised and become infected with the invasive pathogen. 

But, he is concerned about the pattern of fungal evolution. 

“What this does show us is that there’s a problem in the environment where there are fungicides, and those fungicides can drive resistance,” he said.

“There could be other fungi that experience the same selective pressures as Aspergillus fumigatus but are much more pathogenic. So the worry is that as our climate changes and new fungi come into our environments, that there may be that superbug that causes a bigger problem.”

Professor Denning is equally sceptical: “ The problem is, once the the genie is out of the box, you can’t really put it back.”

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