Every year, around 4,000 Britons will be hit by invasive aspergillosis, a severe fungal infection caused by a mould that can lurk in compost heaps, rotting leaves or even pillows and duvets.
Untreated, it is almost always fatal. Even when treatment is available, between a third and a half of patients will die within weeks – it is often spotted late, and usually occurs in patients whose immune systems are damaged and cannot help drugs fight the infection. Sometimes the Aspergillus mould that causes the infection is resistant to treatment.
Little wonder, then, that patients and doctors are excited about the arrival of a new medication, which has been decades in the making.
But there are also fears that pesticides used in farming to fight fungi create ‘superfungi’ that are resilient to medicine – rendering the drugs ineffective before they even hit shelves.
The drug, Olorofim, targets an enzyme that moulds need to grow and replicate. In a trial it worked as well as current drugs but with half the side-effects.
Following those results, the manufacturer is preparing submissions for medical regulators. If approved, Olorofim will be the first new treatment in over 20 years for invasive aspergillosis, a condition where Aspergillus mould spreads into lungs and other organs.
‘We desperately need new treatments, particularly for patients whose infections are resistant to existing drugs or who cannot tolerate them,’ says Lisa McNeil, chair of the Aspergillosis Trust. ‘Having another option can mean hope when existing treatments are limited.’
Lindsey Collins, 38, is one of them. She was diagnosed with an invasive aspergillosis infection in her brain shortly after giving birth to her son, Noah, in 2020.
Lindsey Collins, 38, was diagnosed with an invasive aspergillosis infection in her brain, which led to a series of strokes and a cardiac arrest
She’d had an emergency caesarean after developing pre-eclampsia (dangerously high blood pressure in pregnancy) alongside a chest infection.
After the delivery, she was put in an induced coma to help her body fight the infection – but had a series of strokes and a cardiac arrest.
As Lindsey recovered, a scan revealed masses in her lungs and on her brain, eventually diagnosed (following a biopsy) as Aspergillus fungi. The strokes left her temporarily paralysed.
‘I had to learn how to walk again. By the time I finally got to hold Noah for the first time he was nine weeks old,’ Lindsey recalls. ‘The journey through it was very, very hard – and now I had this other thing on top of it.’
But it was only three years later that she learned how bleak her prognosis really was. ‘The doctor said, “You have up to five years, and we’ll be kind of lucky if we can push it after that”,’ she says.
Now nearing six years since her diagnosis, the conversation hangs over Lindsey, a single mum who lives with her parents in Cork, Ireland.
‘I’m not ready to go,’ she says. ‘But I have prepared for Noah. I got him books on how to understand that I was gone, and where I had gone. I’ve tried to get things in order, but it’s so hard.’
Lindsey has had chronic chest infections for the past six years.
She says: ‘I can’t help but wonder every morning, is this my last day? Will I see Christmas, and the joy it brings Noah?’ she asks.
Her symptoms, such as poor memory and extreme fatigue, meant she had to give up her job as a carer for adults with disabilities. She says: ‘Before I was pregnant with Noah, I was such an active person. I was constantly out. I was working 12-hour shifts.’
Thanks to treatment with potent antifungals, some of the masses on her brain have shrunk – but a large mass at the front of it remains. So the prospect of an alternative drug becoming available is ‘fantastic’, says Lindsey.
The potential problem with Olorofim is that a fungicide called ipflufenoquin, used on crops, targets the same enzyme. When fungus is exposed to an antifungal drug or a fungicide, it gives that fungus the chance to develop resistance to the chemical.
‘The fungus that we get infected with typically comes from the environment – it lives on grasses, soil and things like that,’ says Professor Rebecca Drummond, a specialist in fungal immunology at the University of Birmingham.
‘If they are picking up drug resistance in the environment, then before your patient has even been given a medication, they can be infected with a drug-resistant strain.’
The threat is not purely theoretical, but has played out before with other antifungal drugs known as azoles – one of the most widely used because they are cheap, can be given in various formulations including orally and work against a variety of fungi (Lindsey is being treated with an azole, Cresemba).
A scan of Aspergillus fungi. The mould can lurk in compost heaps, rotting leaves or even pillows and duvets
Lindsey’s symptoms, such as poor memory and extreme fatigue, meant she had to give up her job as a carer for adults with disabilities. She has had chronic chest infections for the past six years
Already, Professor Drummond says, there is ‘quite good evidence that some of the drug-resistant infections that we see in patients [were] acquired in the environment because of agricultural use of antifungal drugs’.
Indeed, resistance to azoles used in farming to protect cereal crops from Aspergillus is a growing problem.
And a study published in the journal Nature Microbiology in 2024 showed that exposing Aspergillus mould to ipflufenoquin led to the development of strains resistant to Olorofim.
David Denning, a professor of infectious diseases in global health at The University of Manchester, who founded the company behind Olorofim, says being faced with a patient whose fungal infection cannot be cured with existing drugs is ‘awful’.
‘There’s the invasive ones, which kill people in the space of a week or two – and then there’s the chronic ones, which just get worse and worse over weeks or months,’ he says. ‘Both of those situations are dire. I’ve seen many patients who have died due to resistant fungi who could have been saved if we had new drugs.’
Most people breathe in hundreds or thousands of Aspergillus spores daily with no ill-effects, he adds – ‘just living your life, walking around, going to bed with a bit of Aspergillus in your pillow and the duvet [where they thrive in the moist, warm conditions] – we are all exposed to this’.
But if someone’s immune system is weakened, such as cancer patients, or they have a lung condition such as cystic fibrosis or chronic obstructive pulmonary disease then they are particularly vulnerable.
Lindsey does not know how or where she picked up the fungal infection, although she fears that renovations in hospital while she was an inpatient might have released spores into the air.
Drug-resistant fungal infections in general are an increasing concern. For example, Candida auris is resistant to many drugs and has caused outbreaks in hospitals globally, including in the UK.
When it comes to antifungal drugs, ‘we don’t have a huge number of options’, says Darius Armstrong-James, a professor of infectious diseases and medical mycology at Imperial College London. ‘If a new one becomes available, then we want to do everything we can to preserve it.’
But it is not as simple as banning fungicides. Globally, some 10 to 23 per cent of crops are lost to fungal infections each year.
‘What we’re talking about is the balance between food security by protecting crops against preserving critical drugs for human use,’ says Professor Armstrong-James.
He was one of 130 experts who wrote to a parliamentary inquiry on antimicrobial resistance last year warning that the UK was ‘lagging behind’ other countries which had specific frameworks in place to assess those risks.
Ipflufenoquin is used on crops such as apples, pears and almonds in Canada, Australia, US and Japan, with EU approval pending. While it’s not used in the UK, Professor Denning believes it ‘very likely’ that resistant fungi would find their way here.
‘There’s a need to protect food resources – the challenge is that many of these fungicides are used in specialised crops,’ he says. ‘You wonder what the equation is, with almonds or almond milk, versus patients who are dying of untreatable fungal infections.’
Separately, Lindsey worries that illnesses in pregnant women are overlooked – she felt her chest infection was dismissed. ‘I’m sure that if I didn’t have the complications I had, this [fungal infection] would have been avoided.
‘People who work in healthcare should always have awareness, understanding and patience.’
Meanwhile, she takes much delight in seeing her ‘caring and lovable’ son flourish, adding: ‘I would like very much to see the man Noah grows up to be.’
