The deadly spores that could be hiding in your home or garden
Originally published on the Daily Mail
As a pharmacist, Sandra Hicks doesn’t need anyone to spell out her predicament. For years now, an infection that has affected her lungs has become resistant to all the usual treatments.
‘At the moment I’m waiting to hear from my doctors what the next step of treatment will be — I just don’t know,’ says the 51-year-old. ‘Obviously, it’s an alarming situation to be in.’
The problem is not, as you might assume, antibiotic-resistant bacteria: Sandra’s infection is caused by a drug-resistant form of fungus.
The fungus, Aspergillus, is present in the air we breathe. For most of us it won’t cause problems, but in Sandra’s case it has led to the disease aspergillosis, which has been slowly causing permanent damage to her lungs.
Before the fungus hit, Sandra, from Verwood in Dorset, who was diagnosed in 2009, had lived life to the full. ‘I was very active,’ she says. ‘I’d walk my dog for miles, and played squash and badminton. Now I get so fatigued and breathless, I find it difficult to walk up a minor incline.’
With her fungal infection now resistant to the main antifungals (one stopped working after just nine weeks), Sandra is so debilitated that she can work only one day a week from home.
Worryingly, there are others in her position as strains of many potentially lethal fungi are rapidly evolving ways to render all drug treatments powerless against them. In the case of Candida auris, a common cause of serious infections, about 90 per cent of strains are resistant to at least one antifungal drug.
‘Drug-resistant fungal infections were almost non-existent in 2003,’ says David Denning, a professor of infectious diseases in global health at the University of Manchester, who runs the National Aspergillosis Centre in Manchester. ‘They now infect about one in five of our patients. We have dozens whose fungal infections we can’t treat. They remain very ill and sometimes they die. Last year, we lost 65 patients out of our total group of 500.’
A report in the journal Science last year described the threat fungi pose to humanity as ‘serious and immediate’.
Exact figures of the numbers infected are hard to come by, as fungi are biologically complex and identifying infections requires specifically targeted blood tests.
However, an assessment in the Journal Of Infection in 2017 by Professor Denning estimated that more than a quarter of a million adults and children in Britain may be infected with two forms alone: Candida auris, which is found in the air and soil, and causes serious infections typically in hospital patients, and Aspergillus fumigatus, which causes aspergillosis and tends to affect the lungs. Aspergillus fumigatus can form a grey, wrinkled cushion on damp walls or microscopic spores that blow through the air. More than a million people in Europe have lung disease caused by aspergillosis infection, says Professor Denning.
Only last week, a form of Aspergillus was implicated in an outbreak at the Royal Infirmary in Edinburgh, where six patients who’d undergone cardiothoracic surgery between March 2017 and November 2018 had developed an ‘unusual and difficult to treat’ fungal infection in their heart valves. Several died.
As well as Aspergillus, two other rarer types of fungi were implicated — Lichtheimia corymbifera (known to infect wounds) and Exophiala dermatitidis (a black yeast that can infect skin, lungs and other organs).
NHS Lothian has since written to 186 patients who had undergone aortic valve surgery at the hospital in the past six months to notify them of a ‘very low’ potential risk from mould infections. As symptoms can take up to six months to appear, patients are being advised to be vigilant.
FUNGUS DEATHS IN HOSPITAL
This follows news of lethal infections involving two other fungi, Mucoraceae and Cryptococcus, which made headlines in recent weeks for having led to the deaths of three patients at Queen Elizabeth University Hospital in Glasgow.
One, Mito Kaur, a 63-year-old grandmother, died on March 14 having been admitted with pneumonia in January. There she contracted mucormycosis, a fungal infection caused by exposure to mucor mould found in soil, plants and decaying fruit and vegetables.
The fungus caused Mrs Kaur’s brain to swell and her heart to become inflamed.
Mucor infections may be killed by the powerful intravenous drug amphotericin B, which breaks down fungal cell walls, but researchers warn that the fungus is becoming increasingly resistant even to this.
Another emerging fungal threat, Cryptococcus, was involved in the deaths of a ten-year-old boy and a 73-year-old woman in December at the same hospital. The fungus is believed to have been growing in pigeon droppings and spores spread through the hospital’s ventilation system.
Cryptococcus fungus can cause serious lung infections that can go on to cause cryptococcal meningitis, which is fatal in 80 per cent of cases.
Until recently, Cryptococcus threatened only people with weakened immune systems, and it has been a leading killer of people with Aids. But in January, a report in the journal Frontiers In Immunology warned that one strain, Cryptococcus gattii, ‘has recently emerged in North America and prefers to target individuals with healthily intact immunity’.
Meanwhile, researchers at McGill University Health Centre in Montreal, Canada, warn that Cryptococcus is becoming increasingly resistant to the few antifungal drugs that can be used against it.
THEY CAN TRAVEL FAST
Infectious fungi are spreading with alarming speed.
While Candida auris was only first identified in a patient in Japan in 2009, Public Health England now reports that there have been outbreaks of infections caused by this fungus in more than 20 NHS trusts and involving more than 200 patients.
In 2017, an outbreak at Oxford University Hospitals NHS Foundation Trust affected 76 intensive-care patients. An investigation discovered that it had been transmitted between patients on reusable thermometers, despite them being cleaned after use.
The fungus had evolved to withstand standard disinfection with ammonium wipes. Fortunately, all the patients survived.
Professor Adilia Warris, co-director at the Medical Research Council (MRC) Centre for Medical Mycology, says there are only three classes of antifungal drugs that doctors can use.
‘Half the Candida auris infections are resistant to two classes,’ she says. ‘There is even a substantial number now that are resistant to all three.
‘In some regions where it is particularly rife, such as Asia and South Africa, they have run out of options against these infections and patients can die as a result.’
We could, one day, face the same situation here. As it is, fungal infections are thought to kill more than half the people they infect, says Professor Denning.
‘Fungal infections can cause people to die from coughing up blood, from respiratory failure caused by all of the scarring on their lungs, or from simply becoming debilitated from the infection,’ he says. ‘It is a horrible way to go.’
An analysis of his patients with chronic aspergillus infection shows that those with the resistant form have a 250 per cent higher death rate.
Of the three available classes of antifungal drug, the most useful have been azole drugs such as clotrimazole and econazole, as they are the only ones that can be taken orally, and their side-effects — such as headache, nausea and stomach pain — are the least problematic.
The drugs interfere with fungal cell walls, causing the contents to leak out and the cells to die.
However, fungi such as aspergillus have become so widely resistant to azoles that the MRC says they are ‘not going to be useful any longer’.
Professor Denning says infectious fungi are also getting more resistant to amphotericin, which clinicians occasionally use as an emergency ‘salvage treatment’ (this strong intravenous drug has severe potential side-effects, including liver damage).
‘Last year, we found resistance to the other intravenous drug that we use, echinocandin,’ says Professor Denning. This was launched only eight years ago and had been hailed as a ray of hope in antifungal therapy.
Professor Denning says resistance is increasing due to human behaviour. Firstly, fungi mutate inside patients treated with antifungals and learn to beat them. The fungi often have plenty of time to do this, as chronic patients are put on drugs for months at a time, and often doses are insufficient.
‘A fungus can mutate to become immune to a drug if it is not exposed to enough of the therapy to kill it,’ Professor Denning explains. However, higher doses bring the threat of severe side-effects. The second reason that fungi become resistant is because fungicides are widely used on such crops as flowers and grapes. One third of all fungicide used contains a form of azole.
FARMING IS PARTLY TO BLAME
Exposure to low, non-lethal concentrations of azole means fungi are able to evolve resistance against it. When it is then used on infected patients, the fungi have already learned to defeat it.
In Denmark, where the number of patients with azole-resistant aspergillus infections has doubled in a decade, ministers said in March they are considering banning agricultural imports from the Netherlands, where the fungicide is used in growing tulip bulbs.
Professor Denning says the biggest problem is that the fungal threat ‘is not high enough in the public consciousness’.
The Government’s latest five-year national antimicrobial resistance action plan does not even mention fungi. And only 2.5 per cent of infectious disease research funding in the UK and U.S. has been spent investigating them.
Ensuring that patients get sufficient drug doses to kill the fungi before they learn to resist is another priority. ‘Patients must be routinely blood-tested to see that their drug levels are high enough,’ says Professor Denning. ‘Some people don’t absorb the drug well, while in others the drug’s power is reduced by interaction with other medicines they are taking.’
We also need far better diagnosis, he adds. ‘Yesterday, I saw a patient whose fungal infection had not been diagnosed for ten years, allowing their condition to worsen.’
Up to half of potentially lethal fungal infections go unnoticed, he warns. ‘Sometimes tests are not done, or the results not acted upon. What’s more, the fungi don’t grow very well in labs, so the GP has to instruct the lab actively to seek it out. But not enough doctors are talking about this.’
FUNGI SMARTER THAN BACTERIA
With early research suggesting that hidden fungal infections may be linked to Alzheimer’s disease, Crohn’s disease and other conditions, the impact of fungi could be greater than many might imagine.
With the threat growing, Professor Warris says another priority is to develop new medicines, including vaccines. Currently no antifungal vaccines exist.
In February, the Department of Health awarded £1.8 million to the Aberdeen-based drug company Novabiotics to develop a novel antifungal called Novamycin for killing Aspergillus fumigatus and Candida auris.
‘Combating them is complex because fungal cells are closely related to human cells,’ its chief executive, Dr Deborah O’Neill, told Good Health. ‘Fungi are cleverer than bacteria and they are structurally much more like us. This means there is a fine line between killing fungal cells and not killing human cells.’
But if all goes well, Dr O’Neill hopes to begin clinical trials with Novamycin in the next two years.
CATS COULD BE AT RISK
Meanwhile, new mutant fungal threats keep appearing. In February, researchers warned that Sporothrix brasiliensis, a previously obscure infection, is now rampant among cats and becoming transmitted lethally to humans through bites and scratches.
Dr Brendan Jackson, a medical officer with the U.S. Centres for Disease Control’s Mycotic Diseases Branch, told reporters that sporotrichosis had been an obscure disease in Brazil 20 years ago but now ‘they’re seeing tens of thousands of cases’.
One mercy is that we now have authoritative British experience in combating fungal infections in our hospitals. When Candida auris colonised 76 patients at Oxford University Hospital, the infectious diseases clinician David Eyre helped introduce emergency infection-control measures that both eradicated the outbreak and helped ensure no lives were lost.
But it took money. ‘We have had to replace reusable items such as thermometers with more costly single-use equipment,’ Dr Eyre told Good Health.
‘We also screened all the patients three times a week — though this is really nothing compared with the cost of having to shut hospital units or suffer from bad patient outcomes,’ he added.
Sandra Hicks, meanwhile, has now developed two serious bacterial infections that commonly co-exist with aspergillosis.
‘Not only is my aspergillosis not responding to antifungal treatment, one of these isn’t responding to the four different antibiotics I am on either,’ she says.
‘I focus a lot of the energy I do have on trying to raise awareness of fungal infections, which at the moment is so poor that even as a healthcare professional I didn’t realise the impact they can have on people’s lives. Now, of course, I know only too well.
‘I am hopeful that a new therapy will come along — not just for me but the many others who find themselves in a similarly unpleasant situation.’
Additional reporting Lucy Elkins
I'd tried so many drugs, options were running out
Retired sales manager Jean Jones, 72, almost died in 2014 after a fungal lung infection became resistant to treatment. Jean lives with husband Keith, 73, a retired panel beater, in Oldbury, in the West Midlands.
It was coming up to Christmas when the consultant told me there was every chance the fungus growing in my lungs might cause a fatal bleed.
I was very, very scared. By then, the fungus had become resistant to numerous drugs and it looked as if I’d run out of options.
I was diagnosed with aspergillosis in 2010, after a CT scan found a ball of fungi in my lungs. I was having one lung infection after another and had developed the most awful cough.
In 2011, I was started on the antifungal drug itraconazole but that didn’t work beyond a few months. The cough improved but I was coughing up blood once every couple of weeks and feeling exhausted. I could only walk 10 minutes round the block.
For two years I tried another drug, voriconazole, but this, too, soon stopped working and the bleeds became more and more frequent.
In 2013, I had two embolisations (using heat to seal blood vessels damaged by the fungi) to stop the bleeds but this didn’t work. I then had AmBisome, an intravenous antifungal treatment, but the fungus was resistant to this, too.
This is when I was warned that the threat of a fatal bleed was becoming very real.
I’d previously been told that surgery to remove the affected part of the lung wasn’t suitable — but with no drugs left that was my only option.
In 2014 they removed most of the left upper lung and part of the lower. Touch wood, I’ve not needed drug treatment since, and although I’m not bouncing around, I am much better than I was — for which I’m very grateful.