A new swathe of vital drugs have stopped working

The world’s medical experts are terrified at the way antibiotics are rapidly becoming useless. Now...

JOHN Phillips has a simple phrase that perfectly describes his terrible predicament: ‘I’m in limbo.’ The 54-year-old father of two is currently enjoying reasonable health, able to pursue his career as an NHS worker and live life as best he can.

But deep inside his lungs lurks an infection so dangerous that it regularly sends

him spiralling into poor health. He suffers bouts of coughing and breathlessness so debilitating that he is left housebound and gasping for air after simply walking up the stairs. Worse still, there are no drugs to treat it and doctors admit they are unable to cure him. John lives under the threat that his condition could become life-threatening. It’s a message that a growing number of Britons are also hearing.

‘It feels like you need to take a deep breath but you can’t,’ admits John, who

lives in Derby with his wife and family. ‘Any exertion can leave me gasping and coughing, as if I’ve just run a sprint. All you can do is sit still, try to stay calm and hope it passes.’

John’s disease – aspergillosis – is caused by inhaling tiny spores of aspergillus mould, which then take hold and grow in the lungs, triggering allergic reactions and inflammation.

Normally, antifungal medication would tackle the problem. But the spores that have invaded his lungs have become immune to these pills.

So, at the moment, John’s only option is treatment to dampen the worst symptoms and ease his breathing. There is a high risk that the mould could grow into a tumour-like lump in his lungs, or the spores could invade his blood, triggering deadly complications.

It means John, and thousands like him with the same untreatable infection, live in fear that one more severe flare-up could be fatal.

‘I’ve not had an attack for the past month or so, but I was in hospital with it at the beginning of the year and I don’t know when it’s going to happen again,’ he says. ‘There is nothing my doctors or I can do to stop it. It’s an odd feeling, to know that no drugs can help me. I’m just waiting for the next dip, and then I don’t know what will happen.’

A CRISIS THAT COULD HIT TEN MILLION PEOPLE

MOST people know about the dangers posed by bacterial superbugs such as MRSA and Clostridium difficile that can shrug off attacks from antibiotics. But there is a newly emerging threat: treatment-resistant fungal infections.

Such is the concern, experts have warned that the ‘global collapse’ of antifungal drugs could spread disease – and threaten food crops – around the world.

The looming crisis is comparable to the socalled antibiotic apocalypse but is ‘under-recognised and under-appreciated’, according to the authors of a recent paper published in the journal Science. ‘The world is in the midst of an unprecedented rise of fungi strains that can’t be tackled with common drugs, they said.

‘It is an enormous problem,’ says Matthew Fisher, a professor of fungal epidemiology at Imperial College London, who was a co-author of a recent scientific review on the rise of resistant fungi.

Fungal spores are microscopic organisms that exist all around us. They are in the air we breathe and on our skin, in the soil, on our food and living in our digestive systems. There are millions of types, and in the main they pose little danger because our immune system simply keeps them in check.

But occasionally the equilibrium is thrown out of balance – due to injury, illness or for other reasons, and then these microbes can grow out of control, invading the body’s tissues, and causing damage, inflammation and pain.

Fungal infections affect millions of Britons each year and can be mild. For instance, athlete’s foot – painful, cracked skin between the toes – and vaginal and oral thrush are all caused by overgrowth of yeast, which is a fungus.

Antifungal drugs, which are used to rein in these infections, are among the most commonly used over-the-counter medications. At present, there are no concerns about the effectiveness of these. However, other fungal infections can be life-threatening, invading the lungs, blood, heart, brain, eyes and bones.

Experts say the threat of medications used to fight these problems becoming useless is an impending public health disaster.

Currently, those with lung diseases, a weakened immune system due to cancer treatment or transplant surgery, the elderly, and newborns are most at risk.

At best, infection will mean severe symptoms and more time in hospital. At worst, there is an increased risk of early death.

And if new ways to combat the spread of these infections aren’t developed, some scientists fear the risk will spread to healthier populations.

One UK study predicts that if policies are not put in place to slow the rise of drug resistance – both antibiotic and antifungal – then ten million people could die worldwide of all such infections in 2050, eclipsing the eight million expected to die that year from cancer.

ASTHMA SUFFERERS ARE AT HIGH RISK

THOSE with asthma – the incurable lung condition that affects 5.4million Britons, including a million children – are particularly vulnerable to fungal infections in the lungs. And John Phillips is one of them. Diagnosed with asthma aged four, he has relied on inhalers for much of his life. These drugs work by relaxing the muscles of the respiratory system that go into spasm.

However, like the 650,000 or so Britons who have severe asthma, he also suffers from recurrent fungal lung infections. Over the years, he has had to rely on antifungal drugs to help eliminate them.

Aspergillosis is caused by one of the most common fungal spores to infect the lungs: aspergillus fumigatus. This mould is widespread in the environment, thriving in soil, flowerbeds and in decaying plant matter, especially compost heaps. Most of us breathe in the tiny spores every day and are unaffected. But in some asthmatics, especially those with the most severe forms, the fungus takes hold, leading to breathlessness, chest pain, extreme fatigue and fever. Often, those affected suffer recurrent infections.

But, alarmingly, some strains of the fungus seem to have become immune to even the most powerful drugs – known as azoles – that once used to kill it off. It is unclear just how many Britons are infected but studies suggest the numbers could already be shockingly high.

One London heart and lung ward found that one in ten patients had azole-resistant aspergillosis.

Another study suggested a quarter of patients admitted to an intensive care unit in the Netherlands had tested positive.

‘I WAS FEVERISH AND STRUGGLED TO BREATHE’

THERE is a drug, amphotericin B, that seems to work where azoles fail. But, frustratingly, the side effects are so severe that the majority of asthma patients – including John – can’t take it. He was first told he had aspergillosis in 2011. ‘My asthma symptoms were getting harder to control,’ he recalls. ‘I was on high doses of steroids, which are given to reduce inflammation in the airways when normal inhalers don’t seem to be working. They have horrible side effects – they damage the bones if you take high doses long-term. In my case, they made my face very puffy and I couldn’t sleep.’

He was put on daily azole tablets, which helped at first. But in 2017, his symptoms began to worsen. ‘I was struggling to breathe all the time, and feverish,’ he says. ‘This time, tests showed the fungal spores in the lungs were drugresistant, which was pretty scary.’

Amphotericin B made his asthma worse, so he is now on steroids again. ‘It’s a case of waiting and hoping for the best.’

Professor David Denning, of Manchester University and director of the National Aspergillus Centre, says: ‘Steroids often don’t control asthma very well, which means constant coughing, not sleeping and not being able to walk very far.

‘For a minority of patients, there is also a greater risk of a fatal asthma attack.’

In fact, oral steroids could make the problem worse, according to a study by another Manchester University team last year. It found severe asthmatics were ten times more likely to have higher levels of mould spores in their lungs when they were taking steroids, something researchers warned most doctors would be unaware of.

‘This is a problem for patients with low immune defences due to cancer treatment, transplant operations, chronic obstructive pulmonary disease and immune system illnesses including AIDS,’ says Prof Fisher. ‘Those with severe influenza are also at risk.’

Some 2,900 patients a year get this potentially deadly form of aspergillosis in the UK. The condition is fatal in between 30 and 70 per cent of cases, depending on the patient group. Those with drugresistant disease have a bleak prognosis: just five per cent survive.

OUTBREAKS IN BRITISH HOSPITALS SINCE 2013

ASPERGILLOSIS is not the only fungal threat causing concern among scientists. Some species of candida yeasts live in the body and on our skin without causing problems, although they can cause thrush and other skin infections if they multiply.

In the past decade however, one species, Candida auris, has become resistant to multiple antifungals.

Since the first reports of infections in Japan in 2009, there have been hospital outbreaks reported in South Africa, India, South American, and the United States.

This has puzzled scientists as fungi are not known to spread directly from person to person in hospitals like bacterial superbugs.

Equally worrying, these new, tougher Candida auris seem resistant to normal cleaning methods.

And, in 2013 the first infections were recorded in the UK. Drugresistant strains have so far been detected in 266 patients at 25 hospitals. In three-quarters of these cases, the patients had the fungus on their skin but did not have symptoms. But 32 had a potentially fatal bloodstream infection.

The worst outbreak was at the Royal Brompton in London, which had 72 cases, and the hospital had to shut its intensive care unit for 11 days.

Public Health England says 13 per cent of those diagnosed with it in the UK have died within 30 days. However, it adds that because these patients were already ill in intensive care units when they became infected, it is difficult to know whether they were killed by the infection or other conditions.

An outbreak at a hospital in Valencia, Spain, saw 41 patients develop bloodstream infections. Seventeen of them died within 30 days.

‘The risk [in the UK] is from patients, probably coming from abroad, bringing the fungus with them,’ says Prof Denning.

FARMING AND FLOWERS COULD BE TO BLAME

AS yet, there is no definitive answer to why fungal diseases become drug-resistant. But fungi, just like bacteria, are evolving defences to survive modern medicines.

The same class of drugs used to treat fungal infections, azoles, are used in farming to spray crops and protect them from rotting. Some experts blame their overuse in agriculture for the rise of superfungi. Others suggest the high levels of fungicide use in the flower bulb industry could be significant after studies found resistant fungal strains in London flowerbeds.

Scientists recognise farmers need to use fungicides, but believe their use could be reduced.

There is an urgent need for new antifungal drugs, and improved hospital diagnosis systems would lead to patients receiving the best treatment more quickly.

Prof Denning is optimistic that new drugs will be found but warns: ‘There may be a period before those drugs are available when infections will be difficult to contain. And during that time we will have more patients who become chronically ill or die.’