20.04.2024

Diseases from ringworm to deadly lung disease are becoming untreatable

An old infectious foe is returning with a vengeance: it’s called ringworm. Despite the name, it is not a worm but a contagious skin fungus that can disfigure — and it has learnt how to defeat our best medicines.

Doctors are reporting multiple cases of drug-resistant infections — which cause large, itchy red rashes and are spread by ‘intimate contact’ — across the UK.

More worrying still, Good Health can reveal that this resurgent ringworm is only the latest in a growing series of fungal infections to emerge with drug-resistant powers — and some can be lethal.

Despite ringworm’s reputation as a scalp disease of Victorian slum-dwellers, it is a common fungal infection today, estimated to affect between 10 and 20 per cent of the population, mainly children. While very contagious, it has been regarded as benign.

Yet the infection sparked global alarm last month when doctors in the U.S. reported that two women, aged 28 and 47, in New York had been diagnosed with a worrying new drug-resistant strain called Trichophyton indotineae; the first known cases in the country.

Jill Fairweather (pictured), a 66-year-old from Maidenhead, in Berkshire, has lived with an aspergillus lung infection for more than four decades

Now UK experts have told Good Health that there are multiple patients suffering with the same drug-resistant strain of ringworm here.

There have been at least 40 new cases of the drug-resistant ringworm diagnosed in UK hospitals, a spokesman for the UK Health Security Agency (UKHSA) told Good Health, adding: ‘these are predominantly in the London area’. However, the number could be significantly higher, partly because there is no mandatory, official reporting system for the infection.

Dr Alireza Abdolrasouli, a clinical scientist in medical mycology [the study of fungal infections] at King’s College Hospital, London, told Good Health: ‘There are multiple cases of Trichophyton indotineae across London and the UK.

‘The infection primarily affects the body, including the trunk, groin and buttock areas and is mostly transmitted by direct skin-to-skin contact. Such skin infections can be chronic and disfiguring and cause affected people psychological distress.’

Crucially, Dr Abdolrasouli warns: ‘This infection is resistant to the antifungal drug terbinafine [the first-line NHS medication] and is difficult to treat.’

Similar cases have been reported by Dr Richard Barton, the principal clinical scientist in mycology at the Leeds Teaching Hospitals NHS Trust. ‘I’m aware of seven cases of Trichophyton indotineae in the Leeds area,’ he told Good Health. ‘Most of the cases I’ve seen are from GPs.

‘If a patient’s infection is resistant to terbinafine, then testing usually shows us that it is susceptible to [another antifungal] itraconazole.’

However, he adds: ‘We have found that even after treatment with itraconazole, the infection can come back again’. This suggests some resistance to some of our best antifungal meds.

‘If we increase the itraconazole dose, we may get side-effects such as gastrointestinal upsets, rashes and liver-function problems. Yet we don’t have many other drug options.’

An old infectious foe is returning with a vengeance: it's called ringworm. Despite the name, it is not a worm but a contagious skin fungus that can disfigure ¿ and it has learnt how to defeat our best medicines

An old infectious foe is returning with a vengeance: it’s called ringworm. Despite the name, it is not a worm but a contagious skin fungus that can disfigure — and it has learnt how to defeat our best medicines

For patients, he says, ‘the worst-case scenario is that the skin infection persists and causes disfiguring and itchy lesions’.

It can also spread and ‘sometimes there is a lot of skin area affected, including the groin,’ he adds.

‘Most of the treatment-resistant ringworm infections we’ve seen have involved a link to travel from countries such as India or the Far East, but not all, so there is probably some spread within the UK.’

And thanks to its infectiousness, ‘we will probably see more of this’, adds Dr Barton.

The news of ringworm’s treatment resistance comes in the wake of increasing cases of treatment-resistant athlete’s foot.

Athlete’s foot can become ‘untreatable’ even with the strongest over-the-counter creams, due to the rise of drug-resistant strains of the fungus Trichophyton rubrum, which most commonly causes the skin infection, it was reported last month.

Previously, one application of the antifungal terbinafine (found in most over-the-counter creams) was sufficient to clear athlete’s foot infections — but now around a third of NHS patients need to use multiple doses, experts say.

If it becomes untreatable, then patients would have to stay on antifungal medications almost continuously to keep their infections under control: even then, the infection might not respond and could get worse (In the case of athlete’s foot, it can affect the toenails — which may thicken, become discoloured or crumble — and even spread to your hands or groin. Athlete’s foot can also make you more vulnerable to bacterial infections, such as cellulitis.)

It’s not just fungal skin infections that are becoming resistant to available treatments. The same resistance is being seen with potentially lethal fungal infections caused by Aspergillus fumigatus, which targets our airways, and Candida auris, which affects the blood.

Aspergillus fumigatus is found widely in the air, soil, food and in decaying organic material such as garden compost.

It spreads via microscopic airborne spores and primarily infects the lungs, where it can cause life-threatening chronic pulmonary aspergillosis — this kills around 60 per cent of those affected.

Candida auris can live on our skin and on hospital and domestic surfaces — but it can enter the bloodstream and spread through the body, killing 30 to 60 per cent of infected people.

Both of these are ‘opportunistic’ fungi, meaning they prey on people with vulnerable immune systems who can’t fight them off.

At the height of the pandemic, for example, researchers at Exeter University warned that as many as a third of patients with severe Covid-19 who were admitted to intensive care became infected with Aspergillus fumigatus.

And in 2019, evidence published in the journal Lancet Respiratory Medicine revealed how aspergillus had evolved into a super-fungus that could afflict otherwise healthy people with viral infections, particularly flu.

One patient in five with severe flu in intensive care gets infected with aspergillus, with the same proportion of immunocompromised people affected, says Darius Armstrong-James, a professor of infectious diseases and medical mycology at Imperial College London. Also, he adds, ‘up to 10 per cent of severe asthma sufferers get aspergillosis’.

The fungus Trichophyton rubrum causes ringworm. the high number of cases of Trichophyton indotineae appearing in India 'probably relate to a lack of drug regulation there'

The fungus Trichophyton rubrum causes ringworm. the high number of cases of Trichophyton indotineae appearing in India ‘probably relate to a lack of drug regulation there’

And increasing resistance to drugs is a significant part of the reason why the five-year mortality rate for chronic pulmonary aspergillosis is so high, with around 60 per cent of patients dying, he says.

What’s more, the problem threatens to worsen.

‘We’re definitely seeing an increase in fungal infections,’ says Professor Armstrong-James.

And with that inevitably comes an increase in drug-resistant infections (the more antifungals are used, the greater the chance of fungi becoming resistant to them).

‘The Netherlands has 25 per cent resistance to antifungal drugs,’ says Professor Armstrong-James. ‘We’re not yet as high as that, but if things don’t change we’ll be in the same situation.

‘At the moment, with the best aspergillosis medication we’re looking at a 50 per cent response rate.’

For some patients, aspergillosis treatment becomes a gruelling cycle of trips to hospital for intravenous infusions of strong antifungal drugs.

This is the prospect that faces Jill Fairweather, a 66-year-old from Maidenhead, in Berkshire, who has lived with an aspergillus lung infection for more than four decades.

‘I’m having a rough time at the moment,’ Jill told Good Health.

‘Aspergillosis is a horrible condition where you cough up blood and you sound like you smoke 40 a day.’

Jill had suffered with severe asthma since she was four; her mother was diagnosed with chronic pulmonary aspergillosis when Jill was 17.

‘They say it’s not hereditary, but my mother told the doctors that my asthma had become uncontrollable and perhaps I had the condition too,’ says Jill.

Her mother died shortly afterwards, in her 50s. Jill was put on the steroid drug prednisolone to calm her lungs’ inflammatory reaction to the aspergillus.

‘Steroids made me balloon in weight,’ she says. ‘I went from a size 8 to a size 16, which was horribly stressful.’

At the end of the 1980s, she was taken off steroids when a new antifungal drug, itraconazole, appeared. It works by slowing the growth of fungi that cause infection. ‘My body couldn’t tolerate it,’ she says. ‘The drug put dangerous pressure on my heart [a rare side-effect] and made my ankles swell.’

Instead, Jill had to stay on large doses of steroids, which caused her to develop type 2 diabetes (a recognised side-effect) but which ‘kept me alive until finally I was put on a new drug called Fungizone in 2014 — which worked wonders,’ she says. It also helped her lose weight, as she stopped taking steroids.

Fungizone works by interfering with the membranes of the fungus cells. ‘Then last year the Fungizone stopped working,’ says Jill. ‘The infection seems to have become resistant to the drug.

‘Hospital scans showed that I had started to develop aspergillomas — fungal balls — in my lungs.’

These occur as the fungus multiplies inside the lung, forming a ball-shaped clump which incorporates dead tissue from the surrounding lung, mucus and other debris.

UK figures suggest that the chances of a patient diagnosed with an aspergilloma dying within the next five years is between 50 and 85 per cent.

Doctors then tried to treat Jill’s resistant infection with antifungal posaconazole tablets, which work by preventing fungi producing a substance called ergosterol, a component of the cell membranes.

‘However, I had another lung scan which showed the fungal balls have only got bigger and thus apparently developed resistance to a new drug again,’ says Jill.

Now she has been told she will have to go regularly into hospital for intravenous infusions of Caspofungin, one of a new class of antifungals, echinocandins, that also attack fungal cell walls.

Jill says: ‘I had one course last year. I had to stay in hospital for more than two weeks.

‘I had six months of feeling quite good, but in February my breathing worsened again. My lung scans show the disease has progressed again. It looks as though I will have to go into hospital for three weeks every three months for more Caspofungin treatment.

‘I’m not looking forward to it. And if that treatment stops working, I’ve run out of options.’ Nevertheless, she adds: ‘I try to keep positive. My husband Martin helps when I’m struggling to cope with daily life.’

In 2018, Jill co-founded the Aspergillosis Trust, a charity that runs an online support group for patients and their relatives. ‘Running the charity helps me to keep going,’ says Jill.

Scientists are trying to fathom what is driving fungi to become more infectious and to resist our best medicines.

Dr Rebecca Drummond, a fungal immunologist at Birmingham University, says global warming seems one likely culprit. ‘Climate change already seems to have affected Candida auris,’ she told Good Health.

‘We had not heard of this species until 2009. Genetic analysis suggests it emerged on different continents at the same time.’

Dr Drummond says climate change may have driven fungi such as Candida auris to adapt to living in warmer situations: ‘Normally fungi don’t like temperatures as warm as the human body. Being hot is one of our best defences against fungal infection.

‘If they are learning to overcome this, there may be a real concern that more of these infections will be likely to afflict us.’

Overuse of current antifungal medicines worldwide is another problem, according to Dr Barton.

He says the high number of cases of Trichophyton indotineae appearing in India ‘probably relate to a lack of drug regulation there’.

‘In India, people use a lot of non-prescription skincare products that contain the antifungal drug terbinafine,’ he says. ‘This may have driven the fungus to develop resistance.’

Such overuse problems have also been seen in Europe, particularly in countries such as the Netherlands, which uses high levels of the ‘azole’ class of antifungals to prevent fungi attacking flower crops — essentially the same drugs are being used on crops as humans.

Numerous reports suggest that this constant exposure has enabled fungi such as aspergillus, which thrive in garden compost and leaf piles, to learn to resist the azole drugs that doctors use as first-line medical treatments for these infections.

Now this story threatens to be repeated. In response to the azole-resistance problem, researchers have developed a promising new antifungal called olorofim, which is in its final clinical trials and could be deployed for use within 12 months.

There are high hopes for olorofim, as it has already shown high effectiveness against fungal infections including azole-resistant aspergillosis. However, a new antifungal — ipflufenoquin — has meanwhile been developed for use in agriculture. Both drugs target the same molecule.

Studies at the University of Manchester have shown that exposure of aspergillus to ipflufenoquin actually spurs the rapid evolution of resistance to olorofim.

As Professor Armstrong-James warns: ‘With olorofim, agricultural use may rapidly cause a repeat of the azole problem. It’s a serious worry.’

His answer, controversially, is to allow the use of genetically modified crops which have DNA that has been artificially engineered to fight off fungal infection.

More immediately, Dr Abdolrasouli says we must have better monitoring of drug-resistant fungal infections in the UK.

‘There is a pattern appearing here with increasing resistance,’ he says. ‘The numbers are growing, so it is very important for us to monitor what’s going on. If we don’t monitor closely, we may

face a major problem that we don’t see coming.’

The emergence of new drug-resistant fungal infections such as ringworm, along with the persistent growth of lethal fungi such as aspergillus and Candida auris, should surely put the world on alert to the growing threat.

But worryingly, we can’t be fully certain from officially released figures how many cases involving these dangerous contagions there are in the UK.

That’s because, as with the ringworm fungus, there is currently no routine system for reporting patient cases of aspergillus infection, as they don’t have a ‘specific reporting code’. This is a code given to an infection for logging it on a central NHS database. If a disease is not coded, its incidence cannot be easily monitored.

Figures from the NHS suggest that there are now as many as 10,000 aspergillosis infections diagnosed in the UK each year, while a 2018 report by the UKHSA indicated that Candida auris had caused large outbreaks in at least three hospitals, with sporadic cases in more than 20 NHS trusts.

But no official body is actively monitoring the actual numbers — and experts fear the true picture may be much worse.

Dr Barton says: ‘We need funding to look at the extent of the infection in the population, as well as studies looking at the sensitivity of the fungus to various drugs and at patient outcomes.’

The health service also needs to be more focused on this — Dr Abdolrasouli warns that currently it is not sufficiently alert to the emerging dangers of drug-resistant fungi.

‘Most of the routine NHS diagnostic laboratories around the country may not be looking at anti- fungal sensitivity testing,’ he says.

‘Major centres in large cities are not performing these tests routinely. It is crucial to introduce national and regional surveillance programmes both in hospitals and in the environment.’

Otherwise we may belatedly wake up to a whole new level of pandemic.

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