Fungal diseases: a silent threat you need to know about

Posted on April 26, 2020   by Gerard Sheehan

Fungal diseases have an enormous public health impact worldwide, with low and middle-income countries disproportionately affected by fungal pathogens. Here, Dr Gerard Sheehan, Research Fellow at the University of Birmingham, explains why it is important to research fungal diseases. 

What are fungi and fungal diseases? 

The word ‘fungi’ usually evokes images of athlete’s foot, mushrooms or common bathroom mould. Ask yourself, can you associate fungi with any other positive or negative impacts on human life? 
Unknowingly, fungal pathogens affect one billion people worldwide. Fungal keratitis (a fungal eye infection) will cause more than a million eyes to go blind. Allergic fungal disease affects ten million people and is particularly common in individuals with lung conditions such as asthma and cystic fibrosis. Serious fungal infections kill approximately 1.6 million people per year; more than malaria and equal to that of tuberculosis (TB). 
Not only do fungal diseases affect humans, they destroy one third of all food crops each and every year – that is enough food to feed 600 million people. A fungal disease of bats known as white-nose syndrome has killed millions of bats in the USA, but interestingly European bats are resistant to this disease. Fungal diseases of insects have been linked to ‘zombie’ or altered behaviour.   

© Gerard Sheehan

Examples of some fungal diseases caused in animals, insects and plants:
(A) White-nose syndrome in bats, caused by Pseudogymnoascus destructans 
(B) Oral candidiasis caused by Candida albicans 
(C) White muscadine disease caused by Beauveria bassiana in insects 
(D) Aspergillus ear rot caused by Aspergillus flavus in corn

What about fungal diseases in Ireland? 

Fungal pathogens will cause an estimated 117,000 serious fungal infections each year in Ireland. Of these, over 90,000 women will get recurrent Candida vaginitis (commonly known as a yeast infection). Approximately 400 people per year will contract invasive Candida infection, which carries a very high mortality or death rate. 
Another common fungal pathogen, Aspergillus (the mould from your bathroom), is the most commonly isolated fungal pathogen from the cystic fibrosis (CF) lung. In Ireland, prevalence of Aspergillus is around 11% in people with CF. Ireland has the highest proportion of people with CF in the world, with more than 1,100 people living with this disease. Aspergillus infections are difficult to treat and frequently can establish co-infections with bacteria in the Pseudomonas genus. Co-infection of Aspergillus and Pseudomonas is associated with poorer clinical outcomes such as decreased lung function. Aspergillus is found growing in the soil and the average person will breath in up to 1,000 spores per day. A healthy immune response eradicates the fungus before any ill health effects are observed. In people that are immunocompromised as a result of cancer chemotherapy, or those who are taking immunosuppressive drugs due to organ transplantation, are at higher risk of developing the invasive type of this disease, which is potentially life threatening.  

Aspergillus lives in the soil and as Ireland's New Children’s hospital is currently under construction in Dublin, there may be significant implications for disease management after the construction finishes. A recent study from St James Hospital outlined the key guidelines associated with addressing this problem. Their main findings recommended regular environmental testing, preventative (or prophylactic) anti-fungal therapy and surveillance to assess the impact of construction, to carefully limit any consequences after the hospital is finished. 

Who are affected the most by fungal infections? 

The reality is that these diseases mostly affect people living in the developing world. For example, fungal meningitis caused by Cryptococcus kills around 181,000 people (which is equivalent to the population of Cork) each and every year. These people are predominately HIV-positive and have no access to anti-HIV or antifungal therapies. In terms of research funding for these diseases, research relating to bacterial meningitis caused by Neisseria meningitidis receives four times higher funding but kills 20 times fewer individuals.  

The recommended treatment for Cryptococcal meningitis is combination therapy of Amphotericin B and flucytosine, which target the fungal lipid membrane and the synthesis of DNA. However, Amphotericin B costs around $100,000 per patient and is only licenced for use in six of 116 developing countries. Flucytosine is a cheaper and effective alternative antifungal drug, but again this isn’t licenced in many of the countries where fungal diseases are a significant public health problem. So, what is used in these cases to treat this disease? Fluconazole: a drug which also targets the lipid membrane surrounding the fungus. But recent data indicates that fluconazole is a sub-optimum treatment and a drug that Cryptococcus can naturally resist. 

An example: eumycetoma 

Some fungal diseases, such as eumycetoma (pronounced eu·my·ce·toma), do not kill their host, but significantly reduce the quality of life of the infected individual. Eumycetoma, associated with tropical and sub-tropical regions, is a chronic disease and is primarily caused by a fungal pathogen Madurella mycetomatis. Over 1,200 cases of mycetoma were reported in the Sudan in just a two and-a-half year period. People affected by this disease have an otherwise healthy immune system.

(A) Madurella mycetomatis fungal cells stained with lactophenol blue
(B) Mycetoma of the hand 
(C) Mycetoma foot

The infection process begins by implantation of fungal particles into the affected tissue. This is usually due to standing on a thorn or a splinter in the hand or foot. The disease presents as massive fungus-like tumours in the tissue and most commonly affects the feet (70% of cases) and hands (12% of cases). If left untreated, it causes severe tissue destruction which can penetrate bone in many cases. Those who come in contact with soil are disproportionally affected by this disease such as farmers, herdsmen and field labourers. Consequently, the disease has severe socio-economic consequences as those infected are usually the providers for the family. Because of the severity and progression of the disease, they can no longer work. Even today after years of significant advances in medicine, this disease remains difficult to diagnose and the only effective treatment is limb amputation and antifungal therapy, but reoccurrence remains an issue. 

Climate change and implications for the very near future? 

Many scientists hypothesise that increasing global temperatures will result in an increase in the incidence of fungal diseases which were commonly associated with tropical regions and see them move into more temperate regions, including Ireland. For instance, some fungal pathogens such as Cryptococcus gattiiHistoplasma capsulatum and Talaromyces marneffei are more abundant in tropical and sub-tropical regions such as South America, Australia, India and mainland China but infections have also been reported in temperate regions such as Europe, the USA and Canada. 

It’s not all bad! 

Fungi also have many benefits and humans have used them for thousands of years to their benefit. In the past hundred years fungi have changed our world. Without fungi we wouldn’t have discovered antibiotics. Penicillin was accidentally discovered from the mould Penicillium, which was inhibiting the growth of a bacterium. Obviously, this discovery is responsible for saving countless lives. 

Without fungi we would have no beer (that means no Guinness!), no wine, no lager. Yeasts provide the enzymes which are essential for fermentation and the production of alcohol. Fungi are also essential in the production of bread, cheese, soya sauce and the meat substitute mycoprotein to name just a few. 

© Gerard Sheehan

 

Fungi can cause mild-to-devasting diseases and affect millions of people worldwide. However, because this is not well known and these diseases predominately affect those in the developing world or people with a compromised immune system, fungal diseases are neglected by research funding bodies, pharmaceutical companies, governments and people in the developed world. 

It is possible that in the coming years these diseases will become more prominent in temperate climates, have detrimental effects on crop production, affecting global food security and threatening the lives of millions worldwide. It is important to know that infections are caused by fungi and not only by bacteria or viruses. Fungii have shaped our daily life, through the beer we drink, to the food we consume, and drugs we take – we can’t neglect fungi any longer.